Biomedical subjects

R Takaki

Publications and source records attributed to R Takaki.

At least 37 records · Page 2Linked to original sources

PubMed1992

Ultrastructural and immunohistochemical similarities between glomerular arteriolar and mesangial lesions in experimental diabetes.

It has thus far been speculated that plasma proteins have leaked and accumulated in diabetic expanded mesangium. We have previously shown that glomerular arteriolar hyalinosis has frequently occurred and has consisted of basement membrane-like extracellular matrix in alloxan diabetic rats. In the present study, the two diabetic glomerular lesions, arteriolar hyaline nodules and increased mesangial matrix, were comparatively evaluated by means of electron microscopy and immunohistochemistry. It was revealed that both of these lesions contained, in common, finely particulate extracellular matrix mingled with cytoplasmic fragments, and exhibited intense immunoreactions for IgG and IgM. It is indicated that both types of diabetic glomerular lesions are essentially of the same nature.

Animals↗

PubMed1992

Similarity of the constituents between glomerular arteriolar and mesangial lesions in experimental diabetes.

In our previous studies in experimental diabetic rats, we have observed close similarities of ultrastructure and accumulation of IgG and IgM between the mesangial expansion and arteriolar hyalinosis of the glomerulus, and have presumed that both diabetic lesions are essentially of similar nature. In the present study, we carried out a further study on the constituents of both these lesions, using the PA-TCH-SP-PD technique for neutral carbohydrates, sialic acid and glycoproteins and the IgG-gold-silver technique for type IV collagen and fibronectin. The above staining and immunolabelings proved to be comparable in both lesions of diabetic glomerulopathies. This argues for the hypothesis of the identity of the two lesions.

Animals↗

PubMed1992

A case of primary biliary cirrhosis associated with Hashimoto's thyroiditis, scleroderma and Sjögren's syndrome.

A 53-year-old woman was admitted because of Raynaud's phenomenon, polyarthralgia and polymyalgia. Biopsy specimens of the liver and thyroid gland revealed characteristic findings of primary biliary cirrhosis (PBC) (stage I by Scheuer's classification) and chronic thyroiditis. Her clinical features were also complicated by scleroderma (type I by Barnett's classification) and Sjögren's syndrome (Sjs) with keratoconjunctivitis sicca. Thyroid hormone replacement therapy led to improvement in thyroid function, normalization of the biliary tract enzymes and alleviation of subjective symptoms.

Autoantibodies↗

PubMed1992

Allergic granulomatosis and angiitis with severe cardiac disease: a case in which cardiac function was extremely improved by long-term steroid therapy.

A 38-year-old man with a history of bronchial asthma developed marked eosinophilia, mononeuritis multiplex and transient pulmonary infiltration. Pathological findings from the lung and nerve biopsy were helpful in determining the diagnosis as allergic granulomatosis and angiitis (AGA). Echocardiogram indicated dilation of the left ventricle with impaired systolic contraction. Coronary arteriography demonstrated significant stenosis only in the peripheral segment of the circumflex artery. After 1 year of corticosteroid therapy, echocardiogram revealed improvement of left ventricular contractility evaluated by ejection fraction (from 28% to 67%). To our knowledge, no previous reports have described amelioration of severe cardiac lesions during long-term steroid treatment in patients with AGA.

Adult↗

PubMed1992

[The effects of isosorbide dinitrate spray on the coronary artery and its modification by the preceding chronic oral therapy with long acting isosorbide dinitrate].

The vasodilatory effect of a new formula of isosorbide dinitrite (ISDN) spray on the left coronary artery was studied by comparing its effects in 46 consecutive patients who subsequently received intracoronary injection with ISDN (2.5 mg). In addition, the influence long acting and ISDN for chronic cases on the vasodilatory effects of ISDN spray and on subsequent intracoronary injection of ISDN was investigated. The patients were divided into two groups, those who had had chronic oral ISDN (Group N; 29 patients) and those who had not (Group O; 17 patients). The vasodilatory effect of ISDN spray was evaluated in segments; 5, 6, 8, 11 and 12 by AHA classification and it dilated those segments by 9.9%, 13.2%, 21.5%, 15.6% and 23.5% respectively. Subsequent intracoronary injection of ISDN dilated those segments by 10.4%, 14.0%, 27.2%, 17.9% and 29.1% respectively. The differences in the degree of vasodilation caused by ISDN spray and that caused by injection in segments 8, 11, 12 were statistically significant. However, the per cent dilation of ISDN spray in segments 5 in group N was 5.9%, and 18.4% in group O, revealing a significant difference depending on previous chronic administration of long acting ISDN. We conclude that ISDN spray did dilate the coronary artery, and subsequent intracoronary administration of ISDN dilated it further in the distal portions of the left coronary artery. Long acting oral ISDN for chronic cases seemed to attenuate the vasodilatory action of ISDN.

Administration, Oral↗

PubMed1991

Evidence for secretion of 7B2 by A- and B-cells of hamster pancreatic islets.

7B2 is a neuroendocrine protein, and in the pancreatic islets the presence of 7B2 in A- and B-cells was immunohistochemically demonstrated. In order to examine 7B2 secretion by A- and B-cells of pancreatic islets, we prepared isolated hamster pancreatic islet cells as well as an A-cell-rich culture, and studied 7B2 secretion under certain stimulations. 7B2 was secreted by isolated hamster pancreatic islet cells. This secretion was stimulated by theophylline and arginine, but glucose had a weak effect on the 7B2 secretion. Such a response of 7B2 to the stimulations was different from that of insulin or glucagon. 7B2 secretion was also noted in the A-cell-rich culture. These results suggest that 7B2 is secreted by both A- and B-cells of the hamster pancreatic islets and its secretion is regulated under certain conditions.

Animals↗

PubMed1991

Autocrinological role of basic fibroblast growth factor on tube formation of vascular endothelial cells in vitro.

When bovine capillary endothelial (BCE) cells plated on type I collagen gel were covered with a second layer of collage gel, BCE cells reorganized into a network of capillary-like structures. In the presence of affinity purified anti-basic fibroblast growth factor (bFGF) antibody, this reorganization was inhibited. By using a computerized image analyzer, the formation of network structures and the effect of anti-bFGF antibody was quantitated. The inhibitory effect of anti-FGF antibody was dose-dependent and maximal inhibition was observed at 2.0 micrograms/ml of antibody. Exogenously added bFGF potentiated network formation of BCE cells and coadministration of bFGF abrogated the inhibitory effect of anti-bFGF antibody. Platelet factor 4, which blocks the binding of bFGF to its receptor, inhibited network formation. These results indicate that bFGF produced by endothelial cells regulates angiogenesis as an autocrine factor.

Adrenal Glands↗

PubMed1991

The stimulatory effect of PDGF on vascular smooth muscle cell migration is mediated by the induction of endogenous basic FGF.

The migration of arterial smooth muscle cells from the media to the intima is a crucial event for the development of the atherosclerotic lesion, and platelet derived growth factor (PDGF) is thought to play an important role in this process. Here we report that the spontaneous migration of bovine smooth muscle (BSM) cells is dependent on endogenously produced basic fibroblast growth factor (bFGF). PDGF stimulates the migration of BSM cells and its effect is abolished by affinity purified anti-bFGF antibody. PDGF induces bFGF mRNA in BSM cells. These results indicate that the effect of PDGF on the migration of BSM cells may be mediated by the induction of endogenous bFGF.

Animals↗

PubMed1991

Inhibitory effects of prostaglandin F2 alpha on mammary carcinogenesis induced by ethyl methanesulphonate in rats.

The effect of prostaglandin F2 alpha (PGF2 alpha) on mammary carcinogens was examined for a new system in female rats, using ethyl methanesulphonate (EMS). The rats were given EMS orally for a period of 12 weeks starting at age 4 weeks. Mammary carcinomas were first detected at the 16th week and were found in all surviving rats at the 32nd week. The concomitant administration of PGF2 alpha for 8 weeks made the development of tumor retarded; i.e., the carcinomas were first detected at the 30th week and final tumor incidence at the 44th week was 61.1%. The incidence of developing mammary carcinomas and multiplicity (number of mammary carcinomas per rat) were significantly lower in PGF2 alpha treated rats than in those given EMS alone. The inhibitory effect of PGF2 alpha on tumor development was apparent when PGF2 alpha was concomitantly given to the rats with EMS at age 4 weeks, while PGF2 alpha injections after oral administration of EMS at age 16 weeks did not significantly retard tumor development. Histologically, no significant difference in morphology was observed between PGF2 alpha-treated and PGF2 alpha-non-treated rats in either the cancerous or noncancerous mammary tissues. The finding demonstrates that PGF2 alpha inhibits the development of EMS-induced mammary carcinomas when given to younger rats, presumably by affecting the hormonal status rather than by direct action on the mammary glands.

Animals↗

PubMed1990

Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells.

Platelet factor 4 (PF-4) blocked the binding of basic fibroblast growth factor (bFGF) to the plasma membrane receptor. Five micrograms/ml of PF-4 completely blocked the specific binding of bFGF to the receptor of NIH 3T3 cells. Endogenously produced bFGF regulates the spontaneous migration of bovine aortic endothelial (BAE) cells as an autocrine factor (Sato and Rifkin, 1988). PF-4 inhibited the spontaneous migration of BAE cells in a reversible and dose dependent manner. The inhibition reached maximum at 5 micrograms/ml of PF-4, where the binding of bFGF to the receptor was completely blocked.

Animals↗

PubMed1990

Estrogen receptor status and effects of endocrine ablative surgery in ethyl methanesulphonate-induced rat mammary carcinoma.

An experimental model of rat mammary carcinoma induced by oral administration of ethyl methanesulphonate (EMS) was characterized with reference to estrogen receptors (ER) and hormone dependency. After the administration of EMS, the mammary carcinomas developed more rapidly in the 4-week old rats than in the 16-week old rats. The developed mammary carcinomas were related to the ER status. Tumor development was prevented by ablative oophorectomy prior to EMS administration, but only partially, by adrenalectomy. These inhibitory effects on tumor development were more obvious when ablative surgery was performed on younger rats at age 4 weeks. In rats subjected to oophorectomy at after EMS administration at age 16 weeks, tumor induction was retarded but not completely prevented. Thus, it appears that mammary tumors induced by EMS are dependent on ovarian hormones and that mammary glands of the younger female rats are more sensitive to carcinogenic actions of EMS.

Adrenalectomy↗

PubMed1990

Effects of glucose and insulin on cultured human microvascular endothelial cells.

The prolonged effects of glucose and insulin on cultured human microvascular endothelial cells from omental tissue (HOMEC) were observed to identify the contribution of sustained hyperglycemia and/or hyperinsulinemia to the pathogenesis of diabetic microangiopathy. When the cells were cultured for 10 days in Medium 199 with 100 or 500 mg/dl glucose, the number of cells was reduced to 78% in the culture of 500 mg/dl glucose as opposed to that of 100 mg/dl glucose. The difference in the number of cells between these two groups became obvious between the 5th and the 7th culture days. The replacement of D-glucose with L-glucose did not show any reduction in the number of cells, indicating the impertinence of high osmolarity, induced by high glucose (305 mOsm/kg) to the number of cells. This reduction resulted from the cellular damage during the culture period rather than the retardation of growth, according to the experiments of [3H]thymidine uptake and the 51Cr release assay. Since the uptake of glucose, measured as the uptake of 3-O-methyl-alpha-D-glucose, was higher and the Na+/K+ pump activity decreased in high glucose condition, it is suggested that the excessive intracellular accumulation of glucose caused the damage of cells through the disturbance of ion exchange. Insulin augmented the reduction in the number of cells induced by high glucose when supplemented together for 10 days at concentrations of 10(-6)-10(-12)M. The uptake of glucose increased further to 154% by the addition of insulin to high glucose as compared to that of high glucose alone, however, the decreased Na+/K+ pump activity by high glucose was restored to the control level by insulin. The aggravating effect of insulin to the cellular damage induced by high glucose seems to be mediation via the mechanism other than the decreased Na+/K+ pump activity. In conclusion, HOMEC were gradually damaged by high glucose and by insulin, and hyperglycemia and hyperinsulinemia would be of pathogenetic importance for diabetic microangiopathy.

Carrier Proteins↗

PubMed1990

Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: circumstantial evidence for impaired Ca2+ channel.

STUDY OBJECTIVE: The aim of the study was to investigate the effects of chronic diabetes mellitus on electromechanical properties of ventricular papillary muscles. DESIGN: Conventional glass microelectrodes and tension recording techniques were used in isolated hearts of rats made diabetic for 30-40 weeks by single intravenous injections of streptozotocin. SUBJECTS: Experimental animals were male Wistar rats of 200-250 g. Diabetic rats (n = 14) were given streptozotocin 65 mg.kg-1; controls (n = 15) were given vehicle only. MEASUREMENTS AND MAIN RESULTS: (1) The maximum upstroke velocity of the action potential duration of diabetic muscles was decreased compared to control, with no difference in the resting potential. (2) At all stimulation frequencies (0.2, 1 and 5 Hz), and particularly the lower ones, the action potential duration of diabetic muscles was longer than control. (3) In diabetic muscles, frequency dependent shortening of the late phase of action potential duration (APD75, APD90) was more pronounced, and frequency dependent lengthening of the early phase (APD25, APD50) was less pronounced. (4) A blocker of transient outward current, 4-aminopyridine, lengthened the early phase of action potential durations by the same amount in diabetic and control muscles. (5) A Ca2+ channel blocker, CoCl2, dramatically shortened all levels of action potential duration, with much greater effect on diabetic muscles. (6) Ryanodine lengthened the early phase of action potential duration and shortened the late phase in both diabetic and control muscles. It enhanced the difference between the groups in the early phase. (7) Developed tension in the presence of ryanodine (ryanodine resistant tension component) was greater in diabetic muscles than in control. CONCLUSIONS: The findings suggest that altered Ca2+ current, but not altered Na(+)-Ca2+ exchange current or altered transient outward current, significantly prolongs action potential duration in diabetic rat ventricular muscles.

4-Aminopyridine↗

PubMed1990

Effects of calcium antagonists on beta-receptors of cultured cardiac myocytes isolated from neonatal rat ventricle.

The effects of calcium antagonists (verapamil, diltiazem, and nicardipine) on beta-adrenergic receptors of cultured cardiac myocytes isolated from neonatal rat ventricle were studied with the hydrophilic ligand [3H]CGP-12177, which identifies cell surface-bound beta-receptors. The three calcium antagonists suppressed spontaneous beating of the myocytes, increased the number of beta-receptors, but did not alter the affinity (Kd). These effects were dose and time dependent. Verapamil (10(-6) M) increased the beta-receptor density by about 13% after 6 hours of incubation, and this increase in density reached a plateau of about 45% after 24 hours of incubation. beta-Receptor density increased by 15% with 5 x 10(-7) M and by 37% with 10(-6) M verapamil. The increased beta-receptors appeared to retain their normal function, as assessed by the increased spontaneous beating of the myocytes in response to applied isoproterenol. The increase in beta-receptors was abolished by colchicine but not by cycloheximide. When the calcium ion concentration of the medium was lowered to 0.1 mM, no significant change occurred in the density of beta-receptors compared with that in 1.8-mM Ca2+ medium. The results suggest that calcium antagonists increase beta-receptors by accelerating recycling by microtubules but not by decreasing the inward calcium current. Such effects of calcium antagonists may be clinically important and promise insight into the mechanism of the withdrawal phenomenon of calcium antagonists.

Animals↗

PubMed1990

Enzyme immunoassay of somatostatin (SS)-like immunoreactive substance in bovine milk.

A sensitive and specific enzyme immunoassay (EIA) for somatostatin (SS)-like immunoreactivity (SS-LI) was developed with the use of beta-D-galactosidase labeled antigen. The minimum amount of SS-like immunoreactive substance (SS-IS) detectable by this method was 1.0 fmol/well (25 pmol/l). The level of SS-IS in bovine foremilk was about 20 pmol/l, and the level was unchanged after delivery. On the other hand, the levels of gastrin releasing peptide (GRP)-IS and vasoactive intestinal polypeptide (VIP)-IS in bovine foremilk were very high, but fell during 1 week after delivery to about 10% of those in foremilk.

Animals↗

PubMed1989

The endocrine pancreas of alloxan-diabetic rats: microangiopathy as revealed by electron microscopy.

We studied the microvasculature of the pancreatic islet with an electron microscope using 15 alloxan-diabetic and 16 control rats. These animals were morphologically examined at 2 weeks, 1, 2, and 4 months after alloxan injection (diabetic rats) or at comparable times (control rats). Control rats were non-diabetic, either sequentially treated with glucose and alloxan (injected controls) or not subjected to any medication (non-treated controls). Body weights, plasma glucose levels, and erythrocyte glycosylated hemoglobin (HbA1c) concentrations were also measured at intervals. All the diabetic rats exhibited retarded growth, hyperglycemia, and increases in HbA1c concentrations. The primary changes in diabetic islet capillaries can be grouped into four categories: (1) narrowing and closing of capillaries and occurrence of possible acellular capillaries, (2) formation of perivascular edema, (3) bulging and projection of endothelial cytoplasm, and (4) perivascular proliferation of collagen-like fibrils together with thickening of the basement membrane. These changes tended to worsen with diabetic duration. They are regarded as pathognomonic for diabetic microangiopathy. It is presumed that the present microvascular lesions of the islet play an important role in the pathogenesis and advancement of the diabetic state.

Animals↗

PubMed1989

[Effect of thyroid hormone on the beta-receptor of cardiac myocytes isolated from rat ventricle].

INTRODUCTION Most of the symptoms in hyperthyroidism, such as an augmented metabolism, tachyarrhythmias and increased myocardial contractility, resemble those of increased sympathetic beta-adrenergic receptor are a major concern, but the exact mechanisms of the effects remain to be clarified. In the present study, the direct effects of triiodothyronine(T3) on the spontaneous beating and beta-receptor in relation to protein synthesis of the cultured ventricular myocytes were investigated. METHODS The cardiac myocytes were prepared from neonatal rat ventricle by enzymatic digestion and incubated at 37 degrees C in the atmosphere of 5% CO2 in air. The culture medium used was DME containing 5% fetal bovine serum and was renewed daily. The spontaneous beating frequencies of the myocytes were measured by the use of optical-video system. The cultured myocytes showed spontaneous beating dependent on Ca2+ concentration about 48 hours after the isolation. Although the beating was irregular and unstable at the beginning, it became regular and steady on the 3rd culture day. The experiments measuring spontaneous beating frequency were performed using the cells of this stage. In these experiments, the effects of T3 on the spontaneous beating frequency were studied after a 15-20 minute incubation with various concentrations of T3 (1 x 10(-10)-1 x 10(-7)M). The spontaneous beating was enhanced by isoproterenol and suppressed by Ca antagonists. The cardiac beta-receptors were identified using the hydrophilic radioligand 3H-CGP-12177 which labels specifically cell surface bound beta-receptors. The effects of T3 on protein synthesis in cultured myocytes were studied by measuring 3H-leucine uptake. RESULTS I. The effects of T3 on the spontaneous beating The effects of T3 on the spontaneous beating were investigated in two different ways. Firstly, the direct effect of T3 was studied by incubating the cells in the medium containing variable concentration of T3. T3 increased the beating frequency dose-dependently, and the maximal accelerating action was observed at the concentration of 10(-8)M. T3 at this concentration increased the spontaneous beating frequency from 131 +/- 25 min to 157 +/- 35 min after the treatment. Higher concentration of T3 induced arrhythmias and seemed to be toxic. Therefore, in the following experiments the concentration of 10(-8)M was used. The cardiac myocytes were incubated in either T3 containing or T3 free medium for 10 days. The incubation medium was renewed every day, and the change in the beating frequency was monitored continuously.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

The effect of prednisolone on cyclosporin-induced damage of pancreatic B cells in Wistar rats.

The combined effects of cyclosporin (CYA) and prednisolone (PSL) on the function and morphology of pancreatic B cells of Wistar rats were investigated. Four 13-day treatment groups were compared; these were the O group (olive oil alone, p.o.), the P group (PSL 3 mg/kg/day, i.m.), the C group (CYA 20 mg/kg/day, p.o.), and the PC group (PSL 3 mg/kg/day, i.m. plus CYA 20 mg/kg/day, p.o.). Glucose tolerance was equally impaired in the C and PC groups. The pancreatic insulin content in the C group was 49.7% of that of the O group, whereas that in the PC group was 81.1%. Morphometric analysis using modified aldehyde-fuchsin staining revealed that 'percent beta-granule area' in the islet was 17.5%, 15.0%, 6.5%, and 7.8% in the O, P, C, and PC groups, respectively. Ultrastructurally, pancreatic B cells in the PC group showed CYA damage; however, a significant number of B cells exhibited hypertrophy of the rough endoplasmic reticulum and the Golgi apparatus, suggesting concomitant B cell hyperactivity in this group. These findings suggest that PSL does not aggravate the toxic effects of CYA on pancreatic B cells during short-term treatment; rather, it might be protective.

Animals↗