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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 595 records · Page 33Linked to original sources

Improved results in the treatment of nasopharyngeal carcinoma using combined radiotherapy and chemotherapy.

A total of 77 patients with nasopharyngeal carcinoma were retrospectively reviewed for the effectiveness of combining chemotherapy (CT) with radical radiotherapy (RT). From 1972 to 1976, 26 patients were treated with a relatively short course of radical RT alone: 52-55 Gy/16 Fx/4 wk (study 1). From 1977 to 1982, 29 patients were also treated with radical RT alone, but with a more prolonged fractionation schedule: 65-70 Gy/26-28 Fx/6.5-7 wk (study 2). In 1983, the policy was to combine CT and RT. From 1983 to 1987, 22 patients received four to six courses of CMU regimen (consisting of cyclophosphamide, methotrexate, and UFT, a 5-fluorouracil analog) after completion of radical RT (study 3). The three studies were comparable with regard to patient characteristics: histologic type, stage, sex, and age distribution. There were no significant differences in survival and relapse figures between study 1 and study 2, but study 3 compared favorably with study 1 and study 2 in actuarial survival, relapse-free survival, relapse rate, and median relapse time. A mild nausea and transient granulocytopenia during CT was the only side effect encountered. In conclusion, the use of CT in combination with RT appeared to increase significantly the chance of long-term survival and probable cure.

Adolescent↗

Immunocytochemical localization of beta-adrenergic receptors in the rat brain.

The localization of beta-adrenergic receptors (beta-AdR) in the rat brain was examined immunocytochemically with antibody against affinity-purified beta 2-receptors. This antibody was confirmed to cross-react with beta 1-AdR. beta-AdR were widely but unevenly distributed in the rat brain. In the forebrain and diencephalon, cells with beta-AdR were abundant in the cerebral cortex, hippocampus, and various hypothalamic nuclei other than the ventromedial hypothalamic nucleus and the suprachiasmatic nucleus. Few or no cells with beta-AdR were found in the thalamus except in the lateral and medial geniculate nucleus, habenular nucleus and paraventricular thalamic nucleus. The striatum, globus pallidus, and accumbens nucleus also contained few beta-AdR. In the lower brainstem, areas related to auditory function, such as the inferior colliculus, the nucleus of the lateral lemniscus and the cochlear nuclei, as well as areas related to cerebellar function, such as the reticulotegmental nucleus of the pons, the pontine nuclei, the lateral reticular nucleus and the inferior olive, were rich in beta-AdR. Considerable immunoreactivity was also found in the parabrachial nucleus and the nucleus of the solitary tract.

Animals↗

Decrease in the fluidity of brush-border membrane vesicles induced by gentamicin. A spin-labeling study.

In our previous paper (Horio et al., Biochim Biophys Acta 858: 153-160, 1986), we reported that the addition of gentamicin in vitro to rabbit renal brush-border membrane vesicles decreases the apparent Vmax of Na+-dependent D-glucose transport without affecting the apparent Km. In the present study, we investigated the effects of gentamicin on the physical state of spin-labeled rabbit renal brush-border membranes, using electron spin resonance spectrometry. Brush-border membrane vesicles were prepared from outer cortex (mainly contains early proximal tubule) and outer medulla (containing primarily late proximal tubule), and the gentamicin toxicities in both preparations were compared. Significant decreases were observed in the membrane fluidity of 5 mM gentamicin-treated brush-border membranes. The fluidity of outer cortical brush-border membranes was affected at both 25 degrees and 35 degrees, whereas that of outer medullary membranes was affected only at 35 degrees. Two different stearic acid spin labels revealed that gentamicin affected the fluidity only in the superficial region of the membranes. We also demonstrated that the gentamicin-induced decreases in Na+-dependent D-glucose transport and in the membrane fluidity were recovered by washing gentamicin-treated brush-border membranes. We suggest that gentamicin binds to the superficial region of brush-border membranes and inhibits Na+-dependent D-glucose transport across brush-border membranes through the decrease in the membrane fluidity.

Animals↗

Attenuation of neutrophil function by inhibitors of arachidonate metabolism reduces the extent of canine myocardial infarction.

To assess the role of neutrophils and arachidonate metabolites in evolving myocardial infarction, the effect of inhibitors of arachidonate metabolism on the extent of myocardial damage and neutrophil function was examined in a 90-minute occlusion/5-hour reperfusion model of canine myocardial infarction. A thromboxane A2 synthetase inhibitor, CV-4151, and a lipoxygenase inhibitor, AA-861, greatly reduced the infarct size. They also attenuated the production of chemoattractant leukotriene B4 and chemotactic activity of neutrophils isolated from peripheral circulation. Under these conditions, both the increases in peripheral leukocyte count and neutrophil infiltration in ischemic myocardium were inhibited. These results indicate that the inhibition of 2 pathways of arachidonate metabolism may decrease infiltration of activated neutrophils in ischemic myocardium by attenuating chemotactic function of neutrophils, resulting in reduction of the extent of myocardial infarction.

Animals↗

Prediction of stroke-prone gerbils and their cerebral circulation.

We attempted to predict the severity of cerebral ischemia, prior to permanent occlusion of a common carotid artery (CCA), in the gerbil by measuring the diameter of the distal CCA before and during temporary ligation and correlated the severity of cerebral ischemia and the pattern of cerebral circulation. All gerbils with reduction of the diameter over 44% after temporary occlusion developed severe neurological signs following permanent ligation. These gerbils lacked any connection between the left and right anterior cerebral arteries (ACA) and the pericallosal arteries originated from the ACA of the occluded side. No gerbils with reduction of less than 30% developed neurological signs and those gerbils possessed a definite anastomosis between the ACAs from both sides. Six of 7 gerbils without connection between the ACAs whose pericallosal arteries originated from the ACA of the non-occluded side proved to be moderately symptomatic. It was concluded that we could reliably predict severely symptomatic and moderately symptomatic gerbils with specific cerebral circulation patterns prior to permanent occlusion of the CCA. The preselected 'stroke-prone' gerbils should be useful for the investigation of cerebral ischemia and the evaluation of pharmacological agents.

Animals↗

Presence of catecholaminergic axon-terminals containing beta-adrenergic receptor in the periventricular zone of the rat hypothalamus.

The present study, using a light microscopic double-immunofluorescence method, has revealed the presence of fibers containing both tyrosine hydroxylase- and beta-adrenergic receptor-like immunoreactivities in the rat hypothalamic periventricular zone. Subsequent immunoelectron microscopic analysis demonstrated that these belong to axon terminals. These findings suggest that presynaptic beta-adrenergic receptor is present in catecholaminergic terminals.

Animals↗

Simultaneous evaluation of insulin secretion and action using a model.

For the simultaneous evaluation of insulin secretion and insulin sensitivity, a glucose regulation model has been developed. In order to estimate the parameters of the model, an intravenous glucose infusion test (GIT, 100 mg/kg.min x 2 min and 10 mg/kg.min x 118 min) was carried out on 15 healthy subjects (N), 12 subjects with impaired glucose tolerance (IGT), 20 non-insulin-dependent diabetics (NIDDM) and 13 patients with chronic pancreatitis (CP). The coefficient (microU/mg) for insulin secretion depending on blood glucose concentration in IGT, NIDDM and CP were lower (35.9 +/- 2.7, 24.5 +/- 3.3, 43.1 +/- 3.1) than in N (77.5 +/- 7.9). The coefficients (microU.min/mg) for insulin secretion depending on rate of change in blood glucose concentration in IGT and NIDDM were significantly lower (6.5 +/- 2.1, 3.8 +/- 1.2) than in N (52.8 +/- 8.8). The insulin sensitivity index (ISI; 10(-2) mg/(microU/ml).kg.min) in NIDDM was lower (4.98 +/- 0.75) than in N (11.37 +/- 1.08). Administration of exogenous insulin did not significantly affect the value of ISI in N and NIDDM. ISI showed a tendency to increase (15.09 +/- 1.92) in CP. It was demonstrated that the proposed model which estimates both insulin secretory ability and insulin sensitivity simultaneously is quite useful for analyzing the mechanism of impaired glucose tolerance.

Adult↗

Cellular analysis of c-Ha-ras gene expression in rat liver after CCl4 administration.

Expression of the c-Ha-ras proto-oncogene is specifically enhanced during liver regeneration, in parallel with increased DNA replication, which suggests that c-Ha-ras may play a role in the control of regeneration. In this study, an in situ hybridization technique was applied for analysis of expression of the c-Ha-ras gene at the cellular level during liver regeneration induced by CCl4 administration. The in situ hybridization was compared with the observation for the p21c-Ha-ras protein, the corresponding protein of the c-Ha-ras gene, by immunohistochemistry. In normal rat liver, a few hepatocytes expressed the mRNAs and the corresponding proteins without any preferential localization. Zonal heterogeneity of c-Ha-ras gene expression first became evident at 12 hr after CCl4 administration, a higher number of gene products being detected in the pericentral zone than in the periportal zone. This heterogeneity became maximal at 24 hr after CCl4 administration. Zonal heterogeneity in the level of the p21c-Ha-ras protein paralleled that in the level of gene expression. Furthermore, both hepatocytes and nonparenchymal cells participated in expression of the c-Ha-ras gene during liver regeneration.

Animals↗

5'-flanking DNA of the human insulin receptor gene and long terminal repeat of mouse mammary tumour virus bind to the same nuclear protein(s).

The interaction of nuclear protein extracted from rat liver and 5'-flanking DNA of the human insulin receptor gene was investigated with the aid of gel mobility shift analysis. When 5'-flanking DNA (-1255/-1206 or -385/-345 base pairs) was incubated with nuclear protein, two or three 32P-DNA species (protein binding DNA fragment(s) and free DNA fragment) were detected. These bands did not disappear in spite of increasing amounts of synthetic poly(dI-dC), showing that nuclear protein binds specifically to 5'-flanking DNA of the insulin receptor gene. Increasing amounts of long terminal repeat of mouse mammary tumour virus resulted in a reciprocal decrease in nuclear protein binding to 5'-flanking DNA of insulin receptor gene. These results suggest that 5'-flanking DNA of insulin receptor gene binds to the same nuclear protein to which long terminal repeat of mouse mammary tumour binds.

Animals↗

Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man.

The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO2) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO2 level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO2 decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO2 which might be related to weakening of mucosal defensive factors.

Adult↗

Semiquantitative evaluation of aortic regurgitation by Doppler echocardiography: effects of associated mitral stenosis.

The accuracy of pulsed and continuous wave (CW) Doppler methods for evaluating aortic regurgitation (AR) was compared in patients with and without mitral stenosis (MS), with aortic root angiography as a gold standard. AR was diagnosed with pulsed Doppler echocardiography, by the detection of broad frequency spectral patterns in the isovolumic relaxation time. If these indications were present, AR was graded by examining the extent of diastolic turbulence in the left ventricular cavity (flow mapping method). With CW Doppler echocardiography, AR was diagnosed by the detection of a peak velocity of greater than 2 m/s; if this velocity was attained, AR was graded by measuring the time from the peak velocity to half the peak velocity (half-time method). The angiographic grade corresponded to that determined by the pulsed and CW Doppler methods in 37 and 37 of 46 patients without MS, respectively. Angiographic grade corresponded to the grade determined by the pulsed and CW Doppler methods in 13 and 17 of the 23 patients with MS, respectively. Eight of 10 discrepancies between pulsed Doppler and angiographic grades were due to overestimation of AR by the flow mapping method, apparently because the transmitral jet produces diastolic turbulence in the left ventricular cavity independent of AR. On the other hand, three of six discrepancies between CW Doppler and angiographic grades were due to the incapability of detecting signals of AR by CW Doppler echocardiography. Thus both the pulsed and the CW Doppler methods are useful to evaluate AR in patients without MS. In patients with MS, however, AR is most accurately diagnosed by the detection of AR signals in the isovolumic relaxation time by pulsed Doppler echocardiography, and the degree of AR is more accurately assessed by the CW Doppler half-time method.

Adult↗

Detection of hepatitis B virus X gene protein and antibody in type B chronic liver disease.

The genome of the hepatitis B virus contains a sequence (X gene) whose role is unclear. The almost complete region of the hepatitis B virus X gene was expressed in Escherichia coli, with the resulting protein being approximately 17 kilodaltons in molecular weight. Sera from 139 subjects were analyzed by Western blot analysis. Of the hepatitis B surface antigen-positive patients, anti-X was not found in 4 patients with acute hepatitis and in 12 healthy carriers, but was present in 41% (21/51) of the patients with chronic hepatitis, 63% (15/24) of those with liver cirrhosis, and 46% (12/26) of those with hepatocellular carcinoma. The expression of the X product in the liver tissues (43 hepatitis B surface antigen-positive patients) was investigated using an indirect immunohistochemical method. The X protein was observed in 64% (21/33) of the patients with chronic hepatitis and 50% (5/10) of those with liver cirrhosis, and was found when the serum was negative for anti-X. Hepatitis B core antigen was frequently expressed together with the X protein in the liver. The conclusions reached were that the frequency of anti-X increases with the length of chronic hepatitis B virus infection, that anti-X may suppress the expression of the X protein in the liver, and that the X protein may be related to hepatitis B virus replication.

Blotting, Western↗

Effect of chronic renal failure on the level of albumin messenger RNA.

The effects of chronic renal failure on the level of albumin mRNA and the transcription rate of the albumin gene were studied in seven of eight nephrectomized rats. A paired feeding procedure was employed to eliminate a nutritional difference between sham-operated control and uremic rats. Total RNA was isolated from the livers of control and uremic rats fasted for 24 or 48 hours. The mRNA level was measured by RNA-cDNA dot blot hybridization, and the transcription rate was measured by the "run-on" transcription assay in isolated nuclei. The albumin mRNA levels in uremic rat livers were reduced to 75% at the 24-hour fasted state, and to 45% at 48-hour fasted state compared with those in the respective control groups. There was no difference in the level of beta-actin mRNA between these groups. However, there was no difference in the transcription rate of the albumin gene between control and uremic rats. Northern analysis showed that albumin mRNA isolated from uremic rat liver was identical in size with that from the control. These results suggested that a posttranscriptional process, involving the destabilization of cytoplasmic mRNA, is responsible for the uremia-induced repression of albumin synthesis.

Animals↗

The value of treatment planning using CT and an immobilizing shell in radiotherapy for paranasal sinus carcinomas.

This article describes a method which uses CT scans and immobilizing shells radiation treatment planning (CT-assisted planning) for paranasal sinus carcinomas and the value of this method on the treatment outcome. Results of the treatment for 82 patients who had CT-assisted planning were compared with that of 88 patients who had no such treatment planning. It has been concluded that the combined use of CT and the shell in treatment planning permitted a 3-dimensional localization of both the tumor and critical normal structures with great accuracy, leading to an improved long-term survival and a reduced complication rate. The multivariate regression analysis for predicting significant prognostic factors also confirmed the valuable role of CT in terms of survival and primary tumor control. The actuarial 5-year survival rate was 51% in all patients, whereas, by using CT-assisted planning, it was improved to 61%. The improved survival was observed among the patients with tumors of the suprastructures where tumors were located adjacent to the critical organs (brain and eye). Major complications attributable to radiation have included instances of brain and ocular damage. CT-assisted planning, however, has been proven effective in avoiding brain necrosis and preserving eye sight.

Adult↗

Right coronary artery occlusion: its role in the mechanism of precordial ST segment depression.

To investigate the mechanism of precordial ST segment depression during right coronary artery occlusion, precordial ST segment shifts and myocardial lactate metabolism were evaluated during coronary angioplasty in 10 patients with (group A) and 7 patients without (group B) precordial ST segment depression during balloon occlusion of the right coronary artery, and in 17 patients with precordial ST segment depression during balloon occlusion of the left anterior descending artery (group C). A 12 lead electrocardiogram was continuously recorded in each patient. Blood lactate in the aorta and great cardiac vein was measured during the procedure, and the lactate extraction ratio in the anterior wall was determined both before and during balloon occlusion. Eight of the 10 patients in group A and 1 of the 7 patients in group B had a dominant large right coronary artery. There were no significant differences in summed ST segment elevation in leads II, III and a VF between group A (0.56 +/- 0.26 mV) and group B (0.46 +/- 0.19 mV) during balloon occlusion of the right coronary artery, and no significant differences in summed ST segment depression in leads V1 to V6 during balloon occlusion between group A (0.44 +/- 0.26 mV) and group C (0.38 +/- 0.14 mV). Lactate extraction ratio before balloon occlusion was similar among the three groups. Patients in group A had a higher lactate extraction ratio during (38 +/- 11%) compared with before (30 +/- 11%) (p less than 0.05) balloon occlusion despite precordial ST segment depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Mechanism of action of angiotensin II on isolated rat glomeruli.

Angiotensin II (Ang II) regulates glomerular filtration rate by contracting mesangial cells and thereby decreasing glomerular filtration surface area. To elucidate the cellular mechanism of this action, we investigated the roles of Ca and protein kinase C (PKC) activation in Ang II-induced glomerular capillary vasoconstriction using 3H-inulin to measure the extracellular (largely intracapillary) volume of isolated decapsulated rat glomeruli. Ang II (1 microM) rapidly decreased the glomerular inulin space (GIS), bringing about a maximal decrease at five minutes, which lasted up to 30 minutes. When incubated in 0.5 mM EGTA-containing Ca-free medium or in the presence of 1 microM diltiazem or verapamil, the sustained phase (after 7 min) was completely inhibited. The initial effect (at 3 and 5 min) was only partially inhibited by these maneuvers but was completely inhibited by trifluoperazine or W-7, which indicated that it was dependent on calmodulin and, accordingly, on Ca probably released from the intracellular store. The sustained effect was mimicked by 12-0-tetradecanoylphorbol-13-acetate (TPA) in the presence of extracellular Ca, but was not in its absence. The sustained effect was also inhibited by H-7, an inhibitor of PKC, and by W-7, which indicated that PKC activation and influx of extracellular Ca are both important. Combined treatment with A23187 and TPA could mimic both the initial and sustained effect of Ang II in the presence of extracellular Ca, though either one of them failed to do so when used alone. These results suggest that the initial effect of Ang II on GIS is mediated by Ca released from the intracellular store, on the one hand, and the sustained effect by extracellular Ca influx and PKC activation, on the other.

Angiotensin II↗