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Biomedical subjects

S Okazaki

Publications and source records attributed to S Okazaki.

At least 19 recordsLinked to original sources
PubMed1992

Effects of intracarotid infusion of neuropeptide Y on cerebral blood flow in rats.

Neuropeptide Y (NPY) was continuously administered to Wistar rats intracarotidly via the external carotid artery and local cerebral blood flow (LCBF) was measured by a quantitative autoradiography using [14C]iodoantipyrine. A remarkable reduction in LCBF was observed in the NPY infused hemisphere. This depression was irregular and was particularly evident in the hippocampus, selective thalamic nuclei and the cerebral cortex.

Animals↗
PubMed1992

Reversibility of catechol-induced rat glandular stomach lesions.

The potential reversibility of glandular stomach lesions induced by the clastogen, catechol, was examined in groups of male F344 rats treated continuously with 0.8% catechol in the diet for 12, 24, 48, 72, or 96 weeks. After a return to basal diet for 84, 72, 48, 24, and 0 weeks, respectively, the animals were killed for histopathological examination. Incidences of submucosal hyperplasia, adenomas and adenocarcinomas, average number of tumors per rat, and the size of tumors in rats treated with catechol for 12, 24, 48, 72, and 96 weeks increased time dependently. After cessation of catechol treatment, although average number of tumors per rat slightly decreased, the size of tumors tended to increase. Labeling indices in both tumorous and nontumorous areas decreased after cessation of catechol treatment. The results thus indicate that whereas some submucosal hyperplasias or adenomas may regress, others have the potential to develop into adenomas or adenocarcinomas. However, tumor growth does depend to a certain extent on continued catechol treatment.

Adenocarcinoma↗
PubMed1992

Influence of caffeic acid and other o-dihydroxybenzene derivatives on N-methyl-N'-nitro-N-nitrosoguanidine-initiated rat forestomach carcinogenesis.

Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10-15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated.

Adenocarcinoma↗
PubMed1992

[A 13-week subcutaneous toxicity study of prednisolone farnesylate (PNF) in rats].

The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study.

Animals↗
PubMed1992

[A 13-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 5 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study.

Administration, Cutaneous↗
PubMed1992

[A 52-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 8 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in alpha 1-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in alpha 1-globulin fraction were observed. Histopathologically, thinning of the skin atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic dose of PNF gel was 0.5 mg/kg/day and the non-toxic dose was 0.125 mg/kg/day in the present study.

Administration, Cutaneous↗
PubMed1992

[A 52-week oral chronic toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in rats with a recovery period of 5 weeks.

The chronic toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 0.4, 2, 10, 50 and 250 mg/kg/day for 52 weeks. The drug was then withdrawn for 5 weeks. The results are summarized as follows: There were no deaths or toxic signs caused by the drug throughout the experimental period. There were no drug-related changes in food consumption, ophthalmological examination, hematology or blood chemistry. Slight suppression of growth was observed in males in the 250 mg/kg group. This change was reversed on withdrawal of the drug. Drug crystals were observed in the urinary sediments of both sexes in the 250 mg/kg group, but this change disappeared on withdrawal of the drug. Gross pathological examination revealed the following changes: enlargement and nodule formation in the pancreas in both sexes given more than 10 mg/kg of the drug; dark red spots in the glandular stomach in males in the 250 mg/kg group; thickening of the small intestinal walls in both sexes given more than 50 mg/kg. Of these organs, no changes were observed in the stomach and small intestine at the end of the recovery period. Increased pancreas weight was observed in both sexes given more than 50 mg/kg of the drug. Examination at the end of the recovery period suggested reversibility, showing a lesser degree of change. Histopathological examination revealed the following changes in the pancreatic acinar cells: acidophilic foci and nodules in both sexes given more than 10 mg/kg of the drug; adenoma in one male in the 250 mg/kg group; increased zymogen granules in both sexes given more than 50 mg/kg of drug; fine vacuolization in females in the 250 mg/kg group. At the end of the recovery period, increased zymogen granules and fine vacuolization of the acinar cells were not found. Furthermore, erosion or healed erosion in the glandular stomach, duodenum and jejunum was observed in a few males or females in the 250 mg/kg group, but those changes disappeared after the recovery period. In the liver, altered cell foci was observed more frequently in males in the 250 mg/kg group than the other groups, but this change also disappeared after the recovery period. In addition, brown pigmentation in the proximal renal tubules of the kidney was observed in both sexes in the 250 mg/kg group, but lesions observed in the examination after the recovery period were less noticeable than in the examination at the end of the administration period.

Administration, Oral↗
PubMed1992

[A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in rats].

The toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 2, 10, 50, 250 and 1250 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks for recovery. The results are summarized as follows: In the 1250 mg/kg/day group, 9 out of 20 males died with decreased body weight and exhaustion. Histopathological examination revealed renal papillary necrosis, ulcer in the urinary bladder, hemostatic lesions in the lungs and liver, ulcer or erosion in the stomach, duodenum and jejunum. The surviving animals in this group showed swelling of the limbs due to synovitis, transient salivation immediately after administration, suppression of growth with decreased food consumption. Urinalysis revealed a low pH, increased ketones and bilirubin excretion, dark yellowish change in color, the appearance of "leaflet-shaped" crystals and increased red blood cells and epithelial cells in the urinary sediment, increased water intake, decreased specific gravity and decreased sodium, potassium and chloride in the urine. Hematologically, there was an increase in the white blood cell count. A biochemical analysis of the blood revealed decreased amylase activity, glucose and total protein levels and increased GOT activity and inorganic phosphorus levels. Pathological changes were observed in the pancreas, kidney, digestive tract, urinary bladder and liver. The pancreas showed macroscopical enlargement and increased organ weight. Histopathologically, there were several alterations in the acinar cells, such as vacuolization due to increased fat droplets, nuclear irregularity, prominent nucleoli, irregular arrangement and vesiculation of rough endoplasmic reticulum (rER), dilatation of developed Golgi apparatus and increased free ribosomes. In the kidney, increased weight and pigmentation in the proximal tubular epithelium were noted. Electron microscopically, these pigments were recognized as secondary lysosomes containing filamentous material and electron dense granules within a lucent matrix. In the digestive tract, ulcer or erosion in the stomach and duodenum, and villous proliferation in the small intestine were observed. Furthermore, hyperplasia and vacuolization were noted in the mucosal epithelium of the urinary bladder. In addition, loss of perilobular fat droplets in the liver and increased adrenal weight without histological change were observed. After a 5-week recovery period, these changes disappeared almost completely. In the 250 mg/kg/day group, slight suppression of growth the appearance of "leaflet-shaped" crystals in the urinary , sediment, increased water intake and decreased sodium in the urine were observed. The pancreas showed enlargement, increased weight, acinar cell hypertrophy with increased zymogen granules, fine vacuolization, slight derangement and vesicular of rER, and dilatation of Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

[Sharp decline in plasma CEA and reduction of liver metastasis after UFT administration in a patient with recurrent gastric cancer].

Carcinoembryonic antigen (CEA) in plasma is useful for the detection of recurrent colonic or gastric cancer and the monitoring of plasma in patients with recurrent cancer displaying therapeutic effect. We report a sharp decline of CEA in a patient with recurrent gastric cancer by 6 months oral administration of UFT. The patient was an 81-year-old male who had undergone gastrectomy for advanced gastric cancer. Eight months post-operatively, the plasma CEA began to rise logarithmically, and recurrent tumor in the remnant stomach and liver metastasis were detected by fibergastroscope (FGS) and abdominal CT. After administration of UFT at a dose of 300 mg per day, CEA abruptly declined logarithmically and normalized in 6 months. Presently marked reduction of recurrent foci and metastases were found by FGS and abdominal CT. Therefore sequential changes in plasma CEA in this patient can be considered to reflect the effect of therapy for recurrent gastric cancer by UFT.

Adenocarcinoma↗
PubMed1992

Membrane-associated phospholipase A2 stimulates DNA synthesis in two murine fibroblasts.

The effect of human membrane-associated phospholipase A2 (M-PLA2) on DNA synthesis in fibroblasts was examined in order to clarify its biological function. Human M-PLA2 added exogenously to the fibroblast cell lines Swiss 3T3 and BALB/3T3 was found to augment their DNA synthesis. This stimulation of DNA synthesis was not affected by treatment with indomethacin. Our results suggest that human M-PLA2 itself has a mitogenic effect on fibroblasts independent of arachidonate products such as prostaglandins.

3T3 Cells↗
PubMed1991

[Evaluation of hepatitis B virus markers for surrogate testing of hepatitis C].

To evaluate the surrogate markers of non-A, non-B hepatitis virus (es) carriage state, the relationship between antibody to hepatitis C virus (HCV) and antibody to HBc/HBs and liver enzyme (ALT) was sought in Saitama prefecture. Out of 36,642 blood donor samples, 410 (1.1%) samples were positive for anti-HCV. Anti-HCV was found in 1.79% of donors with anti-HBs and/or anti-HBc, which is 1.7 fold of the frequency found in donors (1.04%) negative for anti-HBc/HBs. In contrast to the reports from Europe or USA, a poor correlation of anti-HCV with the serological history of hepatitis B infection was observed. These results indicate that hepatitis B and hepatitis C were transmitted independently in the Japanese, which is more homogeneous socioeconomically than the European or American populations. On the other hand, anti-HCV prevalence was in close correlation to ALT level as observed in the USA and in Europe. As we predicted previously, ALT can be expected to reduce the incidence of post-transfusion non-A, non-B hepatitis, however, anti-HBc can not.

Alanine Transaminase↗
PubMed1990

Diffuse low-density areas in white matter on CT scans after intracarotid ACNU infusion--report of three cases.

Since 1984, we have treated 11 malignant glioma patients with intracarotid infusion of ACNU [1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)- 3-nitrosourea hydrochloride] in addition to surgical removal and irradiation. We experienced three patients, who showed clinical manifestation of leukoencephalopathy and computed tomographic (CT) findings of diffuse low-density areas in the white matter on the side of ACNU infusion. Two of the three patients showed an additional CT finding of ring enhancement in the temporo-occipital region. The histological diagnosis of the first case was radiation necrosis, while that of the others was recurrent tumor with coagulation necrosis in the surrounding brain. Our experience suggests that intracarotid ACNU infusion increases the hazard of radiation necrosis, and the optimum dose and effective mode of administration should be evaluated.

Brain↗
PubMed1978

A patient with repeated syncopal attacks after using isosorbide dinitrate.

The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor.

Aged↗