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Biomedical subjects

A Kawase

Publications and source records attributed to A Kawase.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and evaluation of A-ring diastereomers of 1alpha,25-dihydroxy-22-oxavitamin D3 (OCT).

A-ring diastereomers of 1alpha,25-dihydroxy-22-oxavitamin D3 (OCT) (2), 3-epi-1alpha,25-dihydroxy-22-oxavitamin D3 (3-epiOCT) (3) and 1,3-diepi-1alpha,25-dihydroxy-22-oxavitamin D3 (1,3-diepiOCT) (4) were synthesized by the convergent method. In vitro binding affinity for rat vitamin D binding protein and calf-thymus vitamin D receptor, differentiation-inducing activity on HL-60 cells, and transcriptional activity of 3-epiOCT (3) and 1,3-diepiOCT (4) were evaluated in comparison with OCT (2), 1-epi-1alpha,25-dihydroxy-22-oxavitamin D3 (1-epiOCT) (5) and 1alpha,25-dihydroxyvitamin D3 (1).

Animals↗
PubMed2001

Role of structural complexities of septal tissue in maintaining ventricular fibrillation in isolated, perfused canine ventricle.

INTRODUCTION: It is unclear how the patterns of wavelet propagation during ventricular fibrillation (VF) vary between structurally different tissues. We hypothesized that the structural complexities of septal tissue influence the maintenance of reentrant wavelets in the ventricle. METHODS AND RESULTS: Endocardial activation patterns during VF were analyzed in the isolated, perfused canine right ventricular (RV) free wall (n = 9), interventricular septum (n = 5), and left ventricular (LV) free wall (n = 6) using a computerized mapping system (2-mm resolution) with 120-msec consecutive windows. Each tissue sample was cut progressively to reduce the tissue mass until the VF was terminated. More wavelets were seen in the septa than in the RV and LV free walls at baseline (P = 0.004), and VF in the septa displayed a shorter cycle length than in the RV and LV free walls (P = 0.017). As the tissue mass decreased, VF became successively more organized in all regions: the number of wavelets decreased and the cycle length of VF lengthened. Single and "figure-of-eight" stationary, reentrant wavelets often were mapped after tissue mass reduction in the RV free walls and rarely in the LV free walls, but they were not observed in the septa. Less critical mass was required to maintain VF in the septa than in the RV and LV free walls (P = 0.0006). Gross anatomic and histologic examinations indicated that the tissue structure of the septa is more complex than that of the RV and LV free walls. CONCLUSION: VF activation patterns with progressive reduction of tissue mass differ for the septum and the ventricular free walls. The structural complexities of the septal tissue influence the maintenance of fibrillation in the ventricle.

Animals↗
PubMed2001

Electroporation in a model of cardiac defibrillation.

INTRODUCTION: It is known that high-strength shock disrupts the lipid matrix of the myocardial cell membrane and forms reversible aqueous pores across the membrane. This process is known as "electroporation." However, it remains unclear whether electroporation contributes to the mechanism of ventricular defibrillation. The aim of this computer simulation study was to examine the possible role of electroporation in the success of defibrillation shock. METHODS AND RESULTS: Using a modified Luo-Rudy-1 model, we simulated two-dimensional myocardial tissue with a homogeneous bidomain nature and unequal anisotropy ratios. Spiral waves were induced by the S1-S2 method. Next, monophasic defibrillation shocks were delivered externally via two line electrodes. For nonelectroporating tissue, termination of ongoing fibrillation succeeded; however, new spiral waves were initiated, even with high-strength shock (24 V/cm). For electroporating tissue, high-strength shock (24 V/cm) was sufficient to extinguish ongoing fibrillation and did not initiate any new spiral waves. Weak shock (16 to 20 V/cm) also extinguished ongoing fibrillation; however, in contrast to the high-strength shock, new spiral waves were initiated. Success in defibrillation depended on the occurrence of electroporation-mediated anodal-break excitation from the physical anode and the virtual anode. Some excitation wavefronts following electrical shock used a deexcited area with recovered excitability as a pass-through point; therefore, electroporation-mediated anodal-break excitation is necessary to block out the pass-through point, resulting in successful defibrillation. CONCLUSION: The electroporation-mediated anodal-break excitation mechanism may play an important role in electrical defibrillation.

Action Potentials↗
PubMed2001

Lack of noninvasive markers of ventricular repolarization inhomogeneity in patients with idiopathic ventricular tachyarrhythmia.

Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.

Adult↗
PubMed2001

Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with dilated cardiomyopathy.

BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow-up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier event-free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias.

Adult↗
PubMed2001

Clinical usefulness of the combination of T-wave alternans and late potentials for identifying high-risk patients with moderately or severely impaired left ventricular function.

Ventricular tachyarrhythmia (VT) is an independent risk factor for an increased overall mortality in patients with impaired left ventricular (LV) function, but there is not an established noninvasive tool to detect such patients. The present study aimed to clarify the most useful noninvasive approach for identification of patients with moderately or severely impaired LV function complicated by VT. Sixty-seven patients in New York Heart Association (NYHA) classes I-III with an LV ejection fraction (LVEF) less than 40% and an LV end-diastolic dimension (LVDD) of at least 55 mm on echocardiography were enrolled. Impaired LV function was caused by either ischemic (n=30) or nonischemic dilated cardiomyopathy (n=37). T-wave alternans (TWA), QT dispersion (QTD), and late potentials (LP) on signal-averaged electrocardiography were sequentially determined without using antiarrhythmic drugs. VT was defined as more than 6 consecutive ventricular ectopic beats. The mean NYHA class was 1.9+/-0.7, mean LVEF was 31+/-8%, and mean LVDD was 65+/-10mm. A history of VT was present in 26 of the patients (39%). Univariate and multivariate logistic analysis showed that TWA and LP were closely related to VT, whereas NYHA> or =III, LVEF<30%, LVDD> or =70mm, and QTD> or =90ms were not. The combination of TWA and LP had the most significant value (p=0.0004, odds ratio=8.44) by univariate analysis, and only this combination had significant value in multivariate analysis (p=0.04). Therefore, the combination of TWA and LP could be a useful index for identifying those patients with impaired LV function who are at risk for VT.

Action Potentials↗
PubMed2001

Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study.

Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.

Adult↗
PubMed2000

Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.

A novel synthesis of a radioactive compound of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) (1) and its pharmacokinetics are described. Radioactive 1 alpha OHD3 tritiated at 22 and 23 positions ([22,23-(3)H4]1 alpha OHD3) (5) was prepared via key reactions of the reduction of acetylenic side chain in the ketone (12) with tritium gas in the presence of palladium-charcoal and the subsequent Wittig reaction with the A-ring synthon (16). [22,23-(3)H4]1 alpha OHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was used successfully in pharmacokinetics studies with rats. In the pharmacokinetics studies, the plasma concentration level of the active form of vitamin D3, 1 alpha,25-dihydroxy-vitamin D3 [1 alpha,25(OH)2D3], after oral or intravenous administration of [22,23-(3)H4]1 alpha OHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1 alpha,25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1 alpha OHD3 (1) over the treatment of 1 alpha,25(OH)2D3 (2).

Administration, Oral↗
PubMed1998

Syntheses and preventive effects of analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) on bone mineral loss in ovariectomized rats.

Analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (2), 26,27-dimethyl ED-71 (3) and 26,27-diethyl ED-71 (4), were synthesized from lithocholic acid (5). In the study of the preventive effects of these analogues and ED-71 (2) on bone mineral loss in ovariectomized rats, 26,27-dimethyl ED-71 (3) showed the most potent activity.

Animals↗
PubMed1997

[Home parenteral nutrition (HPN) for cancer patients].

We have treated thirty-five cancer patients with HPN since 1987. This paper describes its efficacy and problems. Their average age was 62 years old. The duration of HPN varied from 31 to 573 days (mean: 167 days). The catheter was removed in three cases because of catheter fever or obstruction. Metabolic complications arose in three cases, but they were easily treated. Twenty-three cases underwent pain control. Twelve cases were given cancer chemotherapy. We concluded that HPN for recurrent cancer patients is a relatively safe and effective means to improve the quality of life. We consider the following important in order to carry out HPN more smoothly. 1) Improvement of drug delivery system. 2) Establishment of home care system with other hospitals, clinics, and home care companies. 3) The easing of health-insurance restrictions on making out prescriptions to outpatients.

Adult↗
PubMed1995

Studies on antiulcer agents. II. Antiulcer properties of N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides inhibiting release of histamine from passively sensitized rat peritoneal mast cells.

With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.

Animals↗
PubMed1995

Studies on antiulcer agents. I. Synthesis and pharmacological properties of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate, a new H+/K(+)-ATPase inhibitor possessing mucosal protective activity.

Ethyl 2-[1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate (2) has been synthesized and evaluated for antiulcer properties. Compound 2 is a H+/K(+)-ATPase inhibitor that affords mucosal protection against absolute ethanol-induced gastric lesions in rats after oral and parenteral administrations. On the other hand, omeprazole, a representative H+/K(+)-ATPase inhibitor, showed mucosal protective action only after oral administration, indicating that it required gastric acid secretion to generate activity. The antiulcer activity of 2 in animal models, such as water-immersion stress-induced gastric ulcer in rats and acidified aspirin-induced gastric ulcer in rats, was three times higher than that of cimetidine.

Animals↗
PubMed1995

Studies on antiulcer agents. IV. Antiulcer effects of 2-benzylthio5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds.

With a view to finding more effective antiulcer agents, a series of 2-benzylthio-5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds were synthesized and evaluated in a histamine-stimulated gastric secretion model. The sodium salt of the 2-(dimethylamino)benzylthio derivative (8) showed gastric mucosal protection and gastric antisecretion activities, and was also effective against experimental gastric and duodenal ulcers induced by some ulcerogenic agents. Based on a comparison of the antiulcer properties of 8 with those of the lead compounds (1 and 2) and cimetidine, it appears that, for improvement of antiulcer activity, the reduction of gastric acidity is a more important factor than the reduction of gastric volume output or gastric total acid output.

Animals↗
PubMed1995

[Study of PyNPase activity in patients with gastric cancer--the association with preoperative IAP values].

5'-DFUR manifests its antitumor activity after being converted to 5-FU by pyrimidine nucleoside phosphorylase (PyNPase), an enzyme having high activity in tumor tissue. We surgically removed tissue samples weighing at least 1 g from 28 patients with gastric cancer and measured the PyNPase activity. The tissue samples were taken from gastric carcinomas, normal gastric tissue, metastasis-positive lymph nodes, metastasis-negative lymph nodes, small intestine, spleen, and other organs. The PyNPase activity was higher in gastric carcinomas than in normal gastric tissue. Similarly, metastasis-positive lymph nodes showed higher PyNPase activity than in metastasis-negative lymph nodes. PyNPase activity in the spleen was approximately equivalent to that in gastric carcinomas. Correlations were assessed between the PyNPase activity of gastric carcinomas and their tissue type. Stage and nutritional status, but there was no correlation with PyNPase activity for any of the variables assessed. The relationship between the PyNPase activity of gastric carcinomas and serum IAP concentration measured within one week before operation was similarly assessed. Mean PyNPase activity in the group of 14 patients with low serum IAP concentrations (< 550 micrograms/ml) was 102.8, while that in 11 patients with high serum IAP concentrations (> or = 550 micrograms/ml) was 145.7. Although this difference was not significant, there tended to be a positive correlation between PyNPase activity and serum IAP concentration (r = 0.74). PyNPase activity in splenic tissue was significantly higher in group of 10 patients with low IAP activity (104.7) (p = 0.020). These results indicated that patients with high serum IAP concentrations, generally associated with a poor prognosis, showed a high PyNPase activity in tumor tissue and splenic tissue. PyNPase activity, including its involvement in the immune response, was thus suggested to be somehow related to prognosis.

Adult↗
PubMed1994

[Intraarterial infusion combination therapy with LV and 5-FU in hepatic metastases from colorectal cancer].

Intraarterial infusion combination therapy with LV and 5-FU was performed on 8 patients with hepatic metastases from colorectal cancer. Briefly, immediately after administration of LV 30 mg/body, 5-FU was administrated in doses of 750 to 1,250 mg/body over about 2 hours. The therapy was repeated at every weekly visit to the clinic. The number of courses per patient averaged 22. The response rate was 50% (4 PR). Clinical responses were obtained 6 months on average. The 50% survival period was 300 days. Five patients died, 3 due to metastases to other sites. This therapy on an out-patient basis could be continued in all but one patient who was withdrawn from the treatment because of leucopenia. The results of this study suggest that this combination therapy is effective for hepatic metastasis from colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Association of neonatal thrombocytopenia and maternal anti-HLA antibodies.

In order to evaluate the influence of maternal anti-HLA antibody on neonatal thrombocytopenia, clinical features and maternal anti-HLA antibody of three groups of infants (19 thrombocytopenic and low birth weight, 27 nonthrombocytopenic and low birth weight, and 80 healthy full-term) were investigated. The incidence of positive maternal anti-HLA antibodies in the three groups was 73.7%, 29.6% and 27.5%, respectively. Thrombocytopenia in small-for-gestational-age (SGA) infants was closely related to the presence of maternal anti-HLA antibodies. Among 20 SGA infants (11 thrombocytopenic, 9 non-thrombocytopenic), anti-HLA antibody was detected in 10 mothers (90.9%) of thrombocytopenic SGA infants, while it was positive in only one mother (11.1%) of nonthrombocytopenic SGA infants. Investigation of the SGA infants revealed that in those whose mothers were sensitized to HLA antigen, not only the platelet count but also the leukocyte and lymphocyte counts in the first week of life were significantly lower than in infants whose mothers were not sensitized. The results suggest that the presence of maternal anti-HLA antibody is a cause of neonatal thrombocytopenia especially in SGA infants.

Antibodies↗