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Biomedical subjects

T Igawa

Publications and source records attributed to T Igawa.

At least 55 records · Page 3Linked to original sources

[Ultrastructural and immunohistochemical study of experimental atherosclerosis in Japanese quails].

A marked plaque was produced at the tunica intima of the ascending aorta in all of the Japanese quails of 9 weeks old which fed on atherogenic diet containing 2% cholesterol for 8 weeks, while no structural changes of aortic wall were observed in Japanese quails which fed on normal basic food for the same period. The media of aorta in normal quails consist of smooth muscle cells, myofibroblast-like cells (MF) cells), and many successive elastic membranes. At the atherosclerotic lesion, many MF cells migrated from media into intima, and a part of smooth muscle cells were also differentiated to MF cells. Moreover, the most migrating MF cells differentiated to foam cells at the intimal thickness regions, and a few other MF cells also differentiated into endothelial cells of newly forming capillaries. By the immunohistochemical stainings, medial smooth muscle cells were negatively stained with anti-vimentin antibody, and the majority of cells in the intima (MF cells, foam cells, and endothelial cells) contained vimentin filaments. These results indicate that MF cells play a very important role in the development of atherosclerosis in Japanese quail. The morphologicals study offers some new insights into the evaluation of Japanese quails as an animal model of atherosclerosis.

Animals↗

Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells.

We developed the new system in which the platelet aggregation was detected turbidimetrically using glass cuvettes which were coated cultured vascular endothelial cells. Using this system, we evaluated the effect of cilostazol, having a selective inhibitory effect on cAMP-PDE, on the ADP-induced platelet aggregation in the presence of endothelial cells. Cilostazol inhibited the platelet aggregation dose-dependently in the presence or absence of endothelial cells. The inhibitory effect of cilostazol on platelet aggregation was potentiated by the presence of endothelial cells, and the slope of the dose-response curves were identified to be as the same between both experiments in the presence and the absence of endothelial cells. The pretreatment of endothelial cells with aspirin reversed the potentiated inhibitory effect of cilostazol on the platelet aggregation with endothelial cells. The amount of 6-keto-prostaglandin F1 alpha accumulated in the cuvette was reduced in this condition. On the other hand, the inhibitory effect of prostaglandin E1 on the platelet aggregation was not potentiated by the presence of endothelial cells. These results suggest that the endothelium-derived prostacyclin plays a role on the potentiation of anti-platelet aggregatory effect of cilostazol.

3',5'-Cyclic-AMP Phosphodiesterases↗

The effect of transforming growth factor-beta on the alkaline phosphatase activity in rabbit renal cortical tubular cell cultures.

The effect of various growth regulators including epidermal growth factor and transforming growth factor-beta on the alkaline phosphatase activity of rabbit renal cortical tubular cells has been investigated in a serum-free culture. As a result, it was found that transforming growth factor-beta, known to be a growth inhibitor of renal tubular cells, increased the alkaline phosphatase activity of the tubular cells dose-dependently and that cycloheximide blocked any increase in the activity of this factor. In contrast, epidermal growth factor decreased the alkaline phosphatase activity in the tubular cells.

Alkaline Phosphatase↗

Intranasal administration of human fibroblast interferon in mice, rats, rabbits and dogs.

In previous studies on the nasal administration of human fibroblast interferon (HuIFN-beta), only rabbits have been used. Therefore, this route was investigated in mice, rats, rabbits and dogs. HuIFN-beta could be delivered across the nasal mucosa in mice, rats, rabbits and dogs, when it was mixed with sodium glycocholate as an absorption promoter. However, the pattern of the plasma HuIFN-beta concentration-time curve was different from that in rabbits. Rabbits gave the highest value of the maximum plasma HuIFN-beta concentration (Cmax), but plasma HuIFN-beta declined rapidly thereafter, upon nasal administration of the powder dosage form (8.45 x 10(2) IU/g). In rats and dogs, Cmax was lower than in rabbits, but plasma HuIFN-beta declined slowly after nasal administration of the powder or liquid dosage form (4-6 x 10(2) IU/g). These differences might be attributed to differences of absorption rate constant.

Administration, Intranasal↗

[Transitional cell carcinoma of the renal pelvis in a woman discovered at childbirth].

We report a case of transitional cell carcinoma of a renal pelvis in a woman discovered after childbirth. A 38-year-old woman, who delivered an immature male infant in cesarean section 29 days prior to hospitalization, was admitted complaining of asymptomatic gross hematuria. Excretory urography and retrograde pyelography showed a filling defect of the right renal pelvis, Spontaneous urine cytology indicated class 5. Renal computed tomographic scan demonstrated a mass lesion in the right kidney. Right total nephroureterectomy and partial cystectomy was performed for diagnosis and treatment. Pathological diagnosis was papillary transitional cell carcinoma (grade 2). This is the first case of transitional cell carcinoma of the renal pelvis occurring in a childbearing woman in Japan.

Adult↗

Disopyramide induces insulin secretion and plasma glucose diminution: studies using the in situ canine pancreas.

The mechanism of disopyramide-induced hypoglycemia, a life-threatening complication in the antiarrhythmic drug treatment, is still controversial. To elucidate this, we have evaluated plasma insulin (IRI) and glucagon (IRG) responses in the pancreatic vein (PV) of the in situ pancreas as well as responses of plasma IRI, IRG, and glucose in the femoral artery (FA) to disopyramide phosphate administration in anesthetized dogs. First, infusion of disopyramide at a dose of 50 mg for ten minutes directly into the pancreatic artery, but not the vehicle, increased significantly plasma IRI concentration in the PV (P less than .05 or less), where the IRI response started within three minutes and reached a peak of 2.8-fold preinfusion value at 30 minutes after starting the infusion (n = 7). Plasma IRI concentration in the FA also increased slightly but significantly (P less than .05). Plasma IRG concentration in the PV initially decreased significantly (P less than .05 or less) and in the FA at one point (P less than .05) during the infusion, and then increased significantly after cessation of the infusion, showing a peak of 1.9-fold preinfusion value at 60 minutes in the PV and the FA (P less than .05). Plasma glucose concentration in the FA decreased slowly and significantly after the infusion (P less than .05 or less) and fell by 16% of the baseline value at 60 minutes (P less than .05). Second, serum disopyramide concentration of 13.7 +/- 2.8 micrograms/mL at ten minutes, which corresponds to a twofold to threefold concentration of the human therapeutic level (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of absorption promoters in intranasal administration of human fibroblast interferon as a powder dosage form in rabbits.

The utility of the absorption promoters, sodium glycocholate (GC-Na), ethylenediamine dihydrochloride (EDTA-2Na), sodium caprylate (Cap-Na) and sodium salicylate (Sal-Na), in the intranasal administration of human fibroblast interferon-beta (HuIFN-beta) in rabbits was investigated. The optimal amount of added EDTA-2Na, Cap-Na and Sal-Na with respect to HuIFN-beta was examined for nasal absorption in the powder dosage form. Formulations of HuIFN-beta with GC-Na showed greatly enhanced intranasal HuIFN-beta absorption, as compared to the other absorption promoters. The results of a stability study on HuIFN-beta in homogenates of nasal mucosa suggested that GC-Na behaved as a hydrolysis inhibitor in the nasal mucosa and maintained the activity of HuIFN-beta.

Absorption↗

Plasma levels following intranasal and intravenous administration of human interferon-beta to rabbits.

Rabbits were given single doses (2 x 10(6) IU) of human fibroblast interferon (HuIFN-beta) by the following routes of administration: (a) intravenous injection, (b) dropwise intranasal administration of a liquid dosage form, and (c) spraywise intranasal administration of a powder dosage form. Following the intravenous injection, plasma HuIFN-beta concentrations declined rapidly in a biphasic manner in agreement with a two-compartment model, whilst concentrations following the intranasal administrations conformed to a one-compartment model. Maximum plasma levels and the areas under the plasma concentration-time curve (AUC) in response to dose were studied in the case of the spray administration, and found to be proportional to dose. The systemic bioavailability of HuIFN-beta (administered with sodium glycocholate and excipients) via the nasal routes was about 3% of that via the intravenous route. The elimination half-lives did not differ significantly between these two routes of administration.

Administration, Intranasal↗

Inhibition by endothelial cells of platelet aggregating activity of thrombin--role of thrombomodulin.

Cultured human umbilical vein endothelial cells inhibited the platelet aggregating activity of thrombin in the absence of plasma. Using a new method in which thrombin-induced platelet aggregation was measured in the presence of endothelial cells, we showed that aspirin-treated endothelial cells inhibited platelet aggregating activity of thrombin in an incubation time- and cell number-dependent manner. This inhibitory effect of endothelial cells was partially blocked by the pretreatment of endothelial cells with monoclonal anti-thrombomodulin IgG (anti-TMIgG). It is suggested that (1) endothelial cells play a role in the clearance of thrombin by binding and inactivating this enzyme and that (2) thrombomodulin on endothelial cells, apart from its role for protein C activation, may be involved in this endothelial function.

Aspirin↗

Norepinephrine-induced enlargement of nucleus in cultured myocardial cells.

The change in the nuclear size of neonatal rat myocardial cells was evaluated under the culture conditions of exposure to norepinephrine (NE). Daily administration for 1 week of 0.2, 2, and 20 ng/ml NE induced a significant increase in nuclear size as a result of the dose-dependent quality of the nuclei. NE also stimulated a beating response in the cultured myocardial cells because of this dose dependency. A good correlation was found between the two markers and the NE dose dependency. Single or mononucleated myocardial cells often appeared in the NE-treated groups. Ornithine decarboxylase activity was not acutely stimulated even by 20 ng/ml NE. These observations suggest that administration of NE induces nuclear enlargement and enhances nuclear function through the stimulation of beating. Further, there may not be a direct relation between nuclear enlargement and the polyamine synthesis pathways.

Animals↗

Enhanced growth rate of cultured smooth muscle cells from spontaneously hypertensive rats.

Smooth muscle cells were isolated and cultured from the aortic media of age-matched, stroke-prone and stroke-resistant spontaneously hypertensive rats (SHRSP, SHRSR:SHRs) and Wistar-Kyoto rats (WKY), and the growth rate of cells from the three strains was compared. Under electron microscopical observation the cells were identified as modified (or synthetic-type) smooth muscle cells. Cells occurring at low densities showed the same morphology for both SHRs and WKY, but cells occurring at higher densities were observed to be smaller in SHRs than in WKY. An analysis of the growth curves of cells showed a significantly enhanced replication rate in cells from SHRs compared with those from WKY, especially in the early passages. In later passages (repeated until the 9th passage), however, this distinction was not clear. These growth characteristics were also confirmed in cells from both 12- and 24-week-old, age-matched SHRs and WKY. We could not find any difference between the growth characteristics of cells from SHRSP and SHRSR. It is possible to hypothesize from these findings that the abnormality relating to hypertension (hypertension being a common characteristic of SHRSR and SHRSP) is found in the smooth muscle cells, and is reflected as an enhanced growth rate when they are exposed to mitogenic stimuli, such as in atherosclerosis.

Animals↗

Intranasal administration of beta-interferon in rabbits.

beta-Interferon (IFN) administered intranasally in solution or as a powder without surfactants was not absorbed in rabbits. However, absorption occurred after the addition of surfactants (non-ionic, anionic and amphoteric). Maximum concentrations of IFN in plasma were dependent on the surfactant used, sodium glycocholate being the most effective. Total absorption of IFN following nasal administration with sodium glycocholate was 2.2% of that following intravenous administration.

Administration, Intranasal↗

Comparison of cyclic AMP accumulation and morphological changes induced by beta-adrenergic stimulation of cultured vascular smooth muscle cells and fibroblasts.

Cyclic 3',5'-adenosine monophosphate (cAMP) accumulation and morphological changes induced by isoproterenol (ISO) on cultured vascular smooth muscle cells (SMC) and vascular fibroblasts derived from spontaneously hypertensive rats, their stroke-prone strain and normotensive Wistar Kyoto rats were investigated. At the time points studied, ISO-induced cAMP accumulation in SMC reached a peak level at 5 min. Accumulation was dose-dependent and was maximal at a concentration of 10(-5) M ISO. Maximal cAMP levels were approximately 600-fold higher than basal levels. Maximal cAMP accumulation or half maximal stimulatory ISO concentrations were similar in SMC from the three strains. ISO had no effects on cyclic 3',5'-guanosine monophosphate (cGMP) levels in SMC. Phenylephrine had no effects on cAMP or on cGMP levels. In contrast to SMC, beta-adrenergic stimulation of vascular fibroblasts resulted in only a 4-fold increase of cAMP levels. 1.5 h after administration of ISO to SMC cultures, the morphological changes were apparent in SMC but not in fibroblasts. Morphological changes induced by ISO were reversible and morphological appearances returned to normal 16 h after exposure to ISO. 10(-3) M dibutyryl cAMP had similar effects on the morphologies of both SMC and fibroblasts. These effects were antagonized by 5 X 10(-6) M colchicine, an inhibitor of microtubule assembly. These results indicate that cultured vascular SMC possess the ability to increase markedly their cellular cAMP level in response to beta-adrenergic stimulation, while fibroblasts are less responsive to the stimulation. Furthermore, cAMP accumulation results in morphological changes of SMC and fibroblasts probably through the alteration of intracellular microtubule systems. As the morphological response to intracellular cAMP (or its lipophilic derivatives) is similar in both SMC and fibroblasts, the difference in each cell line's responsiveness to ISO may be due to a difference in: (1) the density or sensitivity of beta-adrenergic receptors on the plasma membrane of each cell type, or (2) the catalytic activity of adenylate cyclase itself.

Adrenergic beta-Agonists↗

Dose-related inhibitory effects of the beta-adrenoceptor blocking drugs carteolol and propranolol on cardiac hypertrophy in spontaneously hypertensive rats.

The inhibitory effect of two kinds of beta-adrenoceptor blocking drugs [propranolol: 1-100 mg/kg per day; carteolol: 0.3-30 mg/kg per day] on the development of cardiac hypertrophy was studied in young spontaneously hypertensive rats (SHR: 4 weeks old). Though neither propranolol or carteolol given for 6 weeks reduced the development of hypertension in SHR, both drugs did reduce the increase in the heart weight/body weight ratio in a dose-dependent manner. This potency of carteolol was about 300 times greater than that of propranolol. The potency of carteolol with regard to the reduction in the myocardial protein/DNA ratio was about 300 times greater than that of propranolol. The beta-blocking potency, estimated from the area under the dose-response curve (beta-blocking action) of carteolol, was also 300 times greater than that of propranolol and correlated well with the extent of the structural changes in the heart. Thus, the possibility that the degree of beta-blocking potency may strongly relate to structural changes in the heart of young SHR has to be given consideration.

Animals↗

Mechanisms of structural vascular changes in genetic hypertension: analyses on cultured vascular smooth muscle cells from spontaneously hypertensive rats.

1. The basic mechanism underlying the structural vascular changes occurring in hypertension was studied in cultured aortic smooth muscle cells (SMC) obtained by an explant method from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with that in normotensive Wistar--Kyoto (WKY) rats. 2. The growth rate of SMC from SHR and SHRSP at the age of 2.5--11 months was greater than that of SMC from WKY rats even after repeated passages. 3. [3H]Thymidine and [14C]leucine incorporation, and ornithine decarboxylase (ODC) activity of SMC were increased in SHR and SHRSP in comparison with WKY rats. 4. The application of isoprenaline but not noradrenaline to the culture media increased ODC activity acutely in SMC from WKY rats and this increase was blocked by propranolol. 5. These results indicate that SMC from SHR and SHRSP are more prone to proliferate than those from WKY rats and that a beta-adrenergic neurohumoral mechanism accelerates SMC growth independently of blood pressure.

Animals↗