Nifedipine-suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits.
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Biomedical subjects
Publications and source records attributed to N Watanabe.
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Phase specificity in the TNF cytotoxic effect and the number of TNF binding receptors was investigated using L-M cells incubated synchronously from the S phase. TNF cytotoxicity was observed to occur at various levels during the cell cycle, with peak effect in the G2-M phase. Analysis with 125I-labeled TNF to determine the number of receptors binding TNF in the various cell phases shewed a phase specificity with the maximum number occurring in the G2-M phase, similar to the peak in cytotoxicity. The results suggest the existence of a cell cycle specificity in the cytotoxicity of TNF which is apparently related to changes in the number of receptors capable of binding TNF.
To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.
The long-term effect of high-glucose condition on insulin binding to IM-9 cells was studied by incubating the cells in RPMI-1640 medium containing 450 mg/dl of glucose. Insulin binding began to decrease after incubation for 6 days in high-glucose-treated cells, and significantly decreased after 14 days due to the reduction of receptor affinity. The number of binding sites for insulin did not change by the treatment. Thus, high-glucose condition per se does not appear to induce the decrease of the number of insulin receptors on target cells, as observed in diabetic patients.
The effects of increased pericardial pressure on blood flow to collateral dependent and normal myocardium were investigated and the mechanisms responsible for these effects evaluated in 10 anaesthetised dogs after collateral inducement by gradual occlusion of a coronary artery. Regional myocardial blood flows were measured with radioactive microspheres during control conditions, mild tamponade, severe tamponade, and severe tamponade with aortic blood pressure held at the control value by blood volume expansion. Mild tamponade increased heart rate by 10% and decreased aortic blood pressure by 15%. Left atrial and central venous blood pressures were moderately increased, and indices of cardiac function were reduced. Blood flow to collateral dependent and normally perfused myocardium was not significantly altered, but the endocardial to epicardial flow ratio was significantly decreased in collateral dependent myocardium. Severe tamponade decreased aortic blood pressure by 45% and cardiac index by 62%. Left atrial and central venous blood pressures were appreciably increased and cardiac function indices considerably depressed. Blood flow to collateral dependent and normally perfused myocardium was decreased similarly (by 54-57%), but the endocardial to epicardial flow ratio was decreased by a greater degree in collateral dependent myocardium. During severe tamponade at control aortic blood pressure, left atrial and central venous blood pressures were further increased, but blood flow to collateral dependent and normally perfused myocardium returned to within 84% of control and endocardial to epicardial flow ratios were normal. Total peripheral vascular resistance increased during severe tamponade, but coronary vascular resistance remained constant. Thus blood flow to collateral dependent and normally perfused myocardium varied according to net coronary perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregulatory closed-loop gain of the right coronary circulation averaged 0.37 +/- 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 +/- 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 +/- 1.0 to 2.9 +/- 0.8 ml O2/min/100 g as pressure was reduced from 160 to 40 mm Hg. Thus, right coronary autoregulation is masked by an opposing change in oxygen demand. When right ventricular oxygen consumption was altered by pacing, a linear flow-oxygen consumption relationship was observed (8.2 +/- 0.4 ml/min/100 g per ml O2/min/100 g). Subtraction of flows associated with pressure-induced changes in metabolism revealed a potential autoregulatory capability of the right coronary circulation similar to that manifested by the left coronary circulation.
We report a patient with unilateral agenesis of the internal carotid artery in whom the oculomotor nerve was paralyzed on the same side as the agenesis after a minor head injury. It is conceivable that the palsy was caused by sudden tension of the nerve between the petroclinoid ligament and the enlarged posterior communicating artery.
As the serological test of streptococcal infection, the measurement of anti-exotoxin antibodies such as ASO is widely practiced. M protein of the cell wall of group A streptococcus has type specificity. To detect the anti M protein antibody is very significant, but it is not easy to apply this to clinical practice because there are many types and because of the difficulty of purifying M protein. C polypeptide has group specificity, so the measurement of the antibody to C polypeptide is very important as the serological test of group A streptococcus.
Chronic idiopathic neutropenia can occur in spite of the normocellular bone marrow in myeloid series with or without anti-neutrophilic antibody. We report a patient with chronic neutropenia and severe polyclonal hypergammaglobulinemia. The patient demonstrated a positive anti-neutrophil antibody by fluorocytometry, although granulocyte-specific anti-nuclear factor and anti-stem cell (CFU-GM) antibody were negative. Thus, neutropenia of this patient appeared to be due to the antibody-mediated destruction of neutrophils. Both neutropenia and hypergammaglobulinemia were normalized by the administration of prednisone.
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To determine right (RV) and left ventricular (LV) volumes, a new technique was developed using ECG-gated single-photon emission computed tomography (SPECT). RV volumes of nine patients and LV volumes of 22 patients measured by SPECT and biplane contrast cineangiography were compared. In addition, volume and ejection fraction (EF) of the RV and LV were obtained by SPECT for 10 normal controls, 21 patients with old myocardial infarction (OMI), eight patients with hypertrophic cardiomyopathy (HCM) and 12 patients with dilated cardiomyopathy (DCM), and these results were compared. The intracardiac blood pool was labeled with Tc-99m sodium pertechnetate and 32 images were recorded through 180 degrees by a rotating gamma-camera. End-diastolic and end-systolic counts during 50 msec were recorded during 50 or 60 cardiac cycles. These counting data were reconstructed as tomographic images of vertical long-axial slices with thickness of a pixel without any attenuation correction. The numbers of voxels within the % cut-off level were summed, and the sum was multiplied by the one voxel volume. The cut-off level for ventricular delineation was determined as 45% by phantom studies. 1. The values obtained from SPECT and contrast angiography correlated well. 2. In normal controls, LV end-diastolic and end-systolic volumes were significantly less than those of the RV (p less than 0.05, p less than 0.001) and LVEF was significantly greater than the RVEF (p less than 0.001). 3. In OMI (single vessel disease), both end-diastolic and end-systolic volumes of the LV were significantly greater than those of normals (p less than 0.01, p less than 0.001) and LVEF was significantly less. In HCM end-systolic volumes of the RV were significantly less (p less than 0.05) than those of the normals. 4. LV volume was greater and LVEF was extremely low both in DCM and in OMI (multivessel disease) compared to that of the normals. In DCM, RV end-systolic volumes was greater and RVEF was lower than that of OMI (multi-vessel disease), indicating the deterioration of RV contractility , primarily in DCM. From these findings, it was concluded that this noninvasive technique may be useful for estimating left and right ventricular volumes.
The internalization process and intracellular distribution of 125I-labeled TNF, in L-M (murine tumorigenic fibroblasts, highly sensitive to TNF cytotoxicity) cells and in HEL (human embryonic lung cells, non-sensitive to TNF cytotoxicity) cells bearing TNF receptor, were elucidated by pulse-chasing and by Percoll density gradient centrifugation. Effect of TNF treatment on the RNA and protein synthesis of target cells was also studied using 3H-UDR and 35S-methionine incorporation. In both L-M and HEL cells, receptor-bound 125I-TNF was rapidly internalized and delivered to lysosomes within 15-30 min, followed by degradation and release into the culture medium. RNA synthesis and protein synthesis were not affected by TNF treatment in HEL cells, but marked stimulation (3.5 times and 4.2 times, respectively) was observed in L-M cells.
Tumor necrosis factor (TNF) is cytokine derived from macrophage and shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Recently, the gene encoding human TNF was expressed in E. coli and the recombinant TNF was purified to homogeneity by ion exchange chromatography, affinity chromatography, and gel filtration. Clinical study of rH-TNF has been launched because human recombinant TNF can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of action of cytotoxic activity. In this article, the mechanism of action of rH-TNF against tumors in vitro and in vivo is reviewed.
TNF is cytokine derived from macrophages and shows much promise for use in cancer therapy because of its marked antitumor effects and its high specificity to tumors. The clinical application (Phase I-II) of TNF has been started because human recombinant TNF (rH-TNF) can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of its cytotoxic action. In this article, the antitumor effects of rH-TNF against human and murine tumors, the mechanism of its action and the synergistic effects of rH-TNF in combination with IFN-gamma, various anticancer drugs or with hyperthermia are reviewed.
Peritoneal function in relation to the occurrence of peritonitis and the osmolarity of the dialysate was studied in 72 CAPD patients with a mean duration of treatment of 16.5 +/- 9.0 months (group 1). Data from 24 of these patients, who were on CAPD for longer than 2 years (average 28.6 +/- 4.9), were subjected to further detailed analysis (group 2). Each group consisted of two subgroups, one of patients who had experienced peritonitis and one of patients who had had no episodes of peritonitis. Results from group 1 revealed that the use of hyperosmolar bags increased in parallel with the duration of CAPD treatment even in the non-peritonitis subgroup, and that peritonitis enhanced the tendency to use hyperosmolar dialysate solutions. This phenomenon was also observed in the peritonitis subgroup of group 2, but was not apparent in the non-peritonitis subgroup of group 2 when examined as a whole: however, individual analysis revealed that some of them had a similar tendency to use hyperosmolar dialysate, as was seen in the peritonitis subgroup. These results confirm that the peritonitis impairs the ultrafiltration capability of the peritoneum. The results also suggest that the long-term use of hyperosmolar dialysate may be associated with decreased ultrafiltration, hence emphasis should be placed upon the use of hyperosmolar dialysate solutions for long-term CAPD.