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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 451 records · Page 25Linked to original sources
PubMed1992

Effect of intravascular ethanol on modulation of gastric mucosal integrity: possible role of endothelin-1.

The influences of intravascular ethanol on gastric mucosal integrity and its relation to gastric circulation were investigated in rats. Ulcer formation of the gastric mucosa correlated with the blood ethanol concentration in the presence of 150 mM HCl in the rat stomach. Furthermore, the gastric mucosal hemoglobin concentration (IHb) and hemoglobin oxygen saturation (ISO2), estimated using organ reflectance spectrophotometry, decreased in a concentration-dependent manner with blood ethanol. In isolated, vascularly perfused rabbit stomach, various concentrations (10-400 mM) of ethanol infused into the celiac artery increased the perfusion pressure and released endothelin-1 (ET-1) from the gastric vasculature in a concentration-dependent manner. Moreover, a significant correlation existed between changes in the perfusion pressure and ET-1 concentration in effluents from the gastric vasculature. Furthermore, anti-ET-1 antibody reduced 100 mM ethanol-induced vasoconstriction in a concentration-dependent manner. The results indicate that intravascular ethanol increases the susceptibility of gastric mucosa to injury induced by intraluminal HCl by causing gastric vasoconstriction mediated by ET-1. Thus intravascular ethanol may play an important role in the mechanism of ethanol-induced gastric mucosal injury.

Animals↗
PubMed1992

Endogenous adenosine blunts beta-adrenoceptor-mediated inotropic response in hypoperfused canine myocardium.

BACKGROUND: Adenosine attenuates beta-adrenoceptor-mediated inotropic responses through GTP-binding protein in vitro. The goal of the present study was to test the hypothesis that endogenous adenosine released from the ischemic myocardium blunts the inotropic response to beta-adrenergic stimulation. METHODS AND RESULTS: In 45 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Coronary perfusion pressure was reduced so that coronary blood flow was decreased to 60% of the basal level by partial occlusion of the bypass tube, and the reduced coronary perfusion pressure was kept constant thereafter. Inotropic responses to isoproterenol were assessed by fractional shortening of the myocardium in the perfused area. After the onset of hypoperfusion, lactate extraction ratio (18.8 +/- 1.2%) and fractional shortening (20.7 +/- 1.1%) were significantly decreased to -8.4 +/- 8.0% and 5.9 +/- 1.5%, respectively, and coronary arteriovenous differences of adenosine were increased from 4.6 +/- 3.6 to 89.4 +/- 10.5 pmol/ml. In the untreated condition, an intravenous infusion of isoproterenol (150 ng/kg/min) augmented fractional shortening from 5.9 +/- 1.5% to 13.6 +/- 0.8%. When adenosine release was attenuated by administration of prazosin (4 micrograms/kg/min i.c.) during hypoperfusion, the response of fractional shortening to isoproterenol (from 5.3 +/- 1.2% to 20.5 +/- 1.4%) was much greater (p less than 0.05) than that in the untreated control condition. Exogenous administration of adenosine significantly attenuated the inotropic response to isoproterenol in the prazosin-treated hearts. In contrast, an adenosine receptor antagonist, 8-phenyltheophylline, also enhanced the inotropic response to isoproterenol. The attenuation of beta-adrenoceptor-mediated inotropic response by adenosine could not be attributed to the inhibition of norepinephrine release from the sympathetic nerve endings, because identical results were observed in the chemically denervated hearts. CONCLUSIONS: Endogenous adenosine released from the ischemic myocardium attenuates beta-adrenoceptor-mediated inotropic response in the ischemic heart.

Adenosine↗
PubMed1992

Silent cerebral infarction as a form of hypertensive target organ damage in the brain.

The incidence, number, size, and location of silent cerebral infarction on 0.1 T magnetic resonance imaging was investigated in 66 hypertensive patients (63 +/- 9 years old; mean +/- SD) and 42 age-matched normotensive subjects (61 +/- 9 years old) to determine the clinical significance of hypertension in silent cerebral infarction. Cerebrovascular risk factors and the severity of hypertensive changes in other major target organs were also investigated. The incidence of silent infarction in hypertensive patients (47%) tended to be higher than that of normotensive subjects (33%) and increased significantly with advancing age. In hypertensive patients, a significantly higher incidence of silent lesions was noted in patients with hypertensive changes in major target organs (72-73% in patients with organ involvement versus 33-39% in those without). The average number of lesions in hypertensive patients was significantly higher than that in normotensive subjects (6.0 versus 2.1), and the lesions in the hypertensive patients were more frequently detected in the brain areas supplied by perforating arteries than those in normotensive subjects (47% versus 24%). These results clearly demonstrate that silent cerebral infarction is frequently seen in older hypertensive patients, especially when moderate hypertensive changes are noted in major target organs, and suggest that hypertensive arterial changes play a crucial role in the occurrence of silent infarction.

Aged↗
PubMed1992

Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity.

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.

5'-Nucleotidase↗
PubMed1992

Assessment of valvular regurgitation using cine magnetic resonance imaging coupled with phase compensation technique: comparison with Doppler color flow mapping.

To elucidate whether or not a newly developed technique in cinematic-displayed (cine) magnetic resonance imaging (MRI) can improve the semiquantitative evaluation of valvular regurgitant flow, 20 patients with valvular lesions were studied. Three pulse sequences of cine MRI, ie, standard, short echo time (TE), and rephasing scans, were compared with reference obtained by Doppler color flow mapping. Short TE technique and rephasing scan technique improved image quality remarkably as compared with standard technique. Each of the three cine MRI techniques showed good correlation with the Doppler method (p < 0.001). However, short TE and rephasing scan techniques gave a faithful estimation of the extent as compared with the Doppler method, whereas standard technique overestimated the regurgitation. Thus, cine magnetic resonance imaging with phase compensation technique can be utilized for the semiquantitative assessment of valvular regurgitation in a manner similar to that of Doppler color flow mapping.

Aged↗
PubMed1992

Blunted cardiac responses to exercise-induced sympathetic stimulation in non-failing aortic regurgitation: insight into role of cardiac dilation in hyporesponse of failing hearts.

Although blunted cardiac response to sympathetic stimulation in patients with heart failure is usually attributed to myocardial beta 1-adrenoceptor downregulation secondary to elevated circulating catecholamines, cardiomegaly per se may also play a role through presynaptic mechanisms such as reduction in cardiac norepinephrine (NE) concentration. To evaluate effects of cardiac dilatation on cardiac response to sympathetic stimulation, we studied left ventricular contractile and heart rate responses to plasma NE levels increased by exercise in 10 asymptomatic patients with a dilated left ventricle due to aortic regurgitation (AR), but with normal resting plasma NE levels, using 10 normal subjects and 10 patients with heart failure due to dilated cardiomyopathy (DCM) as controls. Plasma NE levels, systemic blood pressure, echocardiographic left ventricular dimensions, and heart rate were measured at rest, and at 3 submaximal levels of supine bicycle exercise. The ratio of peak systolic blood pressure to end-systolic dimension (P/D ratio), heart rate, and plasma NE increased with the intensity of exercise. In each subject, both P/D ratio and heart rate increased in a logarithmic manner against plasma NE levels. The slope of the regression line for log (plasma NE)--P/D ratio relation, and that for log (plasma NE)--heart rate relation, were significantly less in patients with AR than in normal subjects (p less than 0.001 and p less than 0.05, respectively), and were less in patients with DCM than in patients with AR (p less than 0.005 and p = 0.051, respectively). Thus, the left ventricular contractile and heart rate responses to sympathetic stimulation are blunted in patients with dilated hearts due to AR, even in the absence of overt heart failure and elevated plasma NE levels. These responses were further decreased in patients with heart failure due to DCM. Cardiac responses to sympathetic stimulation appear to be blunted by cardiac dilatation per se, independently of myocardial beta 1-receptor downregulation secondary to high circulating catecholamines. The decrease in mechanical response to sympathetic stimulation in failing hearts is likely to be combined result of cardiac dilatation and beta 1-receptor downregulation.

Adult↗
PubMed1992

Norepinephrine disrupts cytoskeletal framework of microtubules in rat hearts.

Sympathetic activations may deteriorate myocardial failure due to progression of myocardial cell injury. In the present study, to test whether microtubules, calcium ion (Ca2+) sensitive cytoskeletons, are disrupted by norepinephrine (NE) and whether beta-adrenoceptor antagonist could attenuate the disruption of microtubules, structures of microtubules are studied in rat hearts with continuous subcutaneous infusions of norepinephrine. In the sham operated rats the microtubules stained by immunohistochemical technique showed normal network structures. A low dose of NE infusion (2 micrograms/kg/h) for 6 h resulted in a minimal change in microtubule structures. However, infusion for 24 h of NE (2 micrograms/kg/h) and a large dose of NE infusion (20 micrograms/kg/h) for 6h caused disruptions of microtubules in small patchy lesions (8 +/- 3%, 12 +/- 4% of area, respectively). A large dose of NE infusion for 24 h increased systolic blood pressure from 116 +/- 6 to 152 +/- 4 mmHg and increased plasma NE concentration from 430 +/- 40 to 17100 +/- 3700 pg/ml and further disrupted the network of microtubules in 40 +/- 6% of the total area. Propranolol (500 micrograms/kg/h) markedly attenuated NE-induced disruptions of microtubules. Disruptions of microtubules may be one of the underlying mechanism of deterioration of myocardial failure in chronic heart failure in which sympathetic activity is markedly activated.

Animals↗
PubMed1992

Disruption of microtubules in cultured neonatal rat cardiomyocytes during rapid contractions: protective effects of beta-adrenoceptor antagonist.

Tachycardia may play a key role in the progression of heart failure probably through Ca2+ overload. In the present study, to test whether microtubules, Ca(2+)-sensitive cytoskeletons, are disrupted by rapid contractions and whether the beta-adrenoceptor antagonist, propranolol could attenuate the disruption of microtubules, cultured neonatal rat cardiomyocytes with various contraction rates were studied. The microtubules were stained by immunohistochemical technique and the extent of microtubule disruption was quantified by disruption scores (grade 0-intact; grade 3-severe disruption). In 97% of the non-contracting cells, intact microtubules (grade 0) were observed, whereas in the cells that contract at the rate of 100-120/min, intact microtubules were observed only in 25% of the cells. The disruption scores were significantly correlated with contraction rates of the cells. Treatment with propranolol (10(-6)M) decreased the extent of microtubule disruption associated with a decrease in the contraction rate. However, this treatment did not alter the relationship between the contraction rate and the disruption score of microtubules. These results indicate that rapid contractions may induce disruption of microtubules which can be attenuated by beta-blocker mainly by its negative chronotropic effect. This may be one of the underlying mechanisms of the long-term effect of beta-blockers for chronic heart failure.

Animals↗
PubMed1992

Sequential appearance of fibronectin, collagen and elastin during fatty streak initiation and maturation in hypercholesterolemic fat-fed rabbits.

To elucidate whether tissue fibronectin increases in the early stages of atherogenesis induced by hypercholesterolemia without mechanical trauma, we investigated sequential changes in the distribution of tissue fibronectin during fatty streak initiation and maturation in the aortas of hypercholesterolemic fat-fed rabbits. The presence of fibronectin was examined on immunoperoxidase stained tissue specimens with the aid of a microscope-photometric technique. Twenty male albino rabbits were used. Cholesterol supplemented chow (1%) was given for 4 weeks (n = 6), 8 (n = 5) or 14 weeks (n = 5). A membrane-like layer positive for fibronectin was observed along the endothelium in the normal aorta. After 4 weeks of the cholesterol-feeding, fatty streaks were initiated in the intima, where fibronectin was more densely accumulated than the normal intima. After 8 weeks of the cholesterol-feeding, fatty streaks were expanding, associated with the dense staining for fibronectin. After 14 weeks, fibronectin was still concentrated in the endothelial layer and also in the superficial areas of the thickened intima, but decreased in the deep areas of the thickened intima where collagen and elastin appeared as bundles. The photometric data of fibronectin supported these visual observations. Thus, fibronectin appeared early and disappeared later in the intima during the process of fatty streak initiation and maturation. These findings suggest that in hypercholesterolemia without mechanical endothelial injury, fibronectin may play an important role in an early process of atherogenesis.

Animals↗
PubMed1992

Cetraxate improves ethanol-induced gastric mucosal congestion in anesthetized dogs.

Gastric mucosal microcirculatory disturbance in experimental animals is stressed as an important factor in the development of gastric ulceration induced by ethanol. In this study, we used a reflectance spectrophotometry system to investigate the effect of cetraxate on ethanol-induced gastric mucosal hemodynamics in anesthetized dogs. Forty percent ethanol caused a significant increase in the mucosal blood volume and a significant decrease in mucosal hemoglobin oxygenation. The changes in these parameters indicated mucosal congestion and tissue hypoxia. Topical administration of cetraxate (200 mg in 10 ml saline) prevented the increase in mucosal blood volume and decrease in mucosal hemoglobin oxygenation which had been induced by ethanol loading in the stomach. In conclusion, cetraxate showed a protective effect on mucosal microcirculation that resulted in the maintenance of the gastric mucosal integrity against ethanol loading in the gastric mucosa.

Administration, Topical↗
PubMed1992

Prevalence of carotid atherosclerosis in diabetic patients. Ultrasound high-resolution B-mode imaging on carotid arteries.

OBJECTIVE: To quantitatively assess atherosclerosis of the carotid artery in subjects with and without diabetes. RESEARCH DESIGN AND METHODS: Ultrasound high resolution B-mode imaging of carotid arteries was conducted on 71 nondiabetic subjects without hyperlipidemia or hypertension and 295 diabetic patients to determine IMT of the arterial wall. RESULTS: IMT was linearly related with age in nondiabetic (IMT = [0.0087 x age] + 0.3318) and diabetic subjects (IMT = [0.0155 x age] + 0.32450). The regression coefficient for age was significantly greater in diabetic than nondiabetic subjects. IMT (mean +/- SD) of diabetic subjects aged 20-29 was significantly greater than that of nondiabetic subjects aged 20-29 (0.73 +/- 0.27 vs. 0.52 +/- 0.07 mm, P less than 0.01). Multivariate regression analysis of 275 NIDDM patients indicated smoking, hyperlipidemia, duration of diabetes, hypertension, and age were factors determining thickness of the carotid arterial wall. CONCLUSIONS: Diabetes, along with age, hyperlipidemia, smoking, and hypertension, aggravates carotid atherosclerosis.

Arteriosclerosis↗
PubMed1992

Serum pre-S1 and pre-S2 antigens as prognostic markers in interferon therapy for chronic hepatitis B.

We investigated the changes of serum pre-S1 and pre-S2 antigens before and after interferon therapy in 35 carriers with HBeAg, to examine their clinical significance in the therapy. Both antigens were measured quantitatively by solid-phase enzyme immunoassays using monoclonal antibodies specific to each antigen. The titers of these antigens of responders before therapy were significantly lower (p less than 0.001) than those of non-responders (6.23 +/- 1.09 versus 8.65 +/- 2.09 and 4.46 +/- 1.27 versus 6.50 +/- 1.50, respectively). The titers decreased significantly 6 months after interferon therapy in the responders (p less than 0.05), whereas they did not change in the non-responders. Our findings indicate that pre-S1 and pre-S2 antigens have a close correlation with hepatitis B virus replication and are valuable markers for predicting the responsiveness to interferon therapy.

Adult↗
PubMed1992

Hepatitis B core antigen-specific interferon gamma production of peripheral blood mononuclear cells during acute exacerbation of chronic hepatitis B.

To examine the relationship between hepatitis B core antigen-specific interferon gamma production and the liver injury, we measured the sequential change in this production by peripheral blood mononuclear cells of seven patients with chronic hepatitis B. Four patients who experienced acute exacerbation showed increased interferon gamma production when the serum alanine aminotransferase level peaked or during the recovery phase. In the three patients who did not experience acute exacerbation, interferon gamma production gradually decreased in one who had a low peak of alanine aminotransferase but did not show significant change in the other two. Increased production of hepatitis B core antigen-specific interferon gamma at the time of acute exacerbation suggests that interferon gamma induced by hepatitis B core antigen plays a role in hepatocellular injury of patients with chronic hepatitis B.

Acute Disease↗
PubMed1992

[An ultrasonic study of the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease in Japanese].

The study is to evaluate the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease using noninvasive B-mode ultrasonography and X-ray computed tomography. The sensitivity of bruits for diagnosing severe carotid stenosis was also evaluated. A total of 229 consecutive Japanese patients were recruited for this study, of which 97 had chronic-stage ischemic cerebrovascular disease and remaining 132 patients had at least one risk factor for atherosclerosis. Carotid atherosclerosis was evaluated by B-mode ultrasonography. Ischemic cerebrovascular disease was assessed by history taking, neurological findings and X-ray CT examination. The severity of carotid atherosclerosis was assessed by using two indices; plaque score and maximum percentage diameter stenosis. We also evaluated whether it was ulcerated plaque or not. Plaque score was computed by summing up all carotid plaque thicknesses (mm) on both sides. According to the CT findings, cerebral infarction was divided into two types; deep subcortical infarction and cortical infarction. The incidence of cerebral infarction increased in relation to plaque score and maximum percentage stenosis. Although the incidence of cerebral infarction in patients without carotid atherosclerosis was only 33% (38/116), it in patients with moderate carotid atherosclerosis (plaque score > 5) was 59% (26/44) (p < 0.05, chi-square test). The incidence of ipsilateral infarction was revealed to be higher in patients with severe (50% or more) carotid stenosis (61%) than in cases of mild stenosis (28%) (p < 0.05). Thirteen patients had ulcerated plaques and they suffered more frequently cerebral infarction than patients without ulcerated lesions. Cortical infarction was more frequent in patients with severe carotid stenosis than in patients without carotid atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Protective effect of proton pump inhibitor on the gastric mucosa].

Although many authors reported that proton pump inhibitor showed mucosal protective activity, the precise mechanism is still unclear. In this study, we investigated the effect of proton pump inhibit on gastric mucosal hemodynamics, using a reflectance spectrophotometry system. The proton pump inhibitors had no effect on the gastric mucosal hemodynamics prior to the state of hemorrhagic shock state. However, during the hemorrhagic shock, proton pump inhibitors significantly inhibited the decrease in tissue oxygenation and significantly reduced ulcer formation. In conclusion, proton pump inhibitors maintained tissue oxygenation resulting in reduction of ulcer formation.

Adenosine Triphosphatases↗