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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 397 records · Page 22Linked to original sources

Superoxide radical production in plasma membrane samples from regressing rat corpora lutea.

Plasma membrane samples prepared from regressing rat corpora lutea were examined for production of the superoxide radical. A procedure was developed to purify membrane samples that were enriched approximately 15-fold with the plasma membrane marker enzyme, and superoxide radical levels were determined using electron spin resonance to measure Tiron semiquinone. During prostaglandin F2 alpha-induced and spontaneous regression, there was a significant increase in formation of superoxide radical that was not observed in plasma membrane samples from nonregressing corpora lutea. Plasma membrane incubation experiments indicated that the increase in production was temperature sensitive and reduced with inhibitors of phospholipase A2 and cyclooxygenase. Addition of superoxide dismutase or vitamin E abolished superoxide radical formation in vitro. Following the rise in superoxide radical levels during regression, there was also a significant decrease in the activity of the plasma membrane enzyme, Na+-K+ ATPase. These results indicate that the production of superoxide radical increases in plasma membrane samples prepared from regressing rat corpora lutea and that this increase is mainly due to the products of phospholipase A2 and cyclooxygenase activity.

Animals↗

Inositol trisphosphate and activators of protein kinase C modulate membrane currents in tail motor neurons of Aplysia.

1. We have investigated how activation of the inositol lipid second messenger pathway may contribute to modulation of membrane currents in tail motor neurons of Aplysia. Specifically, we examined the effects of injected inositol 1,4,5-trisphosphate (IP3) and analogues of diacylglycerol (DAG), both of which are products of the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). 2. Injection of IP3 produced an outward current associated with an apparent increase in membrane conductance. Ion substitution experiments, the sensitivity of the response to low concentrations of TEA and its attenuation by intracellular injections of EGTA suggest that the current produced by injection of IP3 is a calcium-activated K+ current (IK,Ca). 3. The response to IP3 was mimicked by intracellular injection of Ca2+. Injection of Ca2+ produced an outward current that was associated with an apparent increase in input conductance of the membrane. The same manipulations that affected the response to IP3 (see above) also affected the response to injections of Ca2+. 4. Injections of activators of protein kinase C (PKC) produced a relatively slow inward current. The inward current has not been fully analyzed, but it does not appear to be due to the actions of any single conventional ion channel. 5. Activators of PKC attenuated responses to subsequent injections of IP3 indicating that one component of PIP2 hydrolysis can attenuate the other. 6. The results suggest that hydrolysis of inositol phospholipids is a mechanism for regulation of membrane properties in tail motor neurons of Aplysia.

Animals↗

Oxygen therapy and vasodilator therapy in patients with chronic lung disease: the effects of episodic pulmonary hypertension during sleep and exercise performance.

In patients with chronic lung disease, we estimated the effectiveness of nocturnal oxygen therapy in eliminating episodes of sleep hypoxemia and concomitant elevations in the pulmonary arterial pressure. We also assessed the effect of vasodilators (ISDN, nifedipine) in improving exercise tolerance. Our results support the efficacy of nocturnal oxygen therapy. Vasodilators examined were not confirmed as effective or safe for wide use.

Blood Pressure↗

Overt diabetes induced by overeating in neonatally STZ-treated impaired glucose tolerant mice: long-term follow up study.

This study has investigated the effect of a long period of overeating on the glycemic control and pancreatic beta-cell function in neonatally streptozocin treated impaired glucose tolerant mice. Neonatally streptozocin (60 mg/kg) treated male ICR mice with 150-200 mg/dl of fed blood glucose levels were divided into two groups at 6 weeks of age. One group was maintained on a cafeteria diet (SZC) and the other on ordinary mouse chow (SZ) until 30 weeks of age. Normal male ICR mice were divided into a cafeteria diet group (CC) and an ordinary chow group (Cont). SZC and CC consumed 134-124% of the caloric intake in SZ and Cont throughout the study. Marked elevation of the fed blood glucose level was observed and the glucose tolerance was progressively impaired in SZC. On pancreas perfusion at 30 weeks of age, insulin secretion to 30 mM glucose in SZC was significantly decreased compared with that in SZ. That in CC was slightly decreased compared with that in Cont. The pancreatic insulin concentration in SZC was significantly less than that in SZ. We conclude that chronic hyperglycemia, induced by the long period of overeating, accelerated the selective loss of beta-cell sensitivity to glucose. Even in normal mice that did not have marked hyperglycemia, insulin secretion to glucose was suppressed, probably by chronic stimulation of the beta-cell due to the long period of dietary excess.

Animals↗

[Clinical study of combination chemotherapy with mitomycin C, vindesine and cisplatin (MVP therapy) in advanced non-small cell lung cancer].

Thirty-seven patients with inoperable non-small cell lung cancer were treated with the combination chemotherapy (MVP therapy) with mitomycin C (8 mg/m2), vindesine (3 mg/m2 X 2) and cisplatin (60 mg/m2). The partial responders were 13 cases (35%), and the median survival time was 271 days. In this study the cisplatin dose was less than in any other report of "MVP" therapy. But both the response rate and the median survival time did not differ from those reported elsewhere. The side effects (bone marrow suppression, renal toxicity, etc.) were mild, and did not prevent the continuance of this therapy. Thus, we could repeat more than 6 courses of "MVP" therapy for 8 patients. Nowadays, it is difficult to obtain complete responders with any chemotherapy for inoperable non-small cell lung cancer. To prolong lives of patients and maintain good quality of life, we recommend chemotherapy with low toxicity in often-repeatable courses.

Adult↗

[Ga-67 citrate accumulation in heart in malignant lymphoma of B-cell type accompanied with repeated ECG abnormalities which were normalized with chemotherapy--report of an autopsy case].

A 37y/o male developed mass formation in right tibia in Oct. 1986. He had generalized lymphadenopathy. Diagnosis of malignant lymphoma of B cell type (follicular, large cell type) stage IV B was made because of bone marrow involvement. Surface marker analysis of pathologic cells in the peripheral blood, bone marrow, lymph nodes revealed that they were of B cell type with positive EA gamma rosette formation, positive surface immunoglobulin with IgM-kappa and cytoplasmic immunoglobulin with IgM-kappa and positive responses to monoclonal antibodies of OKIal and B1. He responded partially to VEPAM therapy but in Jan. 1987 he developed Ga accumulation in heart and ECG abnormalities such as depression of ST and inverted T in II, III, AVF, V1-V6 leads. After treatment with VEP, ECG abnormalities disappeared in a month. The same ECG abnormalities recurred once more and disappeared again. Autopsy findings revealed accumulation of lymphoma cells in epicardium and myocardial degeneration in right ventricle. Ga scan appears to be a valuable method for detection of early cardiac involvement by malignant lymphoma.

Adult↗

Induction of chromosomal aberrations in active oxygen-generating systems. II. A study with hydrogen peroxide-resistant cells in culture.

Cells hyper-resistant to hydrogen peroxide (H2O2) were obtained from a Chinese hamster cell line (CHL) by repeated treatments with H2O2 at stepwise increasing concentrations. A clonal line (R-8) was approximately 10 times more resistant to H2O2 than the parental cells, and retained its resistance for about 2 months in normal medium. However, with further passages after the completion of the present study, the elevated resistance gradually decreased. Although the concentration of H2O2 required to induce chromosomal aberrations in 50% of treated cells was about 10 times higher in R-8 than in the parental cells, there were no distinct differences between the cells in the induction of chromosomal aberrations by 3 alkylating agents (N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosourea and mitomycin C). The catalase activity of R-8 was 10-fold in comparison with the parental cells, but no obvious differences were seen in the activities of superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase. Therefore, the elevated H2O2-resistance seemed to be associated with the enhanced catalase activity. The induction of chromosomal aberrations in two O2- generating systems--xanthine oxidase plus hypoxanthine (XO + HX), and paraquat--was compared between R-8 cells and the ordinary CHL cells. XO + HX produced chromosomal aberrations in the parental cells but not in the R-8, while paraquat induced almost the same level of aberrations in both cell lines. This finding suggests that different active oxygens are responsible for the induction of aberrations in these two O2- generating systems, i.e., H2O2 in XO + HX and O2- in paraquat.

Animals↗

Monoclonal gammopathies in patients with Sjögren's syndrome.

We studied 18 sera of Sjögren's syndrome (SS) with monoclonal gammopathy. Monoclonality was established by typical immunoelectrophoretic findings in all patients and confirmed by idiotypic (Id) studies in 12 patients. Four of the monoclonal gammopathies were of the IgG class, 8 were of the IgA class and 4 were of the IgM class, and 2 patients had 2 M proteins (IgMK/IgGK and IgAK/IgGK). The monoclonal rheumatoid factor (RF) was found in 6 patients (4 IgA and 2 IgM). A review of the literature revealed additional 19 monoclonal gammopathies (2 IgG, 9 IgA, 7 IgM and one Bence Jones protein) in Japanese SS patients. In non-Japanese SS patients, 27 monoclonal gammopathies (4 IgG, 2 IgA, 20 IgM and once Bence Jones protein) were reported. Both Japanese and non-Japanese patients showed a higher incidence of monoclonal gammopathies in primary than in secondary SS. The non-IgM class monoclonal gammopathies were predominant in Japanese SS patients, whereas monoclonal gammopathies were mostly confined to the IgM class in non-Japanese SS patients. These results indicate that monoclonal gammopathy is another significant complication of SS.

Aged↗

An acetylcholine-induced potassium current in tail sensory neurons in the pleural ganglion of Aplysia.

Acetylcholine (ACh) induces a hyperpolarization during current clamp and an outward current during voltage clamp in tail sensory neurons of Aplysia kurodai. This response was proved to be produced by a specific increase in membrane permeability toward potassium ions, the cholinergic antagonists, d-tubocurarine chloride (d-TC), and atropine mildly reduced the ACh response, while tetraethylammonium (TEA) most effectively blocked this response. These findings provide evidence that tail sensory neurons have the inhibitory ACh receptor in addition to the known receptors for serotonin (5-HT), small cardioactive peptide B (SCPB), and neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide).

Acetylcholine↗

[Effect of a newly developed platinum compound cis-1, 1-cyclobutane dicarboxylato-(2R)-2-methyl-1,4-butane diamine platinum (II), on human ovarian tumors transplanted into nude mice].

The therapeutic effect of cis-1, 1-cyclobutane dicarboxylato-(2R)-2-methyl-1,4-butane diamine platinum (II) (NK 121) on 3 human yolk sac tumors of the ovary (YST-1, YST-2 and YST-3), which were transplanted into nude mice, was compared with that of cisplatin (CDDP). While tumors YST-2 and YST-3 exhibited a broad comparable sensitivity to CDDP and NK 121, YST-1 was substantially more sensitive to CDDP than NK 121. A significant weight loss was noted in the non-tumor bearing nude mice treated with CDDP, as compared with the loss in both control and NK 121-treated groups. NK 121 showed a good antitumor activity without showing severe toxicities.

Animals↗