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Biomedical subjects

P Fredman

Publications and source records attributed to P Fredman.

At least 127 records · Page 7Linked to original sources
PubMed1987

Large alterations in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis.

Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids.

Brain↗
PubMed1986

Binding specificities of the lectins PNA, WGA and UEA I to polyvinylchloride-adsorbed glycosphingolipids.

The binding specificities of the lectins PNA (peanut agglutinin), WGA (wheat germ agglutinin), and UEA I (Ulex europeus agglutinin I) against glycosphingolipids were investigated using an enzyme-linked immunosorbent assay (ELISA), utilizing the biotin-avidin system for detection of bound lectin. PNA showed the highest affinity to GA1, but also bound, though less strongly, to GM1 and GD1b. WGA bound to 3'-nLM1 and 6'-nLM1, the former twice as strongly as the latter, but not to any sialic acid containing glycolipid of the gangliotetraose series. UEA I showed a high affinity for the Lea glycolipid which has an alpha 1-4 linked fucose but not for the glycolipids with alpha 1-3 or alpha 1-2 linked fucose. Interestingly, 3'-nLM1 and nLA1, glycolipids lacking fucose, also bound UEA I. The results show that lectins should be used with caution for establishing terminal sugar sequences in glycosphingolipids.

Enzyme-Linked Immunosorbent Assay↗
PubMed1986

Characterization of new gangliosides of the lactotetraose series in murine xenografts of a human glioma cell line.

The major mono- and disialogangliosides of the extensively characterized established human glioma line D54MG were isolated and purified from subcutaneous solid xenografts grown in athymic (nu/nu) mice. Structural determination showed that they belonged to the lactotetraosylceramide series. The sialyllactotetraosylceramide contained 90% N-glycolyl- and 10% N-acetylneuraminic acid linked in an alpha 2-3 linkage (IV3NeuGc-LcOse4Cer, IV3NeuAc-LcOse4Cer). The disialogangliosides had a previously undescribed type of structure with sialic acids linked to the terminal galactose in an alpha 2-3 linkage and to N-acetylglucosamine in an alpha 2-6 linkage. Not only did species with NeuAc or NeuGc occur, but also species with mixtures of the two sialic acids, e.g. NeuAc and NeuGc. The schematic structures of the new disialogangliosides are (Formula:see text).

Animals↗
PubMed1986

Binding specificity of monoclonal antibodies to ganglioside, Fuc-GM1.

The binding specificity of thirteen mouse monoclonal antibodies reacting with Fuc-GM1, Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)-Gal beta 1-4Glc beta 1-1Cer, a ganglioside found to be associated with small cell lung carcinoma (O. Nilsson et al. (1984) Glycoconjugate J. 1, 43-49) was studied. The results are based upon radioimmunodetection of their binding to structurally related glycolipids adsorbed to microtiter plates or chromatographed on thin-layer plates. Four of thirteen antibodies reacted only with Fuc-GM1 and both the fucose and the sialic residues were necessary for binding. Optimal binding was obtained when the sialic acid was N-acetylneuraminic acid. When this sialic acid residue was substituted with N-glycoloylneuraminic acid the binding activity was reduced and up to 10-times more Fuc-GM1 was needed for detection. The ceramide composition did not influence the binding. The other nine monoclonal antibodies cross-reacted with glycolipids containing structures closely related to Fuc-GM1 and differed from the specific ones by recognizing a smaller portion of the carbohydrate moiety in Fuc-GM1. These results indicate that anticarbohydrate monoclonal antibodies, recognizing structures involving a large proportion of the sugar in the glycolipid, possess a high specificity and might be useful for detection of tumor-associated ganglioside antigen.

Animals↗
PubMed1986

Potential ganglioside antigens associated with human gliomas.

Gangliosides in human gliomas were investigated and found to have an altered composition and concentration as compared to normal grey and white matter of brain. The major gangliosides GM1, GD1a, and GT1b were markedly reduced in the tumour tissue and in contrast there was an increase of gangliosides GM3 and GD3, which often appeared as the dominating ones. Moreover, the tumours contained gangliosides, both mono- and oligosialylated, which could not be detected in the normal brain. The concentration of gangliosides, 0.7 +/- 0.4 mumol sialic acid/g, was significantly lower as compared to normal brain grey (p less than 0.001) and white matter (p less than 0.01), which contained 3.5 +/- 0.3 and 1.2 +/- 0.3 mumol sialic acid/g respectively. The tumour tissue concentration of phospholipids was 14 +/- 8 and of cholesterol 19 +/- 12 mumol/g. The appearance in glioma tissue of gangliosides that are not found in normal brain tissue suggests that these are tumour associated and might serve as surface antigens detectable by specific monoclonal antibodies.

Adult↗
PubMed1986

Production and characterization of two human glioma xenograft-localizing monoclonal antibodies.

Multiple fusions following immunization of athymic mice with the extensively characterized human glioma cell line D-54 MG resulted in the selection of several antibodies (Mabs) highly reactive with tumors of neuroectodermal origin and unreactive with normal nervous system tissue. Two Mabs, C12 and D12, which localized specifically to tumors in athymic mouse-human glioma xenograft paired label localization assays, are IgG3 antibodies; both bind readily to staphylococcal protein A in column purification and radioimmunoprecipitation procedures. Both iodinate via the chloramine-T method yielding 125I-immunoreactive product by direct cell surface radioimmunoassay and absorption assay. By indirect cell surface radioimmunoassay, a cultured cell line panel consisting of 17 gliomas, 3 medulloblastomas, 2 neuroblastomas, 2 melanomas, and 2 fetal and 2 adult brain-derived cell lines was examined; the two Mabs were highly similar but distinct in their reactivity profiles. Each was positive with greater than 47% of the gliomas tested (C12, 9 of 17; D12, 8 of 17); and with 1 of 3 medulloblastomas, 1 of 2 melanomas, and cell lines derived from 12- and 16-week-gestation human fetal brain. No reactivity was observed with neuroblastoma or adult brain-derived cell lines or with neutral glycolipids and gangliosides extracted from D-54 MG xenografts or human glioma cell lines. Notable extraneuroectodermal reactivity included that of Mab D12 for splenic trabeculae and the spermatids and Sertoli cells in the testes. Following immunoprecipitation of [3H]leucine labeled cell membrane preparations, Mabs C12 and D12 have consistently yielded unique bands in the Mr 180,000 and Mr 88,000 regions respectively. When used in paired label localization experiments in s.c. D-54 MG xenograft-bearing athymic mice, Mabs C12 and D12 demonstrate similar localization patterns, attaining peak localization indices at day 3 (D12) or 4 (C12); the maximum percentage of injected Mab bound to tumor ranged from 5% (D12) to 8% (C12). The peak tumor/normal brain localization ratios (167-181) attained by these Mabs at days 1-2 followed by their rapid clearance suggest that these Mabs are potentially useful imaging and therapeutic agents for further investigation.

Animals↗
PubMed1985

A monoclonal antibody reacting specifically with ganglioside GD1b in human brain.

A mouse monoclonal antibody directed against one of the major human brain gangliosides, GD1b, has been produced. The antibody binds specifically to the carbohydrate structure of GD1b as it does not react with structurally related gangliosides like GM1, GD2, GT1b or Fuc-GM1, or any other ganglioside of human brain. The results further indicate that terminal galactose as well as the disialosyl group linked to the inner galactose moiety are involved in binding to the antibody.

Animals↗
PubMed1985

Chemical structure of carcinoma ganglioside antigens defined by monoclonal antibody C-50 and some allied gangliosides of human pancreatic adenocarcinoma.

A hybridoma, C-50, obtained by fusion of mouse myeloma cells with spleen cells from a mouse immunized with cells from the colorectal carcinoma cell line COLO 205, produced antibodies that detected ganglioside antigen in human adenocarcinomas in many organs. The major ganglioside antigen fraction isolated from liver metastases of a pancreatic adenocarcinoma, behaving as a homogenous band on thin-layer chromatography, consisted of three different gangliosides. One of them, A (25%), had the same carbohydrate structure as the ganglioside antigen defined by monoclonal antibody 19-9, NeuAc alpha 2-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc beta 1-3Gal beta 1-4Glc-Cer(Fuc-3'-isoLM1) Magnani, J.L., Nilsson, B., Brockhaus, M., Zopf, D., Steplewski, Z., Koprowski, H. and Ginsburg, V. (1982) J. Biol. Chem. 257, 14365-14369). The major ganglioside, B (60%), was the isomeric hexasaccharide ganglioside (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3-Gal beta 1-4Glc-Cer(Fuc-3'-LM1) and the third ganglioside, C, was 6'-LM1, NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer (15%). Ganglioside B, isolated from human kidney, did not react with the C-50 MAb. Based on this result and on studies of COLO 205 cell induced tumours where the ganglioside antigen fraction only consisted of A, it is suggested that the C-50 MAb defines an antigen determinant present in A.

Adenocarcinoma↗
PubMed1985

Comparison of receptors for cholera and Escherichia coli enterotoxins in human intestine.

Extraction of lipids from human small intestinal epithelial cells or brush borders removed specific binding sites for cholera toxin completely, but only about 50% of the receptor sites for Escherichia coli heat-labile enterotoxin. Both cholera toxin and E. coli heat-labile enterotoxin bound strongly to ganglioside GM1 in the lipid extract and, to a lesser extent, to another monosialoganglioside and to GD1b. The results suggest that E. coli heat-labile enterotoxin binds to both ganglioside and glycoprotein receptor sites of the human small intestinal epithelium, whereas cholera toxin binding was restricted to the ganglioside receptors.

Cholera Toxin↗
PubMed1985

Monoclonal antibody 18B8 detects gangliosides associated with neuronal differentiation and synapse formation.

Mouse monoclonal antibody 18B8 detects developmentally regulated antigens in chicken retina and brain. The antigens detected by immunofluorescence appear initially on cell bodies in retinas of 6-13 day embryos. In older embryos during synapse formation and in adults, the antigen is localized in discrete laminae within the inner synaptic layer of retina and also is present in the outer synaptic layer and the outer segments of photoreceptor cells. The antigens from retina and brain were purified partially and were shown to be gangliosides of unknown structure that contain at least two sialic acid residues. Gangliosides that are recognized by antibody 18B8 change both qualitatively and quantitatively during neuronal development. These changes were correlated with the spatial and temporal changes in antigen expression detected histochemically.

Animals↗
PubMed1985

Gangliosides in serum immune complexes from tumor-bearing patients.

Immune complexes in the serum of tumor-bearing patients were adsorbed from whole blood or plasma on a protein A-Sepharose column. The adsorbed material was eluted, precipitated and analyzed for gangliosides. All precipitates obtained from eight patients at different treatment occasions contained gangliosides at concentrations varying from 0.1 to 12.2 nmol sialic acid/mg protein. The compositions of gangliosides were similar among the patients, regardless of the type of cancer, and quite different from that of normal serum. Most (75-85% of total sialic acid) belonged to the gangliotetraose series, of which 26-33% was GM1, 26-34% GD1a, 8-17% GD1b, and 5-13% GT1b. However, the dominant ganglioside in normal serum, GM3, was present in only trace amounts, which ruled out a nonspecific adsorption of serum ganglioside by protein A-Sepharose. Similar results were obtained for whole blood and plasma treatments, and these results suggest a specific interaction between gangliosides of the gangliotetraose series and serum immunoglobulins, either by the gangliosides acting as antigens and forming immune complexes or by their binding to already formed complexes.

Adult↗
PubMed1984

Receptor ganglioside content of three hosts for Sendai virus. MDBK, HeLa, and MDCK cells.

Specific gangliosides GD1a, GT1b and GQ1b isolated from brain have been shown to function as receptors for Sendai virus by conferring susceptibility to infection when they are incorporated into receptor-deficient cells (Markwell, M.A.K., Svennerholm, L. and Paulson, J.C. (1981) Proc. Natl. Acad. Sci. USA 78, 5406-5410). The endogenous gangliosides of three commonly used hosts for Sendai virus: MDBK, HeLa, and MDCK cells were analyzed to determine the amount and type of receptor gangliosides present. In all three cell lines, GM3 was the major ganglioside component. The presence of GM1, GD1a and the more complex homologs of the gangliotetraose series was also established. In cell lines derived from normal tissue, MDBK and MDCK cells, gangliosides contributed 47-65% of the total sialic acid. In HeLa cells, gangliosides contributed substantially less (17% of the total sialic acid). The ganglioside content of each cell line was shown not to be immutable but instead to depend on the state of differentiation, passage number, and surface the cells were grown on. Thus, the ganglioside concentration of undifferentiated MDCK cells was found to be substantially greater than that of MDBK or HeLa cells, but decreased as the MDCK cells underwent differentiation. Changes in culture conditions that were shown to decrease the receptor ganglioside content of the cells resulted in a corresponding decrease in susceptibility to infection. The endogenous oligosialogangliosides present in susceptible host cells were shown to function as receptors for Sendai virus.

Animals↗
PubMed1984

Monoclonal antibody A2B5 reacts with many gangliosides in neuronal tissue.

Monoclonal antibody A2B5, clone 105, obtained from a mouse immunized with 8-day chicken embryo retinas, reacts with most neuronal cells in chicken retina as revealed by immunofluorescence studies [G.S. Eisenbarth, F.S. Walsh, and M. Nirenberg (1979), Proc. Natl. Acad. Sci. USA 75: 4913-4917]. The antibody binds to many antigens, presumably gangliosides, present in ganglioside fractions from chicken brain, chicken retina, and human brain, as detected by autoradiography of thin-layer chromatograms. Most of the antigens, which are found in the mono-, di-, tri-, and polysialoganglioside fractions, do not correspond in chromatographic mobility to any of the major gangliosides of these tissues, as revealed by orcinol reagent. Apart from the fact that only one neuraminidase-labile sialyl residue is required for binding, the carbohydrate sequence recognized by the antibody is not known. There is a qualitative and quantitative change in the ganglioside antigens in chicken brain and retina during development. The less sialylated antigens appear first, followed by the more sialylated ones. The adult tissues contain little ganglioside antigen.

Aging↗
PubMed1983

A monoclonal antibody that precipitates the glycoprotein receptor for epidermal growth factor is directed against the human blood group H type 1 antigen.

Monoclonal antibody 101 produced by a hybridoma obtained by fusion with NS-1 myeloma cells of spleen cells from a mouse immunized with the human epidermoid carcinoma cell line, A431, specifically precipitates epidermal growth factor receptor, a glycoprotein of 170,000 Mr solubilized from A431 cell membranes (Richert, N. D., Willingham, M. C., and Pastan, I. H. (1983) J. Biol. Chem. 258, 8902-8907). The antibody also binds to neutral glycolipids extracted from A431 cells as evidenced by solid phase radioimmunoassay and by autoradiography. Binding of antibody to its target is inhibited by lacto-N-fucopentaose I but not by 2'-fucosyllactose or related oligosaccharides. Thus, antibody 101 is probably directed against the human blood group H type 1 sugar sequence Fuc alpha 1-2Gal beta 1-3GlcNAc . . .. This sequence presumably occurs on the epidermal growth factor receptor. Monoclonal antibody 102 produced by another hybridoma from the same fusion has the same cell specificity as antibody 101 and also binds to neutral glycolipids. However, binding of antibody 102 to its target is inhibited by 2'-fucosyllactose and not by lacto-N-fucopentaose I or related oligosaccharides. Thus, antibody 102 is probably directed against the human blood group H type 2 sugar sequence Fuc alpha 1-2Gal beta 1-4GlcNAc . . .. Antibody 102 does not precipitate solubilized epidermal growth factor receptor. Both antibodies bind to neutral glycolipids extracted from human erythrocytes belonging to blood group O but not to neutral glycolipids extracted from human erythrocytes with the "Bombay" phenotype.

ABO Blood-Group System↗
PubMed1983

Monoclonal antibodies against gastrointestinal tumour-associated antigens isolated as monosialogangliosides.

Monoclonal antibodies were produced after immunization of mice with a colorectal adenocarcinoma cell line or liver metastasis membranes from a patient with colon adenocarcinoma. Many monoclonal antibodies were found to react with colorectal adenocarcinoma cells but not with normal colon mucosa, blood lymphocytes, myeloma cells or lung epithelial carcinoma cells. Three of these 'colorectal tumour-specific' antibodies appear to define different antigens that were found in the complex monosialoganglioside fraction from 60 to 90% of the colorectal and pancreatic adenocarcinoma tumours or metastases examined but essentially lacking in normal colon mucosa and other normal or tumour tissues tested.

Adenocarcinoma↗