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Biomedical subjects

E E Deschner

Publications and source records attributed to E E Deschner.

At least 73 records · Page 4Linked to original sources

Colonic neoplasms in mice produced with six injections of 1,2-dimethylhydrazine.

A highly effective but reduced injection schedule for the induction of the colon cancer in CF1 female mice is reported using 6 subcutaneous inoculations of 1,2-dimethylhydrazine at a dose level of 20 mg/kg body weight. Between the 20th and 45th week of the experiment, 83% of the animals were tumor-bearing with a frequency of 2.1 colonic neoplasms macroscopically visible per mouse. Tumors were isolated in nature and primarily located in the distal large bowel. Some degree of carpeting of the colonic mucosa and uncountable numbers fo tumors occurred in 30% of mice and these areas of confluent neoplasms also occurred predominantly in the distal colon. This spectrum of distribution of tumors closely parallels that seen in man thus enhancing the value of this time conserving colon tumor model.

Animals↗

Gastrointestinal cancer studies in the human to nude mouse heterotransplant system.

Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents.

Adenocarcinoma↗

Radioautographic observations of a 19-month-old ileal conduit.

The influence of an altered environment of the cellular kinetics and histological appearance of ileal mucosa used as a urinary bladder was investigated in a patient with a conduit of 1 year and 7 months' duration. After injection of 10 mc of 3H-TdR, multiple biopsies were taken spanning a 3-day period. No increase in inflammatory cell numbers was seen and villous atrophy was minimal. A generation time or total cell cycle time of 36 hr was observed, with a G1 phase of 22 hr and an S phase of 11 hr. At 1 hr 2.4 3H-TdR-labeled cells per crypt column and a mitotic index of 1.4% were obtained. The complet labeled mitosis curve obtained on the epithelial cells of the 19-month-old ileal conduit mucosa demonstrated a retention of the kinetics and histological characteristics of normal ileal mucosa, contrary to previously documented findings.

Autoradiography↗

Lymphatic drainage of the breast on and through the pectoral muscles: importance in breast cancer.

As proponents of lesser procedures have called into question the necessity of removing the pectoral muscles in surgery for cancer of the breast, there has been a need to establish accurately the relationship of the lymphatics to the pectoral muscles and their fascia. This problem has been approached using the technique of high resolution autoradiography. After histologic review of pectoral muscles from rabbits into whom a tritiated high-molecular-weight dextran was injected subareolarly, a high degree of labeling was found deep within the septa of the pectoral muscle bundles as well as along the investing fascia. It was concluded that lymphatic draining mammary lymph pass deep within the pectoral muscles in this species.

Animals↗

Proliferative patterns in colonic mucosa in familial polyposis.

Microautoradiographic measurements of TdR3H incorporation into epithelial cells of colonic biopsies were compared in normal and eight index cases with familial polyposis, an inherited trait characterized by the development of colonic polyps and carcinomas. Colonic epithelial cells normally synthesized DNA synthesis was proliferated in the deeper two-thirds of the crypts, while DNA synthesis was repressed in the upper one-third. Patients with familial polyposis and patients with isolated single polyps incorporated TdR into epithelial cells lining the surfaces of polyps and occasionally into surface cells of intervening flat mucosa. Symptom-free members of polyposis families also demonstrated TdR3H incorporation into surface epithelial cells in biopsies of morphologically flat mucosa. The findings indicate similar proliferative behavior of epithelial cells in the formation of all adenomas, be they single isolated polyps or multiple familial adenomatous polyps. A sequence of changes occurs involving a loss of the cells' ability to repress DNA synthesis and the appearance of cells with persistent DNA synthesis at the surface and along the upper portion of colonic crypts. These defects are focal and widespread in the colonic mucosa of those with familial polyposis and are expressed at early age.

Adolescent↗

The detection of aberrant DNA synthesis in a member of a high-risk cancer family.

Relatives of patients with multiple polyposis are among those at high risk for development of neoplasms in the colon. Examination of 4 siblings, 3 men and 1 woman, of a patient with multiple polyposis was conducted for the possible presence of colonic polyps. All patients were over 40 years of age and received barium enemas for the radiological detection of excrescences. Proctoscopic examinations were also carried out during which time a biopsy and colonic wash were obtained. Polyps were absent on films as well as on endoscopy, and colonic cytologies of all 4 subjects were within normal limits. However, isotopic incorporation studies revealed the presence of an abnormal labeling pattern in some crypts of the biopsy incubated with TdR-3H of 1 family member. Along with normal crypts with label in the lower two-thirds of the colonic crypts, some were seen to have cells labeled at the surface, a proliferative lesion thought to precede the apperarance of a polyp. Among the surface cells removed by the colonic wash, some were found to be isotopically labeled, that is, engaged in DNA synthesis. Thus, a defect in the regulation of colonic epithelial cell replication was found, suggesting the need for close surveillance in the interest of early colon cancer detection.

Adult↗

Kinetics of absorption of toxin of Vibrio cholerae.

Autoradography of rabbit intestine exposed in vivo to purified tritiated toxin of Vibrio cholerae showed that pharmacologically important amounts of toxin can be rapidly absorbed despite the relatively large size of the toxin molecule and its affinity for binding to the brush border. Cholera toxin and tritiated nontoxic and tritiated nontoxic control substances of comparable size followed a similar time course in spreading down the surface of the villus, and with respect to the villus greater than crypt gradient of labeling of cytoplasm of the mucosal epithelial cells. Absorption of toxin or biologically active toxin fragments provides a mechanism whereby the basal and lateral areas of the cell, which are rich in adenyl cyclase, could participate in the hypersecretory process.

Absorption↗