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Biomedical subjects

J M Ward

Publications and source records attributed to J M Ward.

At least 361 records · Page 20Linked to original sources

Histopathology of neoplastic and nonneoplastic hepatic lesions in mice fed diets containing tetrachlorvinphos.

Tetrachlorvinphos was fed at 8,000 or 16,000 ppm in diets to male and female (C57BL/6N X C3H/HeN)F1 mice for 80 weeks. Surviving mice were killed at 92 weeks, and all mice were completely necropsied. A high incidence of unusual nonneoplastic hepatic lesions in treated mice was present and characterized by pericellular fibrosis, hepatocyte nuclear pleomorphism, and intrasinusoidal foci of macrophages with intracytoplasmic crystalline structures. From 84 to 94% of the treated male mice and from 21 to 23% of the treated females had hepatocellular neoplasms. Only 17% of the control males and 7% of the control females had liver tumors. The induced tumors were frequently multiple in the liver, whereas the tumors in the controls were usually singular. The morphology of 241 liver tumors in 110 treated mice was different from that of tumors in controls. Liver tumors in control mice were generally composed of small basophillic hepatocytes. In treated mice, tumors were hepatocellular carcinomas composed of solid sheets of large basophilic or eosinophilic hepatocytes. Foci of prominent trabecular formation were seen in 51 tumors. Fifteen tumors were composed of small basophilic hepatocytes with oval cells interposed among them. Foci of capillary formation were noted in 3 of these tumors. In addition, 7 more typical hemangiosarcomas forming sinusoids and with thrombosis were observed.

Animals↗

Renal carcinogenic and nephrotoxic effects of the flame retardant tris(2,3-dibromopropyl) phosphate in F344 rats and (C57BL/6N X C3H/HeN)F1 mice.

Tris(2,3-dibromopropyl) phosphate (TBP) was administered in the feed at one of two concentrations to groups of 55 male and 55 female inbred F344 rats and to 50 male and 50 female (C57BL/6N X C3H/HeN)F1 mice. The high and low dietary concentrations of TBP administered orally were 100 and 50 ppm for the rats, respectively, and 1,000 and 500 ppm for the mice, respectively. For each rodent type, 55 animals of each sex were used as contols. In both rodent types, renal epithelial tumors developed at incidences that were significant for male and female rats and mice that received the doses. These tumors included renal tubular cell adenomas and carcinomas that developed from the proximal convoluted tubular epithelium. Among female mice and rats, hyperplasia and/or dysplasia of the proximal convoluted tubular epithelium with or without cystic dilatation of the tubules and increase in the size of cell nuclei were dose dependent and recognized as preneoplastic and/or toxic lesions. The comparative histogenesis of renal tubular neoplasms was discussed.

Adenocarcinoma↗

Histopathology of liver carcinomas in (C57BL/6N X C3H/HeN)F1 mice ingesting chlordane.

(C57BL/6N X C3H/HeN)F1 male mice that ingested 30 or 56 ppm chlordane and female mice that ingested 30 or 64 ppm chlordane in the diet had highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis. They were more poorly differentiated in mice receiving chlordane than in controls.

Animals↗

Evaluation of procedures suggested for reducing the pathology workload in a carcinogenesis testing program.

A sampling procedure for reducing the pathology workload in evaluating a carcinogenicity bioassay was utilized for a rodent bioassay. The use of the procedure resulted in 50 percent fewer tissues being examined histologically, in the control groups and 12 percent fewer tissues in the treatment groups. The obvious saving in pathologist's time was negated by an increase in technician time, interference with quality control procedures and loss of nontumor pathology information.

Animals↗

Correlation between gross observations of tumors and neoplasms diagnosed microscopically in carcinogenesis bioassays in rats.

Microscopic diagnoses of spontaneous and induced neoplasms in F344 rats in two carcinogenesis bioassays were correlated with the gross observations made at the time of necropsy. The results for a negative and a positive compound with reference to carcinogenicity, indicate that of the gross descriptions indicative of tumors, 37 percent and 24 percent respectively, were not diagnosed as neoplasms microscopically. However, some of the gross lesions were diagnosed histologically as nonneoplastic lesions. Of the neoplasms diagnosed microscopically only 70 percent and 76 percent, respectively, were observed grossly. Endocrine tissues, liver and lung had the lowest correlation rates. The implications of these findings are discussed.

Animals↗

Clinical and pathologic conditions of female nude (athymic) mice in two conventional maintained colonies.

Two colonies of female outbred nude (athymic) mice were maintained by conventional standards of husbandry, but with special sanitary methods and segregation from other rodents. A total of 1,526 mice entered the colonies. Of these, 802 were untreated and most remained healthy. Necropsies were performed on 312 untreated mice that were sick and were killed or died naturally, and the tissues were examined microscopically. Clinical and pathologic conditions in the untreated mice included subcutaneous abscessation, dermatitis, subcutaneous edema due to glomerulonephritis (nephrotic syndrome), rectal prolapse, and lymphomas and other neoplasms.

Abscess↗

Dose response to intrarectal administration of N-methyl-N-nitrosourea and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats.

Male F344 rats, 8 weeks of age, were given 16 intrarectal administrations of N-methyl-N-nitrosourea (NMU) at one of three dose levels over a period of 8 weeks. Five days after the final NMU instillation, rats were placed on one of three diets: chow with gelatin beadlets, chow with beadlets containing 0.024% 13-cis-retinoic acid, or chow and beadlets with 0.006% of the trimethylmethoxy phenyl analog of retinoic acid ethylamide. Groups of 20-40 rats were killed at 22-26 weeks after the first carcinogen treatment. The number of rats with colon carcinoma and the number of tumors per rat were dose related. In addition, "blind" histopathologic evaluation of four predesignate colon locations revealed a dose-related incidence of microscopic preinvasive and invasive colon carcinomas. The feeding of diets containing these two retinoids did not significantly alter the incidence of these parameters of carcinogenesis or the mean histopathologic score at predesignated colon locations for preinvasive or invasive neoplastic lesions. Over 90% of the colon neoplasms induced were invasive tubulopapillary adenocarcinomas. The diameters of the tumors correlated significantly with degrees of invasion of the colons. Only 1 tumor (a signet ring carcinoma) metastasized to the peritoneal cavity. Only 2 of 300 rats treated with NMU had tumors at sites other than the colon.

Adenocarcinoma↗

HLA antigens in persistent palmoplantar pustulosis and its relationship to psoriasis.

HLA typing was performed on 93 patients with persistent palmoplantar pustulosis. The incidence of either HLA B13 or BW17 was not significantly increased as compared to controls. In addition the frequency of BW35 was no different from controls. However, the present results document a significantly increased frequency (38.7%) of B8. Taken together these data are good evidence that palmoplantar pustulosis is a genetically distinct disease entity from psoriasis vulgaris, despite the increased incidence of psoriasis in the condition.

Female↗

Pulmonary pathology of the motheaten mouse.

Mice, homozygous for the motheaten gene, developed an unusual pneumonia that was the cause of natural death of mice by 7 weeks of age. Initial lesions consisted of focal accumulations of alveolar macrophages in alveoli, especially adjacent ot bronchioles. Needle-like crystals formed in lysosomes of macrophages and numerous macrophages with crystals filled most alveoli in 5- to 7-week-old mice. Although motheaten mice had lesions in other tissues and were shown by other investigators to have immunological defects, the unusual pneumonia was the only lesion severe enough to cause death.

Animals↗

Evaluation of hepatocellular neoplasms in mice.

Thirty C3H-AvyfB male mice from 3 to 15 months of age were killed, and the genesis of their hepatocellular neoplasms was studied. As the mice aged, the number of tumors per liver and mean diameter of the tumors increased. Histologically, the smallest tumors were composed of solid sheets of cells and were better differentiated than the largest tumors. Small foci of hepatocytes in prominent trabeculae formation was a common characteristic of large tumors. In addition, 18 metastatic hepatocellular carcinomas observed in aged C3H-AvyfB, C3HfC, C3H, C3HfB, (C3HfB x YBR)F1, or C57BL/6 mice were also included for a morphologic study of their primary and metastatic lesions. Invariably, the pulmonary metastases were composed of a well-differentiated sheet of hepatocytes that resembled those in the solid liver tumors. The smallest hepatocellular neoplasms appear to represent early stages in the development of metastatic hepatocellular carcinoma.

Age Factors↗