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Shuzo Kobayashi

Publications and source records attributed to Shuzo Kobayashi.

At least 19 recordsLinked to original sources
PubMed2025

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats.

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats' renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

Animals↗
PubMed2007

Involvement of transglutaminase-2 in pathological changes in renal disease.

BACKGROUND: Transglutaminase (Tg)-2 is shown to be related to renal fibrosis. However, its roles in human kidney disease have not been fully studied. METHODS: Using immunohistochemistry, we examined Tg-2 expression in renal biopsy specimens from 22 patients with IgA nephropathy (IgAN) and correlated the intensity of Tg-2 staining with clinical and histopathological parameters. We compared the distribution and intensity of Tg-2 staining with those of transforming growth factor (TGF)-beta staining. RESULTS: In normal human kidneys, Tg-2 staining was not significant. In IgAN kidneys, glomerular Tg-2 staining correlated with serum creatinine (S-Cr), creatinine clearance (Ccr), urinary protein excretion, glomerular sclerosis, and mesangial cell proliferation. Tubulointerstitial Tg-2 correlated with S-Cr, Ccr, N-acetyl-beta-glucosaminidase, urinary beta(2)-microglobulin, and tubulointerstitial injuries. Tg-2 staining in the vicinity of vascular poles of glomeruli preceded the development of mesangial lesions, and was more remarkable in cases with renal impairment. The distribution and intensity of Tg-2 staining were not consistent with those of TGF-beta staining. In glomerular crescents, Tg-2 staining was remarkable. CONCLUSION: The present study showed a correlation between Tg-2 expression and renal function and pathological changes. Tg-2 expression in the vicinity of vascular poles was notable because that may be an initial marker of glomerular injury.

Adult↗
PubMed2006

Functional polymorphisms in the vascular endothelial growth factor gene are associated with development of end-stage renal disease in males.

This study elucidates the genetic role of vascular endothelial growth factor (VEGF) as a predisposing factor for progression of chronic kidney disease. Single-nucleotide polymorphisms were genotyped and haplotype structures were determined in the 3' untranslated region (UTR) of VEGF gene, and the distribution of each haplotype in male patients with ESRD (n=101) and healthy male control subjects (n=189) was examined. The 936C/T and 1451C/T polymorphisms in the 3' UTR were in nearly absolute linkage disequilibrium, and haplotype analysis demonstrated that they were the primary responsible single-nucleotide polymorphisms. The distribution of the 936CC-1451CC genotype was significantly more frequent among patients with ESRD than among the age-matched healthy control subjects. In addition to case-control association study, the 936CC-1451CC genotype was also associated with significantly higher plasma VEGF levels in healthy individuals, but a significant association was found only in males, not in females. We also examined the effect of the 936C-1451C haplotype on mRNA stability. Consistent with the results of plasma VEGF levels, mRNA carrying 936C-1451C haplotype showed higher stability. The 936CC-1451CC genotype in the 3' UTR showed not only susceptibility for ESRD but also higher plasma VEGF levels and mRNA stability, indicating the contribution of VEGF to chronic kidney disease progression, especially in males.

Adult↗
PubMed2006

A rare case of combined syndrome of inappropriate antidiuretic hormone secretion and Fanconi syndrome in an elderly woman.

An 83-year-old Japanese woman was admitted to our hospital with severe hyponatremia (sodium, 108 mEq/L [108 mmol/L]), hypokalemia, hypochloridemia, hypocalcemia, hypophosphatemia, and hypouricemia. Despite low plasma osmolarity (232 mOsm/kg [232 mmol/kg]), urine osmolarity (320 mOsm/kg) was greater than that of plasma, and she had increased urinary sodium excretion (88 mEq/L [88 mmol/L]) and an unsuppressed high plasma level of antidiuretic hormone (ADH; 5.5 pg/mL [5.1 pmol/L]). These findings indicated that she had syndrome of inappropriate ADH secretion (SIADH). In addition, she had a generalized reabsorption defect of the proximal tubules, including decreased tubular reabsorption of phosphate, increased fractional excretion of uric acid, glycosuria despite a normal blood glucose level, and panaminoaciduria. Thus, combined SIADH and Fanconi syndrome was diagnosed. The cause was thought to be the antidepressant paroxetine, which is a selective serotonin reuptake inhibitor (SSRI). Several of the abnormal values resolved within 1 week after discontinuation of this drug. Although the precise mechanism responsible was not elucidated, we report an extremely rare case of combined SIADH and Fanconi syndrome, probably caused by short-term SSRI therapy.

Aged↗
PubMed2006

Peripheral arterial occlusive disease is more prevalent in patients with hemodialysis: comparison with the findings of multidetector-row computed tomography.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) influences the mortality of patients on hemodialysis therapy. Although the ankle-brachial pressure index (ABI) is used widely to detect PAOD, it yields false-negative results because of calcifications of vascular walls. To more accurately assess the prevalence of PAOD, we investigated which noninvasive method, among ABI, toe-brachial pressure index, transcutaneous Po(2), and skin perfusion pressure (SPP), had superior sensitivity and specificity to the others. METHODS: Multidetector-row computed tomography was performed in 36 hemodialysis patients. We then compared the 4 noninvasive methods with findings of multidetector-row computed tomography and calculated the sensitivity and specificity of each method by means of receiver operating characteristic analysis. Irrespective of symptoms, PAOD is defined as the presence of complete obstruction in the case of lesions below the knee or more than 75% stenosis for lesions above the knee. RESULTS: Seven of 36 patients (19.4%) had an ABI less than 0.9. Sensitivity of the ABI was only 29.9%, whereas an SPP set at 50 mm Hg was more accurate, with sensitivity of 84.9% and specificity of 76.9%. A total of 41.4% of patients had an SPP less than 50 mm Hg. For lesions located above the knee, toe-brachial pressure index provided sensitivity of 91.7% and specificity of 86.7%. CONCLUSION: SPP is the most useful tool for detecting PAOD in hemodialysis patients, with accuracy of 84.9%. There is a strong possibility that more patients than previously expected have early PAOD.

Adult↗
PubMed2006

LDL-apheresis reduces P-Selectin, CRP and fibrinogen -- possible important implications for improving atherosclerosis.

Although it is known that LDL-apheresis improves coronary artery stenosis (CAS) as well as ischemic limbs seen in patients with peripheral arterial occlusive disease (PAOD), the underlying mechanisms remain still unknown. LDL-apheresis might exert its favorable action through anti-inflammatory effects. We studied whether or not serum or plasma levels of P-selectin, high sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1) or fibrinogen could be reduced in patients with PAOD before and after 10 sessions of LDL-apheresis. Sixteen patients (12 patients with hemodialysis, HD) with PAOD were enrolled in the present study. LDL-apheresis was carried out 10 times (treated plasma of 3000 mL) over 5 weeks. Serum levels of P-selectin were significantly reduced from 516 +/- 153 to 290 +/- 52 ng/mL before and after 10-sessions of LDL-apheresis, respectively (P < 0.05). Likewise, serum levels of hsCRP decreased from 9.118 +/- 2.649 to 5.587 +/- 2.445 mg/L (P < 0.01); and plasma fibrinogen levels statistically decreased from 196 +/- 9.82 to 149 +/- 7.97 mg/dL (P < 0.01), whereas serum levels of MCP-1 were not significantly changed. The favorable actions of LDL-apheresis might include anti-inflammatory effects, which could lead to an improvement of CAS and PAOD. Moreover, this intervention might be applicable for patients with atherosclerotic cardiovascular disorders, particularly in patients with HD.

Adult↗
PubMed2006

Impact of hypertension and hypertension-related vascular lesions in IgA nephropathy.

It remains poorly understood whether vascular pathology plays an important role in the progression of renal parenchymal disease in humans. Moreover, in the case of hypertensive patients with mild proteinuria, nephrologists tend to make a diagnosis of benign nephrosclerosis without renal biopsy. Among 172 patients who were treated at our hospital for biopsy-proven IgA nephropathy, we performed quantitative histopathological analysis in 38 patients with mild proteinuria of less than 0.5 g/day. We related these histopathological parameters with clinical data at biopsy and also with follow-up data. The percentage of glomeruli showing global sclerosis exceeded 10% of total glomeruli in 15 of the patients (39.5%) and exceeded 20% in 9 (23.7%). Arteriosclerosis and tubulointerstitial changes significantly correlated with glomerular sclerosis, but mesangial cell proliferation did not. Among the 38 patients, the 12 with hypertension showed more severe glomerular sclerosis, tubulointerstitial changes and arteriosclerosis compared with the 26 without hypertension, but the mesangial cell proliferation was identical between the two groups. Stepwise multiple regression analysis revealed that hypertension and urinary protein excretion (UPE) were independent risk factors for arteriosclerosis. The follow-up data of a mean period of 27.6 months showed that 9 of the 38 patients (23.7%) had an increase in UPE. Hypertension, arteriosclerosis, age, and UPE at biopsy were selected as the important risk factors for an increase in UPE in the follow-up. Our results provide not only clinical but histopathological evidence that hypertension affects the prognosis of mild proteinuric nephropathy through vascular lesions.

Adolescent↗
PubMed2005

Haplotype analysis of NAD(P)H oxidase p22 phox polymorphisms in end-stage renal disease.

NAD(P)H oxidase is one of the most important sources of reactive oxygen species and has been demonstrated to be upregulated by angiotensin II in the kidney. Given the effect of angiotensin-converting enzyme inhibitors on the progression of both diabetic and non-diabetic renal disease, we hypothesized that the polymorphisms of NAD(P)H oxidase are associated with development of end-stage renal disease (ESRD). We examined five polymorphisms in the CYBA gene encoding the p22 phox component of NAD(P)H oxidase, including 242C/T and 640A/G polymorphisms in 467 ESRD patients and 490 healthy individuals. The T allele of the 242C/T polymorphism showed a protective effect against ESRD only in the nondiabetic (non-DM) group (P = 0.0095), and haplotype estimation revealed that the frequency of 242C-640A was higher in the non-DM group (46.7%) than in the control group (39.7%). The CC-AA genotype was still significantly associated with ESRD without diabetes after adjusting for confounding factors (P = 0.035). In contrast, there was no difference between the DM group and the control group. In conclusion, we identified a risk haplotype for nondiabetic ESRD in the CYBA gene using haplotype analysis. Haplotype analysis proved useful for elucidating the genetic contribution of NAD(P)H oxidase p22 phox to ESRD.

Adult↗
PubMed2005

High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination.

The prevalence of coronary artery stenosis (CAS) at the initiation of renal replacement therapy (RRT) in patients with chronic kidney disease (CKD) and no previous history of angina and/or myocardial infarction (MI) has not been fully elucidated. The prevalence of significant CAS was evaluated in 30 asymptomatic stage 5 CKD patients without a history of angina and/or MI by coronary angiography at the initiation of RRT. The correlations of various parameters with the prevalence of CAS were also examined. Atherosclerotic surrogate markers, including intima-media thickness of carotid artery and ankle-brachial BP index (ABI), were also evaluated. Significant CAS (>50% stenosis) was seen in 16 (53.3%) of 30 asymptomatic CKD patients on coronary angiography at the start of RRT. Stress cardiac scintigraphy was not effective for detecting hidden cardiac ischemia among the CKD patients. Univariate analysis showed that diabetes (P = 0.01), left ventricular mass index (P = 0.04), hyperlipidemia (P = 0.04), total cholesterol (P = 0.02), LDL cholesterol (P < 0.01), intima-media thickness (P = 0.04), and fibrinogen (P = 0.01) were positively correlated with the presence of CAS, whereas ABI (P < 0.01) showed a negative correlation with CAS. Stepwise logistic regression analysis revealed that diabetes and fibrinogen were significant and independent risk factors for CAS in asymptomatic CKD patients who started RRT. The results clearly demonstrated that despite the absence of cardiac events, stage 5 CKD patients are already in a very high risk group for CAS at the initiation of RRT, which was also closely associated with a significant decrease in ABI.

Adult↗
PubMed2005

LDL-apheresis improves peripheral arterial occlusive disease with an implication for anti-inflammatory effects.

Although it is known that LDL-apheresis improves ischemic limb seen in patients with peripheral arterial occlusive disease (PAOD), anti-inflammatory effects are not well known. We studied whether or not serum or plasma levels of high sensitivity C-reactive protein (hsCRP), monocyte chemoatractant protein-1 (MCP-1), or fibrinogen could contribute to favorable effects for ischemic limbs after LDL-apheresis. Twenty-eight patients with PAOD (24 men, 4 women) were enrolled in our study. LDL-apheresis was performed 10 times (treated plasma of 3,000 ml) for 5 weeks. Serum levels of logarithmically transformed values of hsCRP significantly decreased from 3.666 +/- 0.126 to 3.482 +/- 0.139 ng/ml before and after a single session of LDL-apheresis (P < 0.001). Serum levels of MCP-1 decreased from 233 +/- 17.5 to 187 +/- 13.5 pg/ml before and after LDL-apheresis (P < 0.05). Likewise, plasma fibrinogen levels statistically decreased from 196 +/- 9.82 to 159 +/- 9.60 mg/dl (P < 0.001). Overall rates of improvement including foot chillness or numbness, and double folds increase in walking distance were 82.1% 3 months after a completion of LDL-apheresis, while gangrene was only improved 14.3%. Intermittent claudication improved in 53.6%. The favorable actions of LDL-apheresis might include anti-inflammatory effects. To avoid amputation, LDL-apheresis should be applied for patients with PAOD at an early stage of the disease process and may be applicable for patients with atherosclerotic cardiovascular disorders.

Adult↗
PubMed2005

Insulin resistance in patients with chronic kidney disease.

BACKGROUND: It has been reported that insulin resistance appears at an earlier stage of chronic kidney disease (CKD). However, few data are available concerning what factors of metabolic abnormalities, such as apolipoprotein (Apo) profile or acidosis, might be associated with insulin resistance in patients with CKD. METHODS: We used the hyperinsulinemic euglycemic glucose clamp technique to examine insulin sensitivity in patients without diabetes (n = 29) with different stages of renal function. Results were compared with those in healthy subjects (n = 10) and related to various affecting variables. RESULTS: In healthy subjects, the glucose disposal rate (GDR) was 9.93 +/- 1.33 mg/kg/min. The GDR of patients with CKD (6.91 +/- 2.46 mg/kg/min) was significantly less than that of healthy subjects ( P < 0.01), which shows diminished insulin sensitivity in patients with CKD. There was a negative correlation between GDR and serum creatinine level ( r = -0.449; P < 0.05) and positive correlations between GDR and creatinine clearance ( r = 0.549; P < 0.01) and Apo A-1/B levels ( r = 0.396; P < 0.05). Of particular relevance is the observed close correlation between GDR and bicarbonate level, with an extremely high predictive value for degree of acidosis ( r = 0.611; P < 0.0005). Stepwise multivariate regression analysis selected bicarbonate (F = 13.28) and Apo A-1/B levels (F = 6.58) as independent contributing variables. CONCLUSION: We found that insulin resistance correlated linearly with decline in renal function. Independent variables related to insulin resistance were bicarbonate and Apo A-1/B levels in patients with CKD.

Adult↗
PubMed2005

Manganese-induced Parkinsonism in a patient undergoing maintenance hemodialysis.

We report a rare case of manganese (Mn)-induced parkinsonism in a patient on maintenance hemodialysis therapy who complained of gait disturbance and dysarthria. His symptoms and abnormal magnetic resonance imaging (MRI) findings of the brain were thought to be caused, at least in part, by long-term ingestion of a health supplement (Chlorella extract) that contained 1.7 mg of Mn in the usual daily dose. Elevated serum and cerebrospinal fluid Mn levels were detected, and brain MRI showed areas of abnormal intensity in the bilateral basal ganglia (low intensity on T1-weighted images and high intensity on T2-weighted images). Edetic acid infusion therapy dramatically improved the MRI abnormalities, after which his symptoms gradually improved 4 months later.

Apiaceae↗
PubMed2005

Correlation between the resistive index by Doppler ultrasound and kidney function and histology.

BACKGROUND: Although duplex Doppler ultrasonography has been used widely, it still is unknown whether resistive index could be related directly to vascular or tubulointerstitial changes in the kidney. METHODS: Thirty-three patients who underwent renal biopsy were included in the present study. Clinical data, including sex; age; time from abnormal urinalysis result to biopsy; serum creatinine level; creatinine clearance; urinary excretion of protein, N-acetyl-beta-glucosaminidase, and urinary beta2-microglobulin; and presence of hypertension, were recorded at biopsy. Histopathologic data, including glomerular sclerosis, interstitial fibrosis/tubular atrophy, interstitial infiltration, and arteriolosclerosis, were evaluated separately by means of a quantitative or semiquantitative method. We examined whether resistive index at biopsy was related to these clinical and histopathologic parameters and, moreover, to renal outcome in patients followed up for more than 2 years. RESULTS: Age, creatinine clearance, urinary beta2-microglobulin excretion, and all histopathologic parameters showed statistically significant correlations with resistive index. However, stepwise multiple regression analysis showed that only arteriolosclerosis was chosen as an independent risk factor for increased resistive index. During the follow-up period of 57.5 +/- 15.6 months in 29 patients, 8 patients (27.6%) had progression of renal impairment, defined as an increase in serum creatinine level greater than 50%. They had a significantly increased resistive index at biopsy compared with patients without progression. CONCLUSION: We show a direct relationship between resistive index and arteriolosclerosis in damaged kidneys. Resistive index at renal biopsy may be useful as one of the prognostic markers for renal outcome.

Acetylglucosaminidase↗
PubMed2005

Amyloidosis associated with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), the most common form of leukemia in Western countries, rarely induces glomerular disease, but membranoproliferative glomerulonephritis or immunotactoid glomerulopathy has been reported. The proliferating cells in CLL are of mature B-cell origin and produce monoclonal immunoglobulin (Ig), thus leading to various kinds of autoimmune disorders or immunotactoid glomerulopathy. Although there have been a few reported cases of amyloidosis accompanying CLL, the type of amyloid fibrils has not been demonstrated nor described in detail, particularly regarding monoclonal Ig productivity. We report a rare case of amyloidosis associated with CLL, in which we detected ?-light chain type monoclonal Ig in the sera, urine, and on the surface membrane of lymphocytes, and discuss an association between monoclonal Ig-related disease and non-Hodgkin's lymphoma.

Amyloidosis↗
PubMed2005

Important role of blood rheology in atherosclerosis of patients with hemodialysis.

Concerning a role of blood rheology for atherosclerosis in patients with hemodialysis (HD), little data are available. It may be due to the fact that the method for evaluating rheologic properties of circulating blood has been limited. We examined blood rheology in 118 HD patients by using microchannel array flow analyzer that makes it possible to directly observe the flow of blood cell elements through the microchannel. Transit time (T(B)) of heparinized whole blood through slit pores (7 x 30 microm) was used as an index of rheology and related with various inflammatory biomarkers such as high-sensitive CRP (hsCRP), monocyte chemotactic protein-1, osteopontin, or fibrinogen (Fg). Moreover, as a surrogate marker of atherosclerosis, carotid intima-media thickness (IMT) and aortic stiffness evaluated by brachial-ankle pulse-wave velocity (baPWV) were studied. In HD patients, T(B) had strong positive correlations with hsCRP (r = 0.427; p < 0.00001), Fg (r = 0.452; p < 0.00001), and osteopontin (r = 0.227; p < 0.0134). Further, T(B) was significantly well correlated with IMT (r = 0.400; p < 0.0001) and PWV (r = 0.470; p < 0.0001). Multivariate regression analysis showed that baPWV, IMT, Fg, hematocrit, white blood cell count, and CRP were chosen as significant explanatory factors for T(B.) These results suggest that blood rheology may play an important role for atherosclerosis in patients with HD.

Adult↗
PubMed2004

Pravastatin has an additional depressor effect in patients undergoing long-term treatment with antihypertensive drugs.

BACKGROUND: Statins have been reported to have direct vascular effects independent of cholesterol reduction. To assess the antihypertensive effect of statins, a crossover study was designed to compare the depressor effect of pravastatin and probucol in hypertensive patients undergoing long-term treatment with antihypertensive drugs. METHODS: The subjects enrolled in this study were 52 hypertensive patients (22 men and 30 women, mean age 62.8 +/- 9.3 years) who were treated with the same antihypertensive drugs for more than 1 year and had serum cholesterol levels of more than 5.69 mmol/L. In 26 subjects, pravastatin at a dose of 10 mg/d was given first for 6 months followed by treatment with probucol at a dose of 500 mg/d, and vice versa in the remaining 26 subjects. Serum lipids, apolipoproteins, glucose, and insulin were measured on the final day of the control period, and pravastatin and probucol treatments. The homeostatic model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance. RESULTS: The blood pressure decreased after pravastatin treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 136.5 +/- 5.3/80.6 +/- 5.1 mm Hg, P <.001/.499), but did not decrease after probucol treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 141.4 +/- 4.9/80.8 +/- 4.9 mm Hg, P =.832/.634). Total cholesterol decreased significantly after pravastatin (6.69 +/- 0.69 to 5.23 +/- 0.77 mmol/L, P <.001) and probucol treatment (6.69 +/- 0.69 to 5.53 +/- 0.64 mmol/L, P <.001). The HOMA-IR was decreased by probucol (1.92 +/- 0.78 to 1.57 +/- 0.59, P =.029), whereas pravastatin had no effect on HOMA-IR. CONCLUSIONS: It can be concluded that the depressor effect of pravastatin may have an additional benefit in the treatment of hypertensive patients with hyperlipidemia without any adverse effect on insulin sensitivity.

Adult↗