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Biomedical subjects

T Takamura

Publications and source records attributed to T Takamura.

At least 73 records · Page 4Linked to original sources

Preferential hydrolysis of phosphatidylethanolamine in rat ischemic heart homogenates during in vitro incubation.

Phospholipid-hydrolyzing activities were examined in rat hearts with ischemia induced by occlusion of the left main coronary artery. When homogenates of ischemic heart were incubated in vitro at 37 degrees C, a significant amount of phosphatidylethanolamine (PE) was degraded, whereas the contents of other phospholipids did not change significantly. During the incubation, a stoichiometrical amount of lysoPE was concomitantly formed. The lysoPE formed had mainly saturated fatty acids and its composition resembled that of fatty acids detected at the sn-1 position in the glycerol backbone of heart PE. No appreciable PE degradation was observed in homogenates prepared from nonischemic rat heart. No difference in phospholipase activities was found between ischemic and nonischemic heart homogenates when exogenous radioactive phospholipids were used as substrates. Rabbit anti-rat 14-kDa type II phospholipase A2 antibody suppressed the degradation of PE observed in ischemic heart homogenates. These findings indicate that the type II phospholipase A2 activity may be involved in the breakdown of endogenous PE in ischemic heart homogenates.

Animals↗

Calcium regulating activity of 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3.

A series of analogs of 1 alpha,25-dihydroxyvitamin D3[1,25(OH)2D3] with alkyl substitutions in 26- and 27-positions were tested for calcium (Ca) regulating activity. The potencies of dialkyl analogs in stimulating bone resorption in neonatal mouse calvaria cultures were the highest in 1 alpha,25-dihydroxy-26,27-dimethylvitamin D3[1,25(OH)2-(Me)2D3], followed by 1,25(OH)2D3, 1 alpha,25-dihydroxy-26,27-diethylvitamin D3[1,25(OH)2(Et)2D3], and 1 alpha,25-dihydroxy-26,27-dipropylvitamin D3[1,25(OH)2(Pr)2D3] in that order. A similar order of potential regarding formation of osteoclast-like cells in mouse bone marrow cell cultures and on bone Ca mobilization with long-term vitamin D-deficient rats was observed in the same series. The relative potencies of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 1,25(OH)2(Et)2D3, and 1,25(OH)2(Pr)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptors were 1:1:0.16:0.036. A similar order of potential in case of intestinal Ca transport in situ was observed in the same series. The potencies of dialkyl analogs in competing with 25-hydroxy-vitamin D3 for binding to rat serum vitamin D binding protein were much lower than that of 1,25(OH)2D3. Effect of 1,25(OH)2(Me)2D3 on osteopenia in rats induced by ovariectomy and right sciatic neurotomy was higher than that of 1,25(OH)2D3. From these results, the lengthening by one carbon at 26- and 27-positions was shown to maintain the Ca regulatory activity of 1,25(OH)2D3.

Animals↗

Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome.

To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy.

Adult↗

Synthesis and biological evaluation of substituted benzenesulfonamides as novel potent membrane-bound phospholipase A2 inhibitors.

A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.

Animals↗

The amplitude of circadian oscillations: temperature dependence, latitudinal clines, and the photoperiodic time measurement.

This paper develops several propositions concerning the lability of the amplitude of Drosophila circadian pacemakers. The first is that the amplitude of the pacemaker's motion, unlike its period, is markedly temperature-dependent. The second is that latitudinal variation in pacemaker amplitude (higher in the north) is responsible for two very different sets of observations on Drosophila circadian systems at successively higher latitudes. One of these is a cline in D. auraria's phase-shifting response to light, which steadily weakens in a succession of more northerly strains. The other, concerning D. littoralis in the very far north, is a cline in the rate at which eclosion activity becomes arrhythmic (the circadian rhythm damps out) in constant darkness; damping is faster in the north. The third proposition concerns a plausible selection pressure for the cline in pacemaker amplitude that we propose underlies the two directly observed clines. Two points are emphasized: (1) The amplitude of the pacemaker's daily oscillation declines as the duration of the entraining light pulse (photoperiod) is increased; and (2) the duration of the daily photoperiods throughout the breeding season is steadily increased as one moves toward the poles. Selection for conservation of pacemaker amplitude (during the breeding season) would produce the latitudinal cline we propose. The fourth, and final proposition is that since the amplitude of the pacemaker's daily motion responds systematically to change in photoperiod, amplitude is clearly one way--and a temperature-dependent way--in which insect circadian systems may sense seasonal change. These propositions concerning the temperature and latitude dependence of pacemaker amplitude may be relevant to a wider array of circadian pacemakers than Drosophila.

Animals↗

26,27-Hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) prevents osteoporosis induced by immobilization combined with ovariectomy in the rat.

The effect of 26,27-hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) on experimental osteoporosis in the rat induced by a combination of immobilization and ovariectomy was evaluated. F6-1,25(OH)2D3 increased the femur score and the photo-density. The administration of F6-1,25(OH)2D3 also significantly increased the dry weight, the ash weight and the ash content of the bone. Both F6-1,25(OH)2D3 and 1 alpha(OH)D3 showed a nearly dose-dependent effect and significant inhibition of the decrease of bone mass. Histomorphometry revealed a significant decrease of resorption by the administration of F6-1,25(OH)2D3. Bone formation rate in the F6-1,25(OH)2D3 treated group significantly decreased compared with the vehicle group. In conclusion, the pharmacological effective dose of F6-1,25(OH)2D3 was considered to prevent the osteoporotic decrease of bone mass by suppressing the elevated bone turnover.

Animals↗

Syntheses and antitumor activities of N6,N6-dimethyladenosine carboxylate analogues.

Several analogues substituted with fatty acid at the 2'-, 3'-, or 5'-position of the ribose moiety of N6,N6-dimethyladenosine were synthesized and tested for antitumor activity against cultured cells of L1210 leukemia and/or Ehrlich ascites. The cytotoxicity and increase of life span obtained with congeners in the N6,N6-dimethyladenosine 3'- or 5'-substituted series were comparable to in vitro or several times better in vivo than those of the mother compound.

Adenosine↗

Latitudinal clines in the properties of a circadian pacemaker.

The circadian rhythm of eclosion activity and its pacemaker were analyzed in a series of latitudinal races of Drosophila auraria ranging from 34.2 degrees to 42.9 degrees N in Japan. The phase of the rhythm (psi EL) to the daily photoperiod (PP) changes as daylength is increased, and the slope of psi EL (PP) changes with latitude. Is is sufficiently greater in the north to cause a phase reversal of northern and southern races on long versus short photoperiods. This reversal is found in assays of the pacemaker's phase (psi PL) as well as that of the rhythm (psi EL). Assay of the pacemaker shows that its period (tau) is longer in northern than in southern races, and that the amplitude of its phase response curve (PRC) is lower in the north. The period of the rhythm in all latitudinal races is longer than 24 hr in short photoperiods (LD 1:23), but is probably less than 24 hr (as an aftereffect of photoperiod) in longer days such as LD 14:10. The observed north-south differences in the phase relation of both pacemaker and rhythm to the light cycle are explained by the latitudinal clines in pacemaker properties and a postulated aftereffect of photoperiod on tau. It is suggested that the latitudinal cline in PRC amplitude has functional significance in conserving the amplitude of the pacemaker's signal to the rest of the system it times. Computer simulation shows that without such a reduction in the perceived light intensity, pacemaker amplitude will be lowered by the increase in duration of the daily light at higher latitudes.

Animals↗

Mechanism of myocardial injury in dogs with hypokalaemia.

Hypokalaemia was induced by infusing polystyrene sulphonate into the colon of mongrel dogs. Sixty minutes after infusion adrenaline 10 micrograms.kg-1 was injected intravenously, which had no effect on serum creatine kinase activity or myocardial histology in the control dogs. However, in dogs with hypokalaemia creatine kinase activity was increased, and pronounced histological changes were seen 60 min after injection. A clear reciprocal relation was found between serum potassium concentration and creatine kinase activity. Premedication with an alpha 1 blocking agent prevented the changes associated with hypokalaemia. Heart mitochondria were prepared from other dogs with hypokalaemia 5 min after adrenaline injection and their calcium content measured. Heart mitochondrial calcium content was increased in parallel with the decrease in serum potassium concentration. Alpha 1 blockade also prevented the increase in mitochondrial calcium content. These results indicate that the intracellular calcium concentration is considerably increased by alpha 1 receptor stimulus under hypokalaemic conditions and that this increase in calcium concentration plays a crucial role in the genesis of myocardial damage. Since adrenaline increases coronary blood flow small doses of adrenaline in subjects with hypokalaemia may lead to the development of myocardial injury not associated with ischaemia.

Animals↗

[A case of early gastric cancer accompanied by Recklinghausen's disease].

In September, 1980, a 57-year-old male, was admitted to hospital for precise examinations to determine if he had Recklinghausen's disease, pneumoconiosis, and a duodenal ulcer. Endoscopy revealed a redness and a shallow depression of the posterior wall of the antrum, and a biopsy of a specimen led to the diagnosis of early gastric cancer, Stage II c. After the examination, the patient did not return to our department again. In May, 1987, however, the man was readmitted to our hospital, suffering from pains in the right back. X-ray and endoscopic findings revealed a gastric cancer with a center depression and a peripheral elevation (II a + II c). Histological findings showed the gastric cancer to be a moderately differentiated tubular adenocarcinoma, with a submucosal invasion that was also seen. This case, uncovered 80 months earlier, represents a rare instance in which an early gastric cancer, accompanied by Recklinghausen's disease, expanded slowly.

Adenocarcinoma↗

Failure of beta-blocking agent to prevent epinephrine-induced myocardial injury in dogs with hypokalemia.

The effect of epinephrine in dogs with hypokalemia was investigated. Injection of epinephrine, 10 micrograms/kg, induced an elevation of serum creatine kinase (CK) activity and histological changes in myocardium of dogs with hypokalemia. The effect of epinephrine was little in dogs with normokalemia. Heart mitochondrial calcium content was elevated in parallel with the decrease in serum K+ in dogs with hypokalemia. Propranolol, a beta-blocker, did not prevent these changes. Since epinephrine increases coronary blood flow, these alterations cannot be ascribed to a reduction in coronary blood flow. It is likely that calcium overload alone, without ischemia, could develop myocardial injury in dogs with hypokalemia, and that beta-adrenergic action is not involved in this pathogenesis.

Animals↗

Severe hypertension in infant with unilateral hypoplastic kidney.

Unilateral renal hypoplasia unlike Ask-Upmark kidney (segmental renal hypoplasia) seldom causes hypertension. A case of an infant whose hypertension disappeared after removal of a hypoplastic kidney is reported. The removed kidney revealed no sign of Ask-Upmark lesion.

Humans↗

Effects of bunazosin and propranolol on ventricular arrhythmias in dogs with hypokalemia.

The arrhythmogenic mechanism in dogs with hypokalemia was investigated in relation to the effects of an alpha 1-blocking agent and a beta-blocking agent. Hypokalemia was induced by inserting an ion-exchange resin into the colon. In the hypokalemia group, nine out of 17 dogs with arrhythmia ratios of over 10% (that is the percentage of the number of ventricular ectopic beats divided by the total number of heart beats during 5 min, after 10 micrograms/kg of epinephrine injection) were observed. In the control group (n = 13), which maintained normal serum K+ levels, only one dog showed an arrhythmia ratio of over 10%. Dogs with lower serum K+ levels showed higher arrhythmia ratios. The Ca2+ content of heart mitochondria, considered to be a reflection of intracellular Ca2+ concentration, was 24.4 +/- 5.7 nmoles/mg protein in the control group 5 min after epinephrine injection, while that of the hypokalemia group was increased to 35.0 +/- 13.4. A good reciprocal correlation between the concentration of serum K+ just before epinephrine injection and mitochondrial Ca2+ content was observed in the hypokalemia group (r = -0.79), while in the control group, no correlation was observed. Clear correlation between mitochondrial Ca2+ content and the arrhythmia ratio was also observed in the propranolol group. Pretreatment with bunazosin, an alpha 1-"blocker," effectively prevented the increase in mitochondrial Ca2+ content, and reduced the arrhythmia ratio. On the other hand, pretreatment with propranolol, a beta-"blocker," did not affect the mitochondrial Ca2+ content and the arrhythmia ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Temperature dependence and evolutionary adjustment of critical night length in insect photoperiodism.

The photoperiodic responses of Drosophila auraria are shown to involve its circadian system functioning as the "clock" that measures the duration of darkness at night. Attempts at further clarification of this finding were based on the widely held assumption that adaptive adjustment of critical night length is caused by change in the circadian system's entrainment behavior. Three different experimental programs yielded data that are incompatible with this starting premise. Collectively, the observations suggest a new interpretation of the lability (phenotypic and genetic) of critical night length based on change in the level of response to all night-length measurements-not on the measurements themselves. This proposition is found especially relevant to the temperature dependence of photoperiodic responses and its role in controlling the onset and termination of the breeding season at different latitudes.

Journal Article↗

[The study of the ABH isoantigen of bladder tumors].

ABH isoantigens in 82 cases with bladder tumor of various grades and stages were investigated by the avidin-biotin-peroxidase complex (ABC) method. Correlation of ABC expression for isoantigens with pathological findings on the grading and staging system of the bladder tumors were as follow: Of 60 cases of low grade tumors, 34 (56.7%) were positive and of 22 cases of high grade tumors, 21 (95.5%) were negative. Of 63 cases of low stage tumors, 35 (55.6%) were positive and all 19 cases of high stage tumors, (100%) were negative. The isoantigens in the tissue of the bladder tumors tended to disappear as the histologic anaplasia of the tumor progressed. There was a high correlation between the histological grade, stage and ABC expression (p less than 0.01). In a follow-up study of 38 patients with low grade, low stage, initial transitional cell carcinoma, 9 of the 24 patients positive for ABC expression (37.5%) showed recurrence during the 1 to 6 year follow-up period, whereas 10 of the 14 patients negative for ABC expression 10 (71.4%) did. There was a high correlation between the recurrence rate and ABC expression (p less than 0.05). Therefore, the analysis in the bladder tumors may be valuable for prediction of malignant potential, especially for the low grade, low stage tumors.

ABO Blood-Group System↗

The effects of ubidecarenone derivatives on the action of phospholipase.

Anti-phospholipase (Plase) action of ubidecarenone (coenzyme Q10, CoQ10, E-0216) derivatives was investigated. CoQ10 and its derivatives prevented the release of fatty acids from canine heart mitochondrial phopholipids induced by PLase A2 and PLase C. The protective effects of the carboxyl derivatives of CoQ10 of the benzoquinone type (BQs) and of the methoxyl type (MPs) were stronger than that of CoQ10. MPs with 3 isoprenoid units (MP-3) was more effective than BQs with 3 isoprenoid units (BQ-3) with respect to PLase A2, while they showed similar protective effect against PLase C attack. The effects of BQ-3 and MP-3 on reperfusion arrhythmias were investigated in anesthetized dogs. Dogs were divided into three groups: the control group (n = 38), the BQ-3 group (n = 11), and the MP-3 group (n = 11). Physiological saline or 5 mg/kg of BQ-3 or MP-3 was premedicated in each group. 20 min after premedication, the left anterior descending coronary artery was occluded for 15 min followed by 5 min reperfusion. 32% of the controls developed reperfusion arrhythmias, while none of the dogs pretreated with CoQ10 derivatives developed arrhythmias. Immediately after 5 min of reperfusion, heart microsomes were prepared from normal and reperfused areas and the PLase activity in microsomes was measured by high performance liquid chromatography. In the arrhythmias cases of the control group, the endogenous PLase activity obtained from reperfused myocardium increased significantly compared with that from normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗