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Biomedical subjects

Y Okazaki

Publications and source records attributed to Y Okazaki.

At least 253 records · Page 14Linked to original sources

Role of active oxygen species in diethyldithiocarbamate-induced gastric ulcer in the rat.

Diethyldithiocarbamate, an inhibitor of Cu,Zn-superoxide dismutase, was recently found to be ulcerogenic in the rat stomach, and active oxygen species were found to be responsible for its ulcerogenicity. To clarify which active oxygen species play a role in ulcerogenesis, the effects of various scavengers and iron-chelators were studied. As superoxide dismutase and catalase reduced the ulcerogenesis induced by diethyldithiocarbamate, the superoxide radical and hydrogen peroxide were considered to play a pathogenic role in this ulcer model.

Animals↗

High resolution ultrasound of the chest wall.

To study the detailed normal ultrasonic anatomy of the pleura and chest wall, high resolution (7.5 MHz) ultrasonograms were obtained from cadaver chest wall specimens and compared with thin section computed tomograms and anatomical specimens. Ultrasonograms show three layers of the intercostal muscles (internal, external and innermost), covered by the "echogenic pleural line." The "echogenic pleural line" is caused by composite echoes from the inner parietal pleura, and the outer endothoracic fascia, with the fatty tissue covering both sides of the fascia, which are located deep to the chest wall muscles. On ultrasonograms, the subpleural fat tissue, when abundant, appeared as an apron-like structure hanging down from the inner surface of the rib (subpleural fat pad), or diffuse fat accumulation mimicking the pleural thickening.

Humans↗

An immunohistochemical study of copper, zinc-containing superoxide dismutase detected by a monoclonal antibody gastric mucosa and gastric cancer.

The immunohistochemical localization of copper, zinc-superoxide dismutase (Cu,Zn-SOD) in human gastric mucosa and gastric cancer was studied using a monoclonal antibody. In gastric mucosa, parietal cells, pyloric glandular cells and foci of intestinal metaplasia showed positive staining in the cytoplasm and/or nucleus. The wide distribution of Cu, Zn-SOD in the gastric mucosa suggests cell function may be vulnerable to active oxygen species. In gastric cancer, 34 of 70 cases showed a positive reaction for Cu, Zn-SOD. There was a relationship between the grade of Cu,Zn-SOD immunoreactivity and the histological type of gastric cancer, well-differentiated types of gastric cancer being more frequently positive. The positive cases of poorly-differentiated adenocarcinoma were characterized by a pattern of diffusely infiltrative invasion. These results suggest that some types of gastric cancer are resistant to active oxygen species.

Adenocarcinoma↗

Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat.

Diethyldithiocarbamate (DDC) was injected subcutaneously in the rat and the mechanism of gastric ulcer formation was investigated. DDC induced gastric ulcers in a dose-dependent manner. DDC significantly suppressed gastric mucosal copper-zinc superoxide dismutase (Cu, Zn-SOD) activity at 2 hr. However, manganese-superoxide dismutase (Mn-SOD) activity was not changed. Gastric mucosal blood flow (GMBF) decreased to 52% of the control level at 2 hr after administration of DDC and gradually increased to reach the control level by 7 hr. A Shay rat preparation (4 hr) was used to study gastric secretion. DDC (200, 400 and 800 mg/kg) inhibited acid secretion to about 80% of the control level. Histopathological examination of the gastric mucosa after administration of DDC revealed mucosal congestive findings from 1 hr to 3 hr. These data suggested that the mechanism of DDC-induced gastric ulcer formation may be attributable to a decreased level of GMBF and O2- production owing to decreased SOD activity.

Animals↗

Ruptured amebic liver abscess.

We treated two patients with a ruptured amebic liver abscess. The diagnosis was made at a relatively early stage and treatment was successful for one patient, but an accurate diagnosis of liver abscess was not made and invasive extraintestinal amebiasis led to multiple organ failure and to death for the other. Neither patient had been outside of Japan, and both were heterosexual. The origins of Entamoeba histolytica infection could not be determined. Though the mortality rate is high in cases of ruptured amebic liver abscess, appropriate management can lead to a good prognosis.

Adult↗

Pharmacological and biochemical assessment of SM-10888, a novel cholinesterase inhibitor.

The effects of the compound SM-10888 (9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate) in a number of pharmacological and biochemical tests were studied and compared to those of tacrine (THA), amiridin, HP-029 and physostigmine. SM-10888 inhibited cholinesterase activity (IC50: 2.3 x 10(-7) M) in rat cortical P2 fraction with almost the same potency as THA, while SM-10888 was 2-4 times more potent than amiridin and HP-029, but about 10 times less potent than physostigmine. When given to mice p.o., SM-10888 induced central (hypothermia) and peripheral (salivation) cholinergic effects. When the ratio of the ED50 value for hypothermia to that for salivation was regarded as the index of the selectivity to the central nervous system (CNS), SM-10888 was shown to be about 3 times more selective to the CNS than the other four drugs in mice. The minimum effective dose of SM-10888 for its increasing effect on acetylcholine (ACh) content in the mouse cerebral cortex was about 10 times higher than that of physostigmine, but 5-10 times lower than those of THA, amiridin and HP-029. These results suggest that SM-10888 is an adequate drug for increasing the brain ACh content with less peripheral cholinergic side effects than THA, amiridin, HP-029 and physostigmine.

Aminacrine↗

Effect of a novel CNS-selective cholinesterase inhibitor, SM-10888, on habituation and passive avoidance responses in mice.

The effects of the tacrine (THA) derivative SM-10888 (9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate) on habituation and passive avoidance responses were studied in mice. We examined its effects on habituation of exploratory activity, measured by photo-cell beam interruptions in a small, simple cage and cycloheximide (CXM)- or electroconvulsive shock (ECS)-induced stepdown type passive avoidance response (PAR) failures in comparison with those of THA, amiridin, HP-029 and physostigmine. SM-10888 (6 mg/kg, p.o.) administered post-acquisition session enhanced the retention of habituation. CXM- and ECS-induced PAR failures were improved by SM-10888 (6 mg/kg, p.o.) administered at pre-training or post-training, respectively. THA enhanced the retention of habituation and improved CXM-induced PAR failure at 30 mg/kg, p.o., but did not affect ECS-induced PAR failure at 1-15 mg/kg, p.o. Amiridin and HP-029 were also effective on habituation and CXM-induced PAR failure at 40-50 mg/kg, p.o., but did not affect ECS-induced PAR failure at the tested doses. Physostigmine showed a moderate improvement only in CXM-induced PAR failure. The results indicate that SM-10888 enhanced habituation and improved PAR failures at much lower doses than THA. This seems to depend on its high selectivity to the central nervous system.

Aminacrine↗

Human serum immuno-reactive copper, zinc-superoxide dismutase assayed with an enzyme monoclonal immunosorbent in patients with digestive cancer.

Two types of monoclonal antibodies, N4 and N6, were raised against human copper, zinc-superoxide dismutase (Cu,Zn-SOD). An enzyme-linked immunosorbent assay for Cu,Zn-SOD was developed in sandwich method using these monoclonal antibodies. The measurable assay range was 1.0-100 micrograms/l and the coefficient of variation within and between series were 7.5% and 8.1%. Sera of 154 healthy control subjects displayed a low level (14 micrograms/l) of immunoreactive Cu,Zn-SOD with a logarithmic normal distribution. On the other hand, serum Cu,Zn-SOD levels were significantly elevated in patients with various digestive cancers.

Antibodies, Monoclonal↗

Low testosterone levels in diabetic men and animals: a possible role in testicular impotence.

Poorly controlled NOD spontaneously diabetic mice were proven to have significantly less plasma and testicular testosterone than well-controlled diabetic mice (489 +/- 15 ng/dl and 3.89 +/- 0.79 micrograms/100 g tissue, vs. 176 +/- 24 and 9.00 +/- 1.24, respectively), and these in turn had significantly less than NOD non-diabetic control mice. These data were consistent with our previous observation of a decrease in total plasma and testicular testosterone levels in streptozotocin diabetic rats. A greater difference between total plasma testosterone levels and free testosterone levels was found in streptozotocin diabetic rats (17 +/- 4 ng/dl vs. 91 +/- 7 ng/dl) than in control rats (660 +/- 141 vs. 352 +/- 77). Fat droplets, depicting blocked testosterone synthesis, were found in the testicular Leydig cells of streptozotocin diabetic rats and disappeared with insulin treatment. No difference was found among plasma total testosterone concentrations in people in different stages of diabetes, as had been previously reported. However, human diabetic males, free of complications but poorly controlled, had less free testosterone than those without complications but well controlled (18.0 +/- 2.0 pg/ml vs. 22.8 +/- 1.3), who in turn had significantly less than age-matched controls (25.3 +/- 1.1 pg/ml). These data suggest gonadal dysfunction in diabetes mellitus.

Animals↗

[Therapeutic effect of stage III breast cancer--comparative study of preoperative intra-arterial infusion chemotherapy and non-infusion therapy].

Between January 1977 and March 1988, 111 patients of stage III breast cancer were treated in Sapporo Medical College. The median age was 51.6 years (range, 26-83 years). Menopausal status was 47 cases of premenopausal, 19 cases of perimenopausal and 45 cases of postomenopausal. Fifty-seven of these patients received intra-arterial infusion chemotherapy. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR or 4'-epi-ADR were jointly or individually made in each artery. Clinico-histological response was studied in 53 out of 57 patients. Clinical response, defined as CR + PR, was noted in 33 patients (62.3%). Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 31 patients (58.5%). Non-infusion group contained 27.7% of stage IIIb, against 72.2% in infusion group. The 5-year overall survival rates were; non-infusion group 62%, 5-FU infusion group 34.1%, and ADR MMC group 66.2%. A significant difference was seen between 5-FU infusion group and ADR-MMC group (p = 0.03). The median disease-free interval was 22.0 months (range, 1-77 months) in infusion group and 28.2 months (range, 1-124 months) in non-infusion group. MMC + ADR combination group revealed the most excellent results in terms of the 5 year survival rate and clinicohistological effect.

Adult↗

[Serial myocardial lactate metabolic changes after intracoronary thrombolysis in evolving myocardial infarction].

To ascertain whether early intracoronary reperfusion (less than 3 hours) preserves aerobic myocardial metabolism in acute myocardial infarction, serial changes in trans-cardiac lactate extraction after intracoronary thrombolysis were examined in 35 patients with acute anteroseptal myocardial infarction. Eight patients without intracoronary reperfusion served as controls. In the chronic phase, we also observed abnormally contracting myocardial segments as an index of infarct size and the regional ejection fraction as an index of chronic regional cardiac function. In the early reperfusion group (less than 3 hours; 15 cases), positive lactate extraction was restored; there were small abnormally-contracting segments and a high regional ejection fraction. However, the intermediate reperfusion group (3-5 hours; 10 cases) had sustained anaerobic lactate extraction, large abnormally-contracting segments and a low regional ejection fraction. The late reperfusion (greater than 5 hours; 10 cases) group showed apparent aerobic lactate extraction, but had large abnormally-contracting segments and a low regional ejection fraction. Thus, early reperfusion preserves aerobic lactate metabolism and good ventricular function in the chronic phase.

Heart Ventricles↗

[Intra-arterial infusion chemotherapy of advanced breast cancer--effects and side effects of adriamycin, 4'-epi-adriamycin and THP-adriamycin].

In 34 patients with primary advanced breast cancer, intra-arterial administration of ADR (50 mg X 3, total dose 150 mg, 10 cases), 4' epi ADR (50 mg X 3, 150 mg, 8 cases; 70 mg X 3, 210 mg, 10 cases) and THP-ADR (50 mg X 3, 150 mg, 6 cases) was performed, and its effects and side effect were analyzed. The clinical and histological response rate were superior in the ADR (150 mg) regimen and 4'-epi-ADR (150 mg) regimen. Signs of systemic toxicity such as gastrointestinal disorders, leukocytopenia and thrombocytopenia were the side effects in patients treated with THP-ADR, but the frequency of alopecia was lower. No cardiotoxicity was recorded in any of the patients. These results indicated that 4'-epi-ADR given the total dose of 150 mg in a single dosage of 50 mg was the most effective agent in intra-arterial infusion chemotherapy for advanced breast cancer.

Alopecia↗