Gangliosides: A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)G(M3) Ganglioside: A ganglioside present in abnormally large amounts in the brain and liver due to a deficient biosynthetic enzyme, G(M3):UDP-N-acetylgalactosaminyltransferase. Deficiency of this enzyme prevents the formation of G(M2) ganglioside from G(M3) ganglioside and is the cause of an anabolic sphingolipidosis.G(M1) Ganglioside: A specific monosialoganglioside that accumulates abnormally within the nervous system due to a deficiency of GM1-b-galactosidase, resulting in GM1 gangliosidosis.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)G(M2) Ganglioside: A glycosphingolipid that accumulates due to a deficiency of hexosaminidase A or B (BETA-N-ACETYLHEXOSAMINIDASES), or GM2 activator protein, resulting in GANGLIOSIDOSES, heredity metabolic disorders that include TAY-SACHS DISEASE and SANDHOFF DISEASE.Glycosphingolipids: Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.Carbohydrate Sequence: The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.Neuraminic AcidsNeuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)Sialyltransferases: A group of enzymes with the general formula CMP-N-acetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of N-acetylneuraminic acid from CMP-N-acetylneuraminic acid to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. EC 2.4.99.-.N-Acetylneuraminic Acid: An N-acyl derivative of neuraminic acid. N-acetylneuraminic acid occurs in many polysaccharides, glycoproteins, and glycolipids in animals and bacteria. (From Dorland, 28th ed, p1518)N-Acetylgalactosaminyltransferases: Enzymes that catalyze the transfer of N-acetylgalactosamine from a nucleoside diphosphate N-acetylgalactosamine to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.Glycolipids: Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)Sulfoglycosphingolipids: GLYCOSPHINGOLIPIDS with a sulfate group esterified to one of the sugar groups.Spectrometry, Mass, Fast Atom Bombardment: A mass spectrometric technique that is used for the analysis of a wide range of biomolecules, such as glycoalkaloids, glycoproteins, polysaccharides, and peptides. Positive and negative fast atom bombardment spectra are recorded on a mass spectrometer fitted with an atom gun with xenon as the customary beam. The mass spectra obtained contain molecular weight recognition as well as sequence information.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Cerebrosides: Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed)Carbohydrate Conformation: The characteristic 3-dimensional shape of a carbohydrate.Guillain-Barre Syndrome: An acute inflammatory autoimmune neuritis caused by T cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. (From Adams et al., Principles of Neurology, 6th ed, pp1312-1314)Globosides: Glycosphingolipids containing N-acetylglucosamine (paragloboside) or N-acetylgalactosamine (globoside). Globoside is the P antigen on erythrocytes and paragloboside is an intermediate in the biosynthesis of erythrocyte blood group ABH and P 1 glycosphingolipid antigens. The accumulation of globoside in tissue, due to a defect in hexosaminidases A and B, is the cause of Sandhoff disease.Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Gangliosidoses: A group of autosomal recessive lysosomal storage disorders marked by the accumulation of GANGLIOSIDES. They are caused by impaired enzymes or defective cofactors required for normal ganglioside degradation in the LYSOSOMES. Gangliosidoses are classified by the specific ganglioside accumulated in the defective degradation pathway.Tetanus Toxin: Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.Gangliosidoses, GM2: A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.Lipidoses: Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.Polyradiculoneuropathy: Diseases characterized by injury or dysfunction involving multiple peripheral nerves and nerve roots. The process may primarily affect myelin or nerve axons. Two of the more common demyelinating forms are acute inflammatory polyradiculopathy (GUILLAIN-BARRE SYNDROME) and POLYRADICULONEUROPATHY, CHRONIC INFLAMMATORY DEMYELINATING. Polyradiculoneuritis refers to inflammation of multiple peripheral nerves and spinal nerve roots.Cholera Toxin: An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Miller Fisher Syndrome: A variant of the GUILLAIN-BARRE SYNDROME characterized by the acute onset of oculomotor dysfunction, ataxia, and loss of deep tendon reflexes with relative sparing of strength in the extremities and trunk. The ataxia is produced by peripheral sensory nerve dysfunction and not by cerebellar injury. Facial weakness and sensory loss may also occur. The process is mediated by autoantibodies directed against a component of myelin found in peripheral nerves. (Adams et al., Principles of Neurology, 6th ed, p1313; Neurology 1987 Sep;37(9):1493-8)Glucosylceramides: Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Sphingosine: An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)Glycoconjugates: Carbohydrates covalently linked to a nonsugar moiety (lipids or proteins). The major glycoconjugates are glycoproteins, glycopeptides, peptidoglycans, glycolipids, and lipopolysaccharides. (From Biochemical Nomenclature and Related Documents, 2d ed; From Principles of Biochemistry, 2d ed)Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.Access to Information: Individual's rights to obtain and use information collected or generated by others.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Immune System Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.Immunologic Tests: Immunologic techniques involved in diagnosis.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Epitopes: Sites on an antigen that interact with specific antibodies.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Standard of Care: The minimum acceptable patient care, based on statutes, court decisions, policies, or professional guidelines.Sphingolipids: A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)

The role of homophilic binding in anti-tumor antibody R24 recognition of molecular surfaces. Demonstration of an intermolecular beta-sheet interaction between vh domains. (1/1980)

The murine antibody R24 and mouse-human Fv-IgG1(kappa) chimeric antibody chR24 are specific for the cell-surface tumor antigen disialoganglioside GD3. X-ray diffraction and surface plasmon resonance experiments have been employed to study the mechanism of "homophilic binding," in which molecules of R24 recognize and bind to other molecules of R24 though their heavy chain variable domains. R24 exhibits strong binding to liposomes containing disialoganglioside GD3; however, the kinetics are unusual in that saturation of binding is not observed. The binding of chR24 to GD3-bearing liposomes is significantly weaker, suggesting that cooperative interactions involving antibody constant regions contribute to R24 binding of membrane-bound GD3. The crystal structures of the Fabs from R24 and chR24 reveal the mechanism for homophilic binding and confirm that the homophilic and antigen-binding idiotopes are distinct. The homophilic binding idiotope is formed largely by an anti-parallel beta-sheet dimerization between the H2 complementarity determining region (CDR) loops of two Fabs, while the antigen-binding idiotope is a pocket formed by the three CDR loops on the heavy chain. The formation of homophilic dimers requires the presence of a canonical conformation for the H2 CDR in conjunction with participation of side chains. The relative positions of the homophilic and antigen-binding sites allows for a lattice of GD3-specific antibodies to be constructed, which is stabilized by the presence of the cell membrane. This model provides for the selective recognition by R24 of cells that overexpress GD3 on the cell surface.  (+info)

Partial purification and properties of porcine thymus lactosylceramide beta-galactosidase. (2/1980)

Porcine thymus lactosylceramide beta-galactosidase was purified by a simple procedure. In the final step of isoelectric focusing the enzyme was separated into two peaks of pI 6.3 (peak I) and 7.0 (peak II), which showed 3,600- and 4,000-fold enhancement of lactosylceramide-hydrolysing activity, respectively. The two peaks had identical mobility on polyacrylamide gel electrophoresis. The apparent molecular weight was 34,000. Neither monosialoganglioside (GM1) nor galactosylceramide was hydrolysed by the purified enzyme fractions. The optimal pH was at 4.6, and sodium taurocholate was essential for the reaction. The apparent Km was 2.3 x 10-5 M. The reaction was stimulated by sodium chloride and linoleic acid, while it was strongly inhibited by Triton X-100 and bovine serum albumin. Galactosylceramide, p-nitrophenyl beta-galactoside, and p-nitrophenol were weak inhibitors. No effects of GM1 and galactose were observed on the hydrolysis of lactosylceramide.  (+info)

Gangliosides of human kidney. (3/1980)

Five gangliosides isolated from human kidney have been characterized. The two main fractions were shown to be typical extraneural gangliosides in having lactose as their neutral carbohydrate moiety. Their structures were identified as: AcNeu(alpha2-3)Gal(beta1-4)Glc(beta1-1)Cer and AcNeu(alpha2-8)AcNeu(alpha2-3)Gal(beta1-4)Glc(beta1-1)Cer. The two main hexosamine-containing gangliosides are structurally related to human blood group substances of glycosphingolipid nature. The following structures are postulated: AcNeu(alpha2-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc(beta1-1)Cer and AcNeu(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc(beta1-1) Cer. The third hexosamine-containing ganglioside belongs to a different series of glycolipids and was shown to have the structure of a major ganglioside of human brain: AcNeu(alpha2-3)Gal(beta1-3)GalNAc(beta1-4)[AcNeu(alpha2-3)]Gal(beta1-4)Glc(beta1- 1)Cer. The fatty acid structure of different gangliosides was shown to resemble that of neutral glycolipids of human kidney with the nonhydroxy acids C16:0, C22:0, and C24:0 as major components.  (+info)

Lipolytic action of cholera toxin on fat cells. Re-examination of the concept implicating GM1 ganglioside as the native membrane receptor. (4/1980)

The possible role of galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1) ganglioside in the lipolytic activity of cholera toxin on isolated fat cells has been examined. Analyses of the ganglioside content and composition of intact fat cells, their membranous ghosts, and the total particulate fraction of these cells indicate that N-acetylneuraminylgalactosylglucosylceramide (GM3) represents the major ganglioside, with substantial amounts of N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM2) and smaller amounts of other higher homologues also present. Native GM1 was not detected in any of these preparations. Examination of the relative capacities of various exogenously added radiolabeled sphingolipids to bind to the cells indicated that GM2 and glucosylsphingosine were accumulated by the cells to extents comparable to GM1. Galactosylsphingosine and sulfatide also exhibited significant, although lesser, binding affinities for the cells. The adipocytes appeared to nonspecifically bind exogenously added GM1; saturation of binding sites for GM1 could not be observed up to the highest concentration tested (2 X 10(-4) M), wherein about 7 X 10(9) molecules were associated with the cells. Essentially all of this exogenously added GM1 was found bound to the plasma membrane "ghost" fraction. Investigation of the biological responses of the cells confirmed their sensitivities to both cholera toxin and epinephrine-stimulated lipolysis, as well as the lag period displayed during the toxin's action. While we could confirm that the toxin's lipolytic activity can be enhanced by prior treatment of the fat cells with GM1, several of the observed characteristics of this phenomenon differ from earlier reported findings. Accordingly, added GM1 was able to enhance only the subsequent rate, but not the extent, of toxin-stimulated glycerol release (lipolysis) from the cells. We also were unable to confirm the ability of GM1 to enhance the toxin's activity at either saturating or at low toxin concentrations. The limited ability of added GM1 to enhance the toxin's activity appeared in a unique bell-shaped dose-response manner. The inability of high levels of GM1 to stimulate a dose of toxin that was ineffective on native cells suggests that the earlier reported ability of crude brain gangliosides to accomplish this was due to some component other than GM1 in the crude extract. While several glycosphingolipids and some other carbohydrate-containing substances that were tested lacked the ability to mimic the enhancing effect of GM1, 4-methylumbelliferyl-beta-D-galactoside exhibited an effect similar to, although less pronounced than, that of GM1. The findings in these studies are unable to lend support to the earlier hypothesis that (a) GM1 is cholera toxin's naturally occurring membrane receptor on native fat cells, and (b) the ability of exogenously added GM1 to enhance the toxin's lipolytic activity represents the specific creation of additional natural receptors on adipocytes...  (+info)

Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion to collagen. (5/1980)

Gangliosides, sialic acid-containing glycosphingolipids, accumulate in atherosclerotic vessels. Their role in the pathogenesis of atherosclerosis is unknown. Gangliosides isolated from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion and enhance platelet adhesion to immobilized collagen. These activities are all mediated by ganglioside effects on the platelet integrin collagen receptor alpha2beta1. Therefore, we hypothesized that gangliosides isolated from atherosclerotic plaques would enhance platelet adhesion to immobilized collagen, a major component of the subendothelial matrix of blood vessels. Furthermore, we questioned whether this effect of atherosclerotic gangliosides might play a role in the pathogenesis of atherosclerosis. To test this hypothesis, we isolated the gangliosides from postmortem aortas of patients with extensive atherosclerotic disease and examined their effects on platelet adhesion. Samples of aortic tissue taken from areas involved with atherosclerotic plaque demonstrated accumulation of gangliosides (64.9+/-6.5 nmol/g wet weight) compared with gangliosides isolated from control normal aortic tissue taken from children who died of noncardiac causes (NAGs; 21.1+/-6.4 nmol/g wet weight). Interestingly, samples of tissue taken from diseased aortas but from areas not involved with gross plaque formation also demonstrated ganglioside accumulation (47.6+/-12.8 nmol/g wet weight). Next, the activity of each of these gangliosides on platelet adhesion to immobilized type I collagen was studied. Atherosclerotic aortic gangliosides (AAGs) as well as those isolated from grossly unaffected areas of the same aorta (UAGs) both increased platelet adhesion compared with control NAGs (OD570, 0. 37+/-0.11 and 0.29+/-0.14 versus 0.16+/-0.07, respectively; P<0.01 and P<0.05, respectively). These OD570 values corresponded to 9x10(5), 8x10(4), and 6x10(3) platelets per well after preincubation with 5 micromol/L AAG, UAG, and NAG, respectively. Increased adhesion was observed after preincubation with as little as 0.5 micromol/L AAG, and maximal adhesion was seen at 2.5 micromol/L, with a plateau extending to the highest concentration tested, 10 micromol/L. The effect of AAGs on platelet adhesion to collagen was abrogated by incubation of treated platelets with F-17 anti-alpha2 monoclonal antibody (OD570, 0.13+/-0.02). Finally, the effects of the major individual gangliosides isolated from atherosclerotic tissues, GM3 and GD3, were tested. GM3 increased adhesion to collagen (OD570, 0.415+/-0.06) as did GD3 (0.31+/-0.08). Similar to that of AAGs, the effect of both molecules was blocked by F-17 (0. 09+/-0.04 and 0.13+/-0.06, respectively). These experiments demonstrate that accumulated atherosclerotic gangliosides promote platelet adhesion to collagen, the major component of the subendothelial matrix. Furthermore, this activity is mediated by an effect of the gangliosides on the collagen-binding integrin alpha2beta1. This activity may provide a mechanism for the development of platelet thrombi at sites where atherosclerotic gangliosides accumulate and help to explain the role of platelets in the process of atherosclerotic disease progression.  (+info)

Antiganglioside antibodies in Guillain-Barre syndrome after a recent cytomegalovirus infection. (6/1980)

OBJECTIVE: To study the association between anti-ganglioside antibody responses and Guillan-Barre syndrome (GBS) after a recent cytomegalovirus (CMV) infection. METHODS: Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. RESULTS: IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. CONCLUSION: Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.  (+info)

The distribution of ganglioside-like moieties in peripheral nerves. (7/1980)

GM1 ganglioside has been implicated as a target of immune attack in some diseases of the peripheral nervous system. Anti-GM1 ganglioside antibodies are associated with certain acquired immune-mediated neuropathies. It is not clear how anti-GM1 antibodies cause nerve dysfunction and injury; however, sodium and/or potassium ion channel dysfunction at the node of Ranvier has been implicated. To gain insight into the pathogenesis of these neuropathies, we examined the distribution of GM1 ganglioside and Gal(beta1-3)GalNAc moieties in nerve fibres and their relationship to voltage-gated sodium and potassium (Kv1.1, 1.5) channels at the nodes of Ranvier in peripheral nerves from human, rat and dystrophic mice. Gal(beta1-3)GalNAc moieties were localized via the binding of cholera toxin and peanut agglutinin. As a control for the specificity of these findings, we compared the distribution of GM1 moieties to that of the ganglioside GT1b. Our study provides definitive evidence for the presence of Gal(beta1-3)GalNAc bearing moieties on the axolemmal surface of mature myelinated fibres and on Schwann cells. Gal(beta1-3)GalNAc binding sites did not have an obligatory co-localization with voltage-gated sodium channels or the potassium ion channels Kv1.1 and Kv1.5 and are thus not likely carried by these ion channels. In contrast with Gal(beta1-3)GalNAc, GT1b-like moieties are restricted to the axolemma.  (+info)

De-N-acetyl-gangliosides in humans: unusual subcellular distribution of a novel tumor antigen. (8/1980)

The disialoganglioside GD3 is a major antigen in human melanomas that can undergo 9-O-acetylation of the outer sialic acid (giving 9-OAc-GD3). Monoclonal antibody SGR37 detects a different modification of the GD3, de-N-acetylation of the 5-N-acetyl group (giving de-N-Ac-GD3). We found that conventional immunohistochemistry of the SGR37 antigen is limited by a reduction in reactivity upon fixation with aldehydes (which presumably react with the free amino group) or with organic reagents (which can extract glycolipids). We optimized conditions for detection of this antigen in unfixed frozen tissue sections and studied its distribution in human tissues and tumors. It is expressed at low levels in a few blood vessels, infiltrating mononuclear cells in the skin and colon, and at moderate levels in skin melanocytes. In contrast, the antigen accumulates at high levels in many melanomas and in some lymphomas but not in carcinomas. In positive melanomas, expression is sometimes more intense and widespread than that of GD3. Both 9-O-acetylation and de-N-acetylation of GD3 seem to occur after its initial biosynthesis. Isotype-matched antibodies against GD3, 9-O-acetyl-GD3 and de-N-acetyl-GD3 were used to compare their subcellular localization and trafficking. 9-O-acetyl-GD3 colocalizes with GD3 predominantly on the cell surface and partly in lysosomal compartments. In contrast, de-N-acetyl-GD3 has a diffuse intracellular location. Adsorptive endocytosis of antibodies indicates that whereas GD3 remains predominantly on the cell surface, de-N-acetyl-GD3 is efficiently internalized into a compartment that is distinct from lysosomes. Rounding up of melanoma cells occurring during growth in culture is associated with relocation of the internal pool of de-N-acetyl-GD3 to the cell surface. Thus, a minor modification of the polar head group of a tumor-associated glycosphingolipid can markedly affect the subcellular localization and trafficking of the whole molecule. The high levels of the SGR37 antigen in melanomas and lymphomas, its selective endocytosis from the cell surface, and its relocation to the cell surface of rounded up cells suggest potential uses in diagnostic or therapeutic approaches to these diseases.  (+info)

  • Positioned in the plasma membrane, gangliosides interact with other lipids and proteins, both laterally in the membrane and via their head groups, acting as cellular receptors that can be recognized by antibodies and other ganglioside-binding molecules. (
  • Antibodies to the GD3 ganglioside can induce partial remission of tumor growth in animals as well as in Humans via enhancement of cytotoxic and proliferative response of lymphocytes. (
  • Although many neurologists attempt to lower titers of antiganglioside autoantibodies, oncologists are developing strategies to augment production of IgM antibodies that will remove immunosuppressive gangliosides from the circulation of patients and target gangliosides and kill tumor cells. (
  • Antiganglioside IgM antibodies can cause leakage of the blood-nerve barrier in a concentration-dependent and complementindependent manner, bind to neuronal gangliosides to create a neuromuscular block and serve as a marker of axonal damage in neuropathies such as multiple sclerosis. (
  • we rarely encounter IgG antibodies to gangliosides in the sera of patients who have been immunized with ganglioside-based vaccines.8NeuAcα2.3GalNAcβ1. (
  • However, through results obtained by myself as part of my PhD research as well as other labs, a particular class of glycolipids (combination of sugars and lipids, called gangliosides are necessary for the toxin to enter neurons. (
  • The antigenic epitope for A2B5 was assumed to include the trisialosyl residue connected to the inner galactose of the hemato- or ganglio-type oligosaccharide structure of gangliosides. (
  • This validation must consider the purity of gangliosides from different commercial sources, the coating of gangliosides onto a solid matrix in a manner that maximizes exposure of oligosaccharide epitopes to IgM paratopes, techniques to minimize background noise and eliminate nonspecific antibody binding, and carefully defined positive and negative controls. (
  • which prevents direct and specific recognition by conventional specific T cells.4Glcβ1Cer NeuAcα2.8 Oligosaccharide residues of gangliosides are unable to bind into the groove of MHC molecules.4Galβ1. (
  • These results were obtained with an improved method for isolating total gangliosides in high yield, by employing DEAE‐Sephadex column chromatography. (
  • Cerebrosides have a single glucose or galactose at the 1-hydroxy position, while gangliosides have at least three sugars, one of which must be sialic acid. (
  • Gangliosides were later classified by Svennerholm according to the number of sialic-acid residues and chromatographic mobility ( 1 ). (
  • Ganglioside-1, -2, and -3 migrated above GD1b, below GQ1b, and far below GQ1b on thin-layer chromatography. (
  • They were discovered by Ernst Klenk in the 1940s, who proposed the term "ganglioside" due to the abundance of these molecules in "Ganglionzellen" (neurons). (
  • Through both mechanisms, tumor-associated gangliosides may affect malignant progression, which makes them attractive targets for cancer immunotherapies. (
  • there is no evidence for isotype switching of antiganglioside IgM or any atypical memory responses mediated by T . Neural tissues and malignant cells overexpress gangliosides.8NeuAcα2.4 Antigen-antibody interactions also may involve salt linkages.3Galβ1. (
  • The structures of these gangliosides were characterized by overlay analysis with glycolipid-specific ligands, product analysis after sialidase or mild acid treatment, and electrospray ionization-mass spectrometry (ESI-MS). Accordingly, G-1, G-2 and G-3 were identified to be GT3, GQ1c and GP1c, respectively. (
  • The large structural variability is related to developmental stage and cell type, and hundreds of gangliosides are known today ( 3 - 5 ). (
  • Abstract- Gangliosides were isolated from purified human myelin in a yield of 62 μg of lipid‐bound sialic acid per 100 mg of dry myelin. (
  • Sialosylgalactosyl ceramide (G 7 ) was found to be a major component of the ganglioside fraction, amounting to 15 per cent of the total sialic acid. (
  • It accounted for 10 per cent of lipid‐bound sialic acid in adult human white matter, making it the third most abundant ganglioside on a molar basis. (
  • Gangliosides perform important functions through carbohydrate-specific interactions with proteins, for example, as receptors in cell-cell recognition, which can be exploited by viruses and other pathogens, and also by regulating signaling proteins, such as the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR), through lateral interaction in the membrane. (
  • Accumulating evidence indicates that many cellular events, including differentiation, growth, signaling, interactions, and immune reactions are highly influenced by gangliosides, and that these molecules may also cause malignancies. (
  • Here, we highlight the function and molecular interactions of gangliosides with high clinical significance. (
  • abstract = "Various reports have appeared indicating that the expression of gangliosides may be largely regulated at the genetic level. (
  • Yowler, B.C., Kensinger, R.D., and Schengrund, C-L. (2002) Botulinum neurotoxin A activity is dependent upon the presence of specific gangliosides in neuroblastoma cells expressing synaptotagmin I. Journal of Biological Chemistry 277:32815-32819. (
  • Phylogenetic analysis of brain gangliosides using the A2B5 preparation demonstrated that c-series gangliosides are enriched in lower animals, especially bony fish of different species. (
  • In this review, we describe how proteins recognize gangliosides, focusing on the molecular recognition of gangliosides associated with cancer immunotherapy, and discuss the importance of these molecules in cancer research. (
  • gangliosides are not presented in the context of MHC molecules. (
  • Factors involved in the regulation of ganglioside expression include the proper translocation and sorting of the glycolipid products in multi-glycosyltransferase systems. (
Plus it
Plus it (
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Human Metabolome Database: Showing metabocard for Ganglioside GM2 (d18:0/25:0) (HMDB0011906) (
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The Gangliosides | SpringerLink (
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FIGURE 10.33 Map of North America showing the continental | bartleby (
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Ganglioside Structure, Function, and Biomedical Potential | Robert Ledeen | Springer (
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Shop and Discover over 51,000 Books and Journals - Elsevier (
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