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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 19 recordsLinked to original sources
PubMed1992

Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose.

To clarify the roles of metalloproteinases and their inhibitor (TIMP) in diabetic glomerulopathy, we studied the effect of a high glucose concentration on the gene expression of metalloproteinase transin and TIMP as well as collagen type IV and laminin in cultured rat mesangial cells (MCs). In the high glucose group, collagen type IV, laminin, and TIMP mRNA levels were all elevated in a concentration-dependent manner, whereas transin expression was suppressed. Osmotic control of high glucose with mannitol selectively stimulated TIMP expression. We hypothesize that high glucose decreases matrix-degrading activity as well as increases matrix productivity in MCs.

Animals↗
PubMed1992

Extracellular matrix contraction by cultured mesangial cells: modulation by transforming growth factor-beta and matrix components.

Cultured glomerular mesangial cells (MCs) have the ability to contract the surrounding collagen gel matrix (CGM). To investigate this phenomenon, we examined the effect of growth factors and extracellular matrix (ECM) components. Among some growth factors tested, transforming growth factor-beta (TGF-beta) and fetal calf serum (FCS) enhanced CGM contraction dose dependently. These factors acted through distinct mechanisms because: (1) when growth-arrested MCs were used, the effect of FCS was inhibited partially but that of TGF-beta was not; and (2) anti-TGF-beta had no influence on CGM contraction induced by FCS. Among the ECM components such as laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin), which were each mixed separately with CGM before gelling, heparin-like proteoglycans and type IV collagen inhibited contraction by MCs. The inhibitory effect of heparin was mediated by the interaction both with CGM and with MCs because: (1) when heparin was added to the culture medium, not into the gel, the inhibitory effect was diminished but still noted; and (2) using growth-arrested MCs, the inhibitory effect of heparin in the medium was reduced but still observed. This culture assay is useful for elucidating the tensional interaction between MCs and surrounding ECM.

Animals↗
PubMed1992

Clinical aspects of polycystic kidney disease.

A total of 316 patients (167 men and 149 women) with autosomal dominant polycystic kidney disease was studied retrospectively by a multi-institute group. With advancing patient age renal function decreased, and blood pressure, prevalence of liver cysts and probability of end stage renal failure increased. The probability of end stage renal failure was 39% in the patients in their sixties. Regression analysis indicated that polycystic kidney disease patients could expect to lose 1.1 ml. per minute of creatinine clearance per year, reaching a level of 10 ml. per minute, a point of end stage renal failure, by the age of 72.7 years. The better prognosis in our study than that reported previously in white patients might be due to the inclusion of more asymptomatic persons and/or milder genotypic expression of polycystic kidney disease in Japan. There was no sex difference in the prevalence of liver cysts (54.6%), pancreatic cysts (7.1%), intracranial aneurysms (8.0%) and hypertension (63.6%). The occurrence of pancreatic cysts was significantly associated with liver cysts. Our study clarifies several clinical characteristics of polycystic kidney disease in Japan.

Adult↗
PubMed1992

Decreased insulin-sensitive Ca2+ transport in cultured vascular smooth muscle cells from spontaneously hypertensive rats.

To investigate the role of insulin on Ca2+ regulation of vascular smooth muscle cells (VSMC) in hypertension, the effect of insulin on Ca2+ transport and intracellular free calcium concentration ([Ca2+]i) was measured in cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured VSMC. The stimulatory effects of insulin were completely inhibited by diltiazem, and partially by H-7, TMB-8, and 5-N,N(hexamethylene)amiloride (HMA), but not by W-7 or trifluoroperazine. Insulin-sensitive 45Ca uptake of SHR VSMC was significantly smaller than that of WKY VSMC. Insulin-sensitive increase in [Ca2+]i of SHR VSMC was also smaller than that of WKY VSMC. It is concluded that insulin increases 45Ca uptake, leading to an increase in [Ca2+]i, presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release, or protein kinase C mediated mechanisms in cultured VSMC. A blunted response of insulin-sensitive Ca2+ uptake and [Ca2+]i in SHR VSMC suggests the differential regulation of Ca2+ transport in response to insulin in primary hypertension.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans.

This study examined the effects of widely used antacids (aluminum hydroxide, magnesium oxide, and calcium carbonate), ferrous sulfate, and ranitidine on the absorption of a fluorinated quinolone, (-)-(S)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro- 7H- pyrido-[1,2,3,-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (DR-3355), in healthy male volunteers enrolled in three separate randomized crossover studies. Study 1 used 100-mg doses of DR-3355 and concurrent doses of aluminum hydroxide (1 g) or magnesium oxide (500 mg), while study 2 used DR-3355 (100 mg) and concurrent ferrous sulfate (160 mg) or calcium carbonate (1 g). Study 3 used DR-3355 (100 mg) and concurrent ranitidine (150 mg). Each study included control doses of DR-3355 (100 mg) alone. When aluminum hydroxide, ferrous sulfate, and magnesium oxide were coadministered with DR-3355, the relative bioavailability of DR-3355 was decreased to 56, 81, and 78%, respectively, of that for DR-3355 (100 mg) alone. Urinary excretion of DR-3355 was also significantly decreased by coadministration of these drugs. Thus, the magnitude of the decrease in the area under the concentration-time curve for DR-3355 varied among antacids, and the ranking of their inhibitory effects correlated with previously reported rankings of stability constants for chelate formation. DR-3355 bioavailability was not influenced by the concurrent administration of calcium carbonate and ranitidine, indicating that changes in gastric pH do not affect DR-3355 absorption.

Adult↗
PubMed1992

Increased Na-K transport in glomerular mesangial cell membrane from spontaneously hypertensive rats.

To investigate the differences in the Na-K transport of the mesangial cell (MC) membrane in hypertension versus normotension, the activity of the Na-K pump and the passive cation permeability were measured in serially passaged cultured MC obtained from both spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. When Na-K pump was active, Na-K pump activity, described as ouabain-sensitive 86Rb uptake, was significantly greater in the cultured MC from SHR than WKY rats. The outward Na-K cotransport, described as the washout rate constant of bumetanide-sensitive 86Rb washout, was also greater in SHR MC than in WKY rat MC. When Na-K pump was inhibited by 1 mM ouabain, overall intracellular Na uptake was significantly greater in SHR MC. A greater 5-(N,N-hexamethylene)amiloride-sensitive Na uptake in SHR MC accounted for this difference. There was no difference in the intracellular concentration of Na and K in the cultured MC from the 2 strains when Na-K pump was active. It is concluded that there is an increased activity of Na-K pump in the cultured MC from SHR, and that this abnormality may be innate to SHR cells. It is also suggested that an increase in Na-K cotransport and Na-H antiport may explain this difference, and that these abnormalities observed in the SHR kidney may be involved in the pathogenesis of hypertension in this model.

Animals↗
PubMed1992

Effect of probenecid on the pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in humans.

A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration.

Administration, Oral↗
PubMed1992

A case of primary leiomyosarcoma of the heart.

A 53-year-old male was hospitalized with complaints of cough, fever and backache. Two-dimensional echo-cardiography showed a pericardial echo-free space and a mass in the right atrium. Based on the MRI findings showing a pericardial mass originating from the atrial tumor, the final diagnosis of leiomyosarcoma was made by a percutaneous pericardial biopsy. Despite various therapies, the patient died after 3 wk. Because of its rareness (to date only 25 case reports), a premortem diagnosis of primary cardiac leiomyosarcoma is generally difficult. However, we feel that MRI and a subsequent biopsy is quite useful for making an early diagnosis of this disease.

Biopsy, Needle↗
PubMed1992

Renal artery thrombosis in a patient with membranous glomerulonephritis.

A 64-year-old man with renal artery thrombosis (RAT) associated with nephrotic syndrome (NS) is reported. Although this patient was diagnosed as NS due to membranous glomerulonephritis (MGN) and treated with prednisolone, RAT occurred as a result of unknown mechanisms and caused mild renal dysfunction. Creatinine clearance has been about 70 ml/min for 9 years since the onset of RAT. The renal scintigraphic image has not changed since the onset. NS responded to prednisolone therapy initially and at the time of the relapse. Recent data have shown proteinuria levels of less than 0.2 g/day.

Glomerulonephritis, Membranous↗
PubMed1992

[A case of hemophagocytic syndrome with multiple myeloma].

A case with multiple myeloma complicated with hemophagocytic syndrome (HS) is presented. Because pancytopenia, liver dysfunction and increase of mature histiocytes in the bone marrow appeared rapidly a diagnosis of HS was made. The patient died of multiple organ failure, despite steroid therapy. Autopsy revealed marked invasion of hemophagocytic histiocytes not only into the bone marrow but also into many other organs such as the liver, lymph nodes and kidneys. HS is a histiocyte proliferative disorders, which is likely to be seen in immunocompromised hosts, but there is no previous report about HS and multiple myeloma.

Bone Marrow↗
PubMed1992

Effect of hyperlipidemic serum on cultured mesangial cells.

Hyperlipidemia may contribute to the progression of focal glomerular sclerosis (FGS) in humans and obese Zucker rats. Zucker rats undergo an increase in their plasma low density lipoprotein (LDL), very low density lipoprotein (VLDL) and oxidized lipids, resulting in the development of FGS. We examined the effects of such hyperlipidemic serum on thymidine uptake into cultured mesangial cells. LDL and VLDL both stimulated the overnight uptake of 3H-thymidine at a concentration of below 10 micrograms/ml and inhibited this uptake at over 50 micrograms/ml in the medium. Modified LDL and VLDL after oxidation, however, inhibited this uptake at a concentration of 1 microgram/ml in the medium. Although 20% serum-containing medium stimulated the thymidine uptake by the mesangial cells, the lipoprotein fraction inhibited the uptake, while the lipoprotein-free fraction markedly stimulated it. We conclude therefore that the lipoproteins in hyperlipidemic serum suppress and the lipoprotein-free fraction stimulates mesangial growth. Both may play a role in the development of FGS in rats.

Animals↗
PubMed1992

A greater stimulation of vascular smooth muscle cell proliferation by serum from spontaneously hypertensive rats.

In an attempt to delineate the differential characteristics of serum from hypertensives on the proliferation of vascular smooth muscle cells (VSMC), we compare the effect of serum from spontaneously hypertensive rats (SHR) with that from normotensive Wistar-Kyoto rats (WKY) in its ability to stimulate proliferation in VSMC. Cell number determination showed that 10% serum from either of the two strains substantially stimulated proliferation of serially passed cultured VSMC, the effect being significantly greater with SHR serum than with WKY serum. 3H-thymidine incorporation into newly synthetized DNA was also tested after treatment with 10% SHR or WKY serum. A substantial increase in the uptake was noted in response to the rat serum, the effect tending to be greater with SHR serum than with WKY serum. No difference was found between the two strains in cell size determined as intracellular water volume. These data provide the evidence of an increased growth stimulating activity of SHR serum. This abnormality may be superimposed on the already-known innate hyperproliferative capacity of VSMC of SHR, leading to an increase in the deterioration of vascular complications seen in this model.

Animals↗
PubMed1992

Captopril ameliorates the posturally induced fall in creatinine clearance in patients with chronic glomerulonephritis.

The clinical usefulness of an angiotensin-converting enzyme inhibitor on the posturally induced fall in creatinine clearance (ClCr) was studied in patients with biopsy-proved chronic glomerulonephritis (CGN). After a change from supine to upright position, ClCr fell significantly in all patients. This fall was significantly ameliorated by the pretreatment with captopril (fall in ClCr 28.8 +/- 14.3% for nontreated vs 16.5 +/- 11.5% for treated patients; n = 12; p less than 0.05). The ameliorating effect was more marked in patients with mesangial cell proliferation (MP) than those without it (fall in ClCr 7.2 +/- 6.3% for MP vs 17.1 +/- 12.3% for no MP; n = 6; p less than 0.05). The results suggest that captopril apparently had a renoprotective effect on the orthostatic acute fall in ClCr in patients with CGN, especially those with MP.

Adult↗
PubMed1992

[High-dose cepharanthin therapy of idiopathic thrombocytopenic purpura].

Clinical efficacy of oral high-dose cepharanthin (40-60 mg/day) was evaluated in nine patients with idiopathic thrombocytopenic purpura who were unable to discontinue the administration of adrenocorticosteroids or immunosuppressive drugs. Mean platelet counts significantly (p less than 0.05) rose from 4.5 +/- 0.9 x 10(4)/microliters to 8.9 +/- 4.2 x 10(4)/microliters without any side effects. Two to five months after the initiation of this therapy, 4 patients, including 3 who could discontinue adrenocorticosteroids, kept their platelet counts over 10 x 10(4)/microliters. It was suggested that the oral administration of cepharanthin could be a beneficial and safe strategy for ITP.

Administration, Oral↗