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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 235 records · Page 13Linked to original sources

Toxic effects of ingested lead shots in domestic fowls.

Lead poisoning from ingested shots is thought to be a major cause of high mortality in waterfowls throughout the world, and some millions of fowls die each year. However, there have been no other Japanese studies regarding lead toxicity in birds from ingested lead shots. We used domestic fowls instead of waterfowls as the experimental birds, in order to make clear the distribution and the toxic effects of lead shot in the birds. In a 1-wk follow-up study, two, four, and eight #4 lead shots were administered orally. A dose-dependent increase of the lead concentrations in blood, brain, liver, kidney, lung, spleen, bone, and epidermis of the gizzard was observed. In the 12-wk follow-up study, twenty domestic fowls were used and eight #4 lead shots were administered to the experimental birds. Lead concentrations in brain, liver, kidney, bone, ovary, fat tissue, and breast muscle increased more than in the 1-wk follow-up study. The observed lead concentrations of organs in the domestic fowls were lower than those of the other species used in past studies. The blood lead concentrations increased up to the third week and a remarkable suppression of delta-aminolevulinic acid dehydratase activity in red blood cells and elevation of free erythropoietic protoporphyrin were observed in the exposed group. Body weight loss, loss of hair, and neurological symptoms were also observed. However, there were no mortalities during the 1- and 12-wk studies.

Administration, Oral↗

Biological half-time and body burden of cadmium in dogs after a long-term oral administration of cadmium.

To investigate the kinetic behavior of cadmium, we conducted a long-term oral administration experiment, using beagle dogs. The experimental animals were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day in the form of cadmium chloride for 8 yr. A single injection of cadmium (as CdCl2) into dogs was also performed in order to obtain fundamental kinetic information for a dog. The kinetic behavior of cadmium in chronic experiment is described theoretically, using a two-compartment model. The model was selected based on the elimination pattern of cadmium from the blood in the single injection experiment. The parameters of the model were estimated from the acute and chronic experimental data. The theoretical value of the cumulative amount of cadmium excreted in urine agreed with the experimental one. This result suggests that the two-compartment model used in this study is useful to elucidate the kinetic behavior of cadmium after a long-term exposure to cadmium. The terminal biological half-time in the two-compartment model was estimated at about 1 to 2 yr for both male and female dogs given 1, 3, 10, and 50 mg of cadmium, and for the male dog given 100 mg of cadmium, but only 0.3 to 0.5 yr for the female dog given 100 mg of cadmium. The amount of cadmium in the central compartment and tissue compartment increased continuously and then gradually reached a steady state. The amount of tissue compartment was much higher than that of the central compartment for each beagle dog.

Administration, Oral↗

Selective depletion of immature thymocytes by oral administration of ethylene glycol monomethyl ether.

Although immunotoxicity of ethylene glycol monomethyl ether (EGME) has been strongly suspected, functional evaluation of the immune response in EGME-treated animals was negative in previous studies. We observed a decrease in thymic cellularity and increases in the various ex vivo immunological assays in mice, orally administered with EGME 0.5 or 1.0 mg/g body weight daily for 5 or 10 days: ex vivo lymphoproliferative responses to concanavalin A, in vitro induction of trinitrophenyl (TNP)-specific cytotoxic T-cell activity of thymocytes and splenocytes. Histopathological examination of the thymus of the treated mice disclosed a markedly atrophic cortex and almost intact thymic medulla. Study of thymocyte surface markers revealed that CD4+/CD8+, Thy-1+, PNA+ immature thymocytes were relatively decreased in EGME-gavaged mice and that, thus, ratios of CD4-/CD8+, H2+ mature thymocytes were enriched. These findings indicate that oral administrations of EGME selectively deplete immature thymocytes in mice. Although the mechanism of action remains unknown, the EGME-induced immature thymocyte depletion is not considered to be due to lymphocidal action of corticosteroids.

Administration, Oral↗

Long-term toxicity/carcinogenicity study of calcium lactate in F344 rats.

The long-term toxicity/carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad lib. in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumours in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats.

Animals↗

Immunogenicity in Aujeszky's disease virus structural glycoprotein gVI (gp50) in swine.

Aujeszky's disease virus (ADV) envelope glycoprotein gVI (gp50) was purified from virus-infected Vero cells by ion-exchange and immunoaffinity chromatography and its usefulness as a subunit vaccine was evaluated in active and passive immunization studies. Four-week-old piglets were immunized intramuscularly (IM) with purified gVI twice two weeks apart and challenged intranasally (IN) 10 days after the second immunization with 30 LD50 (10(8)PFU) of a virulent strain of ADV. Pigs, vaccinated with 100 micrograms of purified gVI, produced virus neutralizing antibodies and did not develop clinical signs after challenge exposure. The challenge virus was not isolated from nasal swabs and tonsils of gVI-vaccinated pigs, whereas non-vaccinated control pigs developed illness after challenge exposure with the same virulent ADV strain which was later recovered from their nasal swabs and tonsils. Pregnant sows vaccinated twice with purified gVI (IM) at a three week interval produced virus neutralizing antibodies in colostrum. Four-day-old sucking piglets born of vaccinated sows were passively protected by colostral antibodies against intranasal challenge with a lethal dose of virulent ADV. Sera from gVI-vaccinated pigs were distinguished from experimentally infected swine sera by their differential reactivity in enzyme-linked immunosorbent assay (ELISA) using four major viral glycoproteins (excluding gVI) as antigen purified by the use of lentil-lectin.

Animals↗

Changes of copper level and cytochrome c oxidase activity in the macular mouse with age.

The macular mouse is an animal model of Menkes disease. The neurological degeneration is caused by decreased cuproenzymes activity, such as cytochrome c oxidase (CCO), associated with copper deficiency in the brain. We investigated the age-related changes in copper concentration and CCO activity in the brain of macular mice which were given a single injection of cupric on postnatal day 7. The copper concentration in the brain of macular mice was always about 40% of that of the age-matched controls. However, the copper concentration of both macular and control mice increased with age gradually. The CCO activity in the brain of macular mice was significantly lower than that of controls at the age of 8 days. However the activity in macular mice increased with growth and reached a level equal to the controls at 180 days. These results suggest that the improvement of CCO activity in the brain of macular mice is due to the brain copper concentration which increased with age. Therefore, parenteral administration of copper is recommended especially during infancy in patients with Menkes disease.

Aging↗

Apocrine adenocarcinoma of the bilateral axillae.

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88-year-old Japanese male who complained of a mass lesion and pus-like discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP-15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma.

Adenocarcinoma↗

[Concentration of nitrosodimethylamine in commercial pelleted experimental animal diets].

To know the conditions of contamination by the chemicals in the experimental animal diets, the contents of nitrosodimethylamine (NDMA) were analyzed in the diets for mice and rats. The raw materials of the diets were also analyzed. In addition, NDMA levels were determined in the diets which were stored long or heated in the autoclaves. The averages of NDMA in these diets were less than 10 ppb. In the raw materials, alfalfa contained a higher levels of NDMA. There was no clear tendency of increase or decrease in NDMA levels, when the diets were stored for six months at room temperature (23-25 degrees C) or at low temperature (7-10 degrees C). Heating the diets at 121 degrees C, no remarkable changes were observed in NDMA levels. It seems that little adverse influences on the conduct of the animal experiments would be anticipated by the NDMA in the commercial diets.

Animal Feed↗

Coronary vasospasm following subarachnoid hemorrhage as a cause of stunned myocardium. Case report.

A patient with subarachnoid hemorrhage was found to have electrocardiographic abnormalities resembling an acute myocardial infarction as well as left ventriculographic findings of cardiac dysfunction. These cardiac abnormalities resolved following surgical clipping of the aneurysm and the patient recovered well from the operation. She died 2 months later from cancer and a postmortem examination at that time revealed no evidence of myocardial necrosis. In this report, the authors discuss coronary vasospasm and reversible postischemic "stunned myocardium," a condition that has not been considered previously in relation to subarachnoid hemorrhage.

Aged↗

[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.

Administration, Oral↗

Pyrogenic responses of the pika, Ochotona rufescens rufescens.

In 3-month-old male and female pikas, Ochotona rufescens rufescens, reared at an ambient temperature of 25 degrees C, the mean within-day body temperature was 39.2 degrees C without significant variance. At an ambient temperature of 35 degrees C it increased markedly in males while decreased slightly at 5 degrees C. The pikas showed lower sensitivity than Japanese white rabbits to a pyrogenic E. coli endotoxin.

Animals↗

Evaluation of primary lung carcinoma using technetium 99m-hexamethylpropylene amine oxime: preliminary clinical experience.

99mTc-labelled hexamethylpropylene amine oxime (HMPAO) is a lipophilic compound with a neutral charge which reflects tumor blood flow and has been previously investigated to estimate brain blood flow. In this study, we attempted to use 99mTc-HMPAO for the evaluation of 18 patients with histologically proven primary lung carcinoma. The eight surgical specimens revealed that viable carcinoma cells were present when the 99mTc-HMPAO accumulated in the tumor, however, extensive tumor necrosis was observed when defective or ring like uptake was seen in the tumor. Qualitative study revealed that when perfusion defects were observed corresponding to the tumor, the possibility of squamous cell carcinoma or large cell carcinoma was high instead of adenocarcinoma. Quantitative analysis revealed that the uptake ratio was statistically different between adenocarcinoma (1.6 +/- 0.1) and squamous cell carcinoma (1.2 +/- 0.4) (P less than 0.05), between squamous cell carcinoma and large cell carcinoma (0.9 +/- 0.1) (P less than 0.05), and also between adenocarcinoma and large cell carcinoma (P less than 0.01). In conclusion, 99mTc-HMPAO may be useful for the evaluation of patients with primary lung carcinoma.

Adenocarcinoma↗

Two-year carcinogenicity study of 6-mercaptopurine in F344 rats.

The carcinogenicity of 6-mercaptopurine (6-MP), an anticancer drug, was examined in F344 rats of both sexes, administered the chemical at dietary levels of 0 (control), 25 ppm or 50 ppm for 2 years. Many tumors developed in all groups including the control group, the organ distribution and histological types being similar to those reported for spontaneous lesions. In males, there was no significant increase in the incidence of any tumor in the treated groups over that in the control group. In females, however, positive trends were noted in the occurrence of C-cell tumors, pheochromocytomas, uterine adenocarcinomas and gliomas, and the incidences of C-cell tumors and pheochromocytomas in the 50 ppm group were significantly higher than the values in the respective control group. In addition, the total numbers of malignant tumors increased significantly in the female 50 ppm group. However, most of the tumors demonstrating increase are frequently observed spontaneous lesions in this strain of rats, and their incidences in the present female control group were lower than in our historical data. In addition, there were no significant differences in the incidences of preneoplastic changes and induction times for the above-listed tumors between the female control and the 50 ppm groups. These results thus indicated that while the carcinogenic potential of 6-MP can not be precluded, it can be only very weak or marginal, after continuous administration in the diet at the 50 ppm level for 2 years. The leukemogenic action of 6-MP was negative under the present experimental conditions.

Animals↗