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Biomedical subjects

S Ohtsuka

Publications and source records attributed to S Ohtsuka.

At least 55 records · Page 3Linked to original sources

Establishment of a concordant xenogeneic splenocyte injection model for the dynamic study of the marginal zone in the spleen.

BACKGROUND: This study was undertaken to establish a simple technique with which we could investigate the relationship between the marginal zone (MZ) in the spleen and antispecies antibody production, as well as to estimate the efficacy of various immunosuppressive treatments in xenotransplantation. METHODS: With a concordant xenogeneic combination (hamster-to-rat), the early phase reaction of the MZ was studied by use of quantitative histologic analysis, and complement-dependent cytotoxic antibody titers were determined in both a heart transplantation model and the splenocyte injection model. Furthermore, changes in the MZ were examined with isogeneic and allogeneic combinations with the splenocyte injection model. Next, the effect of cyclophosphamide, a promising immunosuppressant for concordant xenotransplantation, was examined by use of the splenocyte injection model. RESULTS: With a concordant xenogeneic combination, the MZ enlarged, and antihamster immunoglobulin M antibody synthesis increased after immunization in both models. On the other hand, with an isogeneic combination, the MZ did not expand, and with an allogeneic combination the MZ enlargement was not as great as that with a concordant xenogeneic combination. Cyclophosphamide suppressed the MZ expansion in a dose-dependent manner and effectively diminished antibody production in the splenocyte injection model. CONCLUSION: Dynamic studies of the MZ in the spleen with the splenocyte injection model are useful for the elucidation of the mechanisms of reaction and for estimating the efficacy of various immunosuppressive treatments in concordant xenotransplantation.

Animals↗

Natriuretic peptides in the lung modulated by pneumonectomy.

BACKGROUND: Natriuretic peptides are vasodilator hormones involved in the regulation of blood pressure and volume homeostasis. However, the mechanism of these peptides after pneumonectomy remains obscure. METHODS: We investigated changes in the pulmonary arterial pressure and the localization and changes in the atrial (A-type) natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP) in the lung, using immunohistochemistry and radioimmunoassay (RIA) in anesthetized dogs. Furthermore, we examined guanosine 3', 5'-monophosphate (cGMP) levels in plasma and in the contralateral lung. RESULTS: Pulmonary arterial pressure was significantly increased after pneumonectomy. The immunoreactivities of both ANP and CNP were detected in the endothelium of the pulmonary artery. In the contralateral lung, the concentrations of ANP and CNP were both significantly increased. In plasma, only ANP levels were significantly increased. In contrast, the plasma and lung cGMP levels were significantly reduced after pneumonectomy. CONCLUSIONS: We postulate that the processes from secretion in the vascular endothelial cells to the action via ANP and CNP receptors are effected in the contralateral lung tissue at the acute stage of pneumonectomy.

Animals↗

Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance.

BACKGROUND: The attenuation of intracellular production of cGMP has been known to be a mechanism of nitrate tolerance. A recent in vitro study showed an increase in superoxide levels and a reduced activation of guanylate cyclase in tolerant vessels. We investigated the preventive effect of an antioxidant, vitamin E, on the development of nitrate tolerance. METHODS AND RESULTS: In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD patients) were randomized to receive either vitamin E (200 mg TID vitamin E group) or placebo (placebo group). Vasodilator response to nitroglycerin was assessed with forearm plethysmography by measurement of the change in the forearm blood flow before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin, and at the same time, blood samples were taken from veins to measure the platelet cGMP level. Measurements of the forearm blood flow and blood sampling were obtained serially at baseline (day 0), 3 days after vitamin E or placebo alone was taken (day 3), and 3 days after application of a 10-mg/24-h nitroglycerin tape concomitantly with oral vitamin E or placebo (day 6). The responses of forearm blood flow (%FBF) and cGMP (%cGMP) after sublingual nitroglycerin on day 0 (%FBF: normal volunteers, 32+/-12 versus 31+/-11; IHD patients, 35+/-15 versus 34+/-15; %cGMP: normal volunteers, 38+/-10 versus 35+/-11; IHD patients, 37+/-11 versus 38+/-12, vitamin E group versus placebo group) and day 3 (%FBF: normal volunteers, 33+/-9 versus 32+/-12; IHD patients, 35+/-12 versus 33+/-13; %cGMP: normal volunteers, 38+/-10 versus 37+/-11; IHD patients, 36+/-14 versus 37+/-10, vitamin E group versus placebo group) were not different between the two groups. On day 6, %FBF and %cGMP in the placebo group were significantly lower compared with day 0, and there were significant differences in them between the two groups (%FBF: normal volunteers, 30+/-12 versus 17+/-9, P<.01; IHD patients, 28+/-14 versus 17+/-8, P<.01; %cGMP: normal volunteers, 35+/-11 versus 8+/-5, P<.01; IHD patients, 38+/-10 versus 12+/-4, P<.01, vitamin E group versus placebo group). CONCLUSIONS: These results indicate that the combination therapy with vitamin E is potentially a useful method to prevent the development of nitrate tolerance.

Administration, Oral↗

Effects of enalapril during continuous nitrate therapy: analysis of diameter of coronary arteries and platelet cyclic guanosine monophosphate.

To investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on nitrate tolerance during continuous nitrate therapy, coronary artery diameters and platelet cyclic guanosine monophosphate (cGMP) levels were measured before and 2 minutes after intracoronary injection of nitroglycerin 200 microg in 60 patients with coronary artery disease and were compared among 20 patients treated with nitrates (nitrate group), 20 patients treated with both nitrates and enalapril (enalapril group), and 20 untreated patients (control group). The percent increase in platelet cGMP and coronary dilatation in the nitrate group was significantly less than in the control group, but the percent increase in the enalapril group was significantly greater than that in the nitrate group. These results indicate that enalapril may be helpful as concomitant therapy to maintain the effect of nitrates during continuous nitrate therapy.

Aged↗

Experience of expandable metallic stents for central airway obstruction.

The aim of this study was to investigate retrospectively the efficacy of expandable metallic stents (EMSs) for severe respiratory distress in patients with central airway obstruction. Twenty patients with central airway obstructions were treated with an EMS. An intraluminal stricture was present in 15 and an extraluminal stricture in 5 patients. Of the 15 patients with intraluminal stenosis, 11 exhibited symptomatic improvement. All 11 patients had tumor infiltration occupying less than 50% of the endoluminal diameter. The other four patients with intraluminal stenosis had tumor infiltration occupying > 50% of the endoluminal diameter and demonstrated no improvement. All five patients with extraluminal stenosis were improved. EMS is useful for an extraluminal stricture in the central airway and the effect of EMS for intraluminal stenosis is related to the degree of infiltration and of tumor progression itself.

Adult↗

Dynamic intravenous coronary arteriography using synchrotron radiation and its application to the measurement of coronary blood flow.

We have developed dynamic intravenous coronary arteriography (IVCAG) using a monochromatic (33.3 keV), 2-dimensional X-ray beam (70 x 70 mm) generated from synchrotron radiation. To investigate its use to visualize the coronary arteries and to estimate coronary blood flow, we performed IVCAG in 10 dogs and 1 goat. The animals were irradiated with the synchrotron beam after intravenous injection of a contrast agent, and images were obtained using a TV camera and videorecorder. In the dogs, blood flow in the left anterior descending coronary artery (LAD) was also estimated from the images by applying a transit-time analysis. We obtained dynamic IVCAG images in the dogs and goat and could visualize even a deliberately created coronary stenosis about 1 mm in length. In addition, coronary blood flow could be estimated with an acceptable degree of accuracy. LAD flow calculated from IVCAG was 14.7 +/- 5.1 ml/min, whereas measured LAD flow was 16.6 +/- 4.8 ml/min. There was a close correlation between the estimated and measured LAD flows (r = 0.90, p < 0.01). Thus, dynamic IVCAG is minimally invasive, permits the simultaneous evaluation of coronary anatomy and blood flow, and may be feasible for clinical application.

Animals↗

Relation of a decrease in arterial compliance to ST segment depression on exercise electrocardiograms in patients with hypertension.

Decreased arterial compliance (ACo) and increased arterial resistance are the major alterations of arterial function in patients with hypertension. The influence of decreased ACo on the heart was investigated in patients with hypertension. Patients with a systolic blood pressure of > 140 mmHg, a diastolic blood pressure of > 90 mmHg, or both, who had normal coronary arteriograms were enrolled. These patients were divided into two groups according to the value of ACo: Group I, patients with ACo > or = 0.9 ml/mmHg (n = 15); and Group II, patients with ACo < 0.9 ml/mmHg (n = 13). There were no significant differences in arterial resistance, age, gender, and body surface area between the groups. Echocardiographic, hemodynamic, and exercise stress test variables were compared between the groups. There were no differences between the groups in left ventricular (LV) wall thickness and volume, cardiac output, LV end-diastolic pressure, and LV ejection fraction. However, pulse pressure was higher in Group II than in Group I. Ergometer exercise stress testing revealed that, although exercise duration and the peak rate-pressure product were similar in the two groups, ST segment depression of > or = 1.0 mm on the exercise electrocardiograms was induced more frequently in Group II than in Group I (92% vs. 27%, p < 0.001). Thus, the decrease in ACo in patients with hypertension may not significantly affect LV wall thickness, volume, or ejection fraction; however, it may increase pulse pressure and may adversely affect coronary circulation, as suggested by the ST segment depression on exercise electrocardiograms.

Arteries↗

Thymolipoma: clinical and pathological features--report of three cases and review of literature.

We report three recently resected cases of thymolipoma. Two cases (case 2 and 3) were female and the other (case 1) was male. The age of these three were 41 years, 63 years, and 29 years, respectively. While two cases (case 1 and 2) were asymptomatic, the other (case 3) had associated myasthenia gravis. Preoperative examination in each case was performed using chest CT scan or chest MRI, or both. Only one case (case 1) was diagnosed as thymolipoma preoperatively, and this was by a chest MRI showing the mass in continuity with the thymus. The diagnosis of each lesion was confirmed histologically by their composition of lobules of mature adipose tissue with minute islands of thymic tissue consisting of epithelial cells, lymphocytes, and Hassall's bodies.

Adult↗

Thymolipoma associated with myasthenia gravis.

In a 29-year-old woman with myasthenia gravis and no visible mediastinal mass, the resected thymus was found to contain a small thymolipoma. Relief of the neuromuscular symptoms followed thymectomy. A very small thymolipoma may be associated with myasthenia gravis even if the content of though thymic tissue is low.

Adult↗

Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation.

BACKGROUND: Tetrahydropyranyladriamycin (THP), a derivative of anthracycline, exhibits a stronger antiproliferative activity and a lower cardiotoxicity than the other anthracyclines. The value of THP as an immunosuppressant has not been examined yet, whereas cyclophosphamide, which is another antiproliferative drug, has shown promise as an immunosuppressant in concordant xenotransplantation. METHODS: The effect of THP on the marginal zone in the spleen and anti-species antibody production was evaluated and was compared with that of cyclophosphamide in a concordant xenogeneic splenocyte injection model (hamster-to-rat). Next, THP was used as monotherapy for hamster-to-rat heart transplantation to substantiate the potency of its immunosuppressive activity in concordant xenotransplantation. Finally, combination therapy with THP plus FK506 was tried. RESULTS: THP (5 mg/kg) suppressed the expansion of the marginal zone more than did cyclophosphamide (40 mg/kg) and inhibited the production of antispecies antibody as much as did cyclophosphamide (40 mg/kg) in the splenocyte injection model. THP monotherapy could prolong the survival of hamster-to-rat heart grafts up to 14.5 +/- 3.2 days (n = 21). The rejected grafts in the THP-treated animals did not show any histologic evidence of vascular endothelial damage but did exhibit a mononuclear cell infiltration. Combination therapy with THP plus FK506 provided excellent graft survival. CONCLUSIONS: THP can prevent early phase humoral rejection in concordant xenotransplantation.

Animals↗