Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many tumour-specific antigens in gastrointestinal cancers have carbohydrate immuno-determinants. These epitopes can be identified by lectins and monoclonal antibodies. By using fluorescein-isothiocyanate (FITC)-conjugated peanut agglutinin (PNA) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we have investigated glycoproteins carrying altered carbohydrate epitopes in normal and carcinomatous human colorectal mucosa. In normal mucosa PNA stained goblet cell glycoconjugates in the supranuclear (Golgi) distribution. After neuraminidase pretreatment PNA stained actual mucin goblet itself at all levels of the crypts. Colorectal carcinomas displayed a strong and direct binding of PNA to apical cell membranes of carcinomatous cells and intraluminal secretions. Analysis of the glycoproteins by SDS-PAGE and PNA-labelling revealed four carcinoma-associated glycoproteins (26kD, 32kD, 35kD and 50kD). In addition, four glycoproteins (29kD, 30kD, 33kD and 36kD) common to normal and carcinomatous colorectal mucosa could be identified. All of these glycoproteins differed in their molecular weight from those in red cell controls which bind PNA only after desialylation. The study shows that the expression of PNA-binding sites in colorectal carcinomas signifies a cancer-associated carbohydrate alteration. Four carcinoma-associated glycoprotein antigens could be detected by this lectin. The antigens we have identified might be useful in the isolation and purification of more selective reagents for the serologic detection of colorectal cancer.
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PMID:Identification of glycoproteins expressing tumour-associated PNA-binding sites in colorectal carcinomas by SDS-GEL electrophoresis and PNA-labelling. 243 45

The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we describe the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4-1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive beta-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by boiling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.
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PMID:Mucin-like antigens in a human pancreatic cancer cell line identified by murine monoclonal antibodies SPan-1 and YPan-1. 245 32

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
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PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49

Immunostimulating complexes (ISCOMs) have been prepared from influenza A virus envelope glycoproteins, i.e. haemagglutinin (HA) and neuraminidase (NA). An ISCOM consists of a matrix, which is the micellar form of the glycoside, Quil A, in hydrophobic interaction with both the envelope glycoproteins (HA/NA). The Quil A bound to the ISCOM amounted to 50 micrograms mg-1 (5%) of ISCOM protein. ISCOMs were morphologically identified as symmetrical cage-like structures of approximately equal to 40 nm in diameter with hexagonal or pentagonal subunits of approximately equal to 12 nm. The sedimentation coefficient was approximately equal to 19 S as compared to 30 S for the glycoprotein micelles. The biological activities of the HA and NA are preserved in both ISCOMs and micelles.
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PMID:Influenza virus ISCOMs: biochemical characterization. 335 57

The cancer-associated antigens Ca 125 and Ca 19-9 were demonstrated by radioimmunoassay to form structural units of a mucus glycoprotein in human milk taken from healthy women four days after parturition. The glycoprotein precipitated with the casein fraction at pH 4.6 and was completely absent in the whey as judged from Ca 19-9 assay. It could be effectively enriched by phenol-saline extraction from soluble milk proteins and further purified by gel filtration on Sephacryl S300 and Sephacryl S400. The active component with a bouyant density of 1.41 g/ml in isopycnic density gradient centrifugation (CsCl) shared common physico-chemical and chemical characteristics of mucus glycoproteins. Carbohydrates representing about 68% by weight were conjugated to protein by alkali-labile linkages, exclusively and were essentially free of D-mannose. Activities of Ca 125 and Ca 19-9 were both destroyed by treatment with periodate, mild alkali or neuraminidase suggesting the antigens are sialylated saccharides bound to protein by alkali-labile linkages. The fraction of monosialylated saccharide alditols isolated after reductive beta-elimination from the mucus glycoprotein was shown to inhibit monoclonal antibodies anti-(Ca 125) and anti-(Ca 19-9) in radioimmunoassay.
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PMID:Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk. 392 59

A cancer-associated glycolipid antigen defined by monoclonal antibody 19-9 has the structure NeuAc alpha 2-3Gal Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-Cer. We have (formula; see text) studied its biosynthesis by testing the capacity of a crude microsomal fraction of SW 1116 cells to catalyze the addition of fucosyl or sialyl residues from GDP-fucose or CMP-sialic acid to glycolipid or oligosaccharide precursors. When the tetrasaccharide NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (LSTa) is incubated with GDP-[14C]fucose and SW 1116 microsomes, a 14C-labeled oligosaccharide is formed that can be separated from the incubation mixture on an affinity column containing antibody 19-9 bound to protein A-Sepharose. The product migrates slower than LSTa when analyzed by paper or thin-layer chromatography. After treatment with neuraminidase, it co-migrates with the pentasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (formula; see text) (LNF II) in both chromatographic systems. Similar experiments demonstrate that SW 1116 microsomes catalyze the addition of a sialyl residue to the tetrasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc to form LSTa. However, when LNF II is incubated with CMP-[14C]sialic acid and SW 1116 microsomes, no 19-9-active product is detected by affinity chromatography or by paper or thin-layer chromatography. Results using glycolipid precursors are consistent with these findings and also demonstrate the presence of the Lewis fucosyltransferase in SW 1116 cells. Thus, the biosynthesis of the sialyl-Lea antigen proceeds by addition of sialic acid to a type 1 precursor chain by a sialyltransferase, followed by addition of fucose by the Lewis fucosyltransferase.
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PMID:Biosynthesis of the cancer-associated sialyl-Lea antigen. 401 78

A live attenuated influenza A (H3N2) strain "KO-1" was developed by recombination of wild influenza A/Kumamoto/22/76 (H3N2) with attenuated A/Okuda/57 (H2N2) followed by passage in developing chick eggs in the presence of horse serum inhibitor. The virus strain "KO-1" obtained is inhibitor-resistant, and has hemagglutinating (HA) and neuraminidase (NA) antigenicity derived from the wild parent virus. RNA analysis revealed that one RNA segment (corresponding to M protein) was derived from the A/Okuda/57 strain. The "KO-1" strain shows restricted growth in the lungs of Syrian hamsters as compared with that of the parent A/Kumamoto/76 strain and no transmission of virus from the hamsters infected with "KO-1" strain by inhalation ot untreated hamsters housed in the same cage was detected serologically. In contrast, the parent wild A/Kumamoto/76 strain induced contact infection under the same condition. The attenuated "KO-1" strain was administered by inhalation to a few children of 3 to 4 years old in a preliminary clinical trial. A good antibody response was observed with no clinical reaction.
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PMID:Production of an attenuated influenza A (H3N2) strain "KO-1" by recombination with A/Okuda/57 (H2N2) followed by selection of inhibitor-resistant virus. 743 2

The Thomsen-Friedenreich antigen (T) is the core disaccharide of O-glycosylated complex carbohydrates and is presumed to be a cancer-associated carbohydrate antigen. However, we recently found that the expression of alpha-T and alpha 1-2 fucosyl alpha-T in the gastric surface epithelia was regulated allogeneically. In the present study we addressed their changes in gastric differentiation disorders. Expression of the T-related antigens was studied histochemically with monoclonal antibody MBrl and peanut agglutinin in 22 normal, 14 metaplastic, and 54 cancerous tissues. The sialylated antigens were detected after neuraminidase digestion. Gastric mucins were purified and examined to determine whether they were the carrier molecules of T. Expression of the normal antigens was decreased or not detected in about 80% of both disorders. Neosialylation of the T-related antigens was observed in the goblet cells of all metaplastic tissues. The absorptive cells did not express any T-related antigens. In gastric cancers, blocked synthesis, i.e., precursor accumulation or totally negative expression, was observed in approximately 66% and neosialylation in approximately 40%. The T-related antigens were carried by mucins. We conclude that blocked synthesis of the T-related antigens was found in a cancer-specific manner. Neosialylation was invariably associated with intestinal metaplasia and occasionally with cancer.
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PMID:The Thomsen-Friedenreich antigen-related carbohydrate antigens in human gastric intestinal metaplasia and cancer. 752 63

A survey was conducted at two wildlife management areas of Pennsylvania (USA) to evaluate an antigen capture enzyme-linked immunosorbent assay (AC-ELISA) for the detection of avian influenza viruses (AIV) in cloacal swabs from waterfowl and to determine the influenza A virus subtypes and the distribution of these viruses among waterfowl. We collected 330 cloacal swabs from hunter-killed waterfowl in the fall of 1990 and from cage-captured waterfowl in the summer of 1991. Thirty-one hemagglutinating agents were isolated by chicken embryo inoculation (CEI) of which 27 were influenza A viruses and four Newcastle disease viruses (NDV). The prevalence of AIV infection was 8.2%. Compared to CEI, AC-ELISA was only 15% sensitive and 61% specific. Based on the distribution of AIV by species of waterfowl, mallards (Anas platyrhynchos) and American wigeons (Anas americana) were at equal risk of AIV infection even though most of the AIV isolates came from mallards. Although significant crude effects of sampling site and season on AIV recovery could be established, juvenile age was identified as the primary risk factor of AIV recovery. Twelve AIV subtypes were identified by hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests. The most prevalent subytpes were H4N8 and H6N8. We concluded that AC-ELISA was not useful for the detection of AIV in cloacal swabs from waterfowl and that CEI, HI, and NI tests remain as the method of choice for AIV screening in waterfowl. Based on the results AIV infected preferentially the young which represent the high risk group in waterfowl populations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influenza A viruses isolated from waterfowl in two wildlife management areas of Pennsylvania. 858 35

To assess the potential of quail as an intermediate host of avian influenza, we tested the influenza A/Mallard/ Potsdam/178-4/83 (H2N2) virus to determine whether through adaptation a mallard strain can replicate and transmit in quail, as well as other terrestrial birds. After five serial passages of lung homogenate a virus arose that replicated and transmitted directly to contact cage mates. To test whether adaptation in quail led to interspecies transmission, white leghorn chickens were infected with the wild-type (mall/178) and quail-adapted (qa-mall/178) viruses. The results show that mall/178 H2N2 does not establish an infection in chickens nor does it transmit, while qa-mall/178 H2N2 infects and transmits to contact chickens causing clinical signs like depression and diarrhea. Completed sequences indicate six amino acid changes spanning four genes, PB2, PB1, HA, and NP, suggesting that the internal genes play a role in host adaptation. Further adaptation of qa-mall/178 in white leghorn chickens created a virus that replicated more efficiently in the upper and lower respiratory tract. Sequence analysis of the chicken-adapted virus points to a deletion in the neuraminidase stalk region.
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PMID:Adaptation of influenza A/Mallard/Potsdam/178-4/83 H2N2 virus in Japanese quail leads to infection and transmission in chickens. 1749 63


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