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Biomedical subjects

T Kanazawa

Publications and source records attributed to T Kanazawa.

At least 217 records · Page 12Linked to original sources

Clinical evaluation of bisoprolol in patients with stable angina pectoris: a preliminary report.

Efficacy and safety of the new beta-adrenoceptor antagonist, bisoprolol, in treatment of stable angina pectoris were studied in 36 patients using two types of single-blind design. After 2 weeks of therapy with bisoprolol in doses of 5 mg to 10 mg a day, exercise duration and time to 1 mm of ST-segment depression were significantly prolonged in 7 out of 10 patients who had a positive treadmill exercise test before bisoprolol. Bisoprolol significantly reduced heart rate (HR), systolic blood pressure (SBP), and rate-pressure product (RPP) at peak exercise, which would account for the beneficial effect of bisoprolol on exercise tolerance. Bisoprolol also produced improvement in symptoms for 26 patients with stable effort angina, as indicated by decreased frequency of anginal attacks and nitroglycerin consumption with a once-a-day regimen. Ten patients had no attacks after 5 mg of bisoprolol, and three more did not develop angina after increasing the dose to 10 mg a day. These results suggest that bisoprolol will be a promising, efficacious, and safe drug for the treatment of stable angina pectoris.

Adrenergic beta-Antagonists↗

Clinical significance of serum bone Gla protein and urinary gamma-Gla as biochemical markers in primary hyperparathyroidism.

The serum bone Gla-protein (BGP) and urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in patients with primary hyperparathyroidism (PHP). The mean serum BGP and urinary gamma-Gla levels were 18.6 +/- 2.34 ng/ml and 65.5 +/- 4.62 nmoles/mgCr, respectively, for the 11 patients with the skeletal type of PHP, 5.13 +/- 0.85 ng/ml and 45.2 +/- 1.33 nmoles/mgCr for the 4 with the chemical type, and 7.91 +/- 2.43 ng/ml and 43.2 +/- 3.47 nmoles/mgCr for the 5 with the renal type. Thus, patients with skeletal-type PHP had significantly higher serum BGP and urinary gamma-Gla levels than those with the other type of PHP. Serum BGP levels had significant positive correlations with serum Ca (r = 0.64, P less than 0.005), serum A1-p (r = 0.77, P less than 0.001) and serum PTH (r = 0.45, P less than 0.005). Urinary gamma-Gla levels also had significant positive correlations with serum Ca (r = 0.50, P less than 0.05), serum A1-p (r = 0.67, P less than 0.005), serum 1,25(OH)2D (r = 0.62, P less than 0.02), and serum BGP (r = 0.72, P less than 0.001). Mineral content in the left radius had significant negative correlations with serum BGP levels (r = -0.73, P less than 0.001) and urinary gamma-Gla levels (r = -0.59, P less than 0.01). As these data show, serum BGP and urinary gamma-Gla levels clearly reflect the abnormal bone metabolism and can therefore be useful biochemical markers in PHP.

1-Carboxyglutamic Acid↗

[Clinical evaluation of cefmenoxime in internal medicine, with special reference to infection associated with hematological disorders].

Clinical evaluation of cefmenoxime (CMX, Bestcall) was performed against infections associated with hematological, respiratory tract and other disorders. Clinical effectiveness of CMX against severe infections with hematological disorders including sepsis, pneumonia, pyelitis and so on was 74.4% for good responses and against the respiratory tract infections, 96.2% for good responses was obtained. Neither objective or subjective side effects nor extreme abnormalities in laboratory tests were observed in these patients. It can be concluded, therefore, that CMX is one of the most useful drugs against infectious diseases associated with hematological disorders, respiratory tract and other disorders.

Bacterial Infections↗

Coincidence of H+ binding and Ca2+ dissociation in the sarcoplasmic reticulum Ca-ATPase during ATP hydrolysis.

H+ and Ca2+ concentration changes in the reaction medium following MgATP addition at pH 6.0 were determined with the partially purified Ca-ATPase from sarcoplasmic reticulum vesicles in the presence of 25-50 microM CaCl2 and 5 mM MgCl2 at 4 degrees C. Previously, we showed a sequential occurrence of H+ binding and H+ dissociation in the Ca-ATPase during ATP hydrolysis and further suggested that the H+ binding takes place inside the vesicles (Yamaguchi, M., and Kanazawa, T. (1984) J. Biol. Chem. 259, 9526-9531). The present results demonstrate that the H+ binding occurred coincidently with Ca2+ dissociation from the enzyme upon conversion of the phosphoenzyme (EP) intermediate from the ADP-sensitive form to the ADP-insensitive form in the catalytic cycle of ATP hydrolysis. As KCl decreased in the medium, the extent of the H+ binding increased almost proportionately with the extent of either the Ca2+ dissociation or the accumulation of ADP-insensitive EP. Both the H+ binding and the Ca2+ dissociation were prevented by a modification of the specific SH group of the enzyme essential for the conversion of ADP-sensitive EP to ADP-insensitive EP. In the late stage of the reaction, H+ dissociation from the enzyme occurred coincidently with Ca2+ binding to the dephosphoenzyme which was formed by EP decomposition. These results are consistent with the possibility that the H+ ejection during the Ca2+ uptake with the intact vesicles previously shown by several investigators takes place through a Ca2+/H+ exchange directly mediated by the membrane-bound Ca-ATPase.

Adenosine Diphosphate↗

Enhancement of IgE-dependent eosinophil cytotoxicity to dinitrophenylated schistosomula by a nematode infection.

In order to obtain direct evidence for the involvement of IgE in the eosinophil-mediated cytotoxicity, dinitrophenylated (DNP) schistosomula of Schistosoma japonicum coated with monoclonal IgE antibodies were examined as to whether they were killed by rat peritoneal eosinophils. The results indicated that the cytotoxicity of the eosinophils was dependent on a mouse monoclonal anti-DNP IgE antibody, but not on another monoclonal antibody specific to ovalbumin. Moreover, an enhanced cytotoxicity was observed when eosinophils were obtained from rats 4 weeks after infection with Nippostrongylus brasiliensis.

Animals↗

Monoclonal IgE-dependent eosinophil cytotoxicity to haptenated schistosomula of Schistosoma japonicum: enhancement of the cytotoxicity and expression of Fc receptors for IgE by Nippostrongylus brasiliensis infection.

To obtain direct evidence for the involvement of IgE antibodies in eosinophil-mediated killing of schistosomula of S. japonicum, dinitrophenylated (DNP) schistosomula pretreated with mouse monoclonal IgE antibodies were co-cultured with purified rat peritoneal eosinophils. It was found that the eosinophil-mediated adherence and damage to haptenated schistosomula were dependent on a monoclonal anti-DNP IgE antibody, but not on monoclonal anti-ovalbumin IgE antibody. Moreover, eosinophils from N. brasiliensis-infected rats demonstrated an enhanced ability in the IgE-dependent damage to DNP-schistosomula as compared with the cells from normal rats. The enhancement was associated with an increase in the proportion of eosinophils expressing Fc receptors for IgE.

Animals↗

[Two-dimensional echocardiographic recognition of dilated cardiomyopathy: comparison with postmortem studies].

To elucidate the pathophysiology of dilated cardiomyopathy (DCM), the relationship of two-dimensional echocardiographic wall motion abnormalities (asynergy) to histopathological findings was evaluated in autopsied patients including seven with DCM, five with old myocardial infarction (OMI) and three with the normal heart. The DCM cases were classified morphologically in two groups, namely four of type I and II and three of type III, according to Shozawa's classification. Three short-axis views of the left ventricle were divided into 19 segments; the wall motion was assessed visually and classified as normal motion, hypokinesis, akinesis and dyskinesis. The postmortem specimens were immersed in 10% formalin; transverse sections and wall divisions were prepared corresponding to the two-dimensional echocardiographic views, and the area of each segment was determined by a computer planimetry excluding the papillary muscles and trabeculae. Fibrosis (%) was measured histologically by the point counting method with light microscopy. The results were as follows: In DCM, fibrosis (%) increased with increasing severity of asynergy: 17.1% fibrosis in normal motion; 28.7% in hypokinesis; 40.7% in akinesis and dyskinesis. In OMI, fibrosis (%) also increased with increasing severity of asynergy. On comparison of DCM with OMI, no difference was established relating to fibrosis (%) in the asynergic segments; moreover, in both groups, asynergy was detected more frequently in the segments in which fibrosis (%) exceeded 21%. On comparison of type I+II DCM with type III DCM, fibrosis (%) of type III was significantly less than that of type I+II in the same degree of asynergic segments. Moreover, fibrosis (%) of type I+II tended to be greater in the outer layer than in the inner layer, while fibrosis (%) of type III was evenly distributed throughout the myocardium, or greater in the inner layer than in the outer layer. In type I+II, wall thinning was marked with increasing severity of asynergy; in contrast, these correlations were not observed in type III. In type I+II, a higher fibrotic rate was observed in the left ventricular free wall and an abnormal Q wave appeared frequently on ECG. This tendency was not found in type III. These findings indicate that fibrosis is one of the most important factors in decreasing cardiac muscular contractility in DCM, and suggest that there is a different pathogenesis between type I+II and type III fibrosis.

Adolescent↗

Protonation of the sarcoplasmic reticulum Ca-ATPase during ATP hydrolysis.

pH changes of the reaction medium (pH 6.35) following addition of MgATP were determined at 4 degrees C with sarcoplasmic reticulum vesicles in the presence of 0.1 mM CaCl2 and 5 mM MgCl2. With intact vesicles, a pronounced acidification following a slight alkalinization was induced by MgATP, indicating H+ ejection from vesicles. This agrees with previous observations by several investigators that suggested H+ counter-transport coupled to Ca2+ uptake. When vesicles were made leaky, a markedly enhanced alkalinization occurred after addition of MgATP, and then the pH returned to the level before the MgATP addition. The decay of this alkalinization coincided with the disappearance of phosphoenzyme (EP) which was formed from MgATP and the Ca-ATPase of sarcoplasmic reticulum. The CaCl2 concentration dependence of the alkalinization agreed well with that of EP formation. Furthermore, the alkalinization was prevented by modification of a specific SH group of the enzyme essential for EP decomposition. These findings give evidence that the alkalinization with leaky vesicles represents protonation of the enzyme during ATP hydrolysis. The enhanced alkalinization with leaky vesicles suggests protonation occurring inside vesicles. When CaATP in place of MgATP was added in the absence of MgCl2, neither the H+ ejection from intact vesicles nor the enhanced alkalinization with leaky vesicles occurred. Under these conditions, CaATP did not efficiently support active Ca2+ uptake. These results are compatible with the view that the observed protonation could represent an initial event occurring inside vesicles in the H+ countertransport coupled to Ca2+ uptake.

Adenosine Triphosphate↗

Ca2+-Ca2+ exchange catalyzed by the membrane-bound Ca2+, Mg2+-ATPase of sarcoplasmic reticulum vesicles.

Sarcoplasmic reticulum vesicles were preloaded with either 45Ca2+ or unlabeled Ca2+ X 45Ca2+ efflux and influx, together with phosphorylation of the membrane-bound Ca2+, Mg2+-ATPase, were determined in the presence of either ATP and ADP or acetyl phosphate. ATP induced 45Ca2+ efflux. This ATP-induced 45Ca2+ efflux depended on ADP, external Ca2+, and Mg2+. The Ca2+ concentration dependence of the efflux was quite similar to the Ca2+ concentration dependence of the ATP-induced 45Ca2+ influx and the enzyme phosphorylation. The rate of the efflux was proportional to the steady level of the phosphoenzyme. The affinity for free ADP in this efflux was extremely high, being in good agreement with the affinity for free ADP in the transphosphorylation from the phosphoenzyme to ADP. These results show that the ATP-induced 45Ca2+ efflux represents the Ca2+-Ca2+ exchange (between the external medium and the internal medium) mediated by the phosphoenzyme. In this exchange, Mg2+ was essential for the exposure of the bound Ca2+ of the phosphoenzyme to the internal medium. 45Ca2+ efflux and influx were also activated by acetyl phosphate. This acetyl phosphate-induced efflux required the external Ca2+. The Ca2+ concentration dependence of the efflux agreed closely with that of the enzyme phosphorylation by acetyl phosphate. Furthermore, the rate of the efflux was proportional to the steady level of the phosphoenzyme. These and other findings show that the acetyl phosphate-induced 45Ca2+ efflux represents the Ca2+-Ca2+ exchange mediated by the phosphoenzyme and further demonstrate the direct dissociation of Ca2+ from the Ca2+-bound phosphoenzyme to the external medium in this Ca2+-Ca2+ exchange. The rate of the acetyl phosphate-induced, phosphoenzyme-mediated Ca2+ efflux was much slower than that of the ATP-, ADP-induced, phosphoenzyme-mediated Ca2+ efflux. This is consistent with our previous conclusion that the Ca2+ binding site is partially occluded upon the phosphorylation of the enzyme.

Animals↗

Acetylphosphate-induced Ca2+-Ca2+ exchange that is mediated by (Ca2+,Mg2+)-ATPase in sarcoplasmic reticulum vesicles.

Sarcoplasmic reticulum vesicles were preloaded with either 45Ca2+ or unlabeled Ca2+. 45Ca2+ efflux and influx were determined in the presence and absence of acetylphosphate. Phosphorylation of the membrane-bound (Ca2+,Mg2+)-ATPase by [32P]acetylphosphate was also determined. The rate of efflux with acetylphosphate was considerably higher than that without acetylphosphate. When the acetylphosphate concentration was greatly reduced by diluting the reaction mixture after the start of the reaction, the rate of the efflux decreased markedly. These results demonstrate the acceleration of 45Ca2+ efflux by acetylphosphate. This acetylphosphate-induced efflux required external Ca2+. The external Ca2+ concentration giving half-maximum activation of efflux was 3.8 microM. The Ca2+ concentration dependence of the efflux coincided with that of phosphorylation. When the acetylphosphate concentration was varied, the rate of acetylphosphate-induced efflux changed approximately in proportion to the phosphoenzyme concentration. These and other findings show that acetylphosphate-induced 45Ca2+ efflux represents Ca2+-Ca2+ exchange (between the external medium and the internal medium) mediated by the phosphoenzyme and further demonstrate the direct dissociation of Ca2+ from the Ca2+-bound phosphoenzyme to the external medium in Ca2+-Ca2+ exchange.

Acetates↗

The effects of progesterone on gonadotrophin release in hypogonadal women.

The effect of progesterone on pulsatile and basal release of gonadotrophins was studied in 10 hypogonadal women. The day before progesterone treatment, control blood samples were obtained at 15 min intervals between 15.00 and 20.00 h. The next day, 50 mg of progesterone was administered im at 06.00 h and blood samples again were obtained at 15 min intervals between 15.00 and 20.00 h. Serum progesterone levels were 28.4 +/- 4.4 ng/ml at 15.00 h, 24.2 +/- 3.9 ng/ml at 17.30 h and 20.7 +/- 2.5 ng/ml (mean +/- SD) at 20.00 h. Progesterone prolonged the interval between LH pulses from 85 +/- 27 to 155 +/- 55 min (mean +/- SD), augmented their amplitude 2-fold, and caused average declines in LH and FSH concentrations of 27 and 15%, respectively. The results suggest that progesterone suppresses the mean levels of LH and FSH concentrations by acting in the brain to decrease the pulse frequency of gonadotrophin-releasing hormone.

Adult↗