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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 685 records · Page 38Linked to original sources
PubMed1987

Effects of chronic renal failure on the regulation of pyruvate kinase.

The effects of chronic renal failure on the enzyme activity of pyruvate kinase and the mRNA level of this enzyme were studied in 7 out of 8 nephrectomized rats. The mRNA level was measured by RNA-DNA dot blot hybridization, using cloned pyruvate kinase cDNA as hybridized probe. Neither the activity of M1-type pyruvate kinase nor the level of this enzyme in rat gastrocnemius muscle was affected by chronic renal failure, whereas L-type pyruvate kinase enzyme activity in uremic rat liver was lower than that in control at both fasted and refed states. The levels of L-type pyruvate kinase mRNA were not different between two groups at the fasted state. Induction of L-type pyruvate kinase mRNA after high carbohydrate diet refeeding was suppressed proportionally to the severity of chronic renal failure, which was expressed by the serum creatinine concentrations (r = -.876, P less than .005). These results indicate that the suppression of L-type pyruvate kinase activity in uremia was partly reflected by the decreased accumulation of this enzyme mRNA. There was a significantly negative correlation between L-type pyruvate kinase mRNA levels and plasma glucagon/insulin ratios (r = -.719, P less than .05). Hyperglucagonemia in uremia might play a major role in this suppression.

Animals↗
PubMed1987

Increased production of arachidonate metabolites in an occlusion-reperfusion model of canine myocardial infarction.

To define the role of arachidonate metabolites in evolving ischaemic myocardial damage 10 anaesthetised open chest dogs underwent 90 min occlusion of the left anterior descending coronary artery followed by 5 h reperfusion. Tissue extracts from ischaemic myocardium incubated in vitro were subjected to high pressure liquid chromatography for analysis of lipoxygenase products such as mono hydroxyeicosatetraenoic (HETE) acids and to radioimmunoassay for determining a cyclooxygenase product, thromboxane B2. In ischaemic myocardium the production of 12-HETE (120(35) ng.g-1, mean (SEM)) and thromboxane B2 (18.3(2.4) ng.g-1) was significantly higher than that in normal myocardium (13(2) ng.g-1, p less than 0.01, and 4.2(0.5) ng.g-1, p less than 0.001, respectively). 12-HETE production was linearly correlated with thromboxane B2 production in ischaemic myocardium (r = 0.718, p less than 0.02). The increased production of 12-HETE and thromboxane B2 was in proportion to infarct size as measured by a percentage risk area infarcted (r = 0.732, p less than 0.02, and r = 0.942, p less than 0.001, respectively). Similarly, the increase in production of these eicosanoids was related to the degree of leucocyte infiltration in ischaemic myocardium. These results indicate that altered arachidonate metabolism is strongly associated with the progression of ischaemic myocardial damage, suggesting important roles for these eicosanoids, which may be produced by blood corpuscles during the evolution of acute myocardial infarction.

Animals↗
PubMed1987

Effect of hypocapnia on cerebral oxygen metabolism and blood flow in ischemic cerebrovascular disorders.

Effects of hypocapnia on cerebral oxygen consumption (CMRO2) and blood flow (CBF) in cerebral ischemia were studied in 19 patients. The CMRO2 did not change significantly during hypocapnia within the whole group of patients, because 10 out of 19 cases showed a decrease (p less than 0.001) and other 9 showed an increase (p less than 0.01) of CMRO2 during hypocapnia. The first 10 showed higher resting CMRO2 (p less than 0.001) and arteriovenous differences of oxygen content (AVDO2; p less than 0.02) than the other 9. However, the resting CBF and CO2 reactivity to hypocapnia were not different between them, and clinical situations were also similar. A dissociation between flow and metabolism was suggested in the first 10 with rather preserved CMRO2, while reduced metabolic demands were suggested in the other 9. Different responses of CMRO2 to hypocapnia are expected in cerebral ischemia, i.e. in cases with rather preserved CMRO2 it decreases despite an AVDO2 increase, suggesting a capability of CMRO2 to respond to CBF reduction, while it increases in cases with more decreased CMRO2, as the AVDO2 increase exceeds the CBF reduction to maintain the decreased CMRO2 for a further CBF reduction. The vascular CO2 reactivity, therefore, might be maintained to be constant between these patients.

Adult↗
PubMed1987

Hemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction.

A new cardioselective beta 1-adrenoceptor partial agonist, xamoterol, has been developed for the treatment of heart failure, especially that associated with ischemic heart disease. To investigate the hemodynamic effect of xamoterol in relation to sympathetic nervous activity, hemodynamic variables and plasma norepinephrine (NE) levels were measured at rest and during three graded bicycle exercise tests before and after a single intravenous dose of 0.15 mg/kg xamoterol in 10 patients with mild-to-moderate left ventricular dysfunction. Plasma NE increased with increasing grade of exercise and a linear correlation between plasma NE and heart rate was observed at four time points (at rest and three exercise levels) before and after xamoterol. After administration of xamoterol, the slope of the regression line of plasma NE-heart rate relation was significantly less steep than that before drug. Predose and postdose regression lines crossed at 440 pg/ml of plasma NE. Similar effects were observed on the plasma NE-cardiac index and plasma NE-systolic blood pressure relations (regression lines crossed at 380 and 530 pg/ml of plasma NE, respectively). Thus, xamoterol had a dual agonist-antagonist effect in relation to plasma NE, and the crossover point lay approximately between 400 pg/ml and 500 pg/ml. This level of plasma NE was achieved at a low exercise level and at a heart rate of about 100 beats/min. These results indicate that xamoterol has intrinsic sympathomimetic activity comparable to relatively low sympathetic activity (400 to 500 pg/ml of plasma NE) and therefore acts as a beta 1-agonist when sympathetic nervous activity is below this level and as an antagonist when sympathetic activity is above this level.

Adrenergic beta-Antagonists↗
PubMed1987

Alpha 1-adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs.

The goal of this study was to test the hypothesis that alpha 1-adrenoceptor activity plays a key role in the release of adenosine from the ischemic myocardium. In 51 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery, and adenosine release into the local coronary vein was measured by the radioimmunoassay technique following the reduction of perfusion pressure for 20 minutes under alpha 1-, alpha 2-, and beta-adrenoceptor attenuations. Adenosine and lactate concentrations in the coronary arterial and venous blood sampled from the perfused area were determined, as well as fractional shortening. In the untreated condition, adenosine release was significantly (p less than 0.01) increased from 1.7 +/- 0.8 (SEM) to 8.8 +/- 1.3 nmol/100 g/min, 20 minutes after the onset of hypoperfusion (coronary blood flow: 28 +/- 2 ml/100 g/min) following the initial overshoot release. Neither beta- nor alpha 2-adrenoceptor attenuation affected the increase in adenosine release during hypoperfusion except for the slight attenuation of the overshoot release by beta-attenuation. In contrast, intracoronary infusions of prazosin and phentolamine during coronary hypoperfusion markedly attenuated (p less than 0.01) release of adenosine (1.8 +/- 0.7 nmol/100 g/min at 20 minutes). The extents of decreases in fractional shortening and lactate production were comparable between the untreated and alpha 1-adrenoceptor attenuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

Altered lipoxygenase metabolites and leukocyte involvement in an acute occlusion-reperfusion model of canine myocardial infarction.

We compared amounts of lipoxygenase products with the extent of leukocyte infiltration in the ischemic myocardium with an occlusion-reperfusion model of open-chest dog. Changes in peripheral leukocyte count and leukocyte function estimated by neutrophil aggregation induced by calcium ionophore A23187 were also examined. The ischemic tissue (120 +/- 40 ng/g, mean +/- SEM) showed a marked increase in 12-hydroxyeicosatetraenoic acid (HETE) production compared with the normal tissue (13 +/- 1 ng/g, p less than 0.01). The production of 5-HETE in the ischemic tissue was also augmented as well. When we examined the correlation between production of either 12-HETE or 5-HETE and leukocyte infiltration in the ischemic tissue, the former was augmented markedly in proportion to the extent of the latter. Leukocyte count in peripheral circulation was gradually increased after reperfusion. Similarly, neutrophil aggregation was significantly augmented during reperfusion. These results indicate that production of lipoxygenase metabolites associated with leukocyte infiltration in the reperfused ischemic tissue was increased during the course of myocardial infarction, which was accompanied by activation of leukocyte in peripheral circulation. Further studies should be done to clarify the importance of lipoxygenase metabolites in the evolution of reperfusion-induced myocardial injury.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Thromboxane A2 as an enhancing factor of coronary vasospasticity in variant angina.

To clarify the role of thromboxane A2 (TXA2) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B2 (TXB2: a stable catabolite of TXA2) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 (8 mg/kg, i.v.), a TXA2 synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB2 levels (424 +/- 138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB2 levels (223 +/- 38 pg/ml), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB2 levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB2 levels. In 3 patients, an EM rechallenge at symptomatically quiescent stage resulted in negative test with augmented TXB2 levels being markedly decreased. These findings indicate that increased TXA2 in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA2 production in the enhancement of coronary vascular spasticity.

Adult↗
PubMed1987

[Combined chemotherapy and radiotherapy in recurrent tumors of the head and neck region].

Over the past four years, 27 patients with recurrent tumors of the head and neck region have been treated with chemotherapy. The regimens used were BCMF (bleomycin 15 mg i.v. for 3 days, cyclophosphamide 500 mg i.v., methotrexate 50 mg i.v. and 5-fluorouracil 500 mg i.v.) and CMU (cyclophosphamide 350 mg/m2 i.v., methotrexate 30 mg/m2 i.v. and UFT 600 mg p.o. for 14 days). Of the 27 patients, eight were treated with combined radiation and chemotherapy, and either CR or PR was obtained. Nineteen patients were treated with chemotherapy alone, for which the response (CR + PR) rates were 8% (1/12) for BCMF and 43% (3/7) for CMU, respectively. No serious toxicities were observed as a result of these regimens. It was thus demonstrated that the CMU regimen was of great value in terms of improved response and minor toxicity in the treatment of head and neck tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Binding of 131I-labeled tissue-type plasminogen activator on de-endothelialized lesions in rabbits.

Tissue-type plasminogen activator (t-PA) which has a high affinity for fibrin in the clot, was labeled with 131I by the iodogen method, and its binding to de-endothelialized lesions in the rabbit was measured to assess the detectability of thrombi. The de-endothelialized lesion was induced in the abdominal aorta with a Fogarty 4F balloon catheter. Two hours after the de-endothelialization, 131I-labeled t-PA (125 +/- 46 microCi) was injected intravenously. The initial half-life of the agent in blood (n = 12) was 2.9 +/- 0.4 min. The degree of binding of 131I-labeled t-PA to the de-endothelialized lesion was evaluated at 15 min (n = 6) or at 30 min (n = 6) after injection of the agent. In spite of the retention of the biochemical properties of 131I-labeled t-PA and the presence of fibrin deposition at the de-endothelialized lesion, the binding of t-PA to the lesion was not sufficiently strong. Lesion-to-control ratios (cpm/g/cpm/g) were 1.65 +/- 0.40 (at 15 min) and 1.39 +/- 1.31 (at 30 min), and lesion-to-blood ratios were 1.39 +/- 0.32 (at 15 min) and 1.36 +/- 0.23 (at 30 min). These results suggest that radiolabeled t-PA may be inappropriate as a radiopharmaceutical for the scintigraphic detection of a pre-existing thrombotic lesion.

Animals↗
PubMed1987

Heterogeneous response in hepatic sinusoidal blood flow to acute ethanol ingestion in rats.

The effect of ethanol ingestion on the hepatic sinusoidal blood flow velocity was investigated in rats, using in vivo microscopy system with dual-slit photometric method. In steady state, before ethanol ingestion, the hepatic sinusoidal blood flow velocity determined at 18 points ranged widely from 54 to 245 micron/sec and the mean value was 144 +/- 13 micron/sec. After acute ethanol ingestion (1g/kg), the averaged sinusoidal blood flow velocity increased significantly to 197 +/- 17 micron/sec, while the width of sinusoids showed no apparent change. In some sinusoids, however, the blood flow velocity did not increase. Thus, the heterogeneous response in hepatic sinusoidal blood flow to the ethanol metabolism might induce the development of an imbalance between delivery and demand of oxygen to hepatocytes around those sinusoids after acute ethanol ingestion.

Animals↗
PubMed1987

[Left ventricular asynergy in patients with impending myocardial infarction: two-dimensional echocardiographic assessment].

To determine the clinical significance of regional left ventricular asynergy in patients with impending myocardial infarction, we recorded two-dimensional echocardiograms (2DE) serially and performed coronary angiography immediately after the hospital admission in nine patients with initial impending infarction and their last anginal attacks were within 48 hours. Left ventricular asynergy on the first 2DE was observed in six of nine patients during symptom-free periods (Group A: LV asynergy group). Five of the six patients had significant coronary artery lesions (greater than or equal to 75% stenosis) in at least one major coronary artery. Intracoronary filling defects were detected in four of the five patients. Another three patients without asynergy (Group B) had significant fixed stenosis. Coronary artery spasm was observed in two patients during coronary angiography, but no patient had intracoronary filling defects. Intracoronary nitroglycerin (0.1-0.3 mg) reduced the severity of coronary artery narrowing in two patients. In addition, urokinase (240,000-480,000 IU) via the corresponding vessel (PTCR) in the remaining seven patients resulted in reduction in the severity of coronary artery stenosis in four patients, but not in the remaining three patients. Left ventricular wall movement in the asynergy group improved rapidly and no asynergy was observed by the seventh hospital day in five of the six patients. Successful PTCR treatment resulted in improvement of left ventricular wall movement. No asynergy was found in the non-asynergy group throughout their hospitalizations. These findings indicated that abnormal left ventricular wall movement is found in patients with impending myocardial infarction, even during symptom-free periods, but the wall movement gradually improves. The 2DE observations are useful for estimating the clinical status and for planning precise therapy for impending myocardial infarction.

Adult↗
PubMed1987

[Interstitial irradiation by 192Ir seed assemblies in fixed cervical lymph node metastases].

Eleven patients with fixed cervical lymph node metastases were treated using external irradiation followed by interstitial implants, 137Cs needles were used for one patient and 192Ir seed-assemblies for 10 patients. The local tumor responses were 4 CR, 6 PR and 1 NC. Acute tolerance was good, and there were no major late injuries except for one case of severe subcutaneous fibrosis. No morbidities such as local infection, bleeding or pulmonary injuries were encountered. Clear-cut dose control relationships were demonstrated; the local control of the nodes treated with intervals of more than one month between external and interstitial irradiation was poor. It is considered that adequate treatment is to give 40 Gy over 4 weeks by external irradiation first, then, after an interval of 2 weeks, to give 40-50 Gy over 4-5 days using 192Ir interstitial implants. The interstitial implants appeared to provide an improvement in local control and in the therapeutic ratio of fixed cervical lymph node metastases.

Aged↗
PubMed1987

[Contribution of CT and MRI to radiation therapy].

The contribution of CT to radiation therapy has been enormous. The most basic contribution has been that CT has made almost all malignant tumors visible, which has improved radiation therapy not only in the planning phase but also in the effect-estimating phase. As some examples, CT has improved the effects of radiation therapy for cancer of the maxillary sinus and of the uterine cervix, and the results from our department have already been published. The contribution of MRI to radiation therapy should be very great in future wherever MRI diagnostics are established. Even now, however, its ability to visualize cross-sectional anatomy in any area is an aid to radiation therapy both in planning and in estimating the degree of effect.

Brachytherapy↗