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Biomedical subjects

K Mimura

Publications and source records attributed to K Mimura.

At least 73 records · Page 4Linked to original sources

Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E.

The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis.

Aortic Diseases↗

[Complex formation of ulinastatin with alpha-thrombin].

The inhibition mode of ulinastatin was indicated noncompetitive by the Lineweaver-Burk's double reciprocal plotting method using the production rate of fibrinopeptide A. Consequently Km of alpha-thrombin could be calculated 2.8 mM and its Vmax was reduced from 24 U/l to 15 U/l by the addition of ulinastatin and Ki of ulinastatin was 1.05 x 10(-2) M. The complex of ulinastatin and alpha-thrombin were found. Furthermore, the mixing of alpha-thrombin, AT-III and ulinastatin produced a larger complex on SDS-PAGE at pH 7.0, and it was evident by the use of Western blotting method, that the complex was consisted of alpha-thrombin, AT-III and ulinastatin. Although ulinastatin and thrombomodulin showed multiple similarities in inhibitory functions on alpha-thrombin, still there are some differences functioning on alpha-thrombin, because of the different binding sites of ulinastatin and thrombomodulin on alpha-thrombin, indicating no crossreaction for antithrombomodulin monoclonal antibody relating to alpha-thrombin binding site of thrombomodulin and it could be contributed to form noncompetitive or uncompetitive inhibitors.

Binding Sites↗

Alterations in femoral bone histomorphometry and vitamin D metabolism in neonatal streptozotocin-induced diabetic rat.

Histomorphometric examination and histological observation of femoral bone were performed on long-standing neonatal streptozotocin-induced diabetic rats (n2STZ, n5STZ) as a human model of non-insulin-dependent diabetes mellitus. The growth and strength of femurs decreased in the STZ diabetic rats. Histomorphometric parameters such as cortical bone thickness, number of metaphysical trabeculae and percent trabecular volume of metaphysical area all significantly decreased in the STZ diabetic rats. There were no significant differences in parameters between the n2STZ and n5STZ diabetic rats. Histological findings demonstrated no significant change in the number of osteoclasts in femur nor change corresponding to osteomalacia. Bone absorption in the STZ diabetic rats appeared unchanged. The plasma calcium level did not change in the STZ diabetic rats, although their plasma phosphate or A1-p levels increased. Circulating 24, 25 (OH)2D3 was significantly lower in the STZ diabetic rats than the controls. However, 25 (OH) D3 or biologically active 1, 25 (OH)2D3 was not different between the controls and STZ diabetic rats. Osteopenia is thus present in the femurs of long-standing neonatal STZ diabetic rats, due in part to abnormal vitamin D metabolism.

Animals↗

Fibrinolysis activity promotes tumor invasiveness of B16 melanoma cell lines through a reconstituted gel matrix.

We studied the role of the fibrinolytic function in the invasiveness of murine melanoma B16F1 and F10 cells using a reconstituted matrix on a filter in a modified Boyden chamber. The main species of plasminogen activators (PAs) synthesized in cell lysates and released into conditioned media by these cells was found to be tissue-type PA (t-PA). The invasiveness of these cell lines was enhanced by adding plasminogen to the gel matrix. This enhancing effect of plasminogen was markedly suppressed by adding anti-t-PA IgG and plasmin inhibitors into the gel matrix, but less affected by anti-urokinase-type PA (u-PA) IgG, offering more evidence to the hypothesis that the activation of the fibrinolytic system by PAs plays an important role in the invasiveness of murine melanoma B16 cell lines, and indicating that t-PA contributed more than u-PA to the invasive potential of these cells into the pericellular matrix.

Animals↗

Study on the inhibitory effect of uremic plasma on lipoprotein lipase.

An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.

Adult↗

[Inhibitory effect of ulinastatin on the alpha-thrombin activation of factors V and VIII].

Ulinastatin is a remedy of urine serinprotease inhibitors and also it inhibits enzymatic activities of several blood coagulation factors. The action of ulinastatin on alpha-thrombin shows noncompetitive inhibition with the formation of enzyme-inhibitor complex. In this study, the effects of ulinastatin on the alpha-thrombin activation of factors V and VIII are observed by 5-20% gradient gel SDS PAGE with or without Western blotting method. The addition of ulinastatin to the mixture of factor V and alpha-thrombin inhibits the production of active peptides proceeded in the alpha-thrombin activation process of factor V. Furthermore, using anti-factor VIII 43KDa peptide monoclonal antibody with Western blotting method, the addition of ulinastatin to the mixture of alpha-thrombin and factor VIII indicates to inhibit the release of 43KDa peptide from factor VIII in the process of factor VIII activation induced by alpha-thrombin.

Factor V↗

Cortical modulation of visual contrast.

The mechanisms that produce simultaneous contrast have been thought to depend on retinal gain control and the retina is supposed to send signals to the brain only in terms of local-border contrast (Shapley, 1986). However, it was found that, when an object on a uniform background and border-concealing stimuli are presented to different eyes, the brightness of the object is greatly influenced if the border-concealing stimuli are perceptually superimposed on the border of the object. The change in the object's brightness in this condition is almost identical to that observed when both the object and the border-concealing stimuli are presented to the same eye, suggesting that the brain can compute brightness by using luminosity information when contrast information is disrupted.

Adult↗

Effect of platelet-activating factor on lipoprotein lipase and blood lipids.

We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 micrograms/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 micrograms/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL.

Animals↗

Intercellular communication in cultured rabbit gastric epithelial cells.

The effects of drugs related to cyclic AMP and a tumor promoter, phorbol ester, on intercellular communications via gap junctions were investigated by the Lucifer Yellow-transfer method in cultured rabbit gastric epithelial cells. Cells were in contact with each drug for 4 hr before the microinjection of the dye into a cell. Dye transfer capacity was significantly increased by dibutyryl cyclic AMP (10(-3) M), theophylline (10(-3) M), 3-isobutyl-1-methylxanthine (10(-4) M), forskolin (10(-6) M) and irsogladine (10(-4) M); and it was inhibited by 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml). These results suggest that the intercellular communication between cultured rabbit gastric epithelial cells is upregulated by cyclic AMP.

Animals↗

The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia.

We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood.

Adult↗

Developmental process of visual pattern discrimination in the fly.

It has been found that the development of visual pattern discrimination in the fly is strongly influenced by visual experience in the early stage of post-emergence. Behavioral experiments were performed to determine the details of the temporal conditions of the visual experience and to obtain a lead to the determination of the molecular mechanism underlying the developmental process. By anesthetizing the flies with chilling at various periods post-emergence, it was demonstrated that visual experience during 5 h post-emergence must be followed by normal neuronal activity within a very short time of 15 min for the normal development of visual pattern discrimination to occur. The subsequent development of normal pattern discrimination required the maintenance of normal neuronal activity for at least 5 h. Injection of some protein synthesis inhibitors to the fly head before or immediately after visual experience resulted in impairment of the development of visual pattern discrimination, thus supporting the developmental process revealed by the chilling experiment. Moreover, both the chilling experiment and injection of inhibitors of protein synthesis showed that the neuronal mechanisms were different for phototaxis and for pattern discrimination, suggesting that the former is a natural function while the latter is an acquired function after emergence.

Aging↗

Corticotropin-releasing hormone- and adrenocorticotropin-producing pituitary carcinoma with metastases to the liver and lung in a patient with Cushing's disease.

A 53-yr-old man with Cushing's disease was found to have a pituitary carcinoma with metastases to the liver and lung which produced both CRH and ACTH simultaneously. Despite removal of the pituitary tumor, his Cushing's disease worsened. Endocrinological examination then demonstrated elevated plasma CRH and markedly elevated plasma ACTH, beta-lipotropin, and cortisol concentrations, increased urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion, and no suppression of serum cortisol after low or high dose dexamethasone administration. Urinary 17-hydroxycorticosteroid excretion increased in response to metyrapone, and lysine vasopressin elicited a striking increase in plasma ACTH. A computed tomographic scan of abdomen revealed multiple hypodense areas in the liver and bilateral adrenal hyperplasia. Postmortem histological examination revealed a necrotic hemorrhagic pituitary carcinoma with metastases to the liver, lung, and olfactory bulb. Immunohistochemical staining, gel filtration, and Northern blot analysis of liver and lung metastases revealed evidence of the production of both CRH and ACTH in these metastases. We concluded that the patient's pituitary carcinoma produced both CRH and ACTH.

Adrenocorticotropic Hormone↗

[Discriminant function analysis for evaluating the status of coronary heart disease risk].

We investigated to discriminate those individuals categorized by 1. obesity, 2. hypercholesterolemia, 3. hypertension, 4. low maximal oxygen uptake, 5. an abnormal electrocardiogram reflecting ischemic patterns, and/or 6. real sedentary life, from relatively healthier individuals without coronary heart disease (CHD) risk factors. One hundred and six Japanese women, aged 30 to 72 years, all of whom were in the postabsorptive state, were recruited in a series of tests for anthropometric and physiologic profiles both during the resting state and during the submaximal-maximal cycling exercise. Subjects were categorized into two groups--those who possessed four or more of the above 1, 2, 3, 4, 5, and 6 (high-CHD-risk group, n = 15) and apparently healthy individuals with a minimum number of risk factors (low-CHD-risk group, n = 83). Analyses of the data revealed that a combination of 8 variables extracted from among original 25 variables accurately classified 13/15 (87%) of high-CHD-risk group and 77/83 (93%) of low-CHD-risk group (mean = 90/98 or 92%) into their respective groups. The 8 variables were double product, Katsura index, waist girth, chest girth, TG, TC, and skinfold thicknesses at the subscapular and abdominal sites. Subsequent t-test identified significant differences between groups not only for VO2max, SBP and TC but also for DBP, LDLC, TG, Hb, HR, and HRmax. Most of these differences were of a much greater magnitude compared to the existing difference in chronological age. These findings suggest the usefulness and importance of anthropometric and blood lipid variables in the explanation of differences in the health status between high-CHD-risk women and their counterparts.

Adult↗

Proximal gastric vagotomy with carbon dioxide laser: experimental studies in animals.

Proximal gastric vagotomy has been widely used as a surgical treatment for peptic ulcer disease. However, it is technically complex and time-consuming. Moreover, it may cause circulatory problems in the gastric mucosa. We have reported a new method of blood flow-preserving vagotomy with a carbon dioxide laser (CO2 laser vagotomy) developed in our laboratory. To assess its efficacy, we used cysteamine-induced ulcer and measured gastric mucosal blood flow in rats. The incidence of cysteamine-induced ulcer formation was reduced significantly in the group that underwent CO2 laser vagotomy compared with a group treated with proximal gastric vagotomy. Gastric mucosal blood flow was significantly better in the CO2 laser vagotomy group. Long-term follow-up of acid reduction was evaluated in dogs by the pentagastrin-stimulation test. Acid reduction in dogs was satisfactory during the 12 months of this study. CO2 laser vagotomy is a new, easy, time-saving, and circulatory-preserving technique for peptic ulcer disease.

Animals↗

Minimum enzyme unit for Na+/K+-ATPase is the alpha beta-protomer. Determination by low-angle laser light scattering photometry coupled with high-performance gel chromatography for substantially simultaneous measurement of ATPase activity and molecular weight.

The oligomeric state of canine renal NA+/K+ -ATPase solubilized by octaethylene glycol n-dodecyl ether (C12E8) was studied by means of low-angle laser light scattering photometry coupled with high-performance gel chromatography (HPGC). At around 0 degree C the solubilized enzyme was separated into the (alpha beta)2-diprotomeric and alpha beta-protomeric protein components with Mr values of 302,000 +/- 10,000 and 156,000 +/- 4,000, respectively, in approximately equal quantities. As the temperature of chromatography was increased toward 20 degrees C, the two protein components converged into a single major component. The Mr of this component depended on the monovalent cation included in the elution buffer, and was 255,000 or 300,000 in the presence of 0.1 M NaCl or 0.1 M KCl, respectively. A computer simulation technique showed that the solubilized enzyme was in a dissociation-association equilibrium of 2 protomers = diprotomer at 20 degrees C, and the difference in apparent Mr of the solubilized enzyme between the two species of monovalent cation was interpreted by an association constant (Ka) in the presence of 0.1 M KCl that was about 50-fold larger than in the presence of 0.1 M NaCl. In order to measure ATPase activity and Mr of the solubilized enzyme simultaneously, a TSKgel G3000SW column had been equilibrated and was eluted with an elution buffer containing 0.30 mg/ml C12E8 and 60 microgram/ml phosphatidylserine (bovine brain) as well as the ligands necessary for the enzyme to exhibit the activity at pH 7.0 and 20 degrees C. The solubilized enzyme was always eluted as a single protein component irrespective of the the amount of the protein applied to the column, ranging between 240 and 10 microgram. The Mr of the protein component, however, decreased from 214,000 and 158,000 with the decrease of the protein amount. The specific ATPase activity, however, remained constant at a level of 64 +/- 4% of that of the membrane-bound enzyme even in the range of protein concentration sufficiently low as to allow the enzyme to exist only in the protomeric form. Thus, the alpha beta-protomer is concluded to be the minimum functional unit for the ATPase activity. The value of Ka obtained from the concentration-dependent dissociation curve was 5 . 10(5) M-1 for the enzyme turning over, and 1.1 . 10(7) M-1 for the enzyme inhibited with ouabain. It was discussed, based on the values of Ka obtained, that the enzyme would exist as the diprotomer or the higher oligomer in the membrane.

Animals↗