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Biomedical subjects

D M Marcus

Publications and source records attributed to D M Marcus.

At least 109 records · Page 6Linked to original sources
PubMed1984

Hereditary abnormalities of the OKT4 human lymphocyte epitope in two families.

The lymphocytes of two unrelated black individuals exhibited no immunofluorescent staining by a monoclonal antibody, OKT4, that reacts with T helper/inducer cells, but the lymphocytes reacted normally with four other monoclonal antibodies that identify T helper cells. Four first-degree relatives of these individuals were available for study. They had a normal proportion of OKT4+ lymphocytes but these cells had approximately half the normal number of OKT4 sites. This abnormality appears to be inherited as an autosomal recessive state.

Adolescent↗
PubMed1984

A review of the immunogenic and immuno-modulatory properties of glycosphingolipids.

This review summarizes recent data concerning the immunogenicity and immunomodulatory properties of glycosphingolipids. Many murine monoclonal antibodies that react with glycosphingolipids have been described recently. Most of these antibodies have been elicited by immunization with tumor cells and they may also bind to glycoproteins that contain similar carbohydrate sequences. Immunization with a variety of tissues, murine teratocarcinomas, myeloid leukemia, and carcinomas of the human lung, colon and stomach, has elicited antibodies that react with the sugar sequence Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal----. The suppression of lymphocyte responses to mitogens and antigens by gangliosides in vitro has led to suggestions that these glycolipids possess immunodulatory properties in vivo. The in vitro studies were performed by incubating mononuclear cells with either dispersions of pure gangliosides or ganglioside-containing liposomes. In vivo gangliosides are found only in cell membranes or in lipoproteins, where they represent a small mole percent of total lipids, and there is little information about the transfer of gangliosides from lipoproteins to cells in vivo. A role for gangliosides as modulators of the immune response is an interesting possibility that is not supported by physiologically relevant data at present.

Animals↗
PubMed1984

Lymphocyte subsets and urinary excretion of cytomegalovirus among homosexual men attending a clinic for sexually transmitted diseases.

A significantly higher frequency of urinary excretion of human cytomegalovirus (HCMV) was noted in homosexual men (29 [18%] of 161) than in heterosexual men (3 [4%] of 77) attending a clinic for sexually transmitted diseases. However, differences were not significant when only persons with antibody to HCMV were compared (29 of 157 vs. 3 of 33). The homosexual men who excreted HCMV had a significantly lower mean ratio of T-helper (OKT4+) to T-suppressor (OKT8+) cells (1.13 +/- 0.09) than did the homosexuals who did not excrete HCMV (1.67 +/- 0.1) or than did the heterosexual men (2.28 +/- 0.2). The abnormal ratio resulted from both a decrease in the percentage of OKT4+ and an increase in percentage of OKT8+ lymphocytes. The urinary excretion of HCMV by asymptomatic individuals who exhibit serological evidence of previous infection by this virus may be an indicator of impaired immune competence.

Adolescent↗
PubMed1984

Antibodies to glycosphingolipids in patients with multiple sclerosis.

Antibodies to one or more glycosphingolipids were detected by means of a liposome lysis assay in the sera of 60/81 patients with multiple sclerosis, 24/42 patients with systemic lupus erythematosus and in the majority of patients with cranial trauma or cerebrovascular accidents. Antibodies against ganglioside GM1 and asialo GM1 were found most commonly and they were frequently present in the same sera. Among patients whose sera contained antibodies to glycolipids, anti-GM1 alone occurred more frequently in patients with multiple sclerosis (14/59) than in systemic lupus erythematosus (1/22; p = 0.045) and antiasialo GM1 alone was more common in patients with lupus (9/22) than in patients with multiple sclerosis (8/59, p = 0.007). In 10 sera analyzed, all of the antibodies against these two glycolipids were of the IgM class, and some fluctuation in antibody titers was noted over a three-month period. The role of these antibodies in the initiation or perpetuation of inflammatory diseases of the central nervous system remains to be determined.

Antibodies↗
PubMed1984

Antibodies to glycosphingolipids in patients with multiple sclerosis and SLE.

We used a liposome lysis assay to measure antibodies against a panel of glycolipids. Antibodies to one or more compounds were detected in 34 of 46 patients with multiple sclerosis, 19 of 31 patients with systemic lupus erythematosus (SLE), and in the majority of patients with cranial trauma or cerebrovascular accidents. Antibodies against ganglioside GM1 and asialo GM1 were found most commonly, and they were frequently present in the same sera. The specificity of the antibodies was tested in four sera that contained antibodies to both glycolipids. The anti-GM1 antibodies cross-reacted with asialo GM1, but the converse was not true. Among patients whose sera contained antibodies to glycolipids, anti-asialo GM1 alone was more common in patients with SLE (7 of 17) than in multiple sclerosis (2 of 34; p = 0.004). Anti-GM1 alone was found in 9 of 34 patients with multiple sclerosis and 1 of 17 patients with SLE, a difference that was not statistically significant (0.135). No correlation was observed between the presence of anti-glycolipid antibodies and symptoms related to the nervous system in patients with SLE. Because of our inability to detect these antibodies by a solid phase immunoassay (ELISA), a comparison was made of the titers obtained with three monoclonal anti-glycolipid antibodies in the liposome lysis assay and ELISA. The ELISA was less sensitive in all instances, requiring from four to 1000 times as much antibody as the liposome lysis assay to give a positive test. We conclude that antibodies to glycolipids occur frequently in patients with multiple sclerosis, SLE, major cranial trauma, and cerebrovascular accidents. Their role in the initiation or perpetuation of inflammatory disease of the central nervous system has yet to be determined.

Antibodies↗
PubMed1983

New gangliosides from human erythrocytes.

We have identified a number of gangliosides from human erythrocytes that have not previously been detected in these cells, including two new compounds. The gangliosides were separated into monosialo- and disialoganglioside fractions by DEAE-column chromatography. Two monosialogangliosides that have not been previously detected in these cells are GM2 and GM1. Two other monosialogangliosides have the same carbohydrate structure, NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4) Glc-Cer, but they contain different fatty acids. The compound with higher chromatographic mobility (MG-5) contains a predominance of C22 and C24 fatty acids, whereas the principal fatty acid of the slower compound (MG-6) is C16. Both gangliosides are receptors for human anti-p and anti-Gd cold agglutinins. Six disialogangliosides not identifed previously in human red cells include GD3, GD1a, GD1b, DG-3, (formula: see text). The latter two are newly identified compounds and DG-4 contains a sugar sequence that has not been described previously, sialic acid residues linked to different hydroxyl groups of the same galactose.

Carbohydrate Conformation↗
PubMed1983

Binding of monoclonal antibody A2B5 to gangliosides.

Monoclonal antibody A2B5 (Eisenbarth et al, Proc. Nat. Acad. Sci. (1979, 76:4913-4917), which reacts with neurons, thymic epithelium and peptide-hormone secreting cells of several species, was reported to react specifically with brain tetrasialogangliosides. We have found that A2B5 binds to gangliosides GQ1b, GD3, GD2, disialolactoneotetraosylceramide, and probably to GT1a, when assayed by an immunostaining procedure that detects binding of antibody to gangliosides on a thin-layer plate. Additional data obtained by complement fixation revealed that this antibody reacted most strongly with ganglioside GQ1b almost as well with disialogangliosides GD3, GD2 and disialolactoneotetraosylceramide, weakly with GD1b and GT1b, and very weakly with GM3 and GD1a. These data indicate that A2B5 cannot be regarded as a specific reagent for the recognition of tetrasialogangliosides.

Animals↗
PubMed1983

Diverse specificities of five monoclonal antibodies reactive with glycophorin A of human erythrocytes.

Glycophorin A (GPA), the major sialoglycoprotein of human red cells, bears blood group MN determinants, and is a useful marker of the erythroid lineage in differentiating cells. Five monoclonal antibodies that react with GPA and possess a spectrum of serologic properties and fine specificities were obtained by immunization of mice with umbilical cord erythrocytes. Three antibodies, B22A, D22 and E11B, did not agglutinate En(a-) erythrocytes, genetic variants that lack GPA, and F11 and J11A agglutinated these cells very weakly. Antibodies B22A, E11B, and F11 agglutinated protease-treated cells more strongly than untreated erythrocytes, and they appeared to react with a peptide determinant located on the C-terminal side of the site at which trypsin cleaves GPA in the intact erythrocyte. In contrast to B22A and E11B, the hemagglutinating activity of F11 was not inhibited by purified GPA, nor did it bind to GPA in a solid phase immunoassay, but it immunoprecipitated GPA. Antibodies D22 and J11A appeared to be directed against carbohydrate determinants, or conformational determinants created by hydrogen bonding or electrostatic interactions between carbohydrate and protein. A preferential reaction of antibody J11A with MM over NN GPA was demonstrated by its reactions with enzyme-treated erythrocytes, its inhibition by purified GPA or its tryptic fragments, and by an ELISA assay.

Amino Acid Sequence↗
PubMed1982

Glycosphingolipid receptors for anti-Gd and anti-p cold agglutinins.

Anti-Gd and anti-p cold agglutinins exhibit similar serological properties: neuraminidase treatment of erythrocytes greatly reduces their agglutinability by these antibodies and protease treatment enhances their agglutination. We reported previously that an anti-p cold agglutinin was inhibited by sialosyllactoneotetraosylceramide, NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer, the most abundant ganglioside of human erythrocytes. We now report that two less abundant gangliosides are more potent inhibitors of this antibody, and of the anti-Gd antibodies, than sialosyllactoneotetraosylceramide. These two gangliosides have the same carbohydrate chain, NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(SNH), but they differ in their ceramide moiety. The principal fatty acid of SNH-1 is C16:0, whereas SNH-2 contains a predominance of C22:0, C24:0 and C24:1. No inhibition was produced by the ganglioside, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer. Another monoclonal cold agglutinin, Sa, which shares some serological properties with anti-Gd cold agglutinins, was not inhibited by any of these gangliosides.

Agglutinins↗
PubMed1982

Neutral glycolipid antigens as developmental markers of mouse teratocarcinoma and early embryos: an immunologic and chemical analysis.

Purified rabbit antibodies to neutral glycolipids were analyzed for their binding to mouse embryonal carcinoma cells (ECC) and preimplantation mouse embryos. Antibodies to globotetraosylceramide first bind to 2 to 4-cell embryos and reach a peak of staining intensity with morulae, whereas anti-Forssman antibodies first bind to late morulae and then, most intensely, to early blastocysts. We compared the binding of a monoclonal anti-Forssman antibody with that of rabbit anti-Forssman antibodies and show that although they react similarly with ECC, they do not do so with morulae: The monoclonal antibody stained weakly and unevenly, whereas the rabbit antiserum produced a uniformly bright immunofluorescent staining. Chemical analyses revealed that globotetraosylceramide is the most abundant glycolipid of F9 ECC and that there is poor correlation between the concentration of individual glycolipids in these cells and their reactivity with antibodies to glycolipid molecules. Interestingly, the 2 Forssman antibody-reactive glycolipids of F9 ECC differ in their mobility on TLC plates from the classical Forssman antigen extracted from sheep red blood cells. This illustrates the potential problems in extrapolating from the coincident binding properties of an anti-glycolipid antibody to the chemical structure or abundance of an antigen in different cell types.

Animals↗
PubMed1981

Glycosphingolipids of K562 cells: a chemical and immunological analysis.

The K562 cell line, which was established from a patient with chronic myeloid leukemia in blast crisis, was thought to be myeloid, but recent data indicate that it is an undifferentiated erythroid cell line. We have found that the glycosphingolipid content of these cells differs considerably from that of mature erythrocytes. Globotetraosylceramide, the most abundant glycolipid of mature red cells, was not detected in K562 cells, and neither was globotriaosylceramide. The predominant neutral glycolipids of K562 cells are monohexaosylceramides, which are a mixture of glucosyl- and galactosylceramides, and lactotriaosyl- and lactoneotetraosylceramides were also detected. Secondly, gangliosides which contain N-acetylgalactosamine were much more abundant than those containing N-acetylglucosamine in K562 cells, in contrast to erythrocytes. The most abundant ganglioside of K562 cells, GM2, is present in trace quantities in erythrocytes. A third major difference between these two cells lies in their relative proportions of neutral glycolipids and gangliosides. The molar ratio of neutral glycolipids/gangliosides is approximately 15:1 in erythrocytes and 1:1 in K562 cells. These striking differences between K562 cells and mature erythrocytes indicate that glycolipids may be useful cell surface markers of normal erythrocyte differentiation, and of erythroleukemias.

Adult↗
PubMed1981

Demyelination in vitro. Absorption studies demonstrate that galactocerebroside is a major target.

Myelinated cultures of mouse spinal cord have been exposed to sera raised in rabbits against whole white matter (anti-WM), myelin basic protein (anti-MBP) and galactocerebroside (anti-GC), the major glycolipid of CNS myelin, to determine which factor in central nervous system (CNS) tissue in vitro is the target of serum demyelinating and myelin swelling antibodies. The sera were tested by radioimmunoassay for activity against MBP and against GC and were also specifically absorbed with MBP, GC and control antigens. Studies were also performed with and without active complement. The findings show that demyelination and myelin swelling in vitro are caused by antibodies against GC and not against MBP. Ultrastructurally, the effects of anti-WM and anti-GC sera with and without complement were indistinguishable. This study demonstrates that GC is a major target in antibody-mediated demyelination.

Absorption↗
PubMed1981

Erythrocyte glycosphingolipids of four siblings with the rare blood group p phenotype and their parents.

Erythrocytes that exhibit the rare blood group p phenotype lack the P antigen (globotetraosylceramide) and the Pk antigen (globotriaosylceramide). This phenotype is inherited as an autosomal recessive condition and the red cells of heterozygous individuals, parents and children of p persons, are serologically normal but no chemical analyses of their red cells have been reported. We have studied an unusual family in which all five children exhibit the p phenotype. In addition to the abnormalities described previously, the erythrocytes of four siblings had twice the normal concentration of lactotriaoslyceramide and lactoeotetraosylceramide. These cells also contained 3-5 times as much sialosyllactoneotetraosylceramide and up to a two-fold increase in Gm3 ganglioside. The glycolipids of the parents'erythrocytes were normal. Electrophoretic analysis of the glycoproteins of the proposita's erythrocytes revealed no abnormalities, but her erythrocyte membranes contained approximately 35% less galactosamine than normal red cells. This abnormality resulted from a marked decrease in galactosamine that was soluble in chloroformmethanol. The lipid-extracted residue, which contained the glycoproteins, had a normal galactosamine content.

Blood Group Antigens↗
PubMed1981

Immunochemical relationship between Forssman and globoside glycolipid antigens.

The rabbit antibody response to the human blood group P glycolipid antigen, globoside, GalNAc(beta 1-3)Gal(alpha 1-4)Gal(beta 1-4)Glc-Cer, has been examined with respect to cross-reactions with the structurally related Forssman glycolipid GalNAc(alpha 1-3)GalNAc(beta 1-3)Gal(alpha 1-4)Gal(beta 1-4)Glc-Cer. Immunoadsorbent columns were used to isolate three purified antibody populations from the anti-globoside sera: (1) fraction A, antibodies that cross-react with both glycolipids; (2) fraction B, antibodies that react with Forssman antigen but not with globoside; and (3) fraction C, antibodies that are specific for globoside. The proportion of each fraction in the total antibody response to globoside appears to be related to preexisting immunity to these antigens. A rabbit with a high preimmune titer to Forssman antigen produced a large amount of Forssman-specific antibody, whereas a rabbit with a low or nonexistent preimmune titer of anti-Forssman antibody produced large amounts of globoside-specific antibody. The presence of Forssman-specific antibody in an immune response to globoside is an example of a heteroclitic type of immune response.

Animals↗