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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 505 records · Page 28Linked to original sources

A new transnasal sonde type fiberscope (SSIF type VII) as a pan-enteroscope.

The sonde type enteroscopes (SSIF, Olympus) are long, slender, flexible instruments which resemble the Miller-Abbott or Cantor tube. To date, six types of SSIF (types I-VI) designed for oral insertion have been available. These scopes are introduced into the lower part of the small intestine by peristalsis, and the examination was seldom risky. The patient, however, often complained of pharyngeal discomfort, which reduced his tolerance. A new enteroscope, the SSIF type VII, with no metal hood and slender enough to permit nasal insertion has been developed. Enteroscopy with this fiberscope is adequately tolerable, even in the case of a long examination, and observation of most of the small intestine is possible without risk or discomfort.

Adult↗

Effect of OKY-046, a thromboxane A2 synthetase inhibitor, on arachidonate-induced platelet aggregation: possible role of "prostaglandin H2 steal" mechanism.

To clarify the mode of action of a selective thromboxane A2 (TXA2) blockade in platelet reactivity, we examined the effect of (E)-3-[4-(1-imidazolylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a potent TXA2 synthetase inhibitor, on human platelet aggregation induced by arachidonic acid (1 mM) in the absence and presence of aspirin-treated aortic microsomes containing prostacyclin (PGI2) synthetase activity ex vivo. The production of TXA2 and PGI2 in platelet rich plasma was determined by the amounts of their stable catabolites, TXB2 and 6-keto-PGF1 alpha respectively, measured by radioimmunoassay. In the absence of aortic microsomes, OKY-046 (greater than 10(-5) M) produced more than 90% inhibition of TXA2 production, whereas platelet aggregation was less inhibited, about 40% inhibition over control, by OKY-046 in that concentration. In the presence of aortic microsomes, the inhibitory effect of OKY-046 on platelet aggregation was markedly augmented in a dose-dependent manner in proportion to the increment of PGI2 production, which paralleled the OKY-046-induced inhibition of TXA2. These results suggest that a selective TXA2 blockade produces effects on platelet aggregation mainly in dual fashion in the presence of PGI2 synthetase: one is due to mere inhibition of TXA2 synthetase and the other is due to the enhancement of PGI2 production probably involving "prostaglandin H2 (PGH2) steal" mechanism, in which PGH2 accumulated in platelets is partly converted to a substrate of PGI2 synthetase in aortic microsomes to produce PGI2.

Acrylates↗

Augmented platelet reactivity and thromboxane A2 production possible aggravating factors in unstable angina.

We examined platelet aggregation and plasma levels of thromboxane B2, a stable metabolite of thromboxane A2, in patients with unstable angina and correlated these platelet indices with the response to antianginal conventional therapy such as isosorbide dinitrate and calcium channel blocker. Eight of 36 patients exhibited anginal attacks more than 5 times/week in spite of the therapy, designated refractory unstable angina, associated with augmented platelet aggregation induced by arachidonate (0.3 mM, 71 +/- 3%, mean +/- SEM) and collagen (2 micrograms/ml, 72 +/- 5%), and elevated plasma levels of thromboxane B2 (350 +/- 19 pg/ml). In the remainder of the patients whose anginal attacks were effectively subsided by the therapy, platelet aggregation was much lower (arachidonate: 34 +/- 9%, collagen: 31 +/- 8%, p less than 0.01) and plasma levels of thromboxane B2 were also lower (295 +/- 12 pg/ml, p less than 0.05). To evaluate the effect of selective thromboxane A2 blockade on clinical findings and platelet reactivity in refractory unstable angina, OKY-046 (600 mg/day, p.o.) was administered to another 14 patients with refractory unstable angina in addition to the conventional therapy. We found that platelet aggregation induced by arachidonate (71 +/- 4%) and collagen 65 +/- 8%) was markedly reduced (44 +/- 7% and 24 +/- 3%, respectively, p less than 0.01) and plasma levels of thromboxane B2 (358 +/- 31 pg/ml) and thromboxane B2 production in serum (29 +/- 5 ng/ml) were also significantly reduced after OKY-046 treatment (262 +/- 21 pg/ml, p less than 0.05, and 1.4 +/- 0.2 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Characterization of recombinant cDNA clones for canine cardiac phospholamban.

Complementary DNA clones specific for phospholamban have been isolated from a canine cardiac cDNA library. The amino acid sequence deduced from the cDNA sequence showed that phospholamban consisted of 52 amino acid residues and was synthesized without an amino-terminal signal sequence. The RNA blot analysis revealed that phospholamban mRNAs were represented by two main species of approximately 1.2kb and approximately 2.8kb. These mRNAs appeared to differ primarily in the length of the 3' untranslated region.

Amino Acid Sequence↗

Oxidation of pyrimidine bases and their derivatives with hydrogen peroxide in hydrochloric acid.

Oxidation of cytosine with H2O2 in 1 N-HCl gave 5-chlorocytosine and 5-chlorouracil. The reaction of uracil gave 5-chlorouracil. Treatment of thymine with H2O2 in 0.1 N-HCl gave 5-chloro-6-hydroperoxy-5,6-dihydrothymine, while the reaction in 1 N-HCl gave 5-chloro-6-hydroxy-5,6-dihydrothymine. Heating of 5-chloro-6-hydroperoxy-5,6-dihydrothymine in water gave 5-chloro-5-methylbarbituric acid.

Chemical Phenomena↗

Communication between epidural hematoma and cephalhematoma in a neonate.

A case of neonatal epidural hematoma caused by falling at a premature delivery is presented. It accompanied a cephalhematoma communicating to the epidural hematoma through a fracture of the skull. The mechanism of this peculiar form of neonatal epidural hematoma is discussed.

Birth Injuries↗

[A case-control study of diet and colo-rectal cancer in Japan].

A case-control study of cancer of the colon and rectum was conducted in Kyoto, Japan. A total 62 cases of cancer of the colon and 52 cases of cancer of the rectum were individually matched by age at interview (+/- 5 years) and sex to same number of hospital controls. Cooking with oil and confectionery were significantly increased risk factors for cancer of the rectum. Margarine was a significantly increased risk factor for cancer of the colon. These results suggests that dietary fat plays an etiologic role in carcinogenesis of the large intestine. Factors already demonstrated or thought to affect the development of colo-rectal cancer were also reviewed.

Colonic Neoplasms↗

Separation of cerebral embolism with angiographical criteria--a preliminary report.

Total of 35 cases of cerebral arterial occlusion were studied with repeated angiography. Cerebral embolisms (E group; 18 cases) were distinguished from cerebral thrombosis (T group; 17 cases) by angiographical criteria: recanalization of occluded arteries of demonstration of embolus with distinct contour. Clinical findings and laboratory data of each group were compared and thought to be well separated. Appropriateness and significance of these criteria are discussed.

Aged↗

Functional significance of transient collaterals during coronary artery spasm.

Coronary collateral vessels appear transiently during vasospasm. To examine the functional role of such collaterals in acute myocardial ischemia, regional coronary flow was determined in patients who showed isolated total spasm in the proximal left anterior descending coronary artery associated with (n = 7, group I) and without (n = 9, group II) collaterals, which were donated by the nonspastic right coronary artery during ergonovine provocative test. Aortic pressure and heart rate were not significantly different in the 2 groups before and during spasm. During vasospasm, the levels of pulmonary artery end-diastolic pressure were significantly higher in group II (19 +/- 2 mm Hg, mean +/- standard error) than in group I (15 +/- 1 mm Hg, p less than 0.05). Under these conditions, great cardiac vein flow (GCVF) measured by thermodilution was markedly reduced in group II (from 60 +/- 4 ml/min to 37 +/- 4 ml/min, p less than 0.01), whereas GCVF was slightly reduced in group I (from 56 +/- 4 ml/min to 51 +/- 4 ml/min), indicating that residual GCVF was greater in patients with than in those without collaterals (p less than 0.05). The calculated coronary collateral resistance index during vasospasm was significantly lower in group I (2.06 +/- 0.18 mm Hg min/ml) than in group II (2.91 +/- 0.30 mm Hg min/ml, p less than 0.05). Total left anterior descending coronary artery spasm with collaterals was less frequently associated with ST elevation in the precordial electrocardiogram recorded during spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Purification and characterization of phospholamban from canine cardiac sarcoplasmic reticulum.

Phospholamban, a putative regulator of the Ca2+-dependent ATPase of cardiac sarcoplasmic reticulum (SR), was purified from canine cardiac SR membranes. Cardiac SR was extracted with deoxycholate and fractionated with ammonium sulfate followed by gel permeation high performance liquid chromatography in the presence of the nonionic detergent, octa-ethylene glycol mono-n-dodecyl ether (C12E8), and KI. Further purification was achieved with CM-Sepharose CL 6B column chromatography in the presence of C12E8. The purified phospholamban showed a single band of 22,000 daltons on neutral sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (Weber, K., and Osborn, M. (1969) J. Biol. Chem. 244, 4406-4412) and 27,000 daltons on alkaline SDS gels (Laemmli, U. K. (1970) Nature (Lond.) 227, 680-685). Boiling of phospholamban in 2% SDS produced total conversion into the lower molecular weight component on SDS gels (11,000 on Laemmli gel and 10,500 on Weber and Osborn gel). The apparent molecular weight of phospholamban on SDS gels was slightly increased by cAMP-dependent phosphorylation. The extent of phosphorylation catalyzed by cAMP-dependent protein kinase in the purified phospholamban preparations was about 42 nmol of phosphate/mg of protein when the protein concentration was determined by the method of Lowry et al. (Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) J. Biol. Chem. 193, 265-275), or 138 nmol/mg of protein based on the protein concentration estimated by the dye absorption method. Rabbit antisera were prepared against purified phospholamban. The obtained antisera were found to bind to purified phospholamban as well as that in cardiac SR. No reaction was detected in fast skeletal muscle SR by immunofluorescent staining of Western blots. The present preparation of purified phospholamban and the antisera should facilitate further understanding of the regulatory action of phospholamban on the calcium pump ATPase.

Animals↗

Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarction.

Serial changes in thromboxane B2, a stable catabolite of thromboxane A2, were measured by radioimmunoassay in peripheral plasma of 55 patients with acute myocardial infarction. Twenty two of 31 patients who were admitted within 6 hr after the onset of acute myocardial infarction, exhibited high thromboxane B2 levels (greater than 300 pg/ml plasma) during the first 24 hr, whereas thromboxane B2 levels of 9 patients never exceeded 300 pg/ml during that period. The former cases were associated with a higher frequency of transmural myocardial infarction, accompanying higher cumulative creatine kinase release (1173 +/- 134 mIU/ml, mean +/- SEM), as compared with the latter cases (393 +/- 104 mIU/ml, P less than 0.001). To evaluate the efficacy of selective thromboxane A2 blockade on diminution of propagating acute myocardial infarction, another group of patients (24 cases) showing transmural myocardial infarction were subjected to therapeutic examination employing OKY-1581, a potent thromboxane A2 synthetase inhibitor. Eleven randomly selected patients were treated with an infusion of OKY-1581 (initiated within 6 hr after onset, 2-3 micrograms/kg per min) for 48 hr, while 13 patient served as controls. The treated patients exhibited a precipitous decrease in thromboxane B2 levels, as compared with the controls, returning to the normal range within 12 hr. The creatine kinase release in the treated patients was markedly reduced (978 +/- 97 mIU/ml) as compared with that in the control patients (1295 +/- 95 mIU/ml, P less than 0.05). These results indicate that a marked increase in thromboxane B2 levels is seen during the early phase of transmural myocardial infarction, and that OKY-1581-induced reduction of thromboxane B2 levels is effective in diminishing creatine kinase release. We suggest that an excessive generation of thromboxane A2 is associated with the evolution of transmural myocardial infarction.

Acrylates↗

Development of quantitative analysis of plasma thromboxane B2 by gas chromatography-mass spectrometry.

In order to diagnose patients in thrombotic state, it is quite important to detect increased concentration of plasma thromboxane B2 (TXB2), a stable catabolite of TXA2. To determine plasma TXB2 levels with high sensitivity and selectivity, we employed gas chromatography-mass spectrometry (GC/MS). The trimethylsilyl (TMS) ether derivatives conventionally employed in GC/MS analysis of prostanoids are not suitable for quantitation of plasma prostanoids, because the mass spectra are deficient in ions with high intensity in the high mass range and TMS ether derivatives are sensitive to moisture. To solve these problems we employed tert-butyldimethylsilyl (t-BDMS) ether derivatives, based on the observation that t-BDMS ether derivatives afforded abundant ions at [M-57]+ and showed good hydrolytic stability. The reaction conditions of tert-butyldimethylsilylation were also examined to optimize the selected ion monitoring response. The t-BDMS ether derivatives of prostanoids were successfully analyzed with a short capillary column with a relatively large diameter, with maintaining good separation. In conjunction with the use of reversed-phase high performance liquid chromatography as purification procedure, a sensitive and reproducible stable isotope dilution assay of plasma TXB2 was developed. The values obtained by this method correlated well with those obtained by the radioimmunoassay we have developed.

6-Ketoprostaglandin F1 alpha↗

Comparison of coronary hemodynamic and cardiac metabolic alterations during coronary artery spasm associated with ST segment elevation or depression.

Coronary vasospasms are usually indicated by ST elevation or depression in the electrocardiogram (ECG). To test the hypothesis that ST elevation represents more severe myocardial ischemia than does ST depression, we determined the coronary sinus blood flow (CSBF) and the transcardiac lactate extraction ratio (LER) in 19 selected patients who had focal vasospasms in the left anterior descending artery. In 10 patients, ergonovine (0.11 +/- 0.02 mg, mean +/- SEM) provoked severe (total or subtotal) coronary vasospasm with ST elevation. Under these conditions, CSBF significantly decreased (from 97 +/- 8 ml/min to 79 +/- 5 ml/min, p less than 0.01) with a marked reduction in LER (from 29 +/- 5% to -14 +/- 6%, p less than 0.01). In contrast, 10 vasospastic events with ST depression after ergonovine (0.15 +/- 0.04 mg, NS) were recognized as mild spastic narrowing or severe spasms with well developed collateral circulation. Alteration of CSBF was significant in only a few patients and the overall CSBF response was non-significant (from 106 +/- 12 ml/min to 103 +/- 13 ml/min). The reduction in LER in this group was less pronounced than those in patients with ST elevation (p less than 0.05). These results indicate that coronary vasospasm with ST elevation may be related to the more pronounced reduction in coronary blood flow accompanied by more severe myocardial ischemia. Such observations may support the contention that some ischemic events associated with ST elevation or depression can be interpreted as a continuous spectrum of vasospastic disorders.

Adult↗