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Biomedical subjects

T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 271 records · Page 15Linked to original sources
PubMed1978

Atherogenic mechanisms: enhancement of regression of atheromatous lesions by phthalazinol.

Atherosclerosis was produced in rabbits by feeding 1% cholesterol pellets for 15 weeks to 35 male rabbits divided into two equal groups--the placebo control and phthalazinol group--with a comparable serum cholesterol level. The phthalazinol group was given 20 mg/kg of the compound daily. 13 rabbits of both groups were on 15 weeks of the treatment and the remaining 22 rabbits were treated for 30 weeks. The treated group exhibited a statistically significant increased removal of cholesterol from atherosclerotic aortas and improvement in pathological changes. This enhancing effect was more marked in the animals treated for 30 weeks. Such evidence indicates that there are substances capable of enhancing the removal of cholesterol from atheromatous lesions. In light of the pharmacological properties of phthalazinol, the possible role of thromboxane A2 released from platelets adhered and aggregated on atheromatous plaques, in the progression of atherosclerosis is worthy of continued investigation.

Animals↗
PubMed1978

Glucose tolerance in spontaneously hypertensive rats.

In order to clarify the relationship between essential hypertension and glucose metabolism, and to approach the pathophysiology or the etiology of essential hypertension, we examined glucose tolerance test (GTT) using spontaneously hypertensive rats (SHR) as models. SHR, namely stroke-prone SHR (SHRSP) and stroke-resistant SHR (SHRSR) always had higher serum glucose levels at each GTT phase than normotensive control Wistar-Kyoto rats. They also tended to show higher levels in the young even at 5 weeks of age rather than in the adult. These results indicate that hyperglycemic tendency or lower glucose tolerance may be a characteristic of spontaneous hypertension and may be related to the mechanism of hypertension.

Animals↗
PubMed1978

An observation of thromboxane A2 in arterial blood after cholesterol feeding in rabbits.

Agents responsible for the entry of cholesterol-bearing lipoproteins into the arterial wall represent local risk factors in atherogenesis. In an attempt to identify these agents, we inserted a catheter into the ascending aorta of rabbits and 5 ml of arterial blood sample was withdrawn. The contraction of the aortic strip of rabbit against Piper and Vane's antagonists with application of this sample was observed. Samples obtained after feeding of 1 Gm/Kg of cholesterol and after an intravenous administration of thromboxan A2 (TXA2) contracted the aortic strip. Samples from non-treated rabbits or those obtained after intravenous administration of 10 microgram of epinephrine or norepinephrine did not contract the strip. Previous administration of 20 mg/Kg of indomethacin decreased the contraction developed after feeding of 1 Gm/Kg of cholesterol. It was suggested that TXA2 might be released into the arterial blood by the ingestion of cholesterol and might be one of the agents repsonsible for the entry of lipoproteins.

Animals↗
PubMed1977

Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention.

A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points: 1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment. 2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positve significant correlations between the values obtained by these three methods. 3. It was proved to be highly reproducible and is thought to be useful clinically. By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment.

The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Experimental ischemic heart disease induced by thromboxane A2 in rabbits.

How an acute ischemic attack is induced in a patient with coronary atherosclerosis is unknown and we carried out studies using thromboxane A2 (TXA2) to determine if acute myocardial ischemia and necrosis could be induced in rabbits. TXA2 was perfused through the coronary artery for 5 seconds by means of a Swan-Ganz catheter through the right common carotid artery. Significant serial changes of ST-T on ECG and hypotension were observed from 1 minute to more than 1 day after the perfusion in all 22 rabbits. The TXA2 that was composed of both aggregated platelets and prostaglandin H2 induced the same response, and such was dose dependent. The inactivated TXA2 was without effect. Seventeen of the experimental rabbits were autopsied. Histological studies of the hearts showed focal myocardial ischemia and necrosis in all rabbits except one autopsided 10 minutes after the perfusion. TXA2 is apparently capable of inducing acute myocardial ischemia and necrosis.

Acute Disease↗
PubMed1976

Prenatal diagnosis of osteogenesis imperfecta congenita by means of fetography.

By means of fetography, prenatal diagnosis of osteogenesis imperfecta congenita was performed on two pregnant women in the 34th week of gestation with familial histories of the disease. In 1 of the 2 cases, the fetogram revealed abnormal twisting of the torso, shortening, and severe angulation deformities of the extremities with callus formation and parchmentlike skull despite clear-cut outline of the scalp. On the basis of these findings, the fetus was diagnosed as osteogenesis imperfecta congenita and subsequently confirmed. Thus, the excellent fetal resolving power of fetography permitted successful prenatal diagnosis of the disease far more easily and precisely than plain roentgenography.

Adult↗
PubMed1976

Hyperreactive arterial endothelial cells: a clue for the treatment of atherosclerosis.

Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Ischemic carotid endothelium. Transmission electron microscopic studies.

The endothelium of monkey and rabbit common carotid arteries subjected to ischemia was examined by transmission electron microscopy (TEM). The right carotid artery of 24 rhesus monkeys was occluded by proximal and distal placement of removable surgical clips for periods ranging from five minutes to four hours. A single clip was used to occlude the right carotid artery of 15 rabbits for periods ranging from 5 to 30 minutes. With TEM, numerous blebs, intracytoplasmic vacuoles, membranous whorls, and pseudopodia were found in the endothelium of arterial segments subjected to ischemia by double or single clipping for as little as five minutes. Following occlusion of one hour or longer, disruption of interendothelial junctions was also noted. These TEM findings were compared with earlier TEM studies of the response of endothelium to other injurious stimuli and with previous scanning electron microscopic studies in which the same ischemic models were utilized.

Animals↗
PubMed1975

Cyclic 3',5'-AMP phosphodiesterase of rabbit aorta.

Cyclic AMP and cyclic GMP phosphodiesterase activities (3' : 5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) were demonstrated in the isolated intima, media, and adventitia of rabbit aorta. The activity for cyclic AMP hydrolysis in the intima was 2.7-fold higher than that for cyclic GMP hydrolysis. The activity for cyclic AMP hydrolysis in the media was approximately equal to that for cyclic GMP hydrolysis, but in the adventitia, cyclic GMP hydrolytic activity was 2.1-fold higher than cyclic AMP hydrolytic activity. Distribution of the activator of the phosphodiesterase was studied in the three layers. Each layer contained the activator. The activator was predominantly localized in the smooth muscle layer (the media). The effect of the activator and Ca2+ on the media cyclic AMP and cyclic GMP phosphodiesterase was also briefly studied. The activity of the cyclic GMP phosphodiesterase was stimulated by micromolar concentration of Ca2+ in the presence of the activator. However, the activity of the cyclic AMP phosphodiesterase was not significantly stimulated by Ca2+ up to 100 muM in the presence of the activator. Above 90% of cyclic nucleotide phosphodiesterase activity in the whole aorta was found to be derived from the media. A major portion (60-70%) of the media enzyme was found in 105 000 times g supernatant. Cyclic AMP phosphodiesterase in the supernatant was partially purified through Sepharose 6B column chromatography and partially separated from cyclic GMP phosphodiesterase. Using a partially purified preparation from the 105 000 times g supernatant the main kinetic parameters were specified as follows: 1) The pH optimum was found to be about 9.0 using Tris-maleate buffer. The maximum stimulation of the enzyme by Mg2+ was achieved at 4mM of MgC12. 2) High concentration of cyclic GMP (0.1 mM) inhibited noncompetitively the enzyme activity, and the activity was not stimulated at any tested concentration of cyclic GMP. 3) Activity-substrate concentration relationship revealed a high affinity (Km equals 1.0 muM) and low affinity (Km equals 45 muM) for cyclic AMP. The homogenate and 105 000 times g supernatant of the media also showed non-linear kinetics similar to the Sepharose 6B preparation and their apparent Km values for cyclic AMP hydrolysis were 1.2 muM and 36-40 muM and an enzyme extracted by sonication from 105 000 times g precipitate also exhibited non-linear kinetics (Km equals 5.1 muM and 70 muM). 4) Papaverine exhibited much stronger inhibition on the aorta cyclic AMP phosphodiesterase (50% inhibition of the intima enzyme, I5 o at 0.62 muM, I5 o of the media at 0.62 muM and I5 o of the adventitia at 1.0 muM) than on the brain (I5 o at 8.5 muM) and serum (I5 o at 20 muM) cyclic AMP phosphodiesterase, while theophylline inhibited these enzymes similarly. However, cyclic GMP phosphodiesterases in all tissues examined were inhibited similarly, not only by theophylline but also by papaverine.

Animals↗