Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
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Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.
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PMID:Tumor antigen and acid phosphatase isoenzyme in prostatic cancer. 4 19

In the studies of experimental salmonellosis, immunization of mice with a live vaccine SER of S. enteritidis was found to be effective against further infection with virulent S. enteritidis 116--54. Macrophages obtained from the peritoneal cavity, subcutaneous tissue or liver of immunized mice inhibited intracellular growth of bacteria and resisted cell degeneration caused by engulfment of virulent 116--54 bacteria. This immunity was called cellular immunity. We discovered by chance in 1961 a transfer agent of immunity (TA) from the culture fluid of immunized macrophages. This agent is RNA in nature and can be extracted from the spleen, peritoneal exudate cells or the lymph node of immunized animals and is called immune (i) RNA. We could demonstrate antibody activity in macrophages treated in vitro or in vivo with iRNA by the immune adherence hemagglutination technique. Cellulr immunity against tumor cells could be transferred in vitro or in vivo to lymphocytes through iRNA prepared from the spleen cells of syngeneic, allogeneic and xenogeneic animals immunized with the tumor cells. We prepared iRNA against antigens capable of inducing humoral antibody production in animals, i.e., RBCs, bacterial toxin, bacterial flagella and hapten-protein conjugates. Serum antibody was not demonstrated in recipient animals of iRNA's by single or repeated injections of these agents. However, in these animals an increase in the number of specific antibody-carrying cells was found as rosette-formers. It was found further that prior injection of iRNA could induce immunologic memory and produced a high titer of humoral antibody after a boosting stimulation with a small dose of the corresponding antigen. The required interval between the first iRNA and the second antigenic stimulation, and the minimal effective doses of iRNA and antigen are described. We studied the interaction of iRNA with either T- or B-cells and with both cells using adoptive transfer system, athymic nude mice and neonatally thymectomized (NT) mice. Immune rna's against T-dependent and T-independent antigens could not induce the proliferation of antibody-carrying cells in cyclophosphamide-treated (B-cell depleted) mice. But these agents could induce the proliferation of rosette-formers, implying that iRNA's can replace some role of T-cells even against T dependent antigens. B-cells can be directly activated by treatment with iRNA against both T-dependent and T-independnet antigens, and they differentiated into rosette-formers. Passive transfers of iRNA were successful in establishing immunity against infection with S. enteritidis, or immunity to Salmonella flagella, RBCs and hapten-protein conjugates. The ability of iRNA to confer a secondary response of antibody formation is serially and passively transmissible in recipient animals. These facts suggest the presence of some mechanism that is responsible for the amplification of antigenic stimulation in the immune response...
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PMID:Ribonucleic acid in the immune response. 8 65

The differentiation of DMBA-induced rhabdomyoblastomas was studied during the early stages of tumour growth. Two cell populations were found to constitute the tumour tissue: small cells (SC) and long spindle-shaped cells (LSSC). The SC were the only tumor cells at the earliest detectable stage of tumour growth 10 weeks after intramuscular injection of DMBA. They had small heterochromatic nuclei with a compact nucleolus containing only fibrillar components. The cytoplasm was very rich in SER of tubular type, dense bodies and Golgi apparatus. Centrioles at all stages of the replicative cycle were very frequently observed. The cells did not fuse and showed no tendency to differentiate. The LSSC had large euchromatic nuclei with multiple irregular nucleoli containing both fibrillar and granular components. The cytoplasm had an abundant GER and well-developed Golgi apparatus. These cells formed 100 Angstrom thick cytofilaments the increase of which paralleled reduction of GER. The cells tended to fuse but did not form myofibrils. A rare variant of these cells neither possessed Golgi apparatus nor formed cytofilaments but accumulated dense protein substance in the cisternae of the GER. Myotubes with cross-striated myofibrils were but occasionally observed. The ultrastructural characteristics of both cell types revealed essential differences in the biosynthetic activity and the degree of differentiation. The SC were considered to belong to the myogenic cell line and to be most probably the malignant counterpart of proliferating satellite cells (presumptive myoblasts) and precursors of the LSSC. Morphologically and developmentally the LSSC bore close resemblance to normal myoblasts but the proliferative capacity of some of them seemed to be lost. The differentiation of the malignant myoblasts in the DMBA-induced rhabdomyoblastomas was similar to the early differentiation of the normal muscle tissue.
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PMID:Differentiation of malignant myoblasts in 7,12-dimethyl-benz(a)-anthracene-induced rhabdomyoblastomas. An electron microscopic study. 10 12

Proteoglycans have been isolated from a high speed supernatant fraction of a mouse mastocytoma by procedures which should minimize alteration of the native protein-polysaccharide molecule. The methods used include in vivo labeling proteoglycans with 35S-sulfate, 3H-leucine and 3H-lysine, centrifugation of the tumor homogenate at 105,000 g, cetylpyridinium fractionation of the supernatant, and further purification of some of the fractions obtained by DEAE-cellulose column chromatography, gel filtration on Sepharose 4B and cellulose acetate electrophoresis. Two major sulfated proteoglycans were obtained, one containing keratan sulfate-like material (KSP-S), the other a heparin-like polymer (HP-S). The presence in HP-S of a compound similar to heparin was confirmed by its digestibility with flavobacterium heparinase. HP-S contained about 4 per cent protein. Glycine was the predominant amino acid, and serine did not appear to be involved in the peptide-carbohydrate linkage. The proteoglycan present in HP-S appeared to be homogeneous when examined using cellulose acetate electrophoresis. KSP-S was found to contain sialic acid and its protein content was significantly higher than that of HP-S. Glutamic and aspartic acids were the most abundant amino acids in KSP-S.
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PMID:Proteoglycans of soluble fraction of mouse mastocytoma. 12 69

The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas "5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas "5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j ("5123A), 3.5 ("7316B), and 2.1 ("7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas "5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence.
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PMID:Effect of pyridoxine availability on the activity of serine dehydratase of normal liver, host liver, and three Morris hepatomas. 16 14

BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed.
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PMID:Production of a serine-protease with macrophage migration-inhibitory factor activity by virus-transformed cells and human tumor cell lines. 16 63

CEA was prepared by combined isoelectric precipitation, ultrafiltration and column chromatography under controlled conditions of pH. The resulting immunologically active materials were higher in carbohydrate (85-87%), N-acetyl galactosamine (10-11.5%) and galactose (28-32%) content than that previously reported. Differences in amino acid yield were also noted; the concentrations of aspartate, serine, glycine and alanine being higher and that of lysine, histidine, arginine, proline, valine, isoleucine, leucine and tyrosine were lower than that reported for CEA prepared by previous methods. The tumor tissues for CEA extraction were obtained from two Group O Rh positive deceased. Neither preparation showed Group A or B activity as measured by hemagglutination inhibition. It is suggested that the method of purification influences the carbohydrate and amino acid yields.
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PMID:Preparation of carcinoembryonic antigen (CEA) containing significantly increased amounts of galactose and galactosamine. 17 42

We reported earlier that in cell extracts that were prepared from interferon-treated Ehrlich ascites tumor cells and preincubated and passed through Sephadex G-25 (S60INT), the translation of exogenous mRNA (viral and host) was impaired and the impairment could be overcome to a large extent by adding a crude tRNA preparation from Ehrlich ascites tumor cells but not from Escherichia coli. We find now that the rate of inactivation of some tRNA's (especially those specific for leucine, lysine, and serine) but not those of many others is faster in S30INT than in corresponding extracts from control cells. This increased rate of tRNA inactivation may perhaps account for the need for added RNA to overcome at least partially the impairment of translation in S30INT. The relationship of the increased rate of tRNA inactivation to the antiviral effect of interferon is unclear. So far no significant difference has been detected in the amount of tRNA needed to overcome the impairment of encephalomyocarditis virus RNA translation in S30INT between tRNA from interferon-treated cells and tRNA from control cells. Futhermore, no difference was found in the rate of inactivation in S30INT between leucine-specific tRNA's from interferon-treated and from control cells. tRNA's specific for leucine and lysine were not inactivated (unless very slowly) during incubation under out conditions in an extract from interferon-treated (or from control) cells unless the extract had been passed through Sephadex G-25 or dialyzed. The translation fo exogenous mRNA was, however, impaired in an extract from interferon-treated cells that had not been passed through Sephadex G-25. This impairment was apparently not overcome by added tRNA.
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PMID:Interferon treatment of Ehrlich ascites tumor cells: effects on exogenous mRNA translation and tRNA inactivation in the cell extract. 17 82

A new SER recording system using the bilateral simultaneous peripheral nerve stimulation on cervical, thoracic and lumbar segments was found to be helpful as a diagnostic aid for the localization and the level diagnosis of sensory neuronal lesions including peripheral nerves. SER abnormalities were observed in 32 (76.2%) of the 42 cases with cerebrovascular disease, in 11 (64.7%) of the 17 cases with spinal cord lesions and 12 (75.0%) of the 16 cases with peripheral nerve lesions. As an interesting finding, marked SER abnormalities corresponding with the level and the distribution of the lesions were observed in cases with spinal cord tumor, myelopathy and polyneuropathy. In a case with recurrent myelitis, lesions of different levels of spinal cord were suggested from the SER changes. The recording system gives also valuable information about chronological modifications of the lesions, and may reveal subclinical neuronal damage in a certain neurological disorder.
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PMID:Clinical application of somatosensory cerebral evoked response for the localization and the level diagnosis of neuronal lesions. 18 24

Certain metabolic inhibitors or chemotherapeutic agents that increase the susceptibility of line-1 or line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of the cells to synthesize lipids. A direct correlation was found between the drug-induced increase in sensitivity to antibody-C mediated killing and the inhibition of the ability of the cells to incorporate acetate, glycerol, and fatty acids into complex cellular lipids. Drug-treated cells recultured in drug-free medium regained their resistance to antibody-C mediated killing; these cells recovered their ability for complex lipid synthesis at this time. Thin layer chromatography of CHCl3:CH3OH lipid extracts from these cells indicated that the drug-induced increase in susceptibility to humoral immune attack correlated with the inhibition of acetate, glycerol, and fatty acid incorporation into cardiolipin and triglyceride in line-10 cells and the inhibition of incorporation of these compounds into cardiolipin alone in line-1 cells. No direct correlation was found between the sensitivity of the cells to humoral immune attack and the ability of the cells to incorporate precursors of lipid synthesis into other lipid moieties (sphyngomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidyl glycerol, or cholesterol esters). The synthesis of cardiolipin and triglycerides, therefore, appears to be associated with the mechanism whereby these tumor cells resist antibody-C mediated killing.
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PMID:Identification of lipids associated with the ability of tumor cells to resist humoral immune attack. 20 53


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