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Biomedical subjects

T Sanaka

Publications and source records attributed to T Sanaka.

At least 37 records · Page 2Linked to original sources

The effect of glucose on the proliferation of peritoneal fibroblasts.

The purpose of this study was to clarify the pathophysiological role of glucose and glucose transporters (GLUTs) in the proliferation and production of extracellular matrix (ECM) in peritoneal fibroblasts. Peritoneal fibroblasts from rat omentum were cultured in medium M199 with 5% fetal bovine serum (FBS) with (Group B) and without (Group A) 4% glucose. The rate of cell growth at the M stage of the cell cycle in Group B was higher than that in Group A at 12 and 24 hours after culture. However, cell numbers in Group B were less than in Group A at 24, 72, and 120 hours after culture. The GLUT inhibitor suppressed the proliferation of cells 72 and 120 hours after culture. The procollagen III peptide (PIIIP) contents in the supernatant of cells cultured in a high glucose medium were higher than those of control cells at 24, 72, and 120 hours after culture. PIIIP levels of cells cultured with the GLUT inhibitor were also higher than those of cells without the GLUT inhibitor. These results suggest that initially glucose stimulates cell proliferation and thereafter inhibits its proliferation. GLUTs may accelerate the proliferation of peritoneal fibroblasts. We suggest that glucose stimulates the ECM component PIIIP, and GLUT may have an inhibitory effect on the production of the ECM component PIIIP.

Animals↗

A variety of clinical applicabilities of immobilized dextran sulphate as lipoprotein adsorbent and avoidance of anaphylactoid (anion-blood contact) reaction in its use.

Dyslipidemia including hyper-LDL(low density lipoprotein) cholesterol which is very often refractory to dietary/medical treatments is known to be a risk factor of many arteriosclerotic lesions. An extracorporeal procedure of plasma adsorption, LDL adsorption, utilizing dextran sulphate as a ligand immobilized on cellulose gel beads has been clinically applied in a variety of dyslipidemic conditions as listed below. Its usefulness in secure reduction of the serum LDL level and consequent symptomatic improvements has been confirmed. Familial hypercholesterolemia(FH): A regular repetition of the LDL adsorption ameliorates hyper-LDL cholesterolemia as resulting in regression of the multiple stenoses in the coronary arteries. Focal glomerulosclerosis(FGS): A seesion of the LDL adsorption improves kidney function and reduces a urinary protein excretion in FGS patients with dyslipidemia. Arteriosclerosis obliterans(ASO): More than 60 ASO patients with dyslipidemia have been treated by the LDL adsorption in our center. In over 80% of the patients, marked improvement in clinical symptoms such as leg pain/intermittent claudication has been brought out. Hemodialysis-relevant dyslipidemia(HDDL): HDDL which develops in the long-term HD patients has been treated. Transplantation-relevant dyslipidemia(TXDL): TXDL with deterioration of the transplanted kideny function has been treated by the LDL adsorption. Kidney function improves. Anaphylactoid reaction which is tentatively explained as a result of release of bradykinin in contact of blood with polyanionic material of the adsorbent, dextran sulphate, develops, in particular, while an angiotensin-converting enzyme inhibitor is administered as a depressant. However, it can be avoided in a use of nafmostat mesilate, a protease inhibitor, as an anticoagulant.

Adsorption↗

Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody.

We have established a new method capable of measuring the very low concentrations of oxidized low density lipoprotein (OxLDL). In our previous study, we obtained a novel murine monoclonal antibody against oxidized lipoproteins (Itabe, H. et al. 1994. J. Biol. Chem. 269: 15274-15279). The epitope of this antibody resides in oxidized products of phosphatidylcholine that can form complexes with polypeptides, including apolipoprotein B. When the monoclonal antibody was precoated onto microtiter wells prior to carrying out a sandwich ELISA using an anti-human apolipoprotein B antibody, it was possible to detect 0.5 ng protein of copper-induced OxLDL. The detection of OxLDL was dependent on the presence of monoclonal antibody and was blocked by oxidized phosphatidylcholine (OxPC). Under the same sandwich ELISA condition, native LDL showed a dose-dependent increase of absorbance that was inhibited by complex of OxPC with BSA. These results suggest the possible occurrence of oxidative modification of human plasma LDL, which is recognized by the antibody against OxPC. The level of LDL oxidation of normal human subjects was found to be 0.52 +/- 0.35 units per 5 mu g protein of LDL, where one unit was defined as the reactivity corresponding to 1 ng of copper-induced OxLDL by this assay. Furthermore, we found that the LDL oxidation level in patients who had been receiving hemodialysis treatment was increased more than eightfold over that of normal subjects. We suggest that LDL in human plasma is oxidatively modified under certain conditions and this method for measurement of OxLDL could be used to study the relationship between in vivo oxidation reaction and various pathological conditions.

Antibodies, Monoclonal↗

Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression.

The present study was designed to identify the mechanism of increased oxidant stress in the rat model of anti-glomerular basement membrane nephritis. Sixty-three Sprague-Dawley rats were injected with nephrotoxic serum and evaluated 1 to 24 hours later. In these rats, CeCl3 deposition, an index of hydrogen peroxide production, was observed on the surfaces of glomerular endothelial cells and polymorphonuclear leukocytes, whereas no such depositions were observed in controls. Renal cortical level of lipid peroxidation products (phosphatidylcholine hydroperoxide) was significantly (p < 0.05) elevated at one hour after the injection and remained elevated at least for 24 hours. Protein levels of glomerular Mn-superoxide dismutase (SOD) decreased from 1.55 +/- 0.38 microgram/mg protein to 0.67 +/- 0.18 microgram/mg protein at one hour and normalized by 12 hours after the injection. The activity of the enzyme showed a similar trend. In contrast, Mn-SOD mRNA increased 3.4-fold at 3 hours after the injection. In situ hybridization showed increased Mn-SOD mRNA expression in glomeruli. Cu/Zn-SOD mRNA expression was transiently suppressed. These results indicated that both increase in local production of reactive oxygen species (ROS) and reduction in antioxidant enzyme activities are responsible for the enhanced oxidant stress in the heterologous phase of anti-glomerular basement membrane nephritis. The paradoxical increase in Mn-SOD mRNA expression indicates that the posttranscriptional down regulation of Mn-SOD (i.e., reduction in protein and activity) and the increased ROS may activate transcription of the gene.

Animals↗

Lipid peroxidation as an indicator of biocompatibility in haemodialysis.

Peroxidation of cell membrane (phosphatidylcholine hydroperoxide, PCOOH) was quantitatively assessed using a chemiluminescence-HPLC system to clarify whether haemodialysis patients are damaged by oxidative stress. Patients were divided into two groups, one dialysed with conventional cellulose membranes, and the other with cellulose triacetate for 3 months, subsequently followed by a crossover study of each membrane for 3 more months. The mean value of PCOOH in haemodialysis patients was 508.5 +/- 208.7 pmol/ml (P < 0.01 vs normal controls), which showed a statistically insignificant tendency to increase during each haemodialysis session of 4 h. Two years after commencing haemodialysis, PCOOH was maintained within almost the same range, but significantly greater than normal. There was no significant tendency between an index of aortic sclerosis and plasma PCOOH. However, three patients using conventional cellulose membranes died of myocardial infarction. Plasma PCOOH increased after the commencement of haemodialysis. This tendency was more notable in patients using conventional cellulose membrane compared to the cellulose triacetate. Cellulose triacetate, which we thought to be more biocompatible, did not necessarily produce lipid peroxide. We conclude that it is very important to check production of oxygen radicals when developing new membranes.

Biocompatible Materials↗

Analysis of the expression of cell surface antigens and intercellular adhesion molecules on lymphocytes in CAPD patients.

The aim of the present study was to assess immunological aspects in patients on continuous ambulatory peritoneal dialysis (CAPD). The CAPD patients were divided into two groups. Group A consisted of patients in which high-somolar dialysate was used infrequently, and group B consisted of patients in which high-osmolar dialysate was used frequently. We characterized cell populations in the peritoneal effluent (PE) of CAPD patients. Analysis of the nucleated cell composition revealed that one-third of the PE cells were lymphocytes. Flow cytometric analysis of the surface antigen expression on lymphocytes revealed that the proportion of helper/inducer T-cells was lower in PE than in peripheral blood (PB). By contrast, the rates of DR antigen expression on T-cells and CD45RO antigen expression on helper/inducer T-cells (memory T-cells) were higher in PE than in PB. However, there were no statistically significant differences between the rates of expression of any lymphocyte surface antigens in the two groups. Expression of intercellular adhesion molecules, such as ICAM-1 and LFA-1, was higher in PE than in PB. It is of interest that the expression of ICAM-1 and LFA-1 on T-cells in PB was significantly higher in group B than in group A. In summary, there is an increase in memory T-cells in the PE and up-regulation of intercellular adhesion molecules of PE lymphocytes of CAPD patients. The up-regulation of intercellular adhesion molecules is also observed in PB lymphocytes in whom high-osmolar dialysate is used frequently.

Adult↗

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Adult↗

IGF-I as an early indicator of malnutrition in patients with end-stage renal disease.

The present study was performed to clarify the possibility of IGF-I as an early indicator of malnutrition in patients with end-stage renal disease. Thirty-two patients (19 males, 13 females; mean age 49.6 +/- 10.0 years) undergoing dialysis were enrolled in the study. Body weight, skinfold thickness, and midarm muscle circumferences (MAMCs) were measured for anthropometric nutritional indices. Blood samples were collected to measure the following endocrinological, biochemical and hematological indices: IGF-I, growth hormone, (GH), total protein, prealbumin, albumin, transferrin, hematocrit, and lymphocyte count. Nutritional indices were measured again 1 month later to calculate the percent difference among them. Moreover, 2 patients who showed a decrease in IGF-I and suffered from malnutritional complications, such as hypoproteinemia and emaciation, which could not be successfully treated by conventional therapies were selected in order to confirm the nutritional role of IGF-I mediated by recombinant human GH (r-hGH). The serum IGF-I concentration distribution ranged from 22 to 225 ng/ml. In 15 patients (10 males, 5 females), it fell from 22 to 82 ng/ml below the normal range. Partial correlation coefficient analysis demonstrated that baseline IGF-I and the percent difference of each the body weight, MAMC, prealbumin and albumin were highly significantly correlated (r = 0.431, 0.641, 0.624 and 0.348, respectively; p = 0.014, 0.001, 0.001 and 0.028, respectively). The percent difference of IGF-I did not correlate significantly with that of any other nutritional index during the 1-month observation without administration of r-hGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney.

A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease.

Adolescent↗

[Success of cyclosporine therapy in two patients with PSS].

Two PSS patients, unresponsive to D-penicillamine, steroid, cyclophosphamide and plasma exchange therapy, were treated with cyclosporine. One patient complained scleroderma, dysphagia and dyspnea during movement after treatment with steroid, plasma exchange and cyclophosphamide. He showed a increased Leu3a/2a ratio (6.72). About 3 months after treatment with cyclosporine, these complain decreased with normalization of elevated Leu 3 a/2 a ratio. 1 year after treatment, %DLco increased 86% from 50% and pneumonitis findings of chest X-ray and chest CT were also improved. Another patient who complained Raynaud's phenomenon and scleroderma which had extended over his abdomen despite treatment with steroid and cyclophosphamide. 1 month after treatment with cyclosporine, improvement of these phenomenon were recognized. It is concluded that cyclosporine can be an effective agent in the treatment of PSS.

Cyclosporine↗

[Improvement of malnutrition indices in adult patients with end stage renal disease by recombinant human growth hormone].

Recombinant human growth hormone (r-hGH), 1 U/kg body weight/week, was administered subcutaneously for 2-4 weeks to two end stage renal disease patients with severe malnutrition. Following r-hGH, there were significant increase in hematocrit level and serum concentration of albumin, IGF-1 and GH, and decrease of urea nitrogen. It was concluded that r-hGH exerts a therapeutic effect to nutritional status in renal failure patients by improving severe hypoalbuminemia, susceptibility to infectious disease, intractable ascites and so on.

Adult↗

Effects of endothelin on renal hemodynamics and excretory functions in anesthetized dogs.

The effects of endothelin on renal hemodynamics and excretory functions were investigated in anesthetized dogs. Infusion of endothelin at a rate of 1 ng/kg.min resulted in a slight but significant decrease in renal blood flow and an increase in renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg.min significantly decreased cardiac output, glomerular filtration rate, urine volume, and urinary sodium and potassium excretion, whereas it increased systemic vascular resistance. Mean arterial pressure and heart rate showed a transient decrease and increase, respectively, at doses higher than 50 ng/kg.min. Plasma renin activity and plasma aldosterone concentrations were increased only at the dose of 100 ng/kg.min. These effects lasted for more than 60 min. These results suggest that endothelin may have an important role in the modulation of renal functions as well as in the modulation of systemic hemodynamics.

Aldosterone↗