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Biomedical subjects

D M Young

Publications and source records attributed to D M Young.

At least 55 records · Page 3Linked to original sources

Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates.

10 monkeys (macaques) received adriamycin by monthly intravenous injections at 12 mg/m2 (1 mg/kg). 8 of the 10 monkeys developed congestive heart failure at an average cumulative adriamycin dose (310 mg/m2) well below that considered the safe upper limit (550 mg/m2) in man. Histologically, the myocardial lesions resembled those found in human anthracycline-induced cardiomyopathy. 1 of the 10 monkeys developed acute myeloblastic leukemia after receiving 324 mg/m2 of adriamycin; the 10th monkey is alive and well 26 months after the last dose of drug. Our results suggest that adriamycin is a more potent cardiotoxin in monkeys than in man, and that leukemia may be a consequence of prolonged treatment with this drug.

Animals↗

A court-mandated workshop for adolescent children of divorcing parents: a program evaluation.

This article provides a description and an empirical evaluation of a predivorce workshop established by the Family Court of Allen County, Indiana, for adolescent children (N = 48) of divorcing parents. Highlighted are the concerns of the adolescents, the approaches taken by the workshop staff, and the impact of the program on the participants. Viewpoints on the clinical, ethical, and legal issues involved in "required" predivorce counseling for adolescents are presented. The preventive nature of the program, its means of transforming initial resentment toward the workshop experience into positive feelings, and the implications for future practice and research are also discussed.

Adaptation, Psychological↗

Role of pancreatic L-asparagine synthetase in homeostasis of L-asparagine.

L-Asparagine synthetase from mouse pancreas was found to be associated principally with the exocrine pancreas and to be dependent on the age of the animal, but not on gender, diet, or the presence of tumor under the conditions examined. The function of the pancreatic enzyme appears to be to supply L-asparagine for the synthesis of pancreatic proteins. This function is suggested by the high specific activity of L-asparagine in pancreatic proteins after intravenous treatment of BDF1 mice with L-[U-14C]asparatate. The pancreas is also able to function as a storage depot for L-asparagine under conditions in which the concentration of the amino acid in the blood is in excess. Unlike the liver, the pancreas is unable to add L-asparagine to the circulation when the concentration of the amide is below normal limits.

Age Factors↗

Partial oculocutaneous albinism in Mystromys albicaudatus: nonhomology with the Chediak-Higashi syndrome.

Partially albinic Mystromys albicaudatus were examined to determine if the condition in these animals was homologous with the Chediak-Higashi syndrome. Tissues and cells from partially albinic and normal Mystromys albicaudatus were studied by light and electron microscopy. No evidence of cytoplasmic granule enlargement, which is characteristic of the Chediak-Higashi syndrome, was detected in the cells of the partially albinic rats when compared to controls. It was concluded that the inherited condition of partial albinism of Mystromys albicaudatus was not homologous with the inherited partially albinic disease known as the Chediak-Higashi syndrome.

Albinism↗

In vivo toxicity to lymphoid tissue by 2'-deoxycoformycin.

The enzyme adenosine deaminase has an essential role in lymphocyte metabolism. To examine the in vivo effects of inhibition of this enzyme healthy BDF1 mice were injected intraperitoneally with 2'-deoxycoformycin, a stoichiometric tight-binding inhibitor of adenosine deaminase. Of the treated animals, 20% died of overwhelming infection, and histopathological examination of these, and surviving animals sacrificed 10 days following treatment indicated a selective toxicity to lymphoid cells. No toxicity to tissues other than the lymphoid system was observed, which is consistent with the hypothesis that 2'-deoxycoformycin offers a new and selective approach to the treatment of lymphoid malignancies.

Adenosine Deaminase Inhibitors↗

Quantification of bleomycin pulmonary toxicity in mice by changes in lung hydroxyproline content and morphometric histopathology.

Bleomycin treatment produced dose-dependent changes in lung collagen content and in several measurable histopathological parameters. NIH/Swiss mice were treated twice weekly for 6 weeks with bleomycin, 0, 1, 20, or 40 mg/kg s.c. The two highest doses produced mortalities of 35 and 100%, respectively, as well as loss of body weight and increase in lung wet weight. Lung hydroxyproline content, an index of collagen, increased to 40 to 50% above control levels at 6 and 8 weeks after initiation of treatment with bleomycin 20 mg/kg. Morphometric analysis was applied to the following parameters at light microscopy: number of intraalveolar macrophages and leukocytes, total pulmonary cell count, alveolar wall thickness, and percentage of consolidation of lung parenchyma. The two highest doses produced increases in all of these parameters as compared to controls. The most marked changes occurred in the number of intraalveolar cells, which in the group given 20 mg/kg rose to 150, 190, and 210% of controls at 4, 6, and 8 weeks. The lowest dose of bleomycin, 1 mg/kg twice weekly for 6 weeks, evoked no pulmonary or other toxicity by the parameters examined. This model of chronic pulmonary toxicity may be useful in analog development, in testing potential antidotes, and in examining the effects of other factors that might modify the pulmonary toxicity of bleomycin.

Animals↗

Naturally-occurring Sendai virus infection of athymic nude mice.

Nude (nu/nu) mice, Balb/c-derived, responded to a naturally-occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia.

Animals↗

Histogenesis and Morphology of periosteal sarcomas induced by FBJ virus in NIH Swiss mice.

FBJ virus was injected i.p. into 145 neonatal NIH Swiss [N:NIH(s)] mice. Eighty mice developed a total of 110 neoplasms by 5 months of age. The mean latent period of the tumors was 71 days (26 to 145) postinjection. The frequency of occurrence of neoplasms at different sites was: diaphragm, 45%; ribs, 14%; vertebrae, 14%; femora, 9%; pelvic bones, 5%; tibiae, 4%; sternebrae, 3%; and inguinal area, 7%. The neoplasms were characterized histologically by elongated or rounded cells associated with an abundant connective tissue stroma. Occasional areas of bone formation and apparent osteoid metaplasia were seen. Bone tumors appeared to arise from periosteal cells, to grow by expansion, and to invade locally, but they failed to metastasize. Neoplasms of the diaphragm originated in the central aponeurosis and appeared histologically similar to bone neoplasms. Histochemical studies demonstrated abundant alkaline phosphatase in tumor cells, and ultrastructural observations revealed subcellular characteristics of osteoblasts and chondroblasts. Tumors were readily transplantable and had histopathological characteristics similar to those of the primary viral-induced tumors. The results of this study indicate that the FBJ virus induces in NIH Swiss mice a unique type of chondroosseous neoplasm derived from periosteal cells which has a resemblance to human juxtacortical (parosteal) osteosarcoma.

Alkaline Phosphatase↗

Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study.

Rabbits receiving intramuscular injections of VX-2 carcinoma cells in biceps femoris muscles developed rapidly progressive neoplastic growths at 14 to 21 days associated with a significant hypercalcemia. The biologic behavior of the VX-2 carcinoma was characterized by local infiltration and metastases to regional lymph nodes and lungs. No metastases to skeletal tissues were evident. Femora from intramuscularly injected rabbits had varying degrees of osteophytosis and lysis evident roentgenographically. Histopathologic evaluation of femoral sections revealed periosteal new bone growth, cortical osteolysis, endosteal new bone growth, and in a few long term rabbits, pathologic fractures. Bone lesions were evident histologically in the vicinity of neoplastic growth (i.e., femora, tibiae) but not at distant sites (i.e., humeri and vertebrae). Mineral analyses of VX-2 carcinoma tissues and kidneys from VX-2-bearing rabbits revealed concentrations of calcium 83 and 3 times greater, respectively, than those of skeletal muscle and kidneys from controls. These findings correlated well with histochemical evidence of excessive amounts of calcium in sections of kidneys and VX-2 carcinoma tissues. Rabbits receiving intraperitoneal injections of VX-2 carcinoma cells did not develop hypercalcemia despite an extensive, progressive neoplastic burden with metastases to abdominal and thoracic viscera. Roentgenographic, histopathologic, and physiochemical analyses of selected bones from these rabbits revealed no significant alterations. These findings indicate that VX-2 carcinoma cells need to be in close proximity to skeletal tissues in order to induce hypercalcemia. The development of a significant hypercalcemia in intramuscularly injected rabbits precedes the invasion of osseous tissues by VX-2 carcinoma cells. Therefore, it appears that VX-2 carcinoma cells have the ability to alter skeletal morphology and physiochemistry through a dual humoral/cellular mechanism. The clinicopathologic characteristics of the VX-2 carcinoma in the rabbit suggest that the neoplasm is a good experimental model to study osseous-mediated hypercalcemia of malignancy.

Animals↗