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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 217 records · Page 12Linked to original sources

Immunosuppressive effect of bredinin on cell-mediated and humoral immune reactions in experimental animals.

Bredinin (BR), an imidazole nucleoside isolated from Eupenicillium brefeldianum was previously reported to prolong kidney allograft survival in dogs. The immunosuppressive effect of BR was studied in experimental animals. In beagles, in vitro responses of lymphocytes stimulated by mitogens or allogeneic cells were suppressed by in vitro BR treatment. BR, given in vivo, also showed an inhibitory action against development of delayed hypersensitivity reaction to tubercle bacilli in guinea pigs or against hemagglutinin production following booster SRBC injection in rabbits. Of note may be the fact that BR was found to have an immunosuppressive potency comparable to that of azathioprine and, in addition, to show a decreased hepatotoxicity compared with the latter.

Animals↗

De novo development of hypercholesterolemia and elevated high-density lipoprotein cholesterol: apoprotein A-I ratio in patients with chronic renal failure following kidney transplantation.

Serum lipids, apoprotein and lecithin-cholesterol acyltransferase activities were studied in 27 renal transplant recipients with stable and normal renal function (serum creatinine 0.16 mM/l or less) sustained for more than 1 year following grafting. Hypertriglyceridemia, which was characteristic of hyperlipidemia in 18 hemodialyzed patients with chronic renal failure, was no longer manifest in transplant recipients. On the other hand, de novo hypercholesterolemia was observed posttransplant with mean serum levels of 5.82 +/- 1.34 versus 5.01 +/- 0.88 mM/l in 575 normal controls. As to the high-density lipoprotein metabolism, the cholesterol content (1.72 +/- 0.56 mM/l) was significantly higher in transplant patients than in hemodialyzed patients (0.82 +/- 0.31 mM/l). In contrast, no variation in apoprotein A-I levels was found between both groups of patients, which produced an elevated high-density lipoprotein cholesterol:apoprotein A-I ratio. Thus, derangement in the serum lipid profile, although qualitatively different, continued to be present following transplantation, and its relevance to the cardiovascular morbidity in these patients remains to be evaluated.

Adult↗

De novo development of hypercholesterolaemia and increased HDL-cholesterol: apoprotein A-I ratio in patients with chronic renal failure following kidney transplantation.

Lipid profiles were studied in 27 kidney transplant patients with stable renal function during long term follow-up and 18 haemodialysis patients. Hypertriglyceridaemia resolved after kidney transplantation. In contrast, hypercholesterolaemia developed and persisted in transplant patients. HDL-CHL temporarily elevated at 1-5 years post-transplant compared to decreased values during haemodialysis. HDL-CHL:Apo . A-I ratio became elevated post-transplant, although no variation in Apo . A-I values was observed between either groups. It is suggested that qualitative and quantitative changes of HDL particles develop after grafting.

Adult↗

Effect of dialysis on lipid metabolism in chronic renal failure - acetate versus bicarbonate.

The effect of two dialysate buffer bases--acetate and bicarbonate - on lipid profile in chronic renal failure was studied in nine patients on maintenance hemodialysis, employing a double crossover method. The total cholesterol level and LCAT crossover method. The total cholesterol level and LCAT activity significantly decreased during acetate dialysis compared to bicarbonate dialysis (p less than 0.05), although the HDL-cholesterol level remained low during both modalities of dialysis. Other serum lipids or lipoproteins, such as triglycerides, free fatty acids, phospholipids, VLDL and LDL, showed no manifest variations relevant to the change of the dialysate buffer base. Likewise, the levels of apoproteins A and C were not significantly affected by the difference of dialysate. No evidence was obtained for a more beneficial effect of the bicarbonate dialysis compared to the acetate bath on lipid metabolism of the dialyzed patients.

Acetates↗

Immunosuppressive factors in uraemic sera are composed of both dialysable and non-dialysable components.

The immunosuppressive factors in uraemic sera were studied. Sera were obtained from 46 uraemic patients with a mean serum creatinine of 1.24 mM/1 +/- 0.36 (s.d.) prior to being introduced to dialysis therapy. Normal peripheral blood mononuclear cells, which were incubated in vitro with pokeweed mitogen (PWM) in the presence of 10% uraemic sera plus 10% pooled normal human serum sustaining the culture, showed decreased 3H-thymidine uptake compared to the control culture with normal sera. The immunosuppressive activity of uraemic sera was partially lost by in vitro dialysis, although a moderate degree of suppressive potency to the normal cells cultured with PWM remained in the dialysed uraemic sera. The remaining inhibitory activity in the dialysed sera was found to be unrelated to anti-lymphocyte antibodies.

Adult↗

Chromosomal investigations of the Usubuchi sarcoma. II. Chromosomal alteration of the stem line cells revealed by differential staining techniques.

Stem line cells of the Usubuchi sarcoma (US) were karyologically investigated by means of G-, C-, and N-banding methods in ten samples from the 1,923rd to 2,081st transfer generations, with special attention to the structural alteration of marker-1 chromosome. The US cells showed wide variations in chromosome constitution and number, while the modal number of chromosomes was consistently 64 in all the generations examined. The chromosome constitutions varied widely even in cells with the modal number. In the early stage (1,923rd to 1,936th generations) the US contained two major stem lines characterized by marker combinations such as 1-2-3-4(1)-4(3)-8 and 2-3-4(1)-4(2)-4(3)-8, occurring with nearly similar frequency. From the middle to later transfer stages (from the 2,004th to the 2,081st generations), the 1-2-3-4(1)-4(3)-8 stem line rapidly declined and finally disappeared. In contrast, the 2-3-4(1)-4(2)-4(3)-8 line became a predominant part of the stem line. The G- and C-banding and population analyses of the stem line cells strongly suggested that marker 4(2) might have been derived from marker 1 by a deletion of the distal half of its long arm. The US studied contained a few stem lines and various types of sublines, each karyologically characteristic. G-Banding analysis revealed various types of intra- and interchromosomal rearrangements probably due to occasional chromosomal mutations either in markers or in nonmarkers in both stem lines and sublines. It seems likely that the stem line cells of the US are not always stable, but rather variable, in their chromosome makeup during the course of multiplication and successive transfers.

Animals↗

Effects of a polyunsaturated fatty acid-rich diet on serum lipids in patients with chronic renal failure.

An abnormal level of serum lipids may be one of the major risk factors for the development of atherosclerosis in patients with chronic renal failure (CRF). In the present study, the effect of polyunsaturated fatty acid-rich and low carbohydrate diet on serum lipids and HDL-cholesterol was studied in 6 nonnephrotic and nondialyzed patients with CRF on an isocaloric basis. Serum triglycerides decreased significantly from 2.08 +/- 0.93 mmol/l (183 +/- 82 mg/dl) to 1.49 +/- 0.83 mmol/l (131 +/- 73 mg/dl) by consumption of polyunsaturated diet (p less than 0.01). The 'HDL-cholesterol ratio' increased significantly and LCAT decreased on a polyunsaturated diet. In conclusion, the consumption of a polyunsaturated fatty acid-rich diet tends to normalise increased serum triglycerides and lowered 'HDL-cholesterol ratio' in patients with CRF and may be effective for prevention of atherosclerotic vascular sequellae.

Adult↗

Pseudoplaque formation by cytophilic immunoglobulins in the sera of lupus patients as measured using reverse haemolytic plaque assay.

Normal human peripheral blood lymphocytes cultured in vitro with lupus sera (LS) were studied for their possible immunoglobulin (Ig) secretion using reverse haemolytic plaque assay (RHPA). Plaque forming cells (PFC) produced in cultures with LS (2,323 +/- 858 PFC/10(6) cultured cells) significantly increased in number compared to the control cultures with normal human serum (206 +/- 43, P less than 0.05). However, the artifactual nature of the PFC formation due to cytophilic Ig in LS subsequently became evident from the kinetic curves, trypsinization or medium change at the end of the culture period, radiation of cells on the first day of culture, or by depletion of nylon wool column-adherent cells from the culture system. These cytophilic Ig were observed in 56% of the sera obtained from untreated lupus patients. Thus, their possible interference with the resultant spurious plaque formation might be difficult to eliminate when performing RHPA in lupus patients.

Antibodies↗

Acute and chronic cardiocirculatory effects of oral prazosin in chronic refractory heart failure.

The acute hemodynamic effects of oral prazosin were investigated in 7 patients with chronic refractory heart failure. A single dose of 1 to 3 mg prazosin produced a significant increase in cardiac index (+17.6%, p less than 0.01) associated with substantial decreases in pulmonary arterial diastolic pressure (-31.6%, p less than 0.02), systemic vascular resistance (-29.7%, p less than 0.01), and double product (-24.1%, p less than 0.02). Plasma renin activity was significantly elevated (+42.4%, p less than 0.02). These effects were found maximum at 2 hours and persisted for 8 hours. The chronic hemodynamic effects in 5 patients with chronic refractory heart failure were evaluated by administration of 1 to 2 mg prazosin 3 times daily for 8 weeks, and ventricular function was assessed by echocardiography and carotid pulse recording. All the patients showed improvement in the clinical symptoms of heart failure. Peripheral venous pressure decreased slightly (-12.5%). ET/PEP increased (+24.5%) without any significant changes in EF and mVcf. Plasma renin activity also slightly increased (+17.8%). Thus, prazosin possesses sustained nitroprusside-like actions, and is effective in the management of chronic congestive heart failure refractory to conventional therapy. While, further investigation is necessary to define the effect of prazosin on plasma renin activity.

Administration, Oral↗