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At least 649 records · Page 36Linked to original sources
PubMed1994

Intermediate filaments in rat pancreatic acinar tumors, human ductal carcinomas, and other gastrointestinal malignancies.

BACKGROUND/AIMS: Keratin is a member of the intermediate filament family in epithelial cells. Two-dimensional gel electrophoresis of different epithelial cells has shown 20 different keratin polypeptides. Therefore, mapping of the keratin polypeptides can be used to define a specific tissue. METHODS: Cytokeratin expression was investigated by using monoclonal antibodies in human surgical specimens and autopsy material of pancreatic, gastric, liver, and colon carcinomas and cholangiocarcinomas, and their metastasis to lymph nodes and liver was examined. In addition, rat acinar cell carcinomas were used to compare cytokeratin expression in ductal vs. acinar cell pancreatic carcinomas. RESULTS: Human pancreatic ductal carcinomas expressed keratins 7, 8, 18, and 19, whereas the majority of rat acinar carcinomas did not express keratins typical for ducts in rat pancreas. The keratin patterns of gastric and colon carcinomas were identical with keratins 8, 18, and 19. In contrast, hepatocellular carcinomas expressed the same keratin pattern as pancreatic acinar carcinomas with keratins 8 and 18, whereas cholangiocarcinomas expressed keratin 7, 8, 18, and 19, similar to pancreatic ductal carcinomas. Metastasis of pancreatic ductal and colon carcinomas retained their keratin patterns. CONCLUSIONS: Keratin polypeptide typing of unknown malignant cells can be a useful tool for cell identification.

Animals↗
PubMed1993

Hybrid hybridomas producing bispecific antibodies to CEA and peroxidase isolated by a combination of HAT medium selection and fluorescence activated cell sorting.

A combination of fluorescence-activated cell sorting and HAT medium selection has been used to establish bispecific antibody (biAbs)-producing hybrid hybridomas. For this purpose hypoxanthine-guanine phosphoribosyl transferase (HGPRT)-deficient mutants were isolated from a hybridoma line (D11-DG2) producing anti-CEA antibodies by 8-azaguanine treatment. The resulting HAT-sensitive hybrid cells were stained with the fluorescence marker tetramethyl rhodamine isothiocyanate (TRITC) and fused by polyethylene glycol (PEG) with HAT-non-sensitive unstained hybrid cells producing antibodies to horseradish peroxidase (POD). Fluorescent fused hybrid hybridomas as well as non-fused stained anti-CEA cells were separated from the unstained anti-POD cells using a fluorescent activated cell sorter (FACS). Finally, non-fused enzyme-deficient anti-CEA cells were eliminated by cultivation in HAT selection medium which permits only an outgrowth of HAT-resistant hybrid hybridoma cells containing the genes for producing both antibodies.

Animals↗
PubMed1984

Discriminative effect of gamma-glutamyl transpeptidase inhibitors on metabolism of leukotriene C4 in peritoneal cells.

Leukotrienes are naturally-occurring metabolites of arachidonic acid that are formed via the 5-lipoxygenase pathway in several tissues. Rat peritoneal cells (RPC) can produce leukotrienes C4, D4 and E4 (LTC4, LTD4 and LTE4) in response to stimulation with the calcium ionophore A23187 (1,2). The mechanism of enzymatic conversion of LTC4 to LTD4 is presumed to be via the action of gamma-glutamyl transpeptidase (gamma-GTPase, Figure 1) and has been demonstrated with purified enzymes from rat and porcine kidneys (3-6). We report that RPC contain gamma-GTPase-like activity that catalyzes the liberation of p-Nitroaniline (p-NA) from the chromophoric substrate gamma-glutamyl-p-nitroanilide (gamma-GpNA) in the presence of the acceptor molecules glycylglycine and L-cysteine. Furthermore, we demonstrate that under similar conditions, this preparation catalyzes the conversion of LTC4 to LTD4. Activity with gamma-GpNA is inhibited by D,L-gamma-glutamyl(o-carboxy)-phenylhydrazide (GOP) and serine-borate complex, (competitive inhibitors of kidney gamma-GTPase), and 6-diazo-5-oxo-L-norleucine (DON) and o-diazo-acetyl-L-serine (AZA), (irreversible inhibitors of kidney gamma-GTPase). In contrast, conversion of both endogenously-generated or exogenous LTC4 into LTD4 by RPC is inhibited only by serine-borate complex. These results suggest that RPC contain at least two distinct forms of gamma-GTPase; one capable of recognizing gamma-GpNA and susceptible to inhibition by all four compounds, and a second form utilizing also LTC4 as substrate, and is not inhibited by high concentrations of several "classic" gamma-GTPase inhibitors.

Aniline Compounds↗
PubMedDate not supplied

Carcinogens induce genetic tandem duplications in Salmonella.

Extensive studies have shown that chemical carcinogenesis involves an initiation-promotion pattern. A gene amplification model of carcinogenesis predicts that initiation involves induction of a genetic tandem duplication. We use a system developed by Anderson and Roth to select for tandem duplication of the histidine operon of Salmonella typhimurium by selection for resistance to 3-amino-1,2,4-triazole. Evidence reported here shows that, consistent with prediction, 10 carcinogens are all active in inducing tandem duplications. Two toxic noncarcinogens show little or no activity under the conditions used in inducing tandem duplication but azide, a mutagenic noncarcinogen, did show some activity. 9 types of evidence now support the gene amplification initiation-promotion model of carcinogenesis.

Amitrole↗
PubMed1980

The extra nuclear control of mitosis & cell function. A theory of cellular organisation.

There is evidence to suggest that the extra nuclear cell constituents are the part of the cell which contains all the biochemical mechanisms responsible for implementing all cell functions. These functions include control of cell division, growth, response to injury, replacement of effete cells, maintenance of anatomical and spatial cellular relations and specific cellular function and structure. The energy to perform these functions is derived from the aerobic metabolism of glucose. The energy required for nuclear division appears to be wholly or partly derived from the anaerobic metabolism of glucose. Ethyl alcohol interferes with the aerobic metabolic pathways and thus disrupts or diminishes all aerobically activated cell functions. The speed of all activities motivated by aerobic glycolysis can be increased by appropriate electrical stimulations delivered from any of a range of electromagnetic radiation frequencies tested. In addition to the stimulant effect on aerobic metabolic processes, 434 MHz can stimulate the anaerobic glucose metabolism of cancer with consequent stimulation of cancer growth rate. 434 MHz appears to deliver energy to the anaerobic cancer metabolism by causing a resonance phenomenon amongst one or more of the substrates which comprise the first few stages of glycolysis. This phenomenon permits the selective delivery of electromagnetic radiation energy to cancer cells which, if sufficiently intense, causes injury to cancer cells without harm to the normal cells except when the latter are in the phase of anaerobic metabolism which occurs at some stage of the mitotic cycle. Streptokinase, ethanol and glucose analogues increase the lethal effects on cancers undergoing therapy with 434 MHz radiation and observations of such responses suggest a theoretical basis to explain the rare spontaneous remissions of human cancer. Cancer appears to protect its glucose supplies by elevating the blood glucose levels above normal and by some mechanism which reduces the effectiveness of the body's control of its fasting glucose level. The serum fibrinogen level rises when cancer involves the abdominal viscerae, particularly the liver. A raised serum fibrinogen level appears to be a direct indication that the liver must be included in the treatment regime if longer survival is desired. If the level cannot be corrected then death of that individual appears assured.

Adult↗
PubMed2002

The hexosamine biosynthesis pathway regulates insulin secretion via protein glycosylation in mouse islets.

The hexosamine biosynthesis pathway plays a role in the modification of cellular proteins via the provision of substrate for addition of O-linked N-acetylglucosamine (GlcNAc). The relative importance of the GlcNAc modification of proteins to insulin secretion from pancreatic beta-cells has not been investigated and so remains unclear. In the present study, we show that inhibition of the hexosamine biosynthesis pathway decreases insulin secretion from mouse islets in response to a number of secretagogues, including glucose. This impairment in beta-cell function could not be attributed to reduced islet insulin content, altered ATP levels, or cell death and was restored with the addition of N-acetylglucosamine, a substrate that enters the pathway below the point of inhibition. Western blot analysis revealed that decreased islet protein glycosylation paralleled the decrease in insulin secretion following inhibition of the pathway. In conclusion, the data suggest a role for the hexosamine biosynthesis pathway in regulating the secretion of insulin by altering protein glycosylation. This finding may have implications for the development of type 2 diabetes, as chronic increase in flux through the hexosamine biosynthesis pathway may lead to the deterioration of beta-cell function via abnormal protein glycosylation.

Acetylglucosamine↗
PubMed1975

Immunological observations on patients with Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation.

Three patients with the Lesch-Nyhan syndrome were found to have normal delayed hypersensitivity, peripheral-blood T-lymphocyte counts, lymphocyte responses to P.H.A., and serum IgM, IgA, and IgE levels. However, the percentages of B-lymphocytes, IgG levels, serum-isohaemagglutinin titres, and lymphocyte responses to pokeweed mitogen (P.W.M.) were subnormal. These observations suggest that activity of the salvage pathway of purine synthesis catalysed by hypoxanthine-guanine phosphoribosyl transferase (H.G.P.R.T.) is not required for the responses of T-lymphocytes to mitogenic or antigenic stimulation, but may contribute to the proliferation and function of B lymphocytes. The major role of the de-novo pathway of purine synthesis in human lymphocyte responses to mitogenic or antigenic stimulation is shown by the effects of inhibitors of this pathway, including immunosuppressive agents, and by the effects of congenital deficiency or inhibition of adenosine deaminase.

Adenosine Deaminase↗