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At least 865 records · Page 48Linked to original sources
PubMed1998

Gangliosides of monocyte-derived macrophages of adults with advanced HIV infection show reduced surface accessibility.

Gangliosides of macrophages are potent immunoregulatory molecules. A monoclonal antibody directed at human macrophage gangliosides (25F4) inhibits macrophage migration with relative specificity. Recent reports suggested that greater expression of G(M1) in mononuclear cells accompanies advanced HIV infection, although others failed to demonstrate any differences in vitro. We purified gangliosides from blood monocyte-derived macrophages obtained from HIV-infected adults. Densitometric analysis of chromatograms demonstrated no differences in relative quantities of any macrophage gangliosides among all HIV-positive and -negative donors. Antibody 25F4 showed equivalent ELISA reactivity with purified macrophage gangliosides of HIV-positive and -negative donors. However, intact macrophages of HIV donors with CD4+ cell counts <200/mm3 showed impaired immunofluorescent surface expression of the 25F4 epitope and concomitant loss of migration inhibitory responsiveness. Thus, although relative content is unchanged, macrophage gangliosides become surface-inaccessible in adults with advanced HIV infection. Our data provide further evidence that dysregulation of glycosphingolipid metabolism in HIV-1 infection contributes to immune dysfunction.

Adult↗
PubMed1984

Effects of ganglioside treatments on lesion-induced behavioral impairments and sprouting in the CNS.

Recent findings suggest that exogenous gangliosides improve recovery of a learned behavior (alternation in a T-maze) which is thought to be related to sprouting after lesions of the entorhinal cortex. In the present investigation, we studied an unlearned behavior (the open-field hyperactivity resulting from bilateral entorhinal lesions) to evaluate whether ganglioside treatments reduce the severity of initial postlesion impairments or improve recovery. We also examined whether the treatments enhance the sprouting of septodenate fibers which parallels the recovery of open-field activity. The typical behavioral changes induced by bilateral entorhinal lesions include hyperactivity, reduced habituation of activity, and a gradual time-dependent return toward control levels. We found that rats treated with total brain gangliosides (30 mg/kg) showed a smaller lesion-induced increase, consistently lower levels, and greater within-session habituation of activity than did saline-treated counterparts. Control rats treated with gangliosides did not exhibit a reduction in activity, suggesting that the effect was on lesion-induced hyperactivity rather than on activity, per se. Ganglioside-treated rats showed a slight, but consistently smaller lesion-induced sprouting response by the septodentate pathway than did untreated counterparts at all postlesion intervals examined (3, 5, 7, and 10 days). The present findings indicate that ganglioside treatments reduce the severity of the initial behavioral effects after entorhinal lesions without enhancing the sprouting by septodentate fibers.

Acetylcholinesterase↗
PubMed1979

Growth factors and gangliosides: a possible new perspective in neuronal growth control.

For many permanent cell lines the transition from a growing (P) to a resting (R) state is reversibly controlled by growth factors present in serum. This P-to-R transition was studied in a neuronal cell line (B104) with respect to the action of serum, dibutyryl cyclic AMP (DBcAMP), gangliosides, and a glioma cell-produced growth factor GGF. In this cell system gangliosides seem to act as differentiation and survival factors. The kinetics of uptake of radioactively labeled gangliosides and survival experiments both support the idea of the stable incorporation of exogenously added gangliosides into the cells. Based on the experimental evidence a new model of cell development is proposed. Thus in addition to the R or Go state, which in this cell system is rather unstable and probably regulated by cyclic nucleotides, we postulate a differentiated D state, which is controlled by gangliosides and which is characterized by its stability (survival time). This D compartment seems to be closer to the in vivo differentiated neuron than does the R or P state. tthe possible mechanisms for the action of gangliosides are discussed.

Animals↗
PubMed1979

Ganglioside patterns and cholera toxin--peroxidase labeling of aggregating cells from the chick optic tectum.

2The ganglioside compositions of the chick optic tectum and aggregating tectal cell cultures were examined. Both showed similar trends in changes in ganglioside patterns during development. GD3 and GD1b were the predominant gangliosides early in development, while GD1a and several other multisialogangliosides increased in relative amounts with increasing age in vivo and in vitro. Four gangliosides were present early in development which have not previously been reported. These gangliosides are not present at later developmental times suggesting a possible role for them during the critical early stages of nervous tissue differentiation. Some differences were noted when comparing in vivo versus in vitro ganglioside patterns; these differences may possibly be due to the lack of normal retinotectal connections in the cultures. Cytochemical studies on the localization of the presumed cholera toxin--peroxidase binding site GM1 showed conjugate binding correlates with increasing levels of GM1 in the cultures. In older cultures, the conjugate was uniformly localized on all cells and processes in the aggregates. The conjugate also bound to synaptic membranes and intensely stained the synaptic cleft. This latter observation suggests an enrichment of GM1 in the synaptic cleft region.

Animals↗
PubMed1996

Ganglioside alterations in the central and peripheral nervous systems of patients with Creutzfeldt-Jakob disease.

We have examined the distribution and composition of gangliosides in central and peripheral nervous tissues from two patients with Creutzfeldt-Jakob disease (CJD). There were marked decreases in total ganglioside levels in CJD, with reductions in the cerebral cortex and cerebellum in the order of 20-30% and 50% of control values, respectively, though in spinal cord and sciatic nerve total gangliosides were not significantly altered. The percentage distribution of individual gangliosides was characterized by marked increases in GD3 and GD2, contrasting with severe decreases in GD1a, GD1b, GT1b and GQ1b; such changes were found throughout the patients' nervous tissues. An abnormal long-chain base composition was detected with the d20:1 component being decreased to less than 50% of control values, in the cerebrum, cerebellum and spinal cord. Changes in gangliosides occurred even in those tissues not severely affected neuropathologically. These ganglioside abnormalities are discussed in relationship to the pathogenesis of CJD.

Aged↗
PubMed1984

Brain gangliosides and thermal adaptation in vertebrates.

Comparative studies on brain gangliosides of about 80 species belonging to all classes of vertebrates reveal: a: distinct increases in concentration with phylogenetical progress of nervous organization, b) decreases in number of single fractions, c) changes in the polarity (degree of sialylation, N- or O-acetylation of sialic acids), d) alterations in the preponderance of one of the three possible pathways of biosynthesis. In addition to these phylogenetical trends, clear correlations between the brain ganglioside composition and the state of thermal adaptation were shown: "The lower the environmental (- body) temperature, the higher the polarity of brain gangliosides". This principle was proved for ectotherms being adapted to habitats with extreme temperatures, during seasonal acclimatization and for homeotherms during early neonatal heterothermic development or during hibernation. Surface pressure-area isotherms of monolayers from single ganglioside fractions (GD1a, GD1b) or differently composed ganglioside mixtures from brains of warm- or cold-adapted hamsters as physico-chemical parameters show significant differences in their variability concerning temperature and/or Ca2+-influences. The results are taken as evidence that variations in the composition of synaptic-bound gangliosides may induce alterations in physico-chemical properties of the neuronal membrane, thus modulating synaptic transmission during temperature adaptation.

Acclimatization↗
PubMed1984

Ganglioside induced surface activity and neurite formation of Neuro-2a neuroblastoma cells.

These studies demonstrate that while microtubules are essential for BBG-mediated neurite initiation and elongation, they are not involved in microfilament-dependent ganglioside-mediated surface activity. Microfilaments may be more directly altered by exogenous gangliosides than microtubules since they are the major structural elements of microvilli and are required for neurite branching. Our studies suggest that normal neuritogenesis requires a delicately balanced interaction between various cytoskeletal elements. Since there is a close relationship between membrane-associated lipid molecules and submembranous cytoskeletal elements, the incorporation of gangliosides into membranes may alter this balance and result in neurite formation. The use of gangliosides to enhance neurite production provides a unique model for the study of nerve development. We have shown that bovine brain gangliosides stimulate an immediate sequence of surface-related changes as well as microtubule and microfilament dependent neurite formation in Neuro-2a cells. However, the precise molecular events by which gangliosides enhance neuritogenesis await further study.

Animals↗
PubMed1982

Ganglioside-cholera toxin interactions: a binding and lipid monolayer study.

On t.l.c. plates 125I-cholera toxin binds to a disialoganglioside tentatively identified as GD1b with about 10 times less capacity then to ganglioside GM1. Binding of labeled toxin to both gangliosides was abolished in presence of excess amounts of unlabeled B subunit. Ganglioside extracts from human or pig intestinal mucosa showed toxin binding to gangliosides GM1 and GD1b. In ganglioside-containing lipid monolayers the penetration of the toxin was independent of the ganglioside binding capacity.

Animals↗
PubMed1979

Genetic variability for regional brain gangliosides in five strains of young mice.

The quantitative and qualitative distributions of gangliosides were determined in the cerebrum, cerebellum, and brain stem of five inbred strains (C57BL/6J, DBA/2J, LG/J, C3H/HeJ, BALB/cJ) of mice at 21 days of age. Genetic differences were found among the strains for wet weight, absolute amount of gangliosides per region, and concentration of ganglioside (expressed on bolth a wet and a dry weight basis) in all three regions of the brain. The water content of the various brain regions showed the least amount of genetic variability. Coefficients of genetic determination were used to estimate the magnitude of genetic influence on these traits in each brain region. Significant differences were also found among the five strains for the distribution of certain gangliosides. The DBA strain, which is susceptible to audiogenic seizure at this age, had the highest level of the myelin-enriched ganglioside GM1 in all brain regions. Most of the genetic variation that influences the content and distribution of gangliosides among neurologically normal mice can be considered polygenic. Several possible sources of this genetic variation that may contribute to the differences observed among the strains are discussed.

Age Factors↗
PubMed1989

Ganglioside mapping of a human medulloblastoma xenograft.

The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mumol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II3-alpha-NeuAc-LacCer (GM3) and II3-alpha-NeuAc-GgOse3Cer (GM2) but there were also relatively large proportions of IV3-alpha-NeuAc-LcOse4Cer (3'-isoLM1), IV3-alpha-NeuAc-nLcOse4Cer (3'-LM1) and a further ganglioside of the neolacto-series with an extra lactosamine moiety. The only oligosialoganglioside detected was IV3, II3-alpha-NeuAc2-GgOse4Cer (GD1a).

Animals↗
PubMed1992

Ganglioside antibodies: a lack of diagnostic specificity and clinical utility?

Serum IgG and IgM antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b and GT1b were determined in 210 patients with different degenerative and inflammatory disorders including motor neuron diseases, peripheral radiculopathies and neuropathies, multiple sclerosis and neuroborreliosis. No single disorder was associated specifically with ganglioside antibodies. No characteristic patterns of ganglioside antibodies were observed in any disease category. However, 32% of all patients had pathological antibody titres to at least one ganglioside. Four patients had pathological IgG and IgM titres for all gangliosides evaluated. They suffered from systemic lupus erythematosus [2], neuroborreliosis and schizophrenia, respectively. The results of this study indicate that the introduction of ganglioside antibody determination as a differential diagnostic test in clinical neurology is only helpful in a few patients with typical lower motor neuron syndromes.

Biomarkers↗
PubMed1985

Studies on the turnover and subcellular localization of membrane gangliosides in cultured neuroblastoma cells.

To compare the subcellular distribution of endogenously synthesized and exogenous gangliosides, cultured murine neuroblastoma cells (N1E-115) were incubated in suspension for 22 h in the presence of D-[1-3H]galactose or [3H]GM1 ganglioside, transferred to culture medium containing no radioisotope for periods of up to 72 hr, and then subjected to subcellular fractionation and analysis of lipid-sialic acid and radiolabeled ganglioside levels. The results indicated that GM2 and GM3 were the principal gangliosides in the cells with only traces of GM1 and small amounts of disialogangliosides present. About 50% of the endogenously synthesized radiolabelled ganglioside in the four major subcellular membrane fractions studied was recovered from plasma membrane and only 10-15% from the crude mitochondrial membrane fraction. In contrast, 45% of the exogenous [3H]GM1 taken up into the same subcellular membrane fractions was recovered from the crude mitochondrial fraction; less than 15% was localized in the plasma membrane fraction. The results are similar to those obtained from previously reported studies on membrane phospholipid turnover. They suggest that exogenous GM1 ganglioside, like exogenous phosphatidylcholine, does not intermix freely with any quantitatively major pool of endogenous membrane lipid.

Animals↗
PubMed1982

Gangliosides in various brain areas of three inbred strains of mice.

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p less than 0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri- and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.

Animals↗
PubMed1989

Ganglioside function in the development and repair of the nervous system. From basic science to clinical application.

Gangliosides play important roles in the normal physiological operations of the nervous system, in particular that of the brain. Changes in ganglioside composition occur in the mammalian brain not only during development, but also in aging and in several neuropathological situations. Gangliosides may modulate the ability of the brain to modify its response to cues or signals from the microenvironment. For example, cultured neurons are known to respond to exogenous ganglioside with changes characteristic of cell differentiation. Gangliosides can amplify the responses of neurons to extrinsic protein factors (neuronotrophic factors) that are normal constituents of the neuron's environment. The systemic administration of monosialoganglioside also potentiates trophic actions in vivo and improves neural responses following various types of injury to the adult mammalian central nervous system. The possible molecular mechanism(s) underlying the ganglioside effects may reflect an action in modulating ligand-receptor linked transfer of information across the plasma membrane of the cell.

Animals↗
PubMed2001

Differential distribution of ganglioside GM3 in seminiferous tubule and epididymis of adult rats.

Gangliosides are ubiquitous membrane components in mammalian cells and are suggested to play important roles in various functions such as cell-cell interaction, adhesion, cell differentiation, growth control and signaling. Among all ganglio-series gangliosides, GM3 has the simplest carbohydrate structure, and has been shown as a major ganglioside in male reproductive system. To study GM3 distribution in the seminiferous tubule and epididymis, frozen sections were stained with specific monoclonal antibody (MAb) against ganglioside GM3. In the seminiferous tubule of testis, pachytene spermatocytes and spermatids expressed ganglioside GM3, but not in spermatogonia and sertoli cells. Spermatogonia and sertoli cells near the basement membrane were negatively reacted to anti-GM3. In the epididymis, GM3 was expressed only in some interstitial cells. Taken together, these results suggest that the expression of ganglioside GM3 in rat seminiferous tubule and epididymis is spatio-temporally regulated during spermatogenesis.

Animals↗
PubMed1990

In vivo incorporation of N-acetyl-D-[U-14C]mannosamine into brain gangliosides of rats with quinolinic acid-induced lesions of the forebrain nucleus basalis magnocellularis.

Quinolinic acid, an excitotoxic agent, was applied unilaterally to the nucleus basalis magnocellularis of the rat forebrain, which resulted in neuronal destructions and consequently, loss of cholinergic projections to the cortex. The effects on ganglioside metabolism in brain cortical matter were studied. Total ganglioside contents in lesioned brains (n = 8) were found to be significantly decreased (range, 20-60%) but changes in brain ganglioside patterns on thin layer chromatograms were not apparent. On the other hand, in vivo incorporation of N-acetyl-D-[U-14C]mannosamine into brain gangliosides ranged from 19 to 36% (mean, 26%) of radiolabel in controls, and 5 to 21% (mean, 13%), a significant reduction in lesioned brains. Labeling of brain glycoproteins or of nonganglioside lipids was not affected. Since central cholinergic hypofunctions are also important neurochemical characteristics of Alzheimer's disease, abnormal ganglioside metabolism found in the lesioned rats may be of significance in the human disorder, where reduced brain ganglioside contents have also been reported.

Animals↗
PubMed1988

Gangliosides in neuroblastomas.

Neuroblastomas from children presenting with tumors at various ages and different primary sites (abdominal, adrenals, pelvic, and thoracic) were studied. Analysis of the ganglioside patterns of 53 tumors indicated that patients who were either disease positive 2 yr following surgery or dead of disease, had significantly (p less than 0.005) less GT1b plus GD1b than tumors from patients that were disease free 2 yr post surgery. The presence of GD2 in 45 of the tumors correlates well with the suggestion that it can be used as a marker in neuroblastoma diagnosis. Children with thoracic neuroblastomas have a significantly better prognosis than children with tumors in other anatomic sites. Analysis of the ganglioside composition of these tumors only, indicated that they had a significantly higher (p less than 0.005) concentration of GT1b and GD1b and a significantly lower concentration (p less than 0.025) of monosialogangliosides than those patients who were dead of disease or had persistent disease. These results suggest that low levels of GT1b and GD1b correlate with a poor prognosis. The thoracic neuroblastomas may be comprised of more "differentiated" neuroblastoma cells (ganglioside patterns more similar to the CNS), and this may contribute to the fact that about 85% of children with thoracic neuroblastoma recover. To understand why the ganglioside pattern may serve as a prognostic indicator for neuroblastoma, it is necessary to know whether gangliosides have specific roles in neuronal differentiation. Our approach to this question is to compare the effect(s) of added ganglioside or the corresponding oligosaccharide on neuroblastoma cells. Results obtained suggest that the oligosaccharide from GM1 is able to enhance neuritogenesis by S20Y murine neuroblastoma cells to the same extent that GM1 does.

Cell Division↗
PubMed2001

Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions.

Gangliosides GD3, GD2 and GM2, which are the major gangliosides expressed on most human cancers of neuroectodermal and epithelial origin, have been focused on as effective targets for passive immunotherapy with monoclonal antibodies. We previously developed a chimeric anti-GD3 mAb, KM871, and a humanized anti-GM2 mAb, KM8969, which specifically bound to the respective antigen with high affinity and showed potent immune effector functions. Humanization of anti-ganglioside antibody is expected to enhance its use for human cancer therapy. In the present study, we generated a chimeric anti-GD2 mAb, KM1138, and further developed the humanized form of anti-GD2 and anti-GD3 mAbs by the complementarity-determining regions grafting method. The resultant humanized anti-GD2 mAb, KM8138, and anti-GD3 mAb, KM8871, showed binding affinity and specificity similar to those of their chimeric counterparts. In addition, both humanized mAbs had functional potency comparable to the chimeric mAbs in mediating the immune effector functions, consisting of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The production of these humanized anti-ganglioside mAbs, with potent effector functions and low immunogenicity, precedes the evaluation of the therapeutic value of anti-ganglioside mAbs in passive immunotherapy and the target validation for ganglioside-based vaccine therapy.

Amino Acid Sequence↗