Biomedical subjects

Shuzo Kobayashi

Publications and source records attributed to Shuzo Kobayashi.

27 records · Page 2Linked to original sources

PubMed2004

Asymptomatic cerebral lacunae in patients with chronic kidney disease.

BACKGROUND: It remains unknown whether the prevalence of silent lacunar infarcts increases as renal function declines or what factors known as atherosclerotic risk factors are related to the development of lacunar infarcts. METHODS: Fifty-one patients with chronic kidney disease without diabetes mellitus and 80 patients with essential hypertension with normal renal function were included in the study. The existence of lacunar infarcts was evaluated on brain magnetic resonance imaging scans. We evaluated the severity of carotid atherosclerosis by means of intima-media thickness of 1.0 mm or greater height in bilateral carotid arteries and by affecting factors, including plasma homocysteine levels. RESULTS: Lacunae prevalence was 25% in patients with a creatinine clearance (Ccr) greater than 40 mL/min/1.73 m2, 85% in patients with a Ccr less than 40 mL/min/1.73 m2, and 29% in patients with essential hypertension with normal renal function. Patients with lacunae had significantly lower hematocrits associated with increased fibrinogen and lipoprotein(a) levels compared with those without lacunae. Plasma total homocysteine and insulin levels at 2 hours after a 75-g glucose tolerance test correlated significantly with lacunae. Ischemic heart changes shown by electrocardiogram and thickened carotid intima-media thickness were significantly more frequent in patients with lacunae. However, logistic regression analysis showed that the most strongly contributing factor for lacunar infarcts was decline in Ccr (confidence interval, 0.933 to 0.995; P < 0.05). CONCLUSION: Decreased renal function, even without diabetes mellitus, is a risk factor for silent lacunar infarcts.

Anemia↗

PubMed2004

Galectin-3-positive cell infiltration in human diabetic nephropathy.

BACKGROUND: Galectin-3 has several functions, such as cell proliferation, regulation of apoptosis and interaction of cell adhesion, and has a high binding affinity for advanced glycation end products. In animal models with diabetic nephropathy (DMN) or acute renal failure, galectin-3 is known to be upregulated. However, galectin-3 expression has not been investigated in human kidney diseases. METHODS: Using immunohistochemistry we examined galectin-3 expression in renal biopsy specimens obtained from 37 patients with nephropathy: DMN (n = 9), IgA nephropathy (n = 9), crescentic glomerulonephritis (n = 8), membranous nephropathy (n = 6) and minimal change nephrotic syndrome (n = 5). RESULTS: In normal human kidney, galectin-3 was found in distal tubuli, but not in glomeruli. However, galectin-3-positive cell infiltration was observed in glomeruli of 12 patients. Galectin-3-positive cells, also stained with CD68, were significantly more numerous in glomeruli of DMN than in glomeruli of other nephropathies. The ratio of galectin-3-positive cells to the total number of macrophages in tubules was also significantly increased in DMN. There was a significant correlation between the number of galectin-3-positive cells in glomeruli and urinary protein excretion in all patients (r = 0.616, P<0.001). In diabetic patients, the number of galectin-3-positive cells in glomeruli closely correlated with the regression rate of renal function (r = -0.930, P<0.005). CONCLUSION: These findings suggest that galectin-3-positive cell infiltration may play an important role in the progression of DMN, and the degree of its expression may be predictive of poor prognosis of DMN.

Adult↗

PubMed2003

LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limb.

Although it is known that LDL-apheresis improves ischemic limb seen in patients with peripheral arterial occlusive disease (PAOD), the underlying mechanism(s) still remains unknown. We studied whether vascular endothelial growth factor (VEGF) and/or insulin-like growth factor-I (IGF-I) levels correlated with improvement of ischemic limbs after LDL-apheresis. Sixteen patients with PAOD (13 men, 3 women) were enrolled in our study. LDL-apheresis was performed 10 times (treated plasma 3,000 ml) for 5 weeks. Serum level of VEGF significantly increased from 262 +/- 171 pg/ml to 306 +/- 165 pg/ml before and after LDL-apheresis (P < 0.05). This value further increased up to 441 +/- 175 pg/ml 3 months after the end of this therapy (P < 0.01, compared with the basal value and P < 0.05, compared with the value at the end of 10-times session). Increased levels of VEGF paralleled increases in the ankle-brachial pressure index (ABI). After 10-times therapy, IGF-I significantly decreased (P < 0.05), but increased over the basal value 3 months after this therapy. Plasma fibrinogen statistically decreased and remained low for 3 months. The favorable effects of LDL-apheresis may be ascribed to up-regulation of VEGF and IGF-I associated with decreased fibrinogen levels.

Aged↗

PubMed2003

Vitamin E-bonded hemodialyzer improves atherosclerosis associated with a rheological improvement of circulating red blood cells.

BACKGROUND: Vitamin E-bonded hemodialyzer is known to improve oxidative stress in patients with hemodialysis. However, there is little information available as to whether or not this membrane clinically improves atherosclerosis. Furthermore, it remains unknown whether there is any effect of the membrane on rheology of circulating red blood cells. METHOD: We conducted a randomized, open-labeled, prospective control study (N = 34) for 1 year to investigate the effect of vitamin E-bonded cellulose membrane dialyzer (EE) (N = 17) on carotid atherosclerotic changes [intima-media thickness (IMT) of carotid arteries] and the viscosity, percentage of dysmorphism (%DMR) of red blood cells (RBCs) and their distribution width-standard deviation (RDW-SD), in comparison with cellulose membrane (SU) (N = 17) identical to EE without vitamin E-bonded membrane. Erythropoietin (EPO) dose used for the treatment of uremic anemia was also calculated. RESULTS: The IMT significantly decreased in the EE group, while in the SU group the IMT significantly increased. The viscosity of RBCs in hemodialysis patients (4.70 +/- 0.45 cP) was greater than that in healthy individuals (3.73 +/- 0.15 cP). EE significantly improved the viscosity (from 4.84 +/- 0.41 cP to 4.51 +/- 0.54 cP, P < 0.01), %DMR (from 2.29 +/- 2.17% to 1.90 +/- 1.49%, P < 0.01), and RDW-SD (from 54.4 +/- 7.6 fL to 49.3 +/- 5.9 fL, P < 0.01). On the contrary, these parameters all worsened in the SU group. EPO dose needed for the treatment of anemia was significantly (P < 0.05) reduced from 5383 +/- 2655 U/week to 4235 +/- 3103 U/week in the EE group. During these period, mean blood pressure, Kt/V urea, and serum beta2-microglobulin were not changed between the two groups. CONCLUSION: These findings suggest that vitamin E-bonded hemodialyzer is very useful for improving atherosclerosis from a clinical point of view. As one of the underlying mechanisms, as well as antioxidant effects, we want to address an important role of the improvement of rheology of circulating RBCs, which may also help to reduce the requirement of EPO dose in the treatment of anemia of ESRD patients.

Aged↗

PubMed2002

A composite hormone response element regulates transcription of the rat GHRH receptor gene.

To further elucidate the molecular mechanisms underlying the transcriptional regulation of the GHRH receptor (GHRH-R) gene, hormonal regulation of the promoter activity of this gene was examined. An approximately 3-kb genomic fragment spanning the promoter region of the gene was sequenced and the transcription start site was determined by RT-PCR and RNase protection assay. A major start site was localized at -105 (relative to the translation initiation codon, ATG), and a pit-1 binding sequence characteristic of pituitary specific genes was found at -155 to -146. Deletion and mutation studies demonstrated this site to be functional. In the presence of dexamethasone, the GHRH-R promoter (from -2935 to -11) directed luciferase expression in MtT-S cells, a somatotropic cell line, but not in the PC12 cells that normally do not express GHRH-R. While T(3), all trans-RA, and 9cis-RA alone weakly enhanced the reporter gene expression, each of these substances was found to act as a synergistic enhancer in the presence of dexamethasone. Additional deletion and mutation analyses demonstrated a functional RA response element at -1090 to -1074. Two functional glucocorticoid response elements and a T(3) response element were found in an 80-bp 5'-flanking sequence of the pit-1 site. Interestingly, it is suggested that the 6-bp half-site AGGACA (from -209 to -204) functions as a 3'-half-site of T(3) response element as well as a 5'-half-site of one of the glucocorticoid response elements.

Animals↗

PubMed2002

Angiotensin II and IGF-I may interact to regulate tubulointerstitial cell kinetics and phenotypic changes in hypertensive rats.

Angiotensin II and insulin-like growth factor-I (IGF-I) are known to be actively involved in the pathogenesis of progressive renal injury, particularly in cell proliferation and phenotypic changes that contribute to tubulointerstitial injury. To investigate the possible mechanisms by which angiotensin II type 1 receptor antagonist (AIIA) ameliorates renal injury in a renal ablation model and to determine the contribution of phenotypic changes and IGF-I to morphological changes, we examined 1) whether AIIA attenuated phenotypic changes as markers of alpha-smooth muscle actin (SMA) and vimentin, 2) whether AIIA altered renal IGF-I expression, and 3) the changes of tubulointerstitial cell kinetics between apoptosis (tested via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling, TUNEL) and cell proliferation (a test of proliferating cell nuclear antigen, PCNA). Following a sham operation (sham) or 5/6 nephrectomy (Nx), we administered E4177, a potent, selective competitive angiotensin II type 1 receptor antagonist (AIIA), for 10 weeks. In Nx rats, SMA and vimentin expressions developed in injured tubulointerstitium, particularly in hypoperfused scar-adjacent areas, and there was an increase in renal IGF-I expressions. The TUNEL score increased 5-fold and PCNA increased 8-fold, compared with TUNEL and PCNA measurements in sham-operated rats. Renin expression in the juxtaglomerular apparatus was markedly suppressed in the Nx group, although de novo tubular renin expression appeared in Nx, compared with that in the sham group. E4177, both 10 mg/kg (AIIA 10) and 1 mg/kg (AIIA 1), markedly ameliorated renal injury, although blood pressure was less affected in AIIA 1. Both AIIA 10 and AIIA 1 suppressed the neoexpressions of SMA and vimentin in an association with decreased IGF-I expression. Regarding cell kinetics, neither AIIA 10 nor AIIA 1 decreased the TUNEL score; rather, tended to increase, while PCNA was significantly suppressed by AIIA. In conclusion, one of the underlying protective mechanisms of AIIA in this model may be related to the modulations of angiotensin II-induced phenotypic changes and tubulointerstitial cell kinetics through IGF-I.

Actins↗

PubMed2002

Successfully treated "accelerated" renovascular hypertension with intravascular stenting.

A 76-year-old man developed progressive renal dysfunction with refractory hypertension. Bilateral renal artery stenosis due to atherosclerosis was revealed. Both the hypertension and renal dysfunction were improved by percutaneous transluminal renal angioplasty with stenting. Based on the rapidly progressive elevation of plasma renin activity and the improvement of both renal dysfunction and hypertension after stenting, this was considered a case of "accelerated" renovascular hypertension. There have been an increasing number of patients with bilateral renal artery stenosis due to atherosclerosis. The present case reminds us that a rapid progression of renal dysfunction suggests, in addition to besides rapidly progressive glomerulonephritis with crescent formation, bilateral renal artery stenosis, the incidence of which is on the rise. In the present case, angioplasty with stenting was effective for blood pressure control and preservation of renal function.

Aged↗

PubMed2002

[Two cases of atherosclerotic renal artery stenosis treated by percutaneous transluminal renal angioplasty and intravascular stent placement, leading to improvement of hypertension and renal function].

We describe here two cases of renal artery stenosis(RAS) caused by atherosclerosis. Both patients were treated by percutaneous transluminal renal angioplasty(PTRA) and stent placement, leading to the improvement of renal function as well as hypertension. The two patients were a 75-year-old male(case 1) and a 56-year-old male(case 2), who both showed mild proteinuria, renal dysfunction, and refractory hypertension. Case 1 showed a unilateral ostial stenosis in the left main renal artery. On the other hand, case 2 showed an ostial stenosis in the left renal artery and a widespread narrowing in the right renal artery. After evaluation of the lesions by renal Doppler sonography, renogram, magnetic resonance signal intensity, and magnetic resonance angiography(MRA), each stenosis was treated by balloon angioplasty and intravascular stent placement without any major complications. Thereafter, in addition to hypertension, renal function also ameliorated significantly, and has remained stable for more than 12 months. Non-invasive screening tests and appropriate therapy for renovascular lesion should be considered in the case of elderly patients with refractory hypertension and progressive renal dysfunction, since ischemic nephropathy is increasing as a common cause of end stage renal disease and is showing favorable outcomes of revascularization.

Aged↗

PubMed2002

[Pathological analysis of renal diseases with mild proteinuria].

Proteinuria is an important predictor of renal outcome in a variety of renal diseases. Proteinuria exceeding 0.5 g/day is often considered to be a major indication of renal biopsy. In this study, we analyzed the clinical and histopathological data of 58 patients with mild proteinuria of less than or equal to 0.5 g/day. The histopathological diagnosis included 45 cases(77.6%) of mesangial proliferative glomerulonephritis, 4 cases(6.9%) of lupus nephritis, one case of membranoproliferative glomerulonephritis and only 6 cases(10.3%) of minor glomerular abnormality. The percent sclerotic glomeruli exceeded 10% in 17 cases(29.3%) and reached 71.4% in 2 cases. There were no significant differences in histopathological parameters(percent sclerotic glomeruli, tubulointerstitial change, arterio-arterio sclerotic change) between the groups with or without microhematuria. There was a positive correlation between age and percent sclerotic glomeruli. Percent sclerotic glomeruli in our cases were higher than in the healthy population reported by Kaplan et al. and the influence of glomerulonephropathy was obvious. During the follow-up period(mean 19.7 months), one patient progressed to chronic renal failure and 2 patients had increased urinary protein excretion, but the others did not. These results suggest the importance of clarifying the prognosis by renal biopsy even in cases with mild proteinuria.

Adolescent↗