Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
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The initial rates of transport of uridine, thymidien, purines, choline and 2-deoxy-D-glucose by cultured Novikoff rat hepatoma cells were determined as a function of temperature between 5 and 41 degrees C. Arrhenius plots of all transport systems exhibited sharp breaks in slope; between 17 and 23 degrees for uridine, thymidine and hypoxanthine-guanine transport and between 29 and 32 degrees for choline and 2-deoxy-D-glucose transport. The activation energies for the transport systems changed from 15-26 kcal/mole below the transition temperatures to 4-9 kcal/mole above the transition temperatures. Propagation of the cells in the presence of cis-6-octadecenoic acid which results in marked changes in the lipid composition of cell membrane, had little effect on the temperature characteristics of the various transport systems. Similarly, propagation of the cells for 24 hr in media containing Tween 40 or nystatin had no effect on the capacity of the cells to transport the various substrates or on the temperature dependence of the transport systems. The presence of ethanol, phenethyl alcohol or Persantin at concentrations that inhibited thymidine and 2-deoxy-D-glucose transport between 40 and 70% also did not alter the transition temperatures or activation energies for the transport of these substrates. Cytochalasin B, on the other hand, shifted the transition temperature for 2-deoxy-D-glucose transport to higher temperatures in a concentration-dependent manner, whereas it had no effect on the temperature dependence of thymidien transport.
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PMID:Temperature-dependent changes in activation energies of the transport systems for nucleosides, choline and deoxyglucose of cultured Novikoff rat hepatoma cells and effects of cytochalasin B and lipid solvents. 5 43

Induction of aryl hydrocarbon hydroxylase (AHH) activity in rat hepatoma cell line serves as a simple and rapid method to detect minute (pg) amounts of certain classes of compounds, e.g., dibenzo-p-dioxins, dibenzofurans, and biphenyls. This method may provide a quick screen for such substances in extracts from foods prior to chemical identification. AHH activity is measured by conversion of benzo[a]pyrene (BP) to 3-hydroxy BP in homogenized cell extracts from control and treated cultures and is reported as pmol product formed/mg protein/min. Substances screened by this method include polyhalogenated analogs of dibenzo-p-dioxin (24 compounds), dibenzofuran (11 compounds), biphenyl (7 compounds), and extracts from several food sources. Response of the most reactive compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was used to prepare a standard curve, and the AHH activity induced by mole doses of test substance is reported as an ED50 response (the estimated dose needed to produce 50% maximum enzyme induction). The AHH activity induced by food extracts is equated to the standard curve and reported as TCDD equivalents. A potent ED50 response in cell culture appears to correlate well with known toxic responses in other mammalian and avian systems for certain test substances. This correlation suggests that the cell culture enzyme induction method is a useful model for screening food extracts that are suspected to be contaminated with polychlorinated planar substances. A collaborative study would demonstrate the reproducibility of the method.
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PMID:Induction of enzyme activity in cell culture: a rapid screen for detection of planar polychlorinated organic compounds. 11 36

The M4 isozyme of lactate dehydrogenase was purified to homogeneity from normal rat liver and from two Morris hepatomas (7777 and 7793). Amino-terminal analyses with fluorodinitrobenzene failed to detect the presence of free amino-terminal residues in each enzyme studied. Each enzyme contained between 3.7 and 4.1 moles of protein-bound acetyl groups per mole of enzyme. The amino-terminal peptide, characterized as N-acetylalanylalanine, was isolated from Pronase digests of each isozyme preparation, and quantitative recovery experiments indicated that all acetyl residues were bound at the amino termini. Carboxylterminal analyses demonstrated phenylalanine to be the carboxyl-terminal residue in each enzyme studied. These data indicate no differences in either amino- or carboxyl-terminal regions of the hepatoma M4 isozymes compared to normal liver M4 isozyme.
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PMID:Amino- and carboxyl-terminal analyses of hepatoma lactate dehydrogenase isozymes. 16 83

Antibodies to chromatin proteins of Novikoff hepatoma cells formed precipitin bands in the double-diffusion immunoprecipitation assay with chromatin proteins of Novikoff hepatoma, Walker 256 carcinosarcoma, and 18-day fetal rat liver. The antigen used for preparation of antiserum was the chromatin proteins initially extracted with 3 M NaCl-7 M urea and soluble after dialysis to 0.14 M NaCl-0.35 M urea. The chromatin proteins used for analytical studies were extracted with 0.6 M NaCl containing 0.01 M Tris-HCl (pH 8) and 100 muM phenylmethylsulfonyl fluoride. Corresponding chromatin proteins of normal and 18-hr regenerating rat liver, heart, and kidney did not form precipitin bands. The antigen was purified from the chrmatin of Novikoff hepatoma cells by exclusion chromatography on Sephadex G-150 and preparative nondenaturing polyacrylamide gel electrophoresis. Its migration on denaturing sodium dodecyl sulfate-polyacrylamide gels corresponded to a molecular weight of 26,000. Amino acid analysis showed that the ratio of acidic to basic amino acids was 1.4 to 1.0. Evidence for its homogeneity included its migration as a single protein spot on two-dimensional polyacrylamide gel electrophoresis and its single lysine amino-terminal amino acid. This protein is a glycoprotein, as shown by the presence of 15 moles of galactosamine per mole of antigen. These studies demonstrate the presence of a fetal glycoprotein in the chromatin of two tumors that may have an important role in determining their gene products.
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PMID:A fetal protein in chromatin of Novikoff hepatoma and Walker 256 carcinosarcoma tumors that is absent from normal and regenerating rat liver. 18 70

Adenosine triphosphatase (ATPase) activities of sonically prepared submitochondrial particles of rat liver and Morris Hepatoma 3924A were compared as a function of changes in temperature. On Arrhenius plots, a discontinuity at 18 degrees was observed for the rat liver mitochondrial ATPase, while the hepatoma mitochondrial ATPase revealed a discontinuity at 20.4 degrees. Values for energy of activation of the rat liver and hepatoma mitochondrial ATPases were comparable below the break (34.5 and 35.5 kcal/mole, respectively) and above the break (11.6 and 9.2 kcal/mole, respectively). Solubilization of the mitochondrial membrances with Triton X-100 resulted in constant and similar values of energy of activation for the ATPases Km values of hepatoma and rat liver mitochondrial ATPases for adenosine triphosphate were similar in both the membrane-bound and solubilized states. The lack of uncoupler-stimulated ATPase activity in hepatoma mitochondria is apparently not due to membranous effects on the affinity of the ATPase for adenosine triphosphate.
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PMID:Membranous effects on adenosine triphosphatase activities of mitochondria from rat liver and Morris hepatoma 3924A. 20 Mar 47

The binding of tritiated benzo(a)pyrene (BP) to liver DNA of 25 adult male rats (SIV 50) has been determined 50 h after a single intraperitoneal injection of doses between 40 ug/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a sigmoid step towards 2 mg/kg and a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles BP per mole DNA phosphate. The non-linearity between 1 and 2 mg/kg could be explained on the basis of an induction of metabolizing enzymes. A purely mathematical extrapolation of the tumour incidence from a carcinogenic dose (1 x 40 mg/kg for a 20% hepatoma incidence in newborn mice) to human exposure levels (about 0.1 ug/kg per day) would never have followed a step like the one found in our experiments. Our dose-effect study therefore shows how carcinogenicity data could be extrapolated in a biologically founded way to low doses.
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PMID:Extrapolation of carcinogenicity data to low doses with a dose-response study of the binding of benzo(a)pyrene to rat liver DNA. 27 32

In previous publications, one of us demonstrated that variation in paramagnetic-ion contents is a major contributing factor to the different NMR relaxation times, T1 and T2, of water protons among normal mouse tissues; and between normal tissues and cancer cells. The nature of the paramagnetic ions involved was not determined. In the present communication, we report results of analysis of the contents of three biologically prominent paramagnetic ions (manganese, iron and copper) in 9 normal mouse tissues (brain, heart, small intestine, kidney, liver, lung, voluntary muscle, spleen and stomach); one strain of rat cancer cells (As-30, rat hepatoma); and 6 strains of mouse cancer cells (Ehrlich mammary adenocarcinoma, LSA lymphoma, Krebs carcinoma of the inguinal region; sarcoma 180; Klein TA3 mammary adenocarcinoma; P815 mast cell leukemia). Our data indicate that manganese and iron are by far the two most important paramagnetic ions contributing to the diversity of NMR relaxation times. The average manganese content of all the normal mouse tissues studied (29.6 +/- 4.99 mu mole/kg) is 24 times higher than the average manganese contents of all the cancer cells studied (1.22 +/- 0.27 mu moles/kg) and there is essentially no overlap between the two groups of data. The average iron content of the normal mouse tissues (281.6 +/- 51.2 mumoles/kg) is 4 times the average in cancer cells (66.7 +/- 7.74 mumoles/kg) but there is some overlap here. The observed differences in both the manganese and iron contents are statistically highly significant, with P's below 0.0001. The copper contents of the cancer cells is lower than the average of normal mouse tissues but only by some 20%. The difference is statistically insignificant at the 0.05 level but significant at the 0.2 level.
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PMID:Low paramagnetic-ion content in cancer cells: its significance in cancer detection by magnetic resonance imaging. 159 62

Monoclonal antibody PAL-M1, which was selected to discriminate between nevocellular nevi and cutaneous melanomas, has not been characterized until now. Here we show that PAL-M1 is directed against the transferrin receptor (CD71). The molecules precipitated by PAL-M1 and by anti-transferrin receptor antibodies OKT9 and 5E9 from various human tumor cell lines (melanoma, hepatoma, and lymphoma) show identical characteristics on SDS-PAGE. PAL-M1 also specifically recognized mouse L cells expressing the human transferrin receptor gene. Competition experiments demonstrated that PAL-M1 and OKT9 recognize the same or a spatially close determinant. Immunohistochemical staining of a large series of melanocytic lesions indicates that the transferrin receptor can be considered as a progression antigen in this type of lesion.
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PMID:Monoclonal antibody PAL-M1 recognizes the transferrin receptor and is a progression marker in melanocytic lesions. 236 2

Liposomes entrapping gadolinium-DTPA (Gd-DTPA) were synthesized from 60 mole percent egg phosphatidylcholine (EPC) and 40 mole percent cholesterol or EPC alone entrapping Gd-DTPA in diameters of 100 and 200 nm. Rats bearing Morris hepatoma in their flanks were imaged by MR pre- and post-contrast with free Gd-DTPA and liposomal Gd-DTPA for up to four hours after IV contrast. Comparison of images after free and liposomal Gd-DTPA showed dramatic differences in tumor and organ enhancement. Liposomal Gd-DTPA enhancement of tumor corresponded more closely to histologically proven vascularized portions of tumor than free Gd-DTPA. Hepatic enhancement was greater with liposomal than free Gd-DTPA and time course of liver, kidney and tumor enhancement was prolonged. The 100-nm EPC Gd-DTPA liposomes caused the greatest enhancement. Gd-DTPA liposomes may be useful as liver and blood pool contrast agents. By varying lipid composition and vesicle size, patterns of enhancement may be selectively modified.
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PMID:Liposomal Gd-DTPA: effect of encapsulation on enhancement of hepatoma model by MRI. 281 20

Structures of the sugar moieties of gamma-glutamyl transpeptidases purified from the kidney and the liver of rat, mouse, and cattle were studied after being chemically released as oligosaccharides. The results indicated that both organ-specific and species-specific differences exist in the sugar chains of the enzyme. Comparative studies of sugar chains of the heavy and light subunits of the rat kidney enzyme revealed that high mannose-type sugar chains are found only in the heavy subunit. By the same analysis of the oligosaccharide fractions obtained from four isozymic forms of the rat kidney enzyme, it was found that all these enzymes contain 2 mole of neutral sugar chains but different numbers of acidic sugar chains in one molecule. Comparative studies of oligosaccharides obtained from the enzymes purified from rat AH-66 hepatoma and from normal rat liver revealed that more than 40% of the sugar chains of the hepatoma enzyme contain bisecting N-acetylglucosamine residues which are not found in those of the liver enzyme. By making use of the structural changes associated with malignant transformation, a new diagnostic method or hepatoma was developed. In principle, the method consists of affinity chromatography of the desialylated serum enzyme using an erythroagglutinating lectin agarose column.
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PMID:[Structural changes in the sugar chains of gamma-glutamyltranspeptidase by malignant transformation]. 287 94


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