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Biomedical subjects

T Tateishi

Publications and source records attributed to T Tateishi.

At least 145 records · Page 8Linked to original sources

Beta-migrating very low density lipoprotein attenuates endothelium-dependent relaxation in rabbit atherosclerotic aortas.

We studied the effects of beta-migrating very low density lipoprotein (beta-VLDL) on the vascular responses of isolated thoracic aortic preparations taken from normal and hypercholesterolemic rabbits. The endothelium-dependent relaxation induced by acetylcholine or adenosine triphosphate (ATP) was attenuated in the arteries from hypercholesterolemic rabbits that were fed a cholesterol-rich diet for 12 weeks. In these aortas, the lesional circumference of the atherosclerotic plaques (fatty streaks) was only 12.18 +/- 1.98%. The relaxation induced by the Ca2+ ionophore A23187 or nitroglycerin was not altered. Preincubation with beta-VLDL significantly inhibited the relaxation due to acetylcholine, ATP, or A23187, especially in the aortas of hypercholesterolemic rabbits. However, beta-VLDL did not alter the response to nitroglycerin. Preincubation with high density lipoprotein had no significant effect on vessel relaxation. These results indicated that endothelium-dependent relaxation was already inhibited in the early stages of atherosclerosis, and that the atherogenic lipoprotein, beta-VLDL, further inhibited endothelium-dependent relaxation in atherosclerotic aortas. It may be that beta-VLDL also plays a role in determining the level of vascular tonus in atherosclerosis.

Acetylcholine↗

[Clinical study of watershed infarct dementia].

This clinical study of watershed infarct was carried out in two hospitals for elderly patients. The purpose of this study was an investigation of the clinical specificity of this type of infarct as compared with other types of infarcts. The most important point was to determine which patients with this type of infarct usually become demented. The items of investigation were brain CT findings, measurements of the width of the ventricles and the extent of sylvian fissures from CT images, blood pressure, past history of hypertension, diabetes mellitus, alcohol use and smoking, blood analysis of total cholesterol, HDL-cholesterol, hematocrit, hemoglobin A1 and uric acid and the incidence of patients in whom dementia had improved from the previous state. From CT findings, we classified all patients with brain infarcts into 4 groups; 173 patients with central infarcts, 56 patients with watershed infarcts, 20 patients with subcortical lesions of the Binswanger type and 11 patients with occlusion of main brain arteries. Among all investigated patients, there were 56 non-demented and 162 demented (74.3%) patients. Among the patients with watershed infarcts, there were 10 non-demented and 45 (81.8%) demented patients. In the group of demented patients with watershed infarcts, females were four times as many as males. Demented patients with watershed infarcts in the right hemisphere were twice as frequent as those with infarcts in the left hemisphere, while the number of non-demented patients with this type of infarct in right hemisphere was the same as that in the left hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Determination of serum lipid peroxidase using 10-N methylcarbamoyl-3,7-dimethylamino-10 H-phenothiazine (MCDP)--with special reference to aging and diseases].

We developed an assay for determining serum lipid peroxide (LPO) using MCDP. LPO levels in 125 healthy middle-aged and 70 elderly subjects. LPO level in the healthy and the elderly subjects was 1.45 +/- 1.37 nmol/ml and 2.1 +/- 3.0 nmol/ml, respectively. LPO did not increase with age. There was no correlation in the LPO levels determined by the MCDP and TBA methods. We determined the LPO distribution in the fractions of lipoprotein prepared by ultracentrifugation. In the LDL fraction of the diseased (myocardial infarction), the LPO level was higher than that of healthy subjects. Periodic measurement of LPO levels in 10 surgically operated patients revealed that the LPO level decreased significantly on the first day after operation. Our assay is easy to use and shows a lower level than the TBA method. LPO measured by this method would represent a substance different from that measured by the TBA method, i.e., MCDP mainly measures hydroperoxides, whereas the TBA method measures endoperoxides.

Animals↗

Role of platelet secretory products in modified lipoprotein metabolism in macrophages.

Macrophage-derived foam cells and platelets are found in many lesions of atherosclerosis. Macrophages possess scavenger receptors that take up modified low density lipoproteins (LDL) like acetylated or acetoacetylated LDL (aLDL, aaLDL) resulting in accumulation of esterified cholesterol (EC) and acquisition of the characteristics of foam cells. We obtained a certain platelet secretory product from washed platelet-rich plasma which had been frozen and thawed three times (PSP alpha). We studied the effect of PSP alpha in modified lipoprotein metabolism in macrophages. When mouse or human macrophages were incubated with aaLDL and PSP alpha, much more EC was accumulated than with aaLDL only. Though the increase in EC of macrophages was dependent on the concentration of PSP alpha, it declined in high concentrations of PSP alpha. PSP alpha moderately increased 125I-aaLDL binding and cellular metabolism. PSP alpha also affected 125I-oxidized LDL binding and cellular metabolism, but it did not affect the metabolism of 125I beta-migrating very low density lipoprotein (beta VLDL). These results suggest that substances shed by activated platelets play a role in atherosclerosis as potent mediators of EC accumulation in macrophages and by affecting the receptor-mediated endocytosis of modified lipoproteins.

Animals↗

Combination therapy with diltiazem and nifedipine in patients with effort angina pectoris.

The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly increased from 34.8 +/- 11 to 106.4 +/- 37 ng/ml (p less than .001) by the concomitant administration of diltiazem. These data suggest that exercise tolerance in patients with effort angina is increased by the concomitant administration of diltiazem and nifedipine associated with an increase in the nifedipine plasma concentration.

Adult↗

Chronopharmacological study of furosemide in human subjects.

The present study was undertaken to determine whether the diuretic effects of furosemide depend on the administration time or not. After furosemide 20 mg or a placebo was administered intravenously in 12 human subjects at 09h00 or at 21h00, urine volume and urinary excretion of sodium, chloride and furosemide were determined for 3 h. There were no significant differences in the amount of urine, or of urinary excretion of sodium and chloride between when a placebo was given at 09h00 and when it was given at 21h00. When furosemide was administered at 21h00, the urine volume and urinary excretion of sodium, chloride and furosemide during the first 60 min were significantly greater than those, when the drug was administered at 09h00. There was a marked correlation between the urinary output of furosmeide and the urine volume, urinary sodium and urinary chloride. These results suggest that the diuretic effects of furosemide vary with the time of administration and the observed variations are mainly dependent on the amount of furosemide secreted into urine.

Adult↗

Electrical stimulation of ligament healing. An experimental study of the patellar ligament of rabbits.

To examine the effects of direct electric current on ligament healing in rabbits, a full-thickness defect of the patellar ligament was electrically stimulated for time periods of up to seven weeks. The rabbits were randomly assigned to biomechanical and biochemical studies, and healing was evaluated by these parameters. Electrical stimulation was shown to restore tensile stiffness in a short period of time and to decrease the relative proportion of Type III collagen more rapidly than in the control group. However, electrical stimulation did not change the collagen content of newly formed tissue. Electricity enhances the repair process of the ligament by changing the ratio of collagen types.

Animals↗

Fundamental study on gas monitoring in CELSS.

A mass spectrometer and computer system was developed for conducting a fundamental study on gas monitoring in CELSS. Respiration and metabolism of the hamster and photosynthesis of the Spirulina were measured in a combination system consisting of a hamster chamber and a Spirulina cultivator. They are connected through a membrane gas exchanger. Some technical problems were examined. In the mass spectrometric gas monitoring, a simultaneous multi-sample measurement was developed by employing a rotating exchange valve. Long term precise measurement was obtained by employing an automatic calibration system. The membrane gas sampling probe proved to be useful for long term measurement. The cultivation rate of the Spirulina was effectively changed by controlling CO2 and light supply. The experimental results are helpful for improving the hamster-spirulina system.

Air Conditioning↗

Serum lipid peroxide assayed by a new colorimetric method.

Serum lipid peroxide (LPO) in 72 healthy male subjects was studied using a newly developed assay method based on the reaction of LPO with methylene blue derivative (MCDP; 10-N-Methylcarbamoyl-3,7-dimethylamino-10 H-phenothiazine). This method is specific for lipid hydroperoxide and the relation is equimolar. The value obtained was 7.63 +/- 2.78 nmol/ml. Positive correlations were observed between LPO and height (r = 0.290), body weight (r = 0.244) and hemoglobin (r = 0.248). However, no significant correlation was observed between serum LPO level and other clinical data, including age. In addition, serum LPO value measured by this method did not show significant correlation with that measured by the thiobarbituric acid method in rat serum. This discrepancy might be due to the differences in substrates measured by each method.

Adult↗

[Multiple primary neoplasm--glioblastoma combined with cancer of other organs].

A combination of multiple primary neoplasm (MPN) with glioblastoma and cancer of other organs is extremely rare but might be spurred up in the field of neurosurgery because of increasing number of cured patients from cancer or malignant brain tumor. Four such cases are presented. Two of them are of heterochronous occurrence of tumors. One has survived for 17 years after treating four malignancies: uterus, stomach, breast cancer and glioblastoma multiforme in this order and free of brain tumor for 4 years. The other has survived 18 years after three malignancies: uterus, stomach cancer and glioblastoma but is in morbid neurological state for a year. A case of synchronous primary tumors is a combination with glioblastoma and maxillary cancer and the patient died of brain tumor after 4 years and two months. The other case is an old man with glioblastoma and stomach cancer but died of severe general and neurological condition for three months before treatment was started. The pathogenesis of MPN is unknown. Regarding intrinsic factors, heredity, age, genetic or immunological state have been proposed for possible mechanism of the synchronous occurrence of MPN. While extrinsic factors such as environmental changes due to irradiation or chemical exposure to host might also be important for heterochronous MPN. Discussions based on these cases and literature were also made on the biological nature and clinical characteristics of MPN malignant brain tumor combined with cancer of other organs.

Adult↗

Tryptamine, a substrate for the serotonin transporter in human platelets, modifies the dissociation kinetics of [3H]imipramine binding: possible allosteric interaction.

Tricyclic antidepressants and nontricyclic serotonin (5-hydroxytryptamine) uptake blockers monophasically inhibit [3H]imipramine binding in human platelets. Similarly, serotonin and tryptamine inhibit the binding of [3H]imipramine in the low micromolar range and with a pseudo-Hill coefficient near unity. Dissociation of the [3H]imipramine receptor complex in the presence of uptake inhibitors follows first-order kinetics with a half-life of approximately 60 min. Although serotonin and tryptamine do not decrease [3H]imipramine binding when added under equilibrium conditions, simultaneous addition of serotonin or tryptamine with serotonin uptake inhibitors decreases the rate of ligand-receptor dissociation in a concentration-dependent manner. These data suggest a common site of action for serotonin, which is the substrate of the transporter system, and of tryptamine, its nonhydroxylated analog. This hypothesis is supported by the identification of a high-affinity (Km = 0.55 microM), saturable, and temperature-dependent uptake of [3H]tryptamine in human platelets. Uptake of [3H]tryptamine was inhibited potently by imipramine and nontricyclic serotonin uptake inhibitors with a potency similar to that observed for [3H]serotonin uptake. These data support the hypothesis that in platelets, [3H]imipramine, tricyclic, and nontricyclic serotonin uptake inhibitors bind to a common recognition site that is associated with the serotonin transporter but that differs from the substrate recognition site of the carrier through which serotonin and tryptamine exert a heterotropic allosteric modulation on [3H]imipramine binding.

Allosteric Regulation↗

5-Methoxytryptoline, a competitive endocoid acting at [3H]imipramine recognition sites in human platelets.

5-Methoxytryptoline potently inhibits [3H]imipramine binding to membranes from the cerebral cortex and platelets. Since 5-methoxytryptoline, which appears to occur endogenously with particularly high levels in the human pineal gland, also inhibits 5-hydroxytryptamine (5-HT, serotonin) uptake, it should be considered as a putative endogenous ligand modulating 5-HT transport. As the 5-HT transporter complex comprises the imipramine and the substrate recognition sites, which interact allosterically, it was essential to define the mechanism of inhibition of [3H]imipramine binding by 5-methoxytryptoline. Human platelets show an active and saturable uptake of 5-HT and tryptamine. The uptake of both substrates appears to be mediated by the same carrier and it is inhibited by 5-methoxytryptoline at submicromolar concentrations. 5-HT and tryptamine inhibit [3H]imipramine binding in human platelets with a Hill slope for inhibition close to unity and IC50 values of 3,265 and 3,475 nM, respectively. This inhibition is, however, not competitive because both 5-HT and tryptamine significantly decrease the rate of [3H]imipramine-receptor dissociation. Although 5-methoxytryptoline potently inhibits [3H]imipramine binding (IC50 = 44 nM) in human platelets with a Hill slope of unity, it does not affect the receptor-ligand dissociation rate of [3H]imipramine even at concentrations up to 100 microM. The present experiments show that 5-methoxytryptoline, in spite of its chemical similarity to the indoleamine transporter substrates, interacts with the imipramine receptor through a mechanism of competitive inhibition. This conclusion is supported by a selective effect of 5-methoxytryptoline on the Kd of [3H]imipramine binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗

[Radiation therapy for primary non-Hodgkin's lymphoma of the head and neck].

Thirty-seven previously untreated cases of primary non-Hodgkin's lymphoma in the head and neck were treated at our department from September 1977 through January 1983. The survival rate at three years by stage was 84% in stage I, 44% in stage II and 0% in stage III and IV. Stage, T- and B-cell markers, initial primary site, the level of lymph node involvement (UICC, 1978) and number were important prognostic factors. Chemotherapy in the pre- or post-radiation period was essential, especially in stage II. It was proved that adequacy of radiation portals with special reference to anatomical considerations was necessary.

Adolescent↗

Acute and subacute toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1 ,4-dihydropyridine (PP-1466).

The acute and subacute oral toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1,4 -dihydropyridine (PP-1466) was investigated in several animal species in comparison with nifedipine and nicardipine. A clear species difference in LD50 values was found in acute toxicity of PP-1466, and rabbits were the most sensitive between animal species used, then dogs, mice and rats in order. Prominent acute circulatory failure and associated secondary changes were noticed in toxic signs and autopsy findings. PP-1466 as well as nifedipine was apparently less toxic than nicardipine. In the subacute toxicity studies in rats, deaths occurred only in the 2000 mg/kg/d treated groups of both sexes of PP-1466 and nifedipine. Major changes in various observations and examinations were focussed on the cardiovascular system and liver. On the cardiovascular system, it was revealed as congestion and hemorrhage in the various organs and tissues on autopsy finding in dead rats during the test period. A dose-dependent increase in heart weight was observed in rats sacrificed at the termination of the test period. On the liver, it was revealed as a dose-dependent increase in liver weight, changes in liver lipid levels, changes in several serum biochemistry parameters, such as GOT, GPT and ALP (alkaline phosphatase) activities and lipid levels measured at the termination of the test period. These changes were toxicologically mild and functional except the autopsy findings in dead rats. Female rats were slightly more sensitive than males, and PP-1466 was slightly less toxic than nifedipine on subacute oral toxicity in rats.

Administration, Oral↗