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Biomedical subjects

Y Hirota

Publications and source records attributed to Y Hirota.

At least 343 records · Page 19Linked to original sources

[Clinical studies on endometrial cancer].

One hundred and fifty-two cases with endometrial carcinoma were treated in our clinic between 1973 and 1985. The average age was 55.89 years, and the age range was from 29 to 76 years. Thirty-six cases (23.7%) were nulligravidas and 42 cases (27.6%) were nulliparas. One hundred and ten cases (72.4%) were postmenopausal and the average age at menopause was 49.1 years. The most frequent chief complaint was atypical genital bleeding which was noted in 128 cases (84.2%). The result of a cytologic examination of the uterine cervix was positive in 50.7% and suspicious in 16.9% but results for the endometrium were positive in 63% and suspicious in 21.9%. The cases in this study were classified into 88 cases (57.9%) of T1a, 36 cases (23.7%) of T1b, 12 cases (7.9%) of T2, 3 cases (2.0%) of T3 and 1 case (0.7%) of T4. As to the postoperative diagnosis, there were classified into 86 cases (56.6%) of pT1a, 30 cases (19.7%) of pT1b, 19 cases (12.5%) of pT2, 10 cases (6.6%) of pT3 and 5 cases (3.3%) of pT4. Histopathologically almost all 140 cases (91.41%) were of adenocarcinoma and classified into 88 cases (57.9%) of G1, 39 cases (25.7%) of G2 and 13 cases (8.6%) of G3. The cumulative survival rates after Kaplan-Meier were 95% in pT1a cases, 75.6% in pT1b cases, 67.3% in pT2 cases, 42.2% in pT3 cases and 0% in pT4 cases.

Adenocarcinoma↗

Deoxyribonucleoside-triphosphate imbalance death: deoxyadenosine-induced dNTP imbalance and DNA double strand breaks in mouse FM3A cells and the mechanism of cell death.

The mechanism of deoxyadenosine (dAdo)-induced death of mouse mammary tumor FM3A cells was studied. When the cells were exposed to dAdo at 3 mM, an imbalance of intracellular dNTP pool resulted: dATP concentration was elevated 100-fold and the dGTP concentration was reduced to less than 1% of the control values. The imbalance was followed by breakage of mature DNA. DNA double strand breaks were observed in the dAdo treated cells 12 hr after the administration. We assume that the double strand breaks play an important role in the process of the dAdo-mediated cell death, and that the intracellular dNTP imbalance is the trigger of these events.

Animals↗

Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death.

The mechanism of cytotoxic action of 5-fluorodeoxyuridine (FdUrd) in mouse FM3A cells was investigated. We observed the FdUrd-induced imbalance of intracellular deoxyribonucleoside triphosphate (dNTP) pools and subsequent double strand breaks in mature DNA, accompanied by cell death. The imbalance of dNTP pools was maximal at 8 h after 1 microM FdUrd treatment; a depletion of dTTP and dGTP pools and an increase in the dATP pool were observed. The addition of FdUrd in culture medium induced strand breaks in DNA, giving rise to a 90 S peak by alkaline sucrose gradient sedimentation. The loss of cell viability and colony-forming ability occurred at about 10 h. DNA double strand breaks as measured by the neutral elution method were also observed in FdUrd-treated cells about 10 h after the addition. These results lead us to propose that DNA double strand breaks play an important role in the mechanism of FdUrd-mediated cell death. A comparison of the ratio of single and double strand breaks induced by FdUrd to that observed following radiation suggested that FdUrd produced double strand breaks exclusively. Cycloheximide inhibited both the production of DNA double strand breaks and the FdUrd-induced cell death. An activity that can induce DNA double strand breaks was detected in the lysate of FdUrd-treated FM3A cells but not in the untreated cells. This suggests that FdUrd induces the cellular DNA double strand breaking activity. The FdUrd-induced DNA strand breaks and cell death appear to occur in the S phase. Our results indicate that imbalance of the dNTP pools is a trigger for double strand DNA break and cell death.

Animals↗

A phase II study of (2"R)-4'-0-tetrahydropyranyladriamycin (THP) in hematological malignancies.

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

Acute Disease↗

Thyroid carcinoma and hot nodule.

A 70-year-old woman presented with a nodule in the thyroid gland. 131I scintigraphy of the gland showed a hot nodule. Histology of the resected thyroid revealed a papillary adenocarcinoma. Although a thyroid carcinoma with a hot nodule seen on the radioiodine isotope scan is a very rare occurrence, it is clinically very important because it may indicate a thyroid malignancy.

Adenocarcinoma, Papillary↗

Functional and histopathologic correlation in patients with dilated cardiomyopathy: an integrated evaluation by multivariate analysis.

To correlate left ventricular function and histologic features in patients with dilated cardiomyopathy, precise indexes of hemodynamics and semiquantitative histologic data were combined for multivariate analysis. Right endomyocardial biopsy was performed at the time of cardiac catheterization. Five hemodynamic indexes were used for functional assessment: ejection fraction, ratio of end-systolic stress to volume index, end-diastolic stress, time constant (T) of left ventricular pressure fall, and end-systolic stress. Six histologic findings (disarray of myofibers, hypertrophy of myofibers, scarcity of myofibrils, nuclear changes of myofibers, vacuolization of myofibers and proliferation of collagen fibers) were graded from (-) to (4+). Each finding was assigned to category (-) or (+) according to the absence or presence of significant abnormality. Ordinary statistical analysis revealed that, although ejection fraction was lower in category (+) for proliferation of collagen fibers, ratio of end-systolic to volume index was reduced for category (+) of hypertrophy of myofibers. A significant correlation was present between hypertrophy of myofibers and proliferation of collagen fibers by Spearman rank correlation. When principal component analysis was applied to the hemodynamic data, two principal components could be extracted. Fisher's discriminant analysis could clearly differentiate two categories (-) and (+) in the semiquantitative histologic finding of proliferation of collagen fibers. The analysis indicated that contractility was reduced with elevated afterload in that category (+). Thus, proliferation of collagen fibers may play a pivotal role in deteriorating contractility in patients with dilated cardiomyopathy.

Cardiomyopathy, Dilated↗

Change in tracheal blood flow during endotracheal intubation.

Changes in blood flow in the tracheal mucosa of the dog caused by the pressure exerted by high volume, low-pressure cuffs were measured with the hydrogen clearance method. Before inflating the cuffs, the blood flow of the tracheal mucosa was measured as a control for 12 h in order to confirm that the procedures of the hydrogen clearance method itself had little or no influence on the blood flow in the tracheal mucosa. After inflating the cuffs to create a tracheal wall pressure (TWP) of 1.3 kPa (10 mmHg), 2.6 kPa (20 mmHg), 3.9 kPa (30 mmHg) or 6.0 kPa (45 mmHg), local blood flows of tracheal mucosa (TBF) corresponding to each TWP were measured every hour for 12 h. No significant changes in blood flow were observed in the tracheal mucosa with the hydrogen clearance method before inflating the cuffs. In the groups with TWP of 1.3 and 2.6 kPa, the TBF rose 1 h after inflation of the cuffs, and then returned to the baseline values. In the group with TWP of 6.0 kPa, the TBF decreased markedly already 1 h after inflation of the cuffs, and continued to decrease severely thereafter. In the group with TWP of 3.9 kPa, the TBF followed an intermediate course between the groups with TWP of 2.6 kPa and 6.0 kPa. From the results of the present study, it was found that TBF was significantly impaired by a TWP of more than 3.9 kPa. Therefore, in prolonged intubation, TWP should be kept at or below 2.6 kPa.

Animals↗

Conversion of the alpha component of penicillin-binding protein 1b to the beta component in Escherichia coli.

Among components alpha, beta, and gamma of penicillin-binding protein 1b, the alpha and gamma components were confirmed to represent the primary gene products by agreement of their N-terminal amino acid sequences with those predicted from the nucleotide sequence of the ponB (penicillin-binding protein 1b) gene with exclusion of the first methionine in each component. The generation of beta occurred primarily after cell disruption, and the simultaneous loss of alpha suggested the conversion of alpha to beta. The N-terminal amino acid sequence analyzed for beta showed that the conversion was due to the removal of 24 amino acids from the N terminus of alpha.

Amino Acid Sequence↗

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment.

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.

Adult↗

HLA and thyrotoxic periodic paralysis in Japanese patients.

Periodic paralysis (PP) is a well recognized although rare and peculiar complication of thyrotoxicosis, especially among Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked to certain immunogenetic factors, and increased frequency of certain HLA antigens has been found in patients with Graves' disease. This study was, therefore, undertaken to determine HLA haplotypes in Japanese men with thyrotoxic periodic paralysis (TPP). HLA typing in 35 TPP patients and 263 normal men and women demonstrated highly significant increases (P less than 0.01) in HLA-A2, Cw3, and DRw8 in the TPP patients. In comparing TPP patients with thyrotoxic men who did not have PP, the frequency of DRw8 antigen was 2.5-fold greater in patients with PP than in those without it (62.8% vs. 28.6%). The data suggest that the HLA-DRw8 gene itself may play a significant role in the susceptibility to TPP among Japanese men.

Adult↗

Evaluation of left ventricular contractility in hypertrophic cardiomyopathy from end-systolic pressure-volume relation.

To evaluate myocardial contractility in hypertrophic cardiomyopathy (HC), we obtained the end-systolic pressure-volume relation (ESPVR) and the end-systolic stress-volume relation (ESSVR) by changing loading conditions with Angiotensin II. The left ventricular (LV) stress-shortening relation was also analyzed in order to assess myocardial contractility. LV end-systolic pressure, end-systolic volume, end-systolic stress, and ejection fraction were obtained at rest and during Angiotensin II infusion with simultaneous recordings of pressure and volume in 9 patients with hypertrophic cardiomyopathy and 9 normal subjects (N). The slopes of ESPVR, Emax, showed no significant difference (HC: 3.1 +/- 2.3 vs N: 2.6 +/- 1.4 mmHg/ml, ns). The slopes of ESSVR were statistically similar (HC: 5.2 +/- 2.1 vs N: 6.0 +/- 2.8 g/cm2 ml, ns). The slopes of end-systolic stress-ejection fraction relation were also in the same range in both groups (HC: -0.09 +/- 0.05 vs N: -0.10 +/- 0.05, ns). From these two different analyses of LV contractility, we conclude that myocardial contractility is normal in hypertrophic cardiomyopathy and not supernormal, at both chamber and muscle levels. Considering the increased muscle mass in hypertrophic cardiomyopathy (HC: 134 +/- 46 vs N: 74 +/- 19 g/m2, p less than 0.01), the presence of increased numbers of contractile units does not result in enhanced overall chamber contractility.

Adult↗

Intravenous isosorbide dinitrate infusion in the management of unstable angina pectoris refractory to conventional medical therapy.

During the past 2 years, 102 patients were treated for unstable angina pectoris (AP) in our department. Fifteen of them had recurrent chest pain at rest despite treatment with various anti-anginal agents, or prolonged chest pain unresponsive to sublingual nitroglycerin; they received intravenous isosorbide dinitrate (ISDN) infusion. A rapid bolus injection of 2 to 6 mg followed by an infusion of 2 to 5 mg/hr was given to 10 patients with acute chest pain, and 5 patients, who were free of chest pain at the time, but had repeated episodes of angina in the past 24 hours, were given ISDN infusion without a bolus injection. Chest pain disappeared completely in 13 patients, but recurred in 2 of them when the dose was tapered. Two other patients experienced recurrent chest pain during ISDN infusion, and additional boluses were given. The hospital course was uneventful in 11 patients. Four patients who had recurrent anginal attacks underwent emergency coronary cineangiography under intraaortic ballon counterpulsation and aorto-coronary bypass surgery. There were no hospital deaths, no one had subsequent acute myocardial infarctions, and only 2 patients had mild to moderate headache as a side effect. Although the patient population is small, intravenous ISDN infusion is useful in the management of severe unstable AP.

Acute Disease↗