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A Medline

Publications and source records attributed to A Medline.

At least 37 records · Page 2Linked to original sources
PubMed1991

Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon.

Foci of aberrant crypts (ACF) have been identified in the unsectioned methylene blue stained rodent colons and hypothesized to represent precursor lesions of colon cancer. In the present study, induction and growth characteristics of ACF were investigated in response to a single injection of varying dosages of 1,2-dimethylhydrazine-2HCl (DMH), a colon carcinogen. Female Sprague-Dawley rats were given a single injection of DMH (5-150 mg/kg). Two and 19 weeks after the injection, animals were killed and their distal 10 cm of colons were enumerated for the number and crypt multiplicity of ACF. Number of ACF increased with increasing dosages of DMH plateauing at 100 mg/kg. However, percentage of ACF exhibiting different crypt multiplicity (1 to greater than 4) were similar among different dose groups. Aberrant crypts and normal crypts were enumerated for total number of cells and number and distribution of S-phase cells along the crypt height 19 weeks after DMH injection after autoradiography. The labeling index (LI) (percentage of S-phase cells) and LI along the crypt height were determined. Compared to the surrounding normal crypts, aberrant crypts exhibited significantly higher (P less than 0.05) number of cells (1122 +/- 81 versus 411 +/- 28) and higher (P less than 0.05) LI (21 +/- 1 versus 12 +/- 1). For the eight ACF analysed in the present study, the distribution of S-phase cells in the aberrant crypts were similar to that of normal crypts in that S-phase cells were restricted to the lower two-thirds of the crypts rather than distributed throughout the height of the crypts as reported for adenomatous epithelium.

1,2-Dimethylhydrazine↗
PubMed1990

Promotion of colonic microadenoma growth in mice and rats fed cooked sugar or cooked casein and fat.

We studied the effect of cooked food components on the promotion of microadenoma growth in the colons of mice and rats. CF1 mice and Fisher 344 rats were initiated with azoxymethane, with 152 mice receiving four weekly i.p. injections of 5 mg/kg, 59 rats receiving a single injection of 20 mg/kg, and 24 rats receiving 30 mg/kg. A week after the last injection, the animals were randomly assigned to one of eight diets with identical ingredients, but the three components, sucrose, casein, and beef tallow, either uncooked or cooked. Control animals were given diets with uncooked ingredients. Experimental animals were fed diets in which one, two, or three of the components were cooked in an oven at 180 degrees C until golden brown before they were added to the diet. After 100 days on the diets, the colons were fixed, stained with methylene blue, and scored for microadenomas. The mice and the rats fed cooked sucrose, or casein and beef tallow cooked together, had three to five times more large microadenomas than did the controls (P ranging from 0.02 to 0.0001). No significant increase was observed with the five other cooked diets. Two rats fed the casein and beef tallow cooked together had adenocarcinomas. Thus, a diet containing 20% of cooked sucrose, or 40% of casein and beef tallow cooked together, promotes the growth of colonic microadenomas in initiated mice and rats, and would appear to contain promoters for colon cancer.

Adenoma↗
PubMed1987

Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis.

Liver biopsy specimens (178 percutaneous and 39 transjugular) were assessed from 217 consecutive patients with alcoholic liver disease, 77 noncirrhotics and 140 cirrhotics, whose cases were followed for 5 yr. Cirrhotic patients were categorized into two groups, with and without "hepatitis" using a criteria to define "hepatitis" that included only degrees of inflammation, necrosis, and Mallory bodies that had a prognostic weight in terms of mortality in 1 yr. This classification resulted in a sharp separation between a group of 42 patients with cirrhosis without "hepatitis" and with low mortality, both at 1 yr (7.1% +/- 4.0%) and at 5 yr (31% +/- 7%), and another group of 98 patients with cirrhosis and "hepatitis" and a high mortality both at 1 yr (26.5% +/- 4.5%, p less than 0.01), and at 5 yr (47% +/- 5%, p less than 0.02). Importantly, the 1-yr mortality in patients with cirrhosis and no "hepatitis" was not statistically different from that of patients with no cirrhosis or "hepatitis" (most of whom had only fatty liver) both at 1 yr (6.9% +/- 3.3%) and at 5 yr (24% +/- 6%). There were marked differences in several variables between cirrhosis with and without "hepatitis" [combined clinical and laboratory index: no "hepatitis": 4.9 +/- 0.7, with "hepatitis": 7.8 +/- 0.5, p less than 0.01; score of collagen in space of Disse: no "hepatitis": 2.1 +/- 0.4, with "hepatitis": 3.7 +/- 0.3, p less than 0.01; hepatocyte cross-sectional surface area: no "hepatitis": 682 +/- 51 micron 2, with "hepatitis": 841 +/- 31 micron 2, p less than 0.01]. These findings were more severe in the transjugular group than in the percutaneous group. Collagen in the space of Disse and hepatocyte surface area were not statistically different when cirrhosis without "hepatitis" was compared with a similar no "hepatitis" group of patients having noncirrhotic alcoholic liver disease. In this patient sample the presence of parenchymal nodules and fibrous septa, per se, did not result in an increase in mortality with respect to alcoholic patients without cirrhosis and with no "hepatitis."

Follow-Up Studies↗
PubMed1986

Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.

A single pass perfusion system was used in anaesthetised, restrained rats to examine the effect of changing the composition of the perfusion fluid on the damage caused to the colonic epithelium by deoxycholic acid. Damage to the colonic surface was monitored with light microscopy, transmission and scanning electron microscopy and with measurements of deoxyribonucleic acid and carbohydrate in the perfusate. New scoring techniques for monitoring alterations in surface epithelium of light microscopy sections were used. The damaging effect of 5 mM deoxycholic acid to the colonic epithelium is inhibited by lowering the pH of the perfusion fluid from 7.9 to 5.5, or by increasing the calcium concentration from 0 to 4 mM. This inhibition is shown to be because of a decreased amount of bile acid in solution. Thus it is not the total concentration of deoxycholic acid in the colon that is responsible for the colonic damage, but the concentration in solution. Although extrapolation to the human situation must be made with caution, the concentration of bile acid in solution in the faecal water may be more relevant to colonic mucosal damage than total bile acid concentration.

Animals↗
PubMed1985

Toxicity of orally administered fat to the colonic epithelium of mice.

C57BL/6J mice were given a gavage of from 0.1 to 0.4 ml beef tallow (BT) or corn oil (CO). The damaging effect of the orally administered fat boluses could be visualized 2-4 h later by instilling the excised animal colons with Trypan blue, a vital dye that stains non-viable cells. Microscopic examination of sections prepared at these times revealed that the tall columnar cells on the surface of the normal epithelium were replaced with cells demonstrating flattened, pleomorphic, pyknotic and fragmented nuclei. This phenomenon was quantitated by scoring 100 intercrypt epithelial zones between well-defined crypts. The maximum damage, affecting 25-45% of the epithelial zones, was seen at 2-4 h after treatment with 0.4 ml of BT or CO and the epithelium appeared normal with less than 10% damage at 12 h. The mitotic activity in the colonic crypts was unchanged up to 8 h and then showed a marked increase of 2- to 3-fold at 12-16 h. The severity of the epithelial damage and ensuing mitogenic response was related to the size of the fat bolus. These observations would suggest that the effects of any carcinogens present in the diet or formed in the feces could be enhanced if a fatty meal results in colonic damage and subsequent cell proliferation as we have observed in mice.

Animals↗
PubMed1985

Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene.

Oval cell proliferation in the liver was studied in rats exposed to dietary 2-acetylaminofluorene for 2 weeks with partial hepatectomy performed midway at 1 week. Using autoradiography after either continuous or pulse exposure to [3H]thymidine, histochemical staining for leucine aminopeptidase and gamma-glutamyltransferase, and transmission electron microscopy, we found that every animal showed islands of oval cells with small intestinal metaplasia at 3 weeks. Transitions from these islands of metaplasia to cholangiofibrosis were commonly seen. The importance of small intestinal metaplasia of oval cells in the genesis of cholangiofibrosis is presented and discussed.

2-Acetylaminofluorene↗
PubMed1984

Occurrence of alpha-1-antitrypsin deficiency in 155 patients with alcoholic liver disease.

Liver biopsies from 155 patients with alcoholic liver disease were examined for periodic-acid-Schiff-positive, diastase-resistant (PAS-DR) intracytoplasmic globules in hepatocytes. Seven patients had these PAS-DR globules: each was a heterozygote for a deficiency allele of alpha-1-antitrypsin (AAT), or alpha-1-protease inhibitor, with the PAS-DR globules distributed in a pattern characteristic of this deficiency. One further patient with normal AAT had a few intracytoplasmic PAS-DR globules in occasional hepatocytes. The prevalence of AAT heterozygotes in this series did not differ from that in the reference population. The seven heterozygotes included five of PI (protease inhibitor) type MZ, one of PI type SZ, and one heterozygous for a rare deficiency allele, PI type MMmalton. The M and Mmalton alleles may be difficult to distinguish because they have similar mobilities with isoelectric focusing technics. Therefore, if PAS-DR inclusions are found in the liver of a patient with an apparently normal phenotype, the presence of a defective M variant allele, such as Mmalton, should be considered.

Adult↗
PubMed1984

Electron microscopic study of the peritoneal kinetics of iron dextran during peritoneal dialysis in the rabbit.

Iron dextran, an electron-dense tracer, was given intravenously (100 mg of iron/100 g of body weight) to 8 normal rabbits to study its movement from the plasma to the peritoneal cavity during peritoneal dialysis. The dialysate infused at 75 ml/kg contained 1.5 g/dl of glucose in 4 animals and 4.25 g/dl in the remainder. Peritoneal dialysis was discontinued and the peritoneum was fixed in vivo at various times (20-120 min) after the injection of the iron dextran. Large amounts of tracer were detected in the effluent after draining the peritoneal cavity. Electron microscopic examination of the mesentery showed particles of iron dextran in the endothelial cells of small vessels (capillaries and venules) the interstitium and the mesothelial cells adjacent to vessels irrespective of the dialysate concentration or duration of dialysis. Tracer was not clearly demonstrated in the interendothelial or intermesothelial spaces. In the mesothelial cells, the particles were found exclusively in (small, elongated or large) vesicles, while in the endothelial cells they were both in vesicles and free in the cytoplasm. Our findings suggest that during the 20- to 120-min period after intravenous administration, the intracellular transport of iron dextran, depends on either moving vesicles or the presence of pre-existing tunnels in the mesothelial cells of rabbit mesentery.

Animals↗
PubMed1983

Ultrastructure of normal rabbit mesentery.

The ultrastructure of the mesentery was examined by electron microscope (EM) after in vivo fixation in 7 normal rabbits. In 1, the fixation was performed after intravenous injection of an electron-dense tracer (iron dextran) and intraperitoneal infusion of dialysate 4.25% for 1 h. We studied morphometric data of what is considered to be the active peritoneal dialysis membrane, i.e. capillary endothelial cells, interstitium and mesothelial cells. The mesothelial cells are flattened and overlapping with tight junctions between them. They lie on a continuous basement membrane and they contain numerous intracytoplasmic vesicles, separated or in clusters. The mesenteric microvessels were mainly true capillaries of continuous type and postcapillary venules. Capillary lymphatics and larger lymphatic channels (lacunae) seem to be more extensive than the blood capillaries and venules. The endothelial cells contain many vesicles. The interstitium consists of bundles of collagen, fibroblasts and occasional macrophages. The electron-dense tracer was found in the vesicles of the mesothelial cells suggesting that vesicular transport may play an important part in the transportation of at least molecules of a certain size.

Animals↗
PubMed1983

Early histopathologic events to evolution of colon cancer in C57BL/6 and CF1 mice treated with 1,2-dimethylhydrazine.

After administration of the intestinal carcinogen 1,2-dimethylhydrazine (DMH), C57BL/6J and CF1 mice were observed for early precursor lesions to large bowel cancer. Among the initial events seen following DMH treatment, an abrupt reduction in colonic DNA synthesis was the earliest lesion detectable. The frequency of aberrant colonic nuclei rose shortly after DMH treatment, reaching a maximum value 24 hours later and remaining elevated for 3 days following the exposure. Mucin changes, detected histochemically, and cell kinetic alterations in crypt proliferation rates were observed much later and were a constant feature for both strains following 4 weekly treatments with DMH, while carcinomas appeared in all animals 32 weeks after the start of DMH treatment. The quantitative comparison of these histopathologic observations for the early detection of colon cancer suggests that the induction of colonic nuclear aberrations in the mucosa of the large bowel might provide a sensitive and rapid indication of genotoxicity to this organ and thus might provide the basis for a screening methodology for colon carcinogens.

1,2-Dimethylhydrazine↗
PubMed1983

Sequential analysis of hepatic carcinogenesis. Regeneration of liver after carbon tetrachloride-induced liver necrosis when hepatocyte proliferation is inhibited by 2-acetylaminofluorene.

The effect of inhibition of hepatocyte proliferation by dietary 2-acetylaminofluorene (2-AAF) on the restoration of liver in rats after a necrogenic dose of carbon tetrachloride has been studied. The liver weights remained low during the entire feeding period of the 2-AAF, and virtually no hepatocyte proliferation was seen, as determined autoradiographically after thymidine incorporation and by the absence of mitotic figures. Oval cell proliferation was extensive. Morphometric analysis showed (a) equal and maximum liver cell necrosis by 24 hours in both the experimental and control groups, (b) similar kinetics of removal of dead liver cells, and (c) similar values for the mean liver cell area. The distance between the portal triad and terminal hepatic vein in animals on the dietary 2-AAF was considerably reduced. Massive hepatocyte proliferation began after termination of the 2-AAF diet, and the liver returned to normal appearance within 14 days. The oval cells disappeared during this period of liver cell restoration. A new hypothesis for oval cell proliferation based on differential inhibition of hepatocyte proliferation resulting in unbalanced growth of ductular cells is presented.

2-Acetylaminofluorene↗
PubMed1983

An experimental method for rapid growth of liver in spleen. The survival and proliferation of chemically induced preneoplastic hepatocytes in spleen.

Cellular suspensions (2 x 10(6) cells) of isolated preneoplastic liver cells, obtained from carcinogen-treated rats, were injected in the spleens of syngeneic rats divided into groups on the basis of no treatment, partial hepatectomy (PH), and/or feeding regimens including 2-acetylaminofluorene (AAF). Recipient rats undergoing both PH and AAF showed significantly more rapid proliferation of the preneoplastic liver cell implant, compared with other treatment groups and control. The theoretic basis for this observation, supported by a large body of data derived from hepatocarcinogenesis, is as follows: The phenotype of the donor cells has been altered by chemical carcinogens such that the liver cells develop resistance to growth-inhibiting agents such as AAF. The recipient receives PH and AAF, the former creating a strong proliferative stimulus for hepatocytes, while the latter inhibits regeneration of normal liver cells but not those resistant to the mito-inhibitory effect of AAF, ie, the carcinogen-altered donor cells. These manipulations in donors and recipients thus create a selective environment in which the implant undergoes rapid proliferation. This model of resistance induction followed by selective proliferation, built upon the principles of carcinogenesis and applied to isolated liver cell transplantation, provides an experimental basis for achieving rapid liver growth of the splenic implant.

2-Acetylaminofluorene↗
PubMed1982

Giant cell carcinoma of pancreas with clear cell pattern in metastases.

A case of mucin-positive giant cell carcinoma of the pancreas is presented. Clear cells were a prominent feature of the primary tumor and constituted the majority of the metastatic deposits, a finding not usually associated with pancreatic carcinoma. Results of ultrastructural and histochemical studies are presented, and the significance of a clear cell component in metastases is discussed.

Adenocarcinoma↗
PubMed1982

Role of estrogens as promoters of hepatic neoplasia.

The administration of estrogens to humans has been associated with the development of benign and possibly malignant hepatocellular neoplasms. This study was designed to investigate the mechanism of this association. We present a rat model that demonstrates that stilbestrol (DES) and ethinyl estradiol promote the development of hepatic neoplasms in rats previously initiated with diethylnitrosamine (DEN). Eighty male and 12 female Fischer-344 rats were given a single intraperitoneal injection of either DEN (200 mg. per kg. of body weight) or saline. Beginning 4 weeks after injection, the rats were given an estrogen or corn oil twice weekly for up to 50 weeks. Treatments were stopped at the time of sacrifice or 11 to 29 weeks prior to sacrifice. Estrogen treatments included high dose DES (5 mg. per dose), low dose DES (0.5 mg. per dose), and ethinyl estradiol (0.2 mg. per dose). Male and female rats given both DEN and high dose DES developed grossly visible hepatic hyperplastic nodules (mean, 9.1 per liver) after 20 weeks of DES. Nodules also developed if the onset of DES treatment was delayed until 28 weeks after initiation. Rats given DEN alone or DES alone did not develop nodules after 20 weeks. Microscopic hyperplastic foci also developed in rats given DEN plus DES, DES alone, and DEN alone. The foci in rats given DES alone were largely reversible on cessation of estrogen therapy. Mitotic activity in foci and nodules was prominent during estrogen therapy but declined markedly after cessation of therapy. Similar promoting activity of ethinyl estradiol was observed. Low dose DES was not effective in promoting tumor formation. The data indicate that estrogens promote hepatic neoplasia, perhaps by increasing hepatocyte mitotic activity and thereby facilitating the evolution of previously initiated cells into neoplastic clones. Comparison with human disease should be made with caution, especially because the estrogenic dose administered was approximately 200-fold the usual contraceptive dose in humans. However, the analogy between this model and the development of human oral contraceptive-associated hepatic tumors is evident. It is possible that some women have latent "initiated" cells that divide faster than the surrounding hepatocytes in response to estrogens.

Animals↗
PubMed1981

Mucocele of the appendix: pseudomyxoma peritonei and intracytoplasmic canaliculus-like structures.

A case of pseudomyxoma peritonei associated with mucocele of the appendix is reported. To date there is no general agreement as to whether this entity (pseudomyxoma) should be categorized as a malignant lesion. The presence of intracellular canaliculus-like structures adds support to those investigators who believe that pseudomyxoma peritonei reflects a form of malignant disease.

Appendix↗