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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 199 records · Page 11Linked to original sources

A Cl- channel activated by parathyroid hormone in rabbit renal proximal tubule cells.

Previous data suggested an active Cl- conductance in the renal proximal convoluted tubule, although single channel conductance and regulation were not found. We have investigated the presence and regulation of the Cl- channel in proximal convoluted tubules by patch clamp analysis. The current-voltage relationship of whole cells with 130 mM NaCl in the pipette was nonlinear. The addition of 1-34 PTH (10(-8) M), forskolin, or cAMP significantly increased whole cell Cl- conductance. We found a single Cl- channel in excised apical membranes possessing conductance of 33 picosiemens (pS) at positive and 22.5 pS at negative potential, which was blocked by 4,4'-diisothiocyanostilbene-2,2'- disulfonic acid (10(-4) M) and was selective to Cl- (Cl/Na = 10). The channel was activated by prolonged membrane depolarization, by a catalytic subunit of protein kinase A (PKA), or by purified kinase C (PKC), but not by Ca2+ (1 microM) inside the membrane. During cell-attached patch clamping, the channel was similarly activated by PTH, phorbol ester, or dibutyryl cAMP in a dose-dependent manner. To investigate second messenger contributions to the PTH-action, the PTH-evoked channels were modified further by the subsequent addition of several blockers of the second messengers. This suggested that PKA and PKC were involved in Cl- channel activation. We therefore conclude that renal proximal convoluted tubule cells possess an apical Cl- channel activated by PTH via the PKA and PKC pathways.

Animals↗

Differential effects of antihypertensive agents on proliferation of vascular smooth muscle cells from spontaneously hypertensive rats.

We have previously shown that Ca-antagonists and alpha-blockers substantially inhibit the cellular proliferation of cultured rat vascular smooth muscle cells (VSMC). This study explored whether these inhibitory effects on cellular proliferation differ between cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR VSMC proliferated much faster than WKY VSMC in 10% FCS. Cellular proliferation, determined by both cell number count and 3H-thymidine incorporation, was significantly blunted in the presence of either nifedipine (Nif) or bunazosin (Bun). The magnitude of these inhibitory effects was more pronounced for SHR cells than WKY cells (% reduction of 3H-thymidine uptake with Nif: 62.1 +/- 7.8% for SHR vs 75.3 +/- 10.2% for WKY, n = 6, p less than 0.05, and with Bun: 70.2 +/- 7.8% for SHR vs 82.1 +/- 9.9% for WKY, n = 6, p less than 0.05). In contrast, the intracellular water volume was unaffected by these antihypertensive agents based on equilibrium distribution of 3-O-methyl-D-glucose14C. It is concluded that SHR VSMC grow much faster than WKY VSMC and that this abnormality is innate to the SHR cells. It is also concluded that both Ca-antagonists and alpha-blockers exerted a substantial inhibitory effect on cellular proliferation of the cultured VSMC of either SHR or WKY. Furthermore, the greater inhibition of proliferation in the SHR VSMC suggests that Ca mediated- and/or alpha-receptor mediated processes of cellular proliferation of SHR could differ from that of WKY and that these abnormalities may contribute to the hyperproliferative changes of VSMC in this model.

Adrenergic alpha-Antagonists↗

An experimental study on selective elimination of beta 2-microglobulin using immunoadsorption method in patients with chronic renal failure.

We studied selective elimination of beta 2-microglobulin (beta 2-m) from plasma of patients with chronic renal failure (CRF) by using immunoadsorption method. Anti-human beta 2-m antibody of rabbit IgG was coated with cellulose beads, which were filled into a small-column. One gm of cellulose beads contains 5.0 mg of the protein of antibody. Five to 7 ml of plasma samples with 40 to 70 mg/l of beta 2-m were passed through the column at 1.0 ml/10 min and each effluent was then collected by 1.0 ml consecutively. Before and after passing through the column, beta 2-m and other plasma proteins were measured. Plasma beta 2-m concentrations in all the effluent fractions after passing through the column were greatly reduced to 1/100. But no other plasma protein components than beta 2-m varied in concentration. Neither Immune complex (IC) nor rabbit IgG was detected in any effluent fraction. These results indicate that selective and effective elimination of beta 2-m from plasma in patients with CRF was possible by using our method. In addition, since neither IC nor rabbit IgG was detected in the effluent, this method was considered to be clinically applicable.

Antigen-Antibody Complex↗

[Vesicoureteral reflux and renal scarring. Report of cooperative study of "Progressive renal disease" of Ministry of Health and Welfare].

196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 0.01) from 0.60 +/- 0.89 to 0.084 +/- 0.305 times/patient. year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux. Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR.

Adult↗

[Intravenous cyclophosphamide therapy in patients with steroid-resistant lupus nephritis].

We evaluated short term clinical effects of intravenous cyclophosphamide (iv CyP) therapy performed by every three month in 7 patients with steroid-resistant lupus nephritis. Significant improvements were observed in daily urinary protein excretion (3.1 to 0.83 g/day), creatinine clearance (65.4 to 95.3 ml/min), CH 50 levels (20.8 to 37.4 U/ml), and anti-DNA antibody titer (26.6 to 7.0 U/ml). In addition, the mean daily dose of prednisolone (PSL) could be markedly reduced from 38.6 mg to 13.9 mg at the final observation. Two patients suffered from Herpes Zoster infection at a few months after ivCyP therapy, however this incidence were not considered as critical side effect which reached to the discontinuation of this therapy. We concluded that ivCyP therapy by every three months were safety and achieved beneficial clinical effects on steroid-resistant lupus nephritis as far as short observation. On the contrary, the long term effect of this mode of therapy is to be defined.

Administration, Oral↗

[Concentration of thrombin antithrombin III complex and plasmin alpha 2-plasmin inhibitor complex in nephrotic syndrome].

Plasma concentration of fibrinogen (Fbg), plasminogen (PLG), antithrombin III (AT III), alpha 2-plasmin inhibitor (alpha 2-PI), thrombin antithrombin III complex (TAT) and plasmin alpha 2-plasmin inhibitor complex (PIC) were evaluated in 23 nephrotic patients with proteinuria more than 3.5 g/day, including 4 cases with clinical evidence of thromboembolism. Among patients without thromboembolism, concentration of PLG and AT III was in the normal range but that of Fbg and alpha 2-PI was significantly elevated (p less than 0.01 for Fbg and p less than 0.001 for alpha 2-PI respectively). Also there was a positive relationship between AT III and serum albumin (p less than 0.05). Two fifth of these patients had an had an increased level of TAT, and also had a higher level of PIC compared with normal control (p less than 0.01). There was a positive relationship between TAT and PIC, TAT and Fbg (p less than 0.05), PIC and Fbg (p less than 0.01). TAT and PIC levels were markedly elevated in the patients with thromboembolism. From aforementioned data, it was suggested that patients with nephrotic syndrome would be in the prethrombotic state and the increased level of Fbg is one of the major risk factors of thromboembolic complications in these patients. Furthermore measurement of TAT and PIC are the useful means for the diagnosis of these complications.

Adolescent↗

[A study on treatment of hyperuricemia--effects and kinetics of allopurinol and oxipurinol].

In order to study the effects and pharmacokinetics of allopurinol (hereafter abbreviated to allo.) and oxipurinol (hereafter abbreviated to oxi.) six normal human subjects were given a single oral dose of either allo. (300mg) or oxi. (600mg), followed by serial determinations of serum and urinary levels of allo., oxi., uric acid, hypoxanthine (hereafter abbreviated to hx.) and xanthine (hereafter abbreviated x.) over a six-hour period. With a dose of 300mg of allo. or 600mg of oxi., the patterns of serum uric acid were similar. When 300mg of allo. was given, however, a reduction in the serum uric acid level occurred earlier. Additionally, it was found that urinary excretion of oxi. generally paralleled the plasma concentration. Allo. administration resulted in rises in plasma concentration of x., and urinary excretion of x. and hx. Oxi. administration, on the other hand, did not cause significant changes in the plasma content of x. or urinary excretory volume of hx. Only a slight increase was noted in the amount of x. excreted in the urine. When allo. was compared against oxi., pharmacokinetics of oxypurines, especially x. were found to differ markedly. The results suggested that differences in the reaction sites, varied intra- and extra-cellular distributions of allo. and oxi., and different effects on purine biosynthesis contribute to the aforementioned discrepancies.

Adult↗

Soluble IL-2 receptor in patients with primary nephrotic syndrome.

The soluble interleukin-2 receptor (SIL-2R) levels in 46 patients with primary nephrotic syndrome were examined. The values in the nephrotic patients exceeded those in healthy controls (p less than 0.05), and were the same at the nephrotic and non-nephrotic stages. The serum interleukin-2 (IL-2) levels in the nephrotic patients were low and did not correlate with the serum SIL-2R levels. Only at the nephrotic stage were the latter closely correlated with the serum IgG (p less than 0.001) but not with the serum IgA or IgM. The SIL-2R production by phytohemagglutinin stimulated peripheral blood lymphocytes (PBL) in the nephrotic patients was less at the nephrotic and non-nephrotic stages than that in the healthy controls. The IgG production by pokeweed mitogen stimulated PBL was low at the nephrotic stage but not at the non-nephrotic stage. Based on these findings, it is suggested that SIL-2R determinations should prove useful in clarifying the relationship between cellular and humoral immunological disorders in nephrotic syndrome.

Adult↗

[D-penicillamine induced myasthenia gravis in a patient with rheumatoid arthritis].

We have encountered a 53 year-old female with myasthenia gravis (MG) possibly induced by the treatment with D-penicillamine (D-pc). She has had a long-standing history of rheumatoid arthritis (RA) prior to the onset of MG. The diagnosis for MG was made based on the clinical findings and tests including antiacetylcholine receptor antibody and EMG. Although the drug had been efficacious for RA, it was discontinued after the development of MG. The symptoms and signs for MG were immediately disappeared, whereas clinical manifestations for RA was relapsed shortly after. Since D-Pc has been frequently used for the treatment of RA, an awareness of this side effect appears to be of particular importance for physicians in clinical practice who deal with RA. Furthermore, it may also provide some important immunological insights into the study of pathogenesis of MG.

Arthritis, Rheumatoid↗

Pharmacokinetics of active vitamins D3, 1 alpha-hydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3 in patients on chronic hemodialysis.

Two active forms of vitamin D3, 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25 [OH] 2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha, [OH] D3) are widely used for treating osteodystrophy in patients with chronic renal failure. Since the pharmacokinetics of these agents during long-term oral administration are unclear, we measured the circulating concentrations of 1 alpha, 25 (OH) 2D before and after their long-term oral administration in patients receiving maintenance hemodialysis. After 12 weeks of treatment with a daily dose of 1 alpha, (OH) D3 (0.5 micrograms), the administration of a single dose (2 micrograms) of 1 alpha, (OH) D3 showed that the area under the curve over 24 h (AUC) was increased significantly compared with day 1 of therapy. In contrast, after the treatment with a daily dose of 1 alpha, 25 (OH) 2D3 (0.25 micrograms), a single dose of 1 alpha, 25 (OH) 2D3 (1 microgram) did not exhibit this effect on the AUC. A single dose of each agent produced no significant change in either the peak increment above basal values or the elimination half-time (T 1/2) of circulating plasma 1 alpha, 25 (OH) 2D. The overall basal concentration of 1 alpha, 25 (OH) 2D achieved by 1 alpha, (OH) D3 after 12 weeks of administration was cumulative, but this effect was not observed in patients on 1 alpha, 25 (OH) 2D3. These data indicate that the pharmacokinetics of the two forms of active vitamin D3 did not differ as to peak increment and T1/2 except for the AUC, even after long-term dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Characterization of acute renal failure due to primary nephrotic syndrome.

Acute renal failure (ARF) associated with primary nephrotic syndrome (PNS) was analyzed clinically in order to evaluate the mechanism of onset. The incidence of induced ARF with PNS was found to be cases (2.1%) out of 420 cases attending our outpatient clinic. The renal histological changes included 2 cases of minimal change nephrotic syndrome (MCNS), 6 of focal glomerular sclerosis (FGS) and one of unknown origin. The 6 cases which recovered from ARF were designated as group A. The 3 cases of group B required maintenance dialysis; they included one case of MCNS, one of FGS and one of unknown origin, and showed resistance to aggressive treatments, such as steroid pulse therapy, anticoagulants and plasmapheresis. In the patients of group A, follow up studies for 10 years confirmed that their condition was not progressive. There were no significant differences between the reversed group A cases recovering from ARF and the non-reversed group B cases in terms of their clinical parameters, such as age, sex, urinary protein excretion, initial renal function, blood pressure, renal histological damage and complications. Specific factors associated with the induction of reversibility from ARF could not be identified. Further research is needed to elucidate the precise characteristics of the ARF occurring in PNS.

Acute Kidney Injury↗

Effects of heparin treatment on collateral development and regional myocardial function in acute myocardial infarction.

To define the effects of heparin treatment during the acute stage of the first anterior myocardial infarction on coronary collateral development and regional myocardial function, we evaluated angiographically the extent of a collateral visualization (collateral index: 0-3) to the completely obstructed infarct-related coronary artery and regional wall motion in 18 patients during convalescence after infarction. The patients were divided into two groups depending on the presence (group I) or absence (group II) of heparin treatment (170 to 220 IU/kg per day) during the acute phase of infarction. The collateral index was significantly higher in group I (1.5 +/- 0.9) than in group II (0.4 +/- 0.4; p less than 0.05). The left ventricular ejection fraction tended to be greater in group I than in group II (49 +/- 12% vs 38 +/- 16%), and there was a significant difference in regional wall motion of the infarct area that was evaluated by the percentage of segment shortening between the two groups (group I:7.4 +/- 9.2%, group II:-0.8 +/- 4.5%, p less than 0.05). These findings indicate that heparin treatment for patients with acute myocardial infarction is worthwhile in terms of the preservation of left ventricular function as a result collateral development.

Adult↗