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Masayuki Endoh

Publications and source records attributed to Masayuki Endoh.

17 recordsLinked to original sources

A scoring system to predict renal outcome in IgA nephropathy: from a nationwide prospective study.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis in the world, and a substantial number of patients develop end-stage renal disease (ESRD). Although there are several prognostic indicators, it remains difficult to predict the renal outcome in individual patients. METHODS: A prospective cohort study was conducted in 97 clinical units in Japan from 1995 to 2002. We analysed the data from 2269 patients using proportional hazards models in order to determine the predictors of ESRD in IgA nephropathy and to develop a scoring system to estimate ESRD risk. RESULTS: During the follow-up (median, 77 months), 207 patients developed ESRD. Systolic hypertension, proteinuria, hypoproteinaemia, azotaemia and a high histological grade at initial renal biopsy were independently associated with the risk of ESRD. Mild haematuria predisposed patients to ESRD more than severe haematuria. A scoring system was developed to estimate the 7-year ESRD risk from eight clinical and pathological variables. Actually, this prognostic score accurately classified patients by risk: patients with estimates of 0.0-0.9, 1.0-4.9, 5.0-19.9, 20.0-49.9, and 50.0-100.0% had a 0.2, 2.4, 12.2, 40.2 and 80.8% of ESRD incidence over 7 years, respectively. The corresponding area under the receiver operating characteristic curve was 0.939 [95% confidence interval (CI), 0.921-0.958]. This score was verified in repetitions of the derivation-validation technique. CONCLUSIONS: Although the quality of some data collected by the mail survey is limited and the influence of therapy could not be considered, this scoring system will serve as a useful prognostic tool for IgA nephropathy in clinical practice.

Adolescent↗

A case with membranous lupus nephritis developing after a twenty-year remission of membranoproliferative glomerulonephritis.

A 30-year-old woman who showed remission of membranoproliferative glomerulonephritis (MPGN) 20 years previously developed membranous lupus nephritis (MLN). She had photosensitivity, facial erythema, proteinuria of 2.59 g/24 hr, anti-nuclear antibody and anti-ds-DNA antibody. To confirm whether a misdiagnosis of MPGN was made 20 years ago, the clinical data at that time were evaluated retrospectively. She had only mild proteinuria and hematuria but no photosensitivity or facial erythema. Anti-nuclear antibody was negative. Renal biopsy showed occasional lobulation and glomerular capillary double contour. The diagnosis of MPGN was definite. This might be a rare case of one person suffering from two types of glomerulonephritis, MPGN and MLN.

Adult↗

[Clinical significance of IgM deposition in the mesangium and mesangial hypercellularity in adult minimal change nephrotic syndrome].

Minimal change nephrotic syndrome(MCNS) typically shows no abnormalities in light microscopy. However, there are some minor light microscopic abnormalities that are considered to be MCNS variants. In pediatric nephrology, some researchers have reported that IgM deposition in the mesangium and mesangial hypercellularity are related to the response to steroid therapy and the long-term course. However, it is not clear whether IgM deposition in the mesangium and mesangial hypercellularity is responsible for the clinical course or the steroid response of patients with adult MCNS. To investigate the clinical importance of IgM deposition in the mesangium and mesangial hypercellularity, clinical records, follow up data, and renal samples of 47 patients with MCNS were reviewed. We also compared the histological data with those of a normal control group (n = 5). In our study, the presence of mesangial IgM deposition did not predict the patient's clinical course or responsiveness to steroid therapy. Increase in the number of nuclei in the glomeruli and PAS-positive area also did not correlate with the clinical course or responsiveness to steroid therapy. The data suggest that mesangial IgM deposits and increased mesangial cellularity in adult MCNS may not predict the clinical course or steroid response. However, we investigated only 47 samples in this study, therefore, further studies are necessary to identify the importance of IgM deposition in the mesangium and mesangial hypercellularity in adult MCNS.

Adult↗

[Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance].

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.

Acute Disease↗

Transposon-independent increase of transcription by the Sleeping Beauty transposase.

When a plasmid encoding the Sleeping Beauty (SB) transposase (pCMV-SB) was cointroduced with luciferase expression plasmid DNA into mouse skeletal muscle at a molar ratio of 4:1, luciferase gene expression was 5 times higher than the expression without pCMV-SB on day 28. This enhancement was not dependent on the presence of transposon (Tn) sequence in luciferase expression plasmid. Southern blot analysis failed to detect luciferase gene insertion into the host genome. Then, expression, a luciferase expression plasmid without Tn, was cointroduced into HeLa cells with or without pCMV-SB. With pCMV-SB, the mRNA amount and the luciferase activity were 1.5 times and 2 times higher, respectively, than without pCMV-SB, even though the cells with pCMV-SB had a smaller copy number of luciferase plasmids than the cells without pCMV-SB. These results suggest that SB transposase enhances the transcription of an exogenous gene regardless of the presence of the Tn sequence.

Animals↗

Neutral-pH peritoneal dialysis solution improves peritoneal function and decreases matrix metalloproteinase-2 (MMP-2) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

BACKGROUND: Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs), and these characteristics contribute to membrane dysfunction in PD patients. The formation of GDPs can be reduced by separating the glucose component of the solution from the lactate component during sterilization. This study was carried out to evaluate the clinical effect of dual-chambered neutral-pH PD solution in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Thirteen CAPD patients using conventional PD solution were enrolled in this study. The fast peritoneal equilibration test (fast PET) was performed periodically before and after treatment with neutral PD solution. The concentration of matrix metalloproteinase-2 (MMP-2) in dialysate effluent was measured using 4-h dwelling 2.5% glucose dialysis solution. The patients were categorized into two groups, according to the value of the initial dialysate/plasma (D/P) creatinine ratio: i.e., lower transporters (group L, D/PCr < 0.65) and higher transporters (group H, D/PCr >/= 0.65). RESULTS: The mean D/P creatinine ratio measured by fast PET, was significantly decreased (0.72 +/- 0.09 to 0.60 +/- 0.06; P < 0.03) after treatment with neutral PD solution in group H. The mean glucose level in 4-h dwelling dialysate effluent was elevated (824.6 +/- 195.9 mg/dl to 942.6 +/- 147.8 mg/dl; P < 0.022) in all subjects. In group H, a significant decrease of MMP-2 in the dialysate effluent was recognized from 15 months after the beginning of treatment with the neutral PD solution (141.4 +/- 52.5 ng/ml to 91.3 +/- 15.1 ng/ml; P < 0.05), with the lowest value being shown at 21 months (80.0 +/- 31.8 ng/ml; P < 0.03). CONCLUSIONS: Neutral-pH peritoneal dialysis solution decreased the MMP-2 level in dialysate and improved peritoneal function in high-transporter patients with CAPD treatment.

Adult↗

Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common form of human glomerulonephritis. Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in the progression of IgAN. Activation of T cells requires costimulatory signals through binding of CD28 receptor with cognate ligands (CD80/CD86) located on antigen-presenting cells (APC). To assess the clinical significance of this regulatory pathway participation in the pathogenesis of IgAN, a comprehensive immunohistologic evaluation was conducted on renal tissue of IgAN in different phases of progressive injury. METHODS: Thirty-three cases of IgAN and ten cases of non-IgA mesangial proliferative glomerulonephritis (PGN) with minor tissue damage as controls were investigated. Monoclonal antibodies were used to assess the expression of CD80, CD86, CD68, CD14, CD45RO, human leukocyte antigen-DR (HLA-DR), and intercellular adhesion molecule-1 (ICAM-1) in renal tissues. Clinical and expression data were compared at the time of renal biopsy. RESULTS: CD80+ and CD86+ cells were observed more in IgAN patients with progressive renal injury than in mild cases and controls. CD80 was limited to tubular epithelial cells and was complemented by HLA-DR expression. CD86 was expressed in the glomerulus, periglomerular area, and peritubular interstitium. Activated T cells (CD45RO+), monocytes (CD14+), macrophages (CD68+), and CD86 showed similar distributions. Positive correlations were found between CD86+ cells and CD45RO, CD14, and CD68 positive cells and between CD80+ tubuli and peritubular interstitial CD45RO+ cells. The number of interstitial CD86 positive cells and the percentage of CD80+ tubuli were correlated with renal function. Most CD86+ cells were monocyte/macrophages. CONCLUSION: This study suggested that CD80 and CD86 activate T cells in IgAN, CD80/CD86 expressions correlated with renal function at the time of renal biopsy, and monocyte/macrophages and tubular epithelial cells act as APC.

Adult↗

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities.

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated form (HBdeltatm) of the molecule. HB(uc/uc) mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBdeltatm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control.

Animals↗

HVJ-envelope vector for gene transfer into central nervous system.

To overcome some problems of virus vectors, we developed a novel non-viral vector system, the HVJ-envelope vector (HVJ-E). In this study, we investigated the feasibility of gene transfer into the CNS using the HVJ-E both in vitro and in vivo. Using the Venus reporter gene, fluorescence could be detected in cultured rat cerebral cortex neurons and glial cells. In vivo, the reporter gene (Venus) was successfully transfected into the rat brain by direct injection into the thalamus, intraventricular injection, or intrathecal injection, without inducing immunological change. When the vector was injected after transient occlusion of the middle cerebral artery, fluorescence due to EGFP gene or luciferase activity could be detected only in the injured hemisphere. Finally, luciferase activity was markedly enhanced by the addition of 50 U/ml heparin (P<0.01). Development of efficient HVJ-E for gene transfer into the CNS will be useful for research and clinical gene therapy.

Animals↗

Costimulatory molecules CD80 and CD86 in human crescentic glomerulonephritis.

BACKGROUND: CD80 and CD86, cell-surface molecules found only on antigen-presenting cells (APCs), are required for activation of CD4-postitve (CD4+) T cells by interaction with CD28/cytotoxic T-lymphocyte-associated antigen 4 on T cells. The roles of these molecules in human glomerulonephritis (GN) presently are unknown. METHODS: Twelve cases of crescentic GN, thought to be a T helper cell-directed delayed-type hypersensitivity-like injury, and 10 controls with non-immunoglobulin A proliferative GN were used. Expression of CD80, CD86, CD4, CD14, CD68, HLA-DR, and intercellular adhesion molecule-1 was investigated in renal tissues using monoclonal antibodies and compared with clinical data at the time of renal biopsy. RESULTS: CD80+ and CD86+ cells were observed significantly more in crescentic GN than in controls. CD86 was expressed in the glomerulus and interstitium, especially in the crescent, and adhesion to Bowman's capsule and periglomerular areas corresponding to these changes. Tubular epithelial cells showed no CD86 expression, but they expressed CD80, and some of them expressed HLA-DR. CD4, CD14, CD68, and CD86 showed similar distribution patterns. Positive correlations were found between CD86+ cells and CD4+, CD14+, and CD68+ cells. The number of interstitial CD86+ cells correlated with deterioration of renal function. Most CD86+ cells were monocyte/macrophages. CONCLUSION: This study suggests that the costimulatory molecules CD80 and CD86 have different expressions in human crescentic GN, and CD86 is concerned with crescent formation and CD4+ T-cell accumulations. The majority of APCs are macrophages, and tubular cells also can act as APCs.

Antigens, CD↗

Glomerular expression of connective tissue growth factor mRNA in various renal diseases.

Connective tissue growth factor (CTGF) is a cysteine-rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA-N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA-N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high-resolution in situ hybridization with digoxigenin-labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF-positive cytoplasm, in at least 10 randomly selected cross-sections of non-sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowman's capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA-N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA-positive cells between DN and IgA-N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA-N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end-stage renal failure.

Adult↗

Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats, assessed by auditory brainstem response.

A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats were divided into three groups: hypothermia group (n = 6), normothermia group (n = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia group, but was kept at 37 degrees C in the normothermia and sham control group. Three months later the rats were assessed by auditory brainstem response, then killed. The normothermia group showed increased III-V latencies and wave V abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologically correlated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermia may provide effective and long-lasting neurofunctional as well as histopathologic protection to the immature brain.

Animals↗

[Usefulness of urine analysis in clinical nephrology].

In chronic glomerular nephritis (CGN), it is important to estimate the renal function and 24 hr urinary protein excretion to estimate the effectiveness of the treatment. In this study, we evaluated the usefulness of a microscopic urine test in making pathological diagnosis. As a result, we found that IgA nephritis has a significantly higher urinary RBC count among the CGN group, and found focal glomerular sclerosis and membranoproliferatine GN patients have significantly higher urinary RBC count among nephrotic patients. Among patients who have moderate renal insufficiency, acute tubular necrosis and acute interstitial nephritis have higher levels in urinary RBC counting. In summary, we can estimate the pathology of renal diseases by microscopic urinary tests to a certain extent. In western countries, physician have used the Cockcroft and Gault formula to estimate creatinine clearance, and they also have used urine protein-to-creatinine ratio to estimate 24 hr urinary protein excretion. We evaluated these formulae with Japanese, and as a result, found lower estimation of creatinine clearance and urinary protein excretion, which may be due to lower their muscle mass. We need further evaluation to make suitable changes to these formulae for Japanese.

Humans↗

Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats.

In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.

Age Factors↗

Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound.

Intrauterine injection of naked DNA expressing luciferase, green fluorescent protein (GFP), or beta-galactosidase (beta-gal) and fluorescein isothiocyanate-labeled oligodeoxynucleotide (FITC-ODN), in combination with microbubble-enhanced ultrasound (US), referred to as the "shotgun method" (SGM), produced high-level protein expression in fetal mice. With the SGM, luciferase expression increased approximately 10(3)-fold in comparison with expression after injection of naked DNA alone. Electron microscopic analysis demonstrated transient formation of pores on the skin surface after intraamniotic (i.a.) injection with the SGM. Widespread expression of GFP and beta-gal and delivery of FITC-ODN were observed in multiple fetal tissues adjacent to the injection points. PCR analysis indicated that germline transfection was only transient following intraperitoneal (i.p) injection, and there was no evidence of transfer of the reporter gene to the offspring. Thus, SGM might provide a useful means to clarify the molecular mechanisms of genetic diseases in utero, as well as a tool to develop gene therapies in utero.

Amnion↗

Acute interstitial nephritis with polyclonal B cell infiltration and development of mantle cell lymphoma.

A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic function developed acute renal failure. His clinical and laboratory examinations showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with high IgG levels. Renal biopsy showed interstitial nephritis with predominant B cell and plasma cell infiltration without monoclonality. After corticosteroid treatment, the patient showed remission in clinical symptoms and laboratory findings. However, one year later, he developed mantle cell lymphoma (MCL) with typical lymphocyte markers of cyclin D1 and CD5. When evaluated retrospectively, this patient appeared to have multicentric Castleman's disease initially and developed MCL later.

Acute Disease↗