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Y Orita

Publications and source records attributed to Y Orita.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effect of chronic renal failure on the level of albumin messenger RNA.

The effects of chronic renal failure on the level of albumin mRNA and the transcription rate of the albumin gene were studied in seven of eight nephrectomized rats. A paired feeding procedure was employed to eliminate a nutritional difference between sham-operated control and uremic rats. Total RNA was isolated from the livers of control and uremic rats fasted for 24 or 48 hours. The mRNA level was measured by RNA-cDNA dot blot hybridization, and the transcription rate was measured by the "run-on" transcription assay in isolated nuclei. The albumin mRNA levels in uremic rat livers were reduced to 75% at the 24-hour fasted state, and to 45% at 48-hour fasted state compared with those in the respective control groups. There was no difference in the level of beta-actin mRNA between these groups. However, there was no difference in the transcription rate of the albumin gene between control and uremic rats. Northern analysis showed that albumin mRNA isolated from uremic rat liver was identical in size with that from the control. These results suggested that a posttranscriptional process, involving the destabilization of cytoplasmic mRNA, is responsible for the uremia-induced repression of albumin synthesis.

Animals↗
PubMed1989

Mechanism of action of angiotensin II on isolated rat glomeruli.

Angiotensin II (Ang II) regulates glomerular filtration rate by contracting mesangial cells and thereby decreasing glomerular filtration surface area. To elucidate the cellular mechanism of this action, we investigated the roles of Ca and protein kinase C (PKC) activation in Ang II-induced glomerular capillary vasoconstriction using 3H-inulin to measure the extracellular (largely intracapillary) volume of isolated decapsulated rat glomeruli. Ang II (1 microM) rapidly decreased the glomerular inulin space (GIS), bringing about a maximal decrease at five minutes, which lasted up to 30 minutes. When incubated in 0.5 mM EGTA-containing Ca-free medium or in the presence of 1 microM diltiazem or verapamil, the sustained phase (after 7 min) was completely inhibited. The initial effect (at 3 and 5 min) was only partially inhibited by these maneuvers but was completely inhibited by trifluoperazine or W-7, which indicated that it was dependent on calmodulin and, accordingly, on Ca probably released from the intracellular store. The sustained effect was mimicked by 12-0-tetradecanoylphorbol-13-acetate (TPA) in the presence of extracellular Ca, but was not in its absence. The sustained effect was also inhibited by H-7, an inhibitor of PKC, and by W-7, which indicated that PKC activation and influx of extracellular Ca are both important. Combined treatment with A23187 and TPA could mimic both the initial and sustained effect of Ang II in the presence of extracellular Ca, though either one of them failed to do so when used alone. These results suggest that the initial effect of Ang II on GIS is mediated by Ca released from the intracellular store, on the one hand, and the sustained effect by extracellular Ca influx and PKC activation, on the other.

Angiotensin II↗
PubMed1989

Endothelin-1 receptors in rat renal glomeruli.

Renal glomeruli form a dynamic structure capable of regulating the glomerular filtration rate (GFR). To explore possible regulating effects of endothelin-1 (ET-1) upon glomerular functions, the presence of specific ET-1 receptors and the biological actions of ET-1 were studied in isolated rat renal glomeruli. The specific binding of [125I]ET-1 to glomeruli was time and temperature dependent. Scatchard analysis of the binding data indicated the presence of a single class of high-affinity binding sites with the apparent dissociation constant of 8.3 nM and the maximal binding capacity of 1.5 pmol/mg protein. ET-1 stimulated prostaglandin (PG) E2 production in glomeruli with the time course and the concentration dependency similar to those found in [125I]ET-1 binding to glomeruli. These results indicate the presence of high-affinity binding sites for ET-1 linked to PGE2 production in glomeruli, suggesting a possible role of ET-1 in the regulation of glomerular function.

Animals↗
PubMed1989

Furosemide accelerates gentamicin accumulation in cultured renal cells (LLC-PK1 cells).

Furosemide is known to potentiate gentamicin nephrotoxicity. The mechanism of potentiation is unclear. In our previous studies, we demonstrated that furosemide enhanced gentamicin accumulation in rabbit renal tissues when injected as a bolus [Kidney int. 33:363, 1988] or repeatedly subcutaneously [Diuretics II, Elsevier, New York 1987, pp.693]. In this study, we evaluated the effects of furosemide on gentamicin accumulation in cultured renal cells (LLC-PK1) and hepatoma cells (H4IIE). Thus, we excluded effects secondary to furosemide-elicited hemodynamic changes. Seven days after seeding, the culture medium was exchanged for medium containing 1 mM gentamicin alone [G] or 1 mM gentamicin +1 mM furosemide [GF]. In LLC-PK1 cells, gentamicin concentration in [GF] was significantly higher than that in [G], while gentamicin was not detected in H4IIE cells with or without furosemide. We conclude that furosemide can accelerate gentamicin accumulation in renal tissues and potentiate gentamicin nephrotoxicity.

Animals↗
PubMed1989

Binding of hydrochlorothiazide to erythrocytes.

Hydrochlorothiazide (HCT) was administered orally to healthy volunteers and intravenously to rabbits. HCT concentrations in plasma (Cp) and erythrocytes (Ce) were determined by a high-performance liquid chromatographic method. Ce was about 9-fold that of Cp 24 h after the administration to volunteers, and 8-fold 6 h after the administration to rabbits. From the results of the in vitro binding study which was done with rabbit erythrocytes, at least the presence of three kinds of binding site for HCT was expected. The first binding site was characterized by extremely high affinity and very low capacity, and was unaffected by acetazolamide, known as a carbonic anhydrase inhibitor. The second one was characterized by medium affinity and medium capacity, and disappeared under the presence of acetazolamide and may be due to the carbonic anhydrase of erythrocytes. The third one was characterized by low affinity, but its binding capacity was extremely high and apparently unsaturable in the HCT concentration range studied (0.5-100 micrograms/ml = 1.68-336 microM). The binding of HCT to erythrocytes seems to be dominated by the second binding site in the therapeutic range (under 1 microgram/ml of plasma).

Adult↗
PubMed1989

Enhancement of gentamicin-induced inhibition of phosphatidylinositol hydrolysis in rabbit renal proximal tubular brush-border membrane by furosemide.

Gentamicin inhibited phosphatidylinositol (PI) hydrolysis catalyzed by rabbit renal phospholipase C in a dose-dependent manner. The inhibition was potentiated by furosemide in a dose-dependent manner. Furosemide may enhance gentamicin nephrotoxicity by potentiating the inhibitory effect of gentamicin on brush-border membrane PI degradation.

Animals↗
PubMed1989

Trial of IgG therapy for lupus nephritis--report of two cases with a successful response.

Two cases with systemic lupus erythematosus (SLE) were treated with high-dose intravenous IgG. In patient 1, the IgG therapy dramatically improved both the lupus nephritis and serological titers for SLE. In patient 2, intravenous IgG yielded a partial remission in the lupus nephritis as well as a satisfactory decrease in proteinuria and disappearance of the skin rash characteristic of SLE. IgG therapy is suggested as possibly beneficial for the treatment of SLE based on different mechanisms from those of corticosteroid action. Further studies are needed to determine the detailed efficacy of IgG therapy for SLE.

Adult↗
PubMed1989

Effect of daily energy expenditure on the creatinine clearance and daily urinary protein excretion of patients with mesangial proliferative glomerulonephritis.

In the present study, the relationships among daily energy expenditure, renal function (creatinine clearance, Ccr), and daily urinary protein excretion were examined. In total, 104 adult patients (from 9 renal clinics in Japan) with primary chronic glomerulonephritis were fitted with a portable calorie counter for about two weeks to estimate their daily energy expenditure. On two separate days when the energy expenditure was expected to be contrastingly different, urine collection and blood sampling were performed, and the Ccr and daily urinary protein excretion were determined. Multiple regression analysis of Ccr clearly demonstrated a significant correlation between its acceleration and increase in the daily protein intake or protein excretion. In mesangial proliferative glomerulonephritis showing a constant level of protein intake, the enhancement of Ccr revealed a significant inverse relation to the increase in daily energy expenditure (%BMR). It was demonstrated statistically that a daily energy expenditure exceeding 150 %BMR slowed the Ccr down. This limit was almost the same as the level in healthy adults living in urban cities of Japan. The urinary protein excretion was significantly correlated with the daily protein intake. These results should be taken into consideration in prescribing for each individual patient an allowable degree of labor or any other activity and an adequate dietary regimen, and also in evaluating the efficacy of a drug for glomerulonephritis.

Adolescent↗
PubMed1988

Albumin gene transcription is enhanced in liver of nephrotic rats.

The level of albumin mRNA and the transcription rate of the albumin gene were studied in the liver of control rats and rats with nephrosis induced by injection of the aminonucleoside of puromycin. Total RNA was extracted from liver by the guanidium thiocyanate method. The albumin mRNA level was measured by cDNA-RNA dot-blot hybridization, and the transcription rate of the albumin gene was measured by the "run-on" transcription assay using isolated nuclei. Urinary protein excretion in nephrotic rats was significantly higher than in control rats (258 +/- 132 vs. 12 +/- 2 mg/day), and the serum albumin concentration in nephrotic rats was significantly lower. There was no difference in body weight, liver weight, serum creatinine, or urea nitrogen between the two groups. Both the level of albumin mRNA and the transcription rate of the albumin gene in the nephrotic liver were about twice as high as those in the control liver. There was no difference in the level of beta-actin mRNA between the two groups. Northern blot analysis showed that both putative precursor RNA and the mature form of albumin mRNA were increased in nephrotic rats. We conclude that albumin synthesis is increased in the liver of nephrotic rats and a transcriptional process is responsible for this increase.

Actins↗
PubMed1988

Pharmacokinetic and pharmacodynamic interactions between furosemide and hydrochlorothiazide in nephrotic patients.

We examined the response of 8 patients with nephrotic syndrome (creatinine clearance 70.4 +/- 16.0 ml/min) to oral furosemide (F; 40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT; 100 mg). In the 24-hour period after oral F, HCT was shown to increase urine volume and urinary sodium and chloride excretion. Increment was most significant during the 12- to 24-hour period. Enhancement of the diuresis with HCT was associated neither with a significant increase in the area under the curve of plasma F concentration nor an increase in urinary F excretion. Urinary excretion of glucuronidated F, one of the main metabolites of F, however, was decreased with HCT. In summary, HCT significantly enhanced the response to F in nephrotic patients.

Drug Interactions↗