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Biomedical subjects

T Ohkusa

Publications and source records attributed to T Ohkusa.

At least 91 records · Page 5Linked to original sources

Effects of dihydropyridines on calcium release from the isolated membrane complex consisting of the transverse tubule and sarcoplasmic reticulum.

We have investigated a) the effects of the dihydropyridines (DHPs) nifedipine and nimodipine on depolarization-induced (T-tubule-mediated) Ca2+ release in the vesicles consisting of the complex of the T-tubule and SR, and b) the binding of [3H]nimodipine to these vesicles. These DHPs inhibited the slow but not the fast phase of depolarization-induced release, both of which are mediated via the T-tubule. The DHPs have no effect on caffeine-induced release in which T-tubules are not involved. There are two classes of DHP binding sites: one, with high affinity and small capacity, and another, exhibiting low affinity and a much larger capacity. The inhibition paralleled the low affinity binding of DHP with no correlation with the high affinity binding. These results suggest that the low affinity DHP binding sites located probably in the DHP receptor, rather than the high affinity DHP binding site, are responsible for the inhibition of e-c coupling.

Animals↗

Primary adenocarcinoma of duodenal bulb benefitted by chemotherapy.

A 48-year-old man had primary adenocarcinoma of the duodenal bulb. The extensive hepatic metastasis of the patient did not allow any major surgical procedure. Therefore UFTM chemotherapy was performed and was associated with three years of improvement. Subjective symptoms were relieved and test findings indicated normalization of liver biochemistry as well as CEA and CA 19-9. X-ray, endoscopy, and pathological findings indicated the disappearance of the carcinoma of the duodenal bulb. In addition, both ultrasonic examination and CT of the abdomen showed marked reduction of the hepatic metastasis. The authors do not hesitate to recommend the UFTM therapy as a therapeutic modality for inoperable and metastatic primary adenocarcinoma of the duodenum.

Adenocarcinoma↗

Conformational change of the foot protein of sarcoplasmic reticulum as an initial event of calcium release.

Heavy sarcoplasmic reticulum vesicles were labeled with the thiol-reacting fluorescent probe N-(7-dimethylamino-4-methyl-4-coumarinyl)maleimide (DACM), and the DACM-labeled foot protein moiety was purified. The fluorescence intensity of the DACM attached to the foot protein decreased by the addition of low (activating) concentrations of ryanodine, while it increased at higher (inhibitory) concentrations, suggesting that the lower fluorescence represents the active state of the foot protein, while the higher fluorescence, its inactive state. Under conditions that induce Ca2+ release from SR (Ca2+ jump, addition of Ca2+ release inducing reagents such as caffeine and polylysine), the fluorescence intensity of the protein-attached DACM decreased rapidly (e.g. k congruent to 70 s-1 under optimum conditions). The initial rate of Ca2+ release from the DACM-labeled SR showed a close correlation with the amplitude of the fluorescence change of the foot protein-attached DACM under variety of conditions; e.g. in the presence of Ca2+, polylysine, ATP, and ruthenium red, etc. The fluorescence change of the foot protein was much faster than Ca2+ release from SR under a variety of conditions of Ca2+ release. We propose that the binding of release triggering reagents to the foot protein induces a rapid conformational change, which in turn regulates Ca2+ release.

Animals↗

A high frequency of detection of Helicobacter pylori in whitish exudate of gastric ulcer.

Helicobacter pylori has been implicated in the pathogenesis of chronic gastritis and peptic ulcer. However, no report to date has been made on the presence of H. pylori in the whitish exudate of peptic ulcers. We examined the biopsy specimens of 52 patients (42 men and 10 women, aged 29-78, not taking steroids or nonsteroid antiinflammatory drugs), and evaluated the frequency of detecting the organism in the whitish exudate of gastric ulcers in comparison with that in the ulcer border, gastric fundic gland, and pyloric gland using microaerobic culture and acridine-orange stain. H. pylori was detected in high rates: 38 (73%) of 52 cases by culture, and 50 cases (96%) by staining of the whitish exudate, 42 (81%) of 52 cases by culture, and 46 cases (88%) by staining of the ulcer border. The frequency for the other regions were 81% by culture and 90% by staining of the fundic gland, and 81 and 90% of the pyloric gland, respectively. Of all sites studied by the staining method, H. pylori was detected at the highest frequency in the whitish exudate. The fact that many H. pylori live in the whitish exudate of gastric ulcer, suggests a causal relationship between H. pylori and gastric ulcer.

Acridine Orange↗

The effect of cyclosporine on the immunopathogenesis of viral myocarditis in mice.

The effect of cyclosporine on the immunopathogenesis of viral myocarditis was studied using a murine viral myocarditis model. Mice in the treated group had a higher mortality rate compared with those of the infected control group before day 15 (47/67 vs. 14/31, p less than 0.05). On day 7, treated mice showed higher titers of anti-heart autoantibody than the control group (12 +/- 7 vs 4 +/- 2, p less than 0.05), but no significant difference was seen on day 14 (28 +/- 15 vs. 39 +/- 34). Histologic lesions, lymphocyte subsets in the peripheral blood and heart in situ, the neutralizing antibody, and virus concentrations in the heart showed no significant differences between these groups. This study suggests that with the use of cyclosporine the production of anti-heart autoantibody was enhanced in the early stages of viral myocarditis in mice, and was associated with higher mortality rate.

Animals↗

A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.

Acute and chronic experimental ulcerative colitis models were produced in mice by providing them with drinking water containing synthetic dextran sulfate sodium. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding, and weight loss within 6-10 days after ingesting 3%-10% dextran sulfate sodium. On postmortem examination, multiple erosions and inflammatory changes including crypt abscesses were found on the left side of the large intestine. Mice that developed chronic colitis showed signs of erosions, prominent regenerations of the colonic mucosa including dysplasia, shortening of the large intestine, and frequent formation of lymphoid follicles after 5 administration cycles, where each cycle was composed of 7 days' consumption of drinking water containing 5% dextran sulfate sodium followed by 10 days' consumption of distilled water. The population of intestinal microflora, Bacteroides distasonis and Clostridium spp., increased significantly in mice with acute and chronic ulcerative colitis. Further, morphological studies suggest that the administered dextran sulfate sodium was partially phagocytized by macrophages in the colonic mucosa.

Acute Disease↗

Myocardial uptake of antimyosin monoclonal antibody in a murine model of viral myocarditis.

The myocardial uptake of 125I- and 131I-antimyosin monoclonal antibody Fab in experimental myocarditis in BALB/c mice induced by encephalomyocarditis virus was studied. The biodistribution of 125I-antimyosin demonstrated that the highest ratio of radioactivity appears in the heart of infected mice on day 14 (the ratio of percent dose per gram for the organ to percent dose per milliliter for blood; 9.75 +/- 2.79 vs. 1.27 +/- 0.78 at 24 hours in inoculated mice vs. control mice). There was no statistically significant difference between the mean activity ratios of tissues other than the heart in control and inoculated mice. The uptake ratio for the heart increased significantly 3 days after virus inoculation and reached a maximum on day 14 when myocardial lesions were most extensive and prominent. The uptake ratio decreased significantly, but it still remained high compared with controls on day 28 when cellular infiltration had decreased and fibrosis was evident. The scintigraphic images obtained with 131I-antimyosin monoclonal antibody clearly demonstrated that visualization of the heart in experimental myocarditis was possible 24 hours after administration of radiotracer, and localized activity was still observed in the 48-hour image. We conclude that antimyosin monoclonal antibodies localize selectively in the heart from the acute to subacute stage of viral myocarditis. These findings indicate that antimyosin scintigraphy is a reliable noninvasive method for the evaluation of patients suspected of having myocarditis.

Animals↗

[Serial assessment of cardiac function during and after exercise by an ambulatory ventricular function monitor (VEST)].

Cardiac function was serially assessed during and after exercise by an ambulatory ventricular function monitor (VEST) in 31 patients who received coronary angiography. Based on the study of fluctuation during the baseline recording, greater than or equal to 6% change in ejection fraction (EF) was considered significant. The serial changes in EF during exercise was divided into 5 types, including continuous increase (type A), initial increase but return to the baseline (type B), no change (type C), initial increase but later decrease below the baseline (type D), and continuous decrease (type E). Among 8 normal subjects, their EF changes during exercise showed type A in 3, type B in 2, type C in 2, and type D in 1. Among 21 patients with coronary artery disease, the EF changes showed type A in 5, type B in 4, type C in 4, type D in 5 and type E in 3. Thus, there was a significant overlap in EF response between normal and coronary patients. However, every patient showing type A and B had single-vessel disease, and 63% of them had persistent thallium defect without redistribution. After the exercise, 29 patients showed rapid increase in EF. The time to the peak EF was significantly longer in coronary patients (1.88 +/- 1.24 min) than that in normal cases (0.88 +/- 0.55 min) (p less than 0.05) particularly in patients with multi-vessel disease (2.22 +/- 1.29 min). In addition, those showing type C, D or E tended to have a longer time to peak EF and more increase in EF after exercise than those showing type A or B. These data suggest that VEST is suitable for continuous measurement of cardiac function during and after exercise which provided valuable indices for assessment of severity of ischemia in coronary artery disease.

Adult↗