Bile acid-induced alterations of mucin production in differentiated human colon cancer cell lines.

Damage to the gastrointestinal tract mucous layer may render underlying cells susceptible to intraluminal toxins or carcinogens. Our aim was to determine the effect of bile acids on mucin, the primary constituent of mucous. Differentiated Caco-2 and HT29 cells were used as models of human colonic epithelial cells.

Mouse gastric mucin: cloning and chromosomal localization.

Mucins protect gastric epithelium by maintaining a favourable pH gradient and preventing autodigestion. The purpose of this study was to clone a mouse gastric mucin which would provide a foundation for analysis of mucin gene regulation. Mucin was purified from the glandular portion of gastric specimens and deglycosylated by HF solvolysis.

Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression.

Background & Aims: Secretory mucins play an important role in gastric cytoprotection and are derived from a heterogeneous family of genes. The aim of this study was to determine the specific type and location of mucin gene expression in the human stomach.

Methods: Expression cloning was performed by screening a human gastric complementary DNA expression library with antisera against deglycosylated gastric mucin.

Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium.

Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and metastases. Human mucins are derived from a heterogeneous family of genes, labeled MUC1-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens.

Experimental model of upper intestinal adenocarcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine in C57BL/6 mice.

The purpose of this study was to develop a model of gastrointestinal carcinogenesis using C57BL/6 mice. Treatment regimens consisted of one control group and 2 groups which received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water: 50 micrograms/ml x 52 weeks and 100 micrograms/ml x 27 weeks. In addition, 2 protocols using adjuvant agents intended to increase tumor formation were used: MNNG (100 micrograms/ml) x 27 weeks + 0.

Heterogeneity of mucin gene expression in normal and neoplastic tissues.

To determine the relative expression of distinct mucin genes in normal and neoplastic tissue, antibodies and cDNA probes that recognize the core tandem repeat sequences of membrane-bound (MUC1) and secreted (MUC2 and MUC3) mucins were used for immunohistochemical and RNA Northern and slot-blot analysis. MUC1 mRNA was detected in all epithelial tissues tested. MUC1 core peptide, recognized by monoclonal antibodies 139H2 and DF3, was highly expressed on apical membranes of bronchus, breast, salivary gland, pancreas, prostate, and uterus, and was sparsely expressed in gastric surface cells, gallbladder, small intestine, and colonic epithelium.

Studies of ammonia loading: effects of rate of delivery and enhanced removal of NH4 on blood levels of ammonia and coma induction.

Using dose-response curves, the dose of NH4Ac inducing coma in one-half of the animals was increased by 60 to 80% after 1 mmol of arginine. The larger increase occurred in larger rats but was not proportional to the increase in weight. Incremental subcoma doses of NH4 raised the amount of NH4 required for inducing coma and the brain level of ammonia at the point of coma.

Valproic acid induction of coma in rats: synergism with NH4+ and pentobarbital.

Dose-response curves for the incidence of coma after intraperitoneal injections of various doses of valproic acid (VP) and octanoic acid (OA) showed that, mole for mole, valproic acid was less toxic than octanoic acid. However, a simultaneous subcoma dose of pentobarbital (PB) enhanced the toxicity of VP more than that of OA. The dose-response curve for NH4Cl was affected by simultaneous subcoma doses of VP and OA but not by PB.

Effect of endotoxin and immunoglobulin on the course of experimental hepatic encephalopathy.

A single intraperitoneal dose of endotoxin (500 micrograms) shortened the time for development of hepatic coma by 27% in 300-g rats that had an end-to-side portacaval shunt followed within 48 hr by hepatic artery ligation. The body temperature of the rats was maintained at 37 degrees C, and the endotoxin was injected just after the hepatic artery was ligated. Controls were injected similarly with saline.

Hepatic regenerative enzyme activity after pericentral and periportal lobular toxic injury.

Pericentral and periportal liver injuries involving less than 50% of the parenchyma were produced with acetaminophen and allyl alcohol, respectively. Doses were selected to produce comparable peak serum malate dehydrogenase, sorbitol dehydrogenase, and SGPT activities. The regenerative response was assessed by serial measurements of hepatic thymidine kinase (TK) activity and ornithine decarboxylase (ODC) activity.

Ammonia toxicity: comparative protective effect of various arginine and ornithine derivatives, aspartate, benzoate, and carbamyl glutamate.

Ornithine and arginine compounds were highly effective in preventing an increase in blood ammonia and in preventing or minimizing encephalopathy after acute subcoma, coma-inducing, or lethal doses of NH4+. Similar protection was seen after subacute loading with glycine. Ornithine ketoacid derivatives were no more effective than ornithine alone or ornithine glutamate.

Acetaminophen liver injury: sequential changes in two biochemical indices of regeneration and their relationship to histologic alterations.

Massive liver injury was produced in fasting male Sprague-Dawley rats weighing 200 +/- 25 gm each by gastric administration of 1400 mg/kg acetaminophen. The time sequence of changes in liver ornithine decarboxylase (ODC) activity, which reflects the earliest phases of cell multiplication, liver thymidine kinase (TK) activity, which reflects DNA synthesis, and liver histology (necrosis, mitosis, and repair processes) was recorded. ODC showed the usual biphasic response.

Ammonia, octanoate and a mercaptan depress regeneration of normal rat liver after partial hepatectomy.

Four injections of subcoma doses of ammonium acetate, octanoic acid or dimethyl disulfide during the first 24 hr after two-lobe hepatectomy in normal rats markedly depressed DNA synthesis as reflected by liver thymidine kinase activity or the incorporation of tritiated thymidine into hepatic DNA. Recovery from the depressant effects of the three toxins took 16 to 28 hr. Similar doses of the same toxins injected hourly for 3 or 5 hr after the two-lobe hepatectomy had similar depressant effects on the early peak of ornithine decarboxylase activity measured at 4 or 6 hr.

Brain methanethiol and ammonia concentrations in experimental hepatic coma and coma induced by injections of various combinations of these substances.

In normal rats in a coma induced by NH+4 alone or by methanethiol alone, the brain and blood levels of ammonia or methanethiol are much higher than those observed in rats in experimental hepatic coma. When various smaller dosage combinations of NH+4, methanethiol, and octanoic acid were injected simultaneously, coma occurred at lower brain and blood concentrations of ammonia and methanethiol. Brain ammonia and methanethiol concentrations in normal rats receiving 0.

Urea excretion, galactose elimination, and aminopyrine disappearance during normal liver regeneration after partial hepatectomy. Comparison with other function tests reported.

After removal of 70% of normal rat liver, liver weight was 37% of control at 3 1/2 hours and 49% at 24 hours. Urea formation per gram liver after an NH4+ load and galactose elimination per gram liver were well-preserved during this early posthepatectomy period. At 46 hours after removal, galactose elimination was transiently less than would be expected from liver weight.

Toxicity of a fatty acid and ammonia: interactions with hypoglycemia and Krebs cycle inhibition.

In rats, hypoglycemia induced with insulin and Krebs cycle inhibition produced by fluoroacetate poisoning augmented the encephalopathic effects of octanoic acid and NH4Cl. Blood sugars in the range of 25 to 45 mg/dl resulted in a decrease of approximately 30% in the doses of NH+4 and of octanoate required to induce coma in otherwise normal rats. Mild fluoroacetate poisoning resulted in a corresponding decrease of 25% in the dose of NH+4 and 10% in the dose of octanoate.

Encephalopathic effect of phenol in rats.

The coma-inducing effect of phenol was studied in normal 300 +/- 50 gm Sprague-Dawley rats. Dose-response curves were developed which showed that one-half the animals became deeply comatose with 540 mumol of intraperitoneal phenol and 100% with 600 mumol. Five stages of encephalopathy were readily distinguished.