Liver lesions in mice treated with diethylnitrosamine and inoculated with the Tyzzer's organism.
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Biomedical subjects
Publications and source records attributed to S Inoue.
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The effects of captopril monotherapy and combination therapy with thiazide diuretics or with methyldopa on glucose tolerance test (GTT) were investigated in 71 diabetic hypertensives. After the baseline evaluation, captopril (37.5-75 mg/day) was given. GTT and insulin assay were performed again between 10 and 12 weeks after the initiation of captopril therapy. We also studied the effects of chronic captopril therapy (6-12 months) on GTT in patients with essential hypertension. Captopril was well tolerated in all patients and no adverse reactions were observed. Chronic captopril therapy produced a significant (p less than 0.01) fall of blood pressure in all patients. There was no significant deterioration of the insulinogenic index or the time course curves of plasma glucose and insulin after GTT. These results indicate that captopril therapy does not affect glucose metabolism. Thus captopril may have an advantage for clinical use in hypertensive patients with or without impaired glucose metabolism.
This paper describes evaluation and correction of count rate characteristics of POSITOLOGICA II, a multi-slice whole body positron emission tomography system. The present study was performed using three phantoms; a 5 cm inner diameter, water-filled lucite cylinder, a 20 cm inner diameter, water-filled lucite cylinder and a chest phantom. After injection of high activity (about 1.85 GBq (50 mCi] of 13N ammonia into each phantom, rates of true coincidence, random coincidence and single photon detections were measured during decay of the isotope through more than two orders of magnitude of activity. At very high levels of activity, count rate characteristics of the system were saturated and limited to 660 kcps of total coincidence rate, which was the sum of rates in on-time and off-time windows, by the FIFO (first-in first-out) output frequency. Below those levels of activity the relationship between count loss and true coincidence rate was not unique but depended on the phantom configurations, suggesting that count loss correction using the above relationship was inadequate for quantitative study. However, the relationship between count loss and single rate was almost independent of the phantom configurations. Thus in conclusion count loss could be corrected using single rate for POSITOLOGICA II. A practical method of count loss correction was also proposed.
Eighteen cases of idiopathic osteonecrosis of the femoral head were studied. Serum concentrations of 25(OH)D3, 24, 25(OH)2D3 and 1,25(OH)2D3 were 19.4 +/- 8.7 ng/ml, 1.04 +/- 0.44 ng/ml and 16.7 +/- 7.9 pg/ml (mean +/- SD) respectively. These values were significantly lower than those of control (26.5 +/- 15.5 ng/ml, 1.91 +/- 0.77 ng/ml and 26.9 +/- 13.7 pg/ml, respectively) (p less than 0.01). Abnormal values of serum calcium (Ca) were detected in two cases, inorganic phosphate (iP) in two cases and alkaline phosphatase (Al-Pase) in two others with no other abnormal values in blood biochemistry. Histological findings in nine cases of iliac bone were those of osteomalacia in five cases and those of osteoporosis in four cases. These results suggest the possibility of bone metabolism abnormalities due to abnormal vitamin D3 metabolism as a background of osteonecrosis of the femoral head.
Neosurugatoxin (NSTX) which contains two sugars (myoinositol and xylopyranose) and bromine in the chemical structure, has been shown previously to be a selective antagonist of nicotinic receptors in guinea pig ileum and in murine brain. To study the role of sugar moiety and bromine in the antinicotinic activity by NSTX, we have examined the action of NSTX (compound I) and the structurally related compounds (compound II, III and IV) on the nicotine-induced contraction of guinea pig isolated ileum and on specific [3H]nicotine binding in rat forebrain membranes. Among four compounds examined, compound I was the most potent in inhibiting the nicotine-induced contraction of guinea pig isolated ileum (pA2 = 9.1 +/- 0.1, pD2' = 8.0 +/- 0.1) and also in inhibiting specific [3H]nicotine binding in rat forebrain (IC50 = 83 +/- 9 9 nM). Compared to compound I, compound II and III which are devoid of one and two sugars, respectively, in the chemical structure of compound I were 2 or 3 times less potent in the antinicotinic activity in both tissues, and compound IV which lacks bromine in addition to two sugars was two orders of magnitude less potent. Thus, the present study demonstrates that bromine rather than sugar moiety in the chemical structure of compound I (NSTX) is an important determinate of its high affinity for nicotinic receptors.
Congenitally athymic nude (nu/nu) mice have been thought to exhibit no T cell functions despite the presence of some Thy-1 positive (Thy-1+) cells. However, we detected a significant number of Con A-responsive cells in spleens of nu/nu mice after the age of 2 months when the spleen cells were cultured in a medium containing 5% human plasma or human serum, but not when they were cultured in fetal calf serum. Cytotoxic test using anti-Thy-1.2 antibody plus complement has revealed that these Con A-responsive cells are indeed Thy-1+. The Con A-responsive T cells increase with age. PHA-responsive and alloreactive T cells are also detected in the spleens of 11-month-old nu/nu mice. To probe the origins of the T-lymphocytes of the nu/nu mice we examined extensively and systematically the thymic remnants in the mediastinum and neck region of the nu/nu mice in search for T cell development in thymic rudiments. In these investigations we regularly found small accumulations of cells comprising almost entirely Thy-1+ lymphocytes surrounding accumulations surrounded by epithelial cells. These findings suggest that apparent sites of T cell development in thymic rudiments are indeed present in nude mice and appear to be functioning to induce expression T cell markers on precursor cells in the lymphoid lineage. Together with our prior findings the evidence presented in this report shows that a pathway exists in nude mice. In the converse these findings suggest that the thymus is the sole site for induction of the differentiation of stem cells or precursor T cells into mature T-lymphocytes. The findings suggest that indications of alternative differentiation pathways for T-lymphocytes must seek the location of these pathways within the thymus itself.
The concentrations of FT, 5-FU and uracil in lung cancer tissue, healthy lung tissue and serum were measured in 10 patients with primary lung cancer to whom UFT (600 mg) had been administered for one week. No remarkable difference was found in the concentration of FT between both tissues. The concentration of 5-FU in lung cancer tissue was 0.099 +/- 0.051 microgram/g and significantly higher than the level of 0.009 +/- 0.003 microgram/ml in serum (p less than 0.001) and 0.039 +/- 0.021 microgram/g in normal lung tissue (p less than 0.01). The ratio of 5-FU concentration in cancerous tissue to that in the serum was 11.0, while the ratio of the level in cancerous tissue to that in normal lung tissue was 2.5. The concentration of uracil was much higher in cancerous tissue than in normal lung tissue and serum. Maintenance therapy with UFT proved possible for a long period in 11 primary lung cancer patients with negligible digestive side effects.
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Experimental chemotherapy with cisplatin and carboplatin was performed against nine human tumor xenografts serially transplanted into nude mice. Tumors used for the experiment were seven gastric (St-4, St-15, St-40, H-111, SC-2-JCK, SC-6-JCK and Exp-4), one breast (MX-1) and one colon (Co-4) carcinomas. Cisplatin 9 mg/kg and carboplatin 100 mg/kg were administered intraperitoneally (ip). Carboplatin 25 mg/kg was also given ip 4 times every 4 days. The efficacy rates of cisplatin and carboplatin by bolus injection were 77.8% and 66.7% respectively with no statistically significant differences. However, carboplatin was found more effective when given by bolus. The antitumor spectra of both drugs were similar. From these results, these two platinum compounds seemed to be effective against human gastric carcinomas.
To investigate whether insulin regulates triglyceride secretion from the liver in vivo, triglyceride secretion rate (TGSR) and serum insulin were measured in the following three experiments: in rats 12 weeks after ventromedial hypothalamic (VMH) lesions (Exp. 1), in rats 12 weeks after a high fat diet-feeding (Exp. 2), and in rats 10 days after streptozotocin treatment (65 mg/kg) (Exp. 3). Under hexobarbital anesthesia, overnight fasted rats were bled for measuring insulin and triglyceride. Rats were again bled 45 and 90 minutes after Triton WR 1339 (120 mg) injection, for measuring triglyceride. TGSR was calculated from serum triglyceride values measured before and after Triton injection. In Exp. 1, VMH obese rats had higher serum insulin concentrations and TGSR than control rats. There was a significantly positive correlation between serum insulin concentrations and TGSR in VMH lesioned rats alone (r = 0.939, P less than 0.001) and in VMH lesioned and control rats combined (r = 0.958, P less than 0.001). In Exp. 2, high fat diet-fed rats gained more weight than control rats, but they had the same levels of serum insulin concentrations and TGSR as those of control rats. In Exp. 3, streptozotocin treated rats had lower serum insulin concentrations and TGSR than control rats. There was a significantly positive correlation between serum insulin concentrations and TGSR in the two groups of rats combined (r = 0.680, P less than 0.05). From the results of these three sets of in vivo studies, we conclude that insulin increases TGSR in vivo.
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In order to determine the culture characteristics of human leukemic cells in long-term bone marrow cultures (LTBMC), we cultured three specimens from three patients with acute non-lymphoblastic leukemia (ANLL) at diagnosis or during relapse. The kinetics of granulocyte-macrophage colony-forming cell (CFU-C) generation in non-adherent cell fractions were compared with the kinetics of CFU-C generation by 16 control specimens. In addition, the adherent cells of the three ANLL specimens were cytogenetically characterized and the karyotypes were compared with those of corresponding fresh specimens. Two of the three ANLL specimens showed a greater decline in the number of CFU-C by weekly CFU-C assay of non-adherent fractions than did the control specimens at the corresponding week of culture. At the end of LTBMC, these two specimens contained karyotypically identifiable leukemic cells in the adherent layers. In contrast, one of the three specimens generated no CFU-C during the first four weeks of culture, but CFU-C were generated between weeks 5 and 9 with a peak at week 8. This specimen's adherent layers contained no metaphases identifiable as leukemic cells, even although the fresh sample before culture had yielded abnormal metaphases in 100% of the cells examined. This biological heterogeneity of ANLL leukemic cells may be significant in understanding the marked variability in the clinical courses of ANLL patients. A large prospective study that incorporates LTBMC would be of value in determining the clinical correlations.