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Biomedical subjects

E E Deschner

Publications and source records attributed to E E Deschner.

At least 55 records · Page 3Linked to original sources
PubMed1982

Cancer induction after pyloroplasty in rats: treatment with N-methyl-N'-nitro-N-nitrosoguanidine.

Nineteen male Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water (83 mg/L) to initiate glandular adenocarcinoma of the stomach; eight control rats received tap water. After 12 weeks a pyloroplasty was performed on nine rats receiving MNNG and three control rats. Ten MNNG-treated rats and five control rats had no operation. All were observed for 38 weeks before being killed. No difference in the incidence of antral adenocarcinomas was found between the MNNG-treated groups; however, those without operation showed in situ changes in the duodenum and those treated with pyloroplasty showed five invasive adenocarcinomas. In this model pyloroplasty alone did not increase the risk of gastric cancer but increased the risk of duodenal tumors. Pyloroplasty apparently accelerated the gastric evacuation rate, resulting in greater insult to the duodenal mucosa. Such a condition may require a higher proliferative rate in the duodenum and may increase subsequent formation of malignant tumors.

Adenocarcinoma↗
PubMed1982

The kinetics of the protective effect of beta-sitosterol against MNU-induced colonic neoplasia.

The effect of dietary supplementation with beta-sitosterol (0.2% of diet) was followed in Fischer rats after both acute and chronic feeding. Compared to controls after 3 and 7 days, the number of epithelial cells per crypt column in both plant sterol fed groups was shifted to lower values; moreover, fewer cells above cell position 12 were engaged in DNA synthesis. Continued feeding of beta-sitosterol for 28 weeks revealed the number and position of 3HTdR-labeled cells per crypt column after 1 pulse labeling to be similar to that seen in the acute phase. However, differences were more marked after 24 h showing the maximum number of labeled cells per column to be at least 25% less than the untreated group and the leading edge of labeled cells moving more slowly up the crypt wall. Rats treated with N-methyl-N-nitrosourea (MNU) intrarectally (8 mg/animal) while simultaneously consuming beta-sitosterol demonstrated a reduction in the size of the proliferative compartment as well as the number of labeled cells per crypt column as compared to rodents receiving just the carcinogen (3.3 and 5.4 mean labeled cells per column, respectively). At this time, MNU-treated rats fed beta-sitosterol had a significantly decreased colonic tumor incidence (Raicht et al. 1980). This plant sterol which passes through the digestive tract relatively unabsorbed appears to slow colonic epithelial cell proliferation resulting in a reduced expression of neoplastic transformation.

Animals↗
PubMed1982

Possibility of detection of an in vitro expression of a group of human cancer-prone genes by automated methodologies.

Increased in vitro hyperdiploidy has been considered to be an in vitro expression of some cancer-prone genes in human dermal monolayer cultures. Examination of metaphases in chromosome preparations does not lend itself to studies on either large high-risk kindreds or populations. It is postulated that increased in vitro hyperdiploidy should be detected by 2 different automated assays for cellular DNA content: (a) incorporation of [3H]thymidine during logarithmic growth and (b) the occurrence (%) of cells with double (4n) and greater than double (greater than 4n) DNA content by flow cytophotometry. Concurrence between these two assays and with the metaphase assay should make feasible the use of this in vitro abnormality in the identification of individuals at increased cancer risk.

Adolescent↗
PubMed1982

Murine colonic mucosal metabolism and cytotoxicity of benzo [alpha] pyrene.

Homogenates of colonic mucosa from seven mouse strains metabolized 14 C-benzol [alpha] pyrene (BP) to alkali-soluble and water-phase products. In those strains in which liver aryl hydrocarbon hydroxylase activity is inducible by beta-naphthoflavone (beta-NF), the C57Bl/6, BALB/c, C3H and random-bred Swiss CD-1, colonic metabolism of BP was also induced by intraperitoneal treatment with 150 mg/kg beta-NF 24 h before assay. No increase in the colonic metabolism of BP was seen after beta-NF treatment of the noninducible strains, AKR, DBA and SWR. A detailed study of the products formed was carried out with C57BL/6 male mice. High-performance liquid-chromatography analysis of the products of BP metabolism revealed that phenolic derivatives predominated, but that a small percentage of the BP was converted into the proximate carcinogen, the BP-7,8-diol. Addition of uridine 5'-diphosphoglucuronic acid to the incubation mixture caused an increase in total product formation and a shift from alkali-soluble to water-phase products. Of the water-phase products formed by beta-NF-induced colonic mucosal homogenates, about 40% were nondialyzable and associated with precipitable material. In a study of the cellular effects of BP on the colonic mucosa, intrarectal administration of 1 mg BP had a significant cytotoxic effect, as indicated by the number of pyknotic cells and 3H-thymidine-labeling index, and prior treatment with beta-NF afforded significant protection against this cytotoxicity.

Animals↗
PubMed1981

[Markers in the detection and prevention of colorectal carcinomas (author's transl)].

The ever increasing frequency of colorectal carcinomas in Western countries justifies the search for, and development of early detection and prevention methods. The use of markers should improve the prognosis of such cancers in the near future. With the exception of occult blood testing, which has been used in mass screening, most markers are still reserved for high risk population studies. These markers will also help to detect pre-neoplastic conditions where prevention would be possible.

Adult↗
PubMed1981

Kinetic and morphologic alterations in the colon of a patient with multiple polyposis.

The histologic and proliferative characteristics of 16 colonic biopsies taken from an operative specimen of a 38-year-old female patient with multiple polyposis are presented. Kinetic measurements are based on 3HTdR incorporation accomplished in vitro, using both single and double labelling techniques. Epithelial cells in adenomatous tissue were more actively engaged in DNA synthesis than those normal-appearing mucosa (L.I.13.0 +/- 6.9 versus 9.3 +/- 1.6); however, because of extreme variability between biopsies, the difference was not significant. No difference in S phase duration was found, but a faster turnover time (Tg) than that in the normal appearing colonic mucosa was estimated (Tg 52.6 hours versus 74.2 hours). Only two of ten biopsies containing normal-appearing mucosa had a completely normal incorporation pattern with proliferative cells located only in the lower two thirds of crypts. Eight biopsies showed extension of the proliferative compartment to the luminal surface. One of these eight also expressed an additional proliferative defect, namely, a shift of the major zone of DNA synthesis to the middle and upper regions of the crypts. This specimen had been located adjacent to an area of microscopic adenoma. Subpopulations of labelled epithelial cells showing transition from normal to hyperplastic or to adenomatous appearance were in the otherwise normal-appearing crypts. The majority of labelled hyperplastic-appearing cells occupied the lower thirds of the crypts, whereas 68% of labelled adenomatous-appearing cells were located in the middle and upper zones of the glands. Based on these observations, the development of an adenoma is believed forecast by the redistribution of the proliferative compartment toward the surface. A further stage in tumorogenesis before the appearance of a focus of neoplasia is the emergence of actively proliferating cells transforming to a more adenomatous appearance primarily in that same location, that is, the middle and upper third of the colonic crypts.

Adenoma↗
PubMed1981

Acute and chronic effect of dietary cholic acid on colonic epithelial cell proliferation.

Administration of cholic acid (1.0% of the diet) to male Fisher rats for 3 days resulted in increased numbers of DNA synthesizing epithelial cells per colonic crypt column as compared to those found in either control or 0.2% cholic acid-fed rats. The middle third of the crypt was the area stimulated to contribute the additional proliferating cells. The maximum number of 3H-TdR-labeled cells was doubled by 24 h and migration had processed further up the colonic crypt of the 1% cholic acid-fed rats than the 0.2% cholic acid or control animals. Compared with cholic acid-deprived rats, long-term dietary intake of 0.2% cholic acid (26 weeks) was found to heighten the numbers of labeled cells per column and expand the proliferative compartment. The enhanced manifestation of colonic neoplasia in MNU-induced rats consuming cholic acid (previously reported by us) appears related to the elevated levels of cell proliferation brought about in response to the deleterious action of the bile acid on the mucosa. Increased numbers of epithelial cells undergoing DNA synthesis in cholic acid-treated animals would allow the earlier expression of malignant transformation in the large intestine.

Animal Feed↗
PubMed1979

Relationship between dose, time, and tumor yield in mouse dimethylhydrazine-induced colon tumorigenesis.

Colorectal tumor yield and volume data were obtained using 355 CF1 mice serially sacrificed up to 84 weeks following various dose levels of the carcinogen 1,2-dimethylhydrazine dichloride (DMH). Several conclusions were reached: (a) With increasing doses of DMH, there was an increased tumor yield and decreased latency period. (b) With repeated doses, there was a rapidly cumulative tumor yield. (c) New tumors continued to accumulate in the colon and rectum even at long intervals after the DMH treatments. This was substantiated by a positive correlation between the number of tumors per colon and the delay after DMH. In addition, when several tumors were present in the same mouse, their sizes were graded rather than uniform. These observations are consistent with a 2- or multi-step carcinogenesis mechanism. The latter implies that DMH induces a permanent transmissible alteration within some cells which thereafter will be at risk for further alterations capable of initiating cancer growth.

Animals↗
PubMed1979

Influence of bile on kinetic behavior of colonic epithelial cells of the rat.

The acute effect of bile deprivation on colonic epithelial cell proliferation in Sprague-Dawley rats was investigated and compared with its effect on jejunum and ileum. 2. days after the creation of bile fistula, tritiated thymidine was injected and animals sacrificed 1 and 24 h later. Compared with control untreated animals, sham-operated restrained rats had a reduced labeling and mitotic index of the colonic epithelial cell population as well as a slower migration of cells to the lumen. Colonic cell proliferation in animals deprived of bile flow was reduced a further 50%. Moreover, no evidence of cell migration or appreciable decline in grain density was seen over 24 h in bile fistula rats. Alterations in cell proliferation in both sham and bile fistula treated rats became less marked as one proceeded proximally to the small bowel. Therefore, significant alterations in cell kinetics result when normal bile flow is interrupted, suggesting its importance in the regulatory control of colonic cell proliferation.

Animals↗
PubMed1979

Sequential histopathology and cell kinetic changes in rat pyloric mucosa during gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The effect of administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at a dose level of 83 mg/liter in the drinking water was followed in the pyloric mucosae of male noninbred Wistar rats. Autoradiographic studies were done on animals killed after 10, 15, 26, and 36 weeks of treatment. In the normal-appearing mucosae of the rats treated with MNNG for 10 weeks, the number of epithelial cells per pit column was significantly increased over that in control rats. Simultaneously, a shift in the major zone of epithelial cell proliferation was noted in the treated rats. Along with the formation of a longer pit in MNNG-treated rats, the greatest number of DNA-synthesizing cells was displaced from the middle third of the pit in a downward direction toward the muscularis mucosa. In addition, at this early experimental time period, pits lined with more immature, cuboidal, mucus-depleted cells were recognizable. These pits not only had higher labeling indices than normal-appearing pits of the same animals but also expressed a dual nature with increased proliferative activity extending either upward to the luminal surface or further in a downward direction. Focal areas of cellular atypism were present by week 10 of treatment with a threefold to sevenfold greater DNA synthesis activity than that found in the normal-appearing mucosa of the same animal. A wide range of values in proliferative activity was found not only among invasive pyloric tumors within the same animal but also within different areas of the same tumor. The mechanism for the formation of adenomas and invasive adenocarcinomas is believed to be related to the dual character of the hyperplastic pits described.

Animals↗
PubMed1978

[3H]thymidine-labeled colonic epithelial cells and mucosa in mice and man.

Since normal epithelial cell proliferation occurs chiefly in the lower two thirds of colonic crypts, the presence of aberrant DNA-synthesizing cells (tritiated thymidine labeled) at the mouth and on the surface of colonic crypts is being assessed as a predictive indicator of the development of neoplasia in patients at high risk. These would include patients with previous polyps or colon cancer or family history of either or both. Surface cells are obtained by pulsatile saline lavage of the lower bowel and incubated with tritiated thymidine ([3H]TdR) for autoradiographic observation. Findings in each high-risk category are presented and compared with [3H]TdR labeling data from a biopsy taken at the close of the procedure. The lavage technique has also been carried out on mice injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). Mice were demonstrated to have [3H]TdR-labeled cells and cellular atypic while being hemoccult negative and asymptomatic for overt disease. Evaluation of human material preliminarily demonstrated the presence of surface-labeled epithelial cells in a high percentage of patients at risk for colon cancer.

Adolescent↗
PubMed1977

Early detection of colonic neoplasia in patients at high risk.

An abnormal zone of DNA synthesis at the surface and upper portion of colonic crypts has been thought to be related to future adenomatous polyp development and to express a regulatory defect in the mechanism that normally terminates synthesis in the upper third. As part of a screening program for early colon cancer detection, patients over 40 years of age found to have occult blood in their stool (Ho+) are evaluated by barium enema and colonscopy as well as isotopic incorporation studies of biopsy and lavage specimens. This proliferative abnormality occurred most frequently among patients with an adenoma or adenocarcinoma although the frequency varied among simultaneous biopsies from the same patient. Specimens from Ho+ patients with a tumor often contained small areas of focal atypism in the biopsy or fragments of atypical epithelial cells in the lavage sample. A small group of Ho+ patients in whom no overt neoplasm could be detected also demonstrated surface-labeled epithelial cells with morphological alteration of these cells. Based on the microscopic findings presented, continued surveillance of these patients is suggested, as well as extension of these studies to include other high risk groups.

Adult↗
PubMed1977

Tritiated thymidine incorporation into epithelial cells of normal-appearing colorectal mucosa of cancer patients.

A radioautographic analysis of the number and position of labeled epithelial nuclei after in vitro incorporation of tritiated thymidine ([3H]TDR) was carried out with 30 specimens of histologically normal colorectal mucosa from 26 patients, of whom 13 were being treated for rectal or sigmoid cancer and 13 were controls. A higher mean labeling index was found in the cancer than in the control group (9.8% +/- 1.2 and 7.9% +/- 0.9, respectively). Because of wide individual variations, this difference was not statistically significant. However, a highly significant upward shift of the proliferating cell compartment was observed in the cancer group, resulting in a specific modification of the [3H]TDR labeling pattern in 6 of 17 specimens. DNA synthesis predominated in the middle or middle and upper thirds of the crypts of Lieberkühn rather than in the lower third as observed in controls. The patchy alteration of epithelial cell renewal frequently accompanying colorectal cancer was suggestive of a defect in the regulatory control mechanism. This in vitro [3H]TDR incorporation assay could provide a valuable discriminatory parameter in studies of high-risk populations.

Adult↗