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1.
Glycoconj J ; 36(5): 419-428, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31297734

RESUMO

Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What's more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Gangliosídeo G(M3)/sangue , Neoplasias/diagnóstico , Adulto , Idoso , Área Sob a Curva , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Cromatografia Líquida , Diagnóstico Diferencial , Feminino , Gangliosídeos/sangue , Gangliosídeos/classificação , Humanos , Antígeno Ki-67/sangue , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Análise de Componente Principal , Prognóstico , Curva ROC , Espectrometria de Massas em Tandem
2.
Electrophoresis ; 33(12): 1778-86, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22740466

RESUMO

A strategy combining high-performance thin layer chromatography (HPTLC), laser densitometry, and fully automated chip-based nanoelectrospray (nanoESIchip) performed on a NanoMate robot coupled to QTOF-MS was developed, optimized, and for the first time applied for mapping and structural identification of gangliosides (GGs) extracted and purified from a human angioblastic meningioma specimen. While HPTLC pattern indicated only seven fractions migrating as GM3, GM2, GM1, GD3, GD1a (nLD1, LD1), GD1b, GT1b, and possibly GD2, due to the high sensitivity, mass accuracy, and ability to ionize minor species in complex mixtures, nanoESIchip-QTOF MS was able to discover significantly more GG species than ever reported in meningioma. Thirty-four distinct glycosphingolipid components of which five asialo, one GM4, nine GM3, two GM2, two GD3, nine GM1, and six GD1 differing in their ceramide compositions were identified. All structures presented long-chain bases with 18 carbon atoms, while the length of the fatty acid was found to vary from C11 to C25. MS screening results indicated also that the diversity of the expressed GM1 structures is higher than expected in view of the low proportions evidenced by densitometric quantification. Simultaneous fragmentation of meningioma-associated GM1 (d18:1/24:1) and GM1 (d18:1/24:0) by MS/MS using CID confirmed the postulated structures of the ceramide moieties and provided data on the glycan core, which document that for each of the GM1 (d18:1/24:1) and GM1 (d18:1/24:0) forms both GM1a and GM1b isomers are expressed in the investigated meningioma tissue.


Assuntos
Gangliosídeos/análise , Meningioma/química , Espectrometria de Massas em Tandem/métodos , Sequência de Carboidratos , Cromatografia em Camada Fina/métodos , Gangliosídeos/química , Gangliosídeos/classificação , Humanos , Masculino , Procedimentos Analíticos em Microchip , Pessoa de Meia-Idade , Nanotecnologia , Sensibilidade e Especificidade
3.
J Neurochem ; 116(5): 926-35, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21214571

RESUMO

Gangliosides are considered to be involved in the maintenance and repair of nervous tissues. Recently, novel roles of gangliosides in the regulation of complement system were reported by us. In this study, we compared complement activation, inflammatory reaction and disruption of glycolipid-enriched microdomain (GEM)/rafts among various mutant mice of ganglioside synthases, i.e. GM2/GD2 synthase knockout (KO), GD3 synthase KO, double KO (DKO) of these two enzymes and wild type. Up-regulation of complement-related genes, deposits of C1q, proliferation of astrocytes and infiltration of microglia also showed similar gradual severity depending on the defects in ganglioside compositions. In the expression of inflammatory cytokines such as IL-1ß and tumor necrosis factor α, only DKO showed definite up-regulation. Immunoblotting of fractions from sucrose density gradient ultracentrifugation revealed that lipid raft markers such as caveolin-1 and flotillin-1 tended to disperse from the raft fractions with intensities of DKO > GM2/GD2 synthase KO > GD3 synthase KO > wild type. Decay-accelerating factor and neural cell adhesion molecule tended to disappear from the raft fraction. Phospholipids and cholesterol also tended to decrease in GEM/rafts in GM2/GD2 synthase KO and DKO, although total amounts were almost equivalent. These results indicate that destruction of GEM/rafts is caused by ganglioside deficiency with gradual intensity depending on the degree of defects of their compositions.


Assuntos
Cerebelo/patologia , Gangliosídeos/metabolismo , Inflamação/metabolismo , Microdomínios da Membrana/metabolismo , Doenças Neurodegenerativas/patologia , Regulação para Cima/genética , Fatores Etários , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Proliferação de Células , Cerebelo/metabolismo , Colesterol/metabolismo , Cromatografia em Camada Fina/métodos , Modelos Animais de Doenças , Gangliosídeos/classificação , Inflamação/genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Microdomínios da Membrana/genética , Camundongos , Camundongos Knockout , N-Acetilgalactosaminiltransferases/deficiência , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , RNA Mensageiro/metabolismo , Sialiltransferases/deficiência , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
Neurol India ; 59(5): 727-32, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22019659

RESUMO

BACKGROUND: Guillain-Barré syndrome (GBS) has been the most common cause of flaccid paralysis in children after the decline in the incidence of poliomyelitis. There are not any published data from the Indian subcontinent documenting electrophysiological patterns and antiganglioside antibodies in pediatric GBS. MATERIALS AND METHODS: The study population included children with GBS referred for electrodiagnostic evaluation and also children with GBS admitted to our institute between August 2006 and July 2007. Nerve conduction studies were done to determine GBS subtypes and serum antiganglioside antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and electrophysiological features were correlated with antiganglioside antibody results. RESULTS: Of the 43 (male to female ratio = 2.1:1) children studied, 97.6% had motor weakness, 76.7% had cranial nerve palsies, 13.9% had autonomic disturbances and respiratory paralysis was found in 9.3% children. Antecedent illness was recorded in 69.8% children. The GBS subtype distribution was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 21 (48.8%), acute motor axonal neuropathy (AMAN) in 19 (44.2%), and 3 (6.9%) children were unclassified. The severity of illness was similar in both AMAN and AIDP subtypes and the recovery in both the subtypes was complete without any significant difference in the duration of recovery. Preceding diarrheal illness was more common in AMAN subtype as compared to AIDP subtype (57.9% vs. 4.7%, P = 0.007). Sensory symptoms were more common in AIDP subtype than in AMAN subtype (66.6% vs. 21%, P = 0.03}. The commonest ganglioside antibody was IgM GM2. Anti GM3 antibodies were exclusively seen in children with AMAN and IgG GD1b was significantly associated with (36.7 vs. 4%; P = 0.007) AMAN subtype. IgG GT1b was identified in 50% of patients with AIDP as compared to 22.7% in patients with AMAN. CONCLUSION: In this study, AMAN subtype accounted for a significant proportion of pediatric GBS. AMAN was associated with diarrhea and specific antiganglioside antibodies. Recovery in children with GBS was complete, irrespective of the subtype.


Assuntos
Autoanticorpos/sangue , Gangliosídeos/imunologia , Síndrome de Guillain-Barré , Condução Nervosa/fisiologia , Adolescente , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Eletrocardiografia/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Gangliosídeos/classificação , Síndrome de Guillain-Barré/classificação , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Estações do Ano , Fatores Sexuais
5.
J Neurochem ; 104(1): 140-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18173730

RESUMO

We previously observed that gangliosides GM2, GM1, and GM3 inhibit Ca2+-uptake via the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in neurons and in brain microsomes. We now systematically examine the effect of various gangliosides and their analogs on Ca2+-uptake via SERCA and demonstrate that an exposed carboxyl group on the ganglioside sialic acid residue is required for inhibition. Thus, asialo-GM2 and asialo-GM1 have no inhibitory effect, and modifications of the carboxyl group of GM1 and GM2 into a hydroxymethyl residue (CH2OH), a methyl ester (COOCH3) or a taurine-conjugated amide (CONHCH2CH2SO3H) drastically diminish their inhibitory activities. We also demonstrate that the saccharides must be attached to a ceramide backbone in order to inhibit SERCA as the ceramide-free ganglioside saccharides only inhibit SERCA to a minimal extent. Finally, we attempted to use the ceramide-free ganglioside saccharides to antagonize the effects of the gangliosides on SERCA; although some reversal was observed, the inhibitory effects of the gangliosides were not completely abolished.


Assuntos
Cálcio/metabolismo , Gangliosídeos/química , Gangliosídeos/metabolismo , Ácido N-Acetilneuramínico/farmacologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/fisiologia , Animais , Encéfalo/ultraestrutura , Relação Dose-Resposta a Droga , Gangliosídeos/classificação , Microssomos/ultraestrutura , Naftalenossulfonatos , Ratos , Espectrofotometria/métodos
6.
J Child Neurol ; 22(4): 432-4, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17621523

RESUMO

This article presents a 6-year-old girl who developed acute unilateral third cranial nerve palsy in the absence of any other sign of central nervous system involvement. Raised titers of immunoglobulin M antibodies against GM1, GD1a, and GD1b ganglioside components were demonstrated. Ten days earlier, the girl had experienced acute gastroenteritis with positive specific immunoglobulin M antibodies against enterovirus. The results of all other laboratory tests usually performed for infectious diseases were negative, and neuroradiologic findings were also normal. Oral prednisone was administered for a few days, and the ophthalmoparesis fully resolved within 1 month. Two months later, a second episode of isolated ophthalmoparesis occurred, again associated with a positive immunoglobulin M reaction against GM1, GD1a, and GD1b antigens. This report discusses the relationship between acute isolated ophthalmoparesis and antiganglioside antibodies.


Assuntos
Anticorpos/sangue , Anticorpos/imunologia , Infecções por Enterovirus/complicações , Gangliosídeos/imunologia , Oftalmoplegia/imunologia , Criança , Feminino , Gangliosídeo G(M1)/imunologia , Gangliosídeos/classificação , Humanos , Oftalmoplegia/etiologia , Oftalmoplegia/virologia
7.
J Mol Endocrinol ; 59(1): 93-104, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28500248

RESUMO

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.


Assuntos
Dislipidemias/sangue , Metabolismo dos Lipídeos , Metaboloma , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Glicemia/metabolismo , Ceramidas/sangue , Ceramidas/classificação , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/patologia , Feminino , Gangliosídeos/sangue , Gangliosídeos/classificação , Glicerofosfolipídeos/sangue , Glicerofosfolipídeos/classificação , Humanos , Insulina/sangue , Resistência à Insulina , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia , Pré-Menopausa/fisiologia , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Triglicerídeos/sangue , Triglicerídeos/classificação
8.
Cancer Res ; 61(10): 4244-52, 2001 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-11358851

RESUMO

Expression levels of gangliosides and glycosyltransferase genes responsible for their syntheses in human lung cancer cell lines and a normal bronchial epithelial cell line were analyzed. Both non-small cell lung cancers and small cell lung cancers (SCLCs) mainly expressed G(M2) and G(M1), whereas only SCLCs expressed b-series gangliosides, such as G(D2), G(D1b), and G(T1b). Accordingly, many SCLC cell lines showed up-regulation of the G(D3) synthase gene. Consequently, we introduced G(D3) synthase cDNA into a SCLC line with low expression of b-series gangliosides and analyzed the effects of newly expressed gangliosides on tumor phenotypes. The transfectant cells expressing high levels of G(D2) and G(D3) exhibited markedly increased growth rates and strongly enhanced invasion activities. Addition of anti-G(D2) monoclonal antibodies into the culture medium of these cells resulted in the marked growth suppression of G(D2)-expressing cell lines with reduced activation levels of mitogen-activated protein kinases but not of nonexpressants, suggesting that G(D2) plays important roles in cell proliferation. Moreover, G(D2)-expressing cells treated with anti-G(D2) antibodies showed features of apoptotic cell death at 30 min after addition of antibodies, i.e., shrinkage of cytoplasm, binding of Annexin V, and staining with propidium iodide, followed by DNA fragmentation. This G(D2)-mediated apoptosis was associated with caspase-3 activation and partly inhibited by a caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. The finding that anti-G(D2) antibodies suppressed the cell growth and induced apoptosis of SCLC cells strongly suggested the usefulness of G(D2) as a target for the therapy of disastrous cancer, although the precise mechanisms for apoptosis remain to be clarified.


Assuntos
Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Gangliosídeos/biossíntese , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Apoptose/fisiologia , Sequência de Carboidratos , Carcinoma de Células Pequenas/genética , Divisão Celular/fisiologia , DNA Complementar/genética , Citometria de Fluxo , Gangliosídeo G(M1)/biossíntese , Gangliosídeo G(M2)/biossíntese , Gangliosídeos/classificação , Gangliosídeos/imunologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Dados de Sequência Molecular , N-Acetilgalactosaminiltransferases/biossíntese , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , Fenótipo , Sialiltransferases/biossíntese , Sialiltransferases/genética , Sialiltransferases/metabolismo , Transfecção , Regulação para Cima
9.
Acta Neuropathol Commun ; 4: 23, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26936605

RESUMO

INTRODUCTION: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in acute paralysis through inflammatory attack on peripheral nerves, and currently has limited, non-specific treatment options. The pathogenesis of the acute motor axonal neuropathy (AMAN) variant is mediated by complement-fixing anti-ganglioside antibodies that directly bind and injure the axon at sites of vulnerability such as nodes of Ranvier and nerve terminals. Consequently, the complement cascade is an attractive target to reduce disease severity. Recently, C5 complement component inhibitors that block the formation of the membrane attack complex and subsequent downstream injury have been shown to be efficacious in an in vivo anti-GQ1b antibody-mediated mouse model of the GBS variant Miller Fisher syndrome (MFS). However, since gangliosides are widely expressed in neurons and glial cells, injury in this model was not targeted exclusively to the axon and there are currently no pure mouse models for AMAN. Additionally, C5 inhibition does not prevent the production of early complement fragments such as C3a and C3b that can be deleterious via their known role in immune cell and macrophage recruitment to sites of neuronal damage. RESULTS AND CONCLUSIONS: In this study, we first developed a new in vivo transgenic mouse model of AMAN using mice that express complex gangliosides exclusively in neurons, thereby enabling specific targeting of axons with anti-ganglioside antibodies. Secondly, we have evaluated the efficacy of a novel anti-C1q antibody (M1) that blocks initiation of the classical complement cascade, in both the newly developed anti-GM1 antibody-mediated AMAN model and our established MFS model in vivo. Anti-C1q monoclonal antibody treatment attenuated complement cascade activation and deposition, reduced immune cell recruitment and axonal injury, in both mouse models of GBS, along with improvement in respiratory function. These results demonstrate that neutralising C1q function attenuates injury with a consequent neuroprotective effect in acute GBS models and promises to be a useful new target for human therapy.


Assuntos
Complemento C1q/metabolismo , Via Clássica do Complemento/fisiologia , Gangliosídeos/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Animais , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Complemento C1q/genética , Via Clássica do Complemento/genética , Diafragma/metabolismo , Diafragma/patologia , Transportadores de Ácidos Dicarboxílicos/genética , Modelos Animais de Doenças , Gangliosídeos/classificação , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/metabolismo , Síndrome de Guillain-Barré/patologia , Humanos , Infiltração Leucêmica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/fisiopatologia , Receptores Nicotínicos/metabolismo , Respiração/efeitos dos fármacos , Respiração/genética , Especificidade da Espécie , Simportadores/genética , Volume de Ventilação Pulmonar/efeitos dos fármacos , Volume de Ventilação Pulmonar/genética
10.
Biochim Biophys Acta ; 752(2): 291-300, 1983 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-6860704

RESUMO

The ganglioside content of hog skeletal muscle was 27 nmol/g wet weight when calculated as lipid-bound sialic acid. The elution profile on DEAE-Sephadex A-25 column chromatography showed that the monosialoganglioside fraction (61% of total lipid-bound sialic acid) contained at least seven major gangliosides and that the disialoganglioside fraction (25%) contained four major ones. These gangliosides were purified by latrobeads column chromatography, and from the results of sugar analysis, specific enzymatic hydrolysis, a permethylation study and CrO3 oxidation, the structures of these gangliosides were determined to be as follows: A, GM3(NeuAc); B, GM3(NeuGc); C, sialosylparagloboside(NeuAc); D sialosylparagloboside (NeuGc); E, GM1(NeuAc); F, GM1(NeuGc); G, sialosyllactosaminylparagloboside(NeuAc) (monosialogangliosides) and H, GD1a(NeuAc, NeuAc); I, GD1a(NeuAc, NeuGc); J, GD1a(NeuGc, NeuGc); K, GD1b(NeuAc, NeuAc) (disialogangliosides), where NeuAc is N-acetylneuraminic acid and NeuGc is N-glycolylneuraminic acid as sialyl groups. The major fatty acids of gangliosides A, D and G were mainly C16:0, but those of the others, E, F, H, J and K, were C16:0, C18:0, C22:0 and C24:0. The long-chain bases were predominantly C18:1 sphingosine in all gangliosides.


Assuntos
Gangliosídeos/isolamento & purificação , Músculos/análise , Animais , Carboidratos/isolamento & purificação , Fenômenos Químicos , Química , Cromatografia Gasosa/métodos , Ácidos Graxos/isolamento & purificação , Gangliosídeos/classificação , Suínos
11.
Biochim Biophys Acta ; 1631(1): 94-106, 2003 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-12573454

RESUMO

Gangliosides (GS) were evaluated in Swiss cow's milk (SCM), Italian buffalo milk (IBM) and its serum, Pakistan buffalo colostrum (PBC), Pakistan buffalo mature milk (PBM), and Pakistan buffalo milk from rice-growing areas (PBR). Dairy GS were obtained from the Folch's upper (hydrophilic) and lower (lipophilic) extraction phases, respectively, and determined as lipid-bound sialic acid (LBSA) by colorimetry. Molar ratios of LBSA in the hydro- and lipophilic GS fractions were 52:48 to 79:21. Mature buffalo milk types had 40-100% more LBSA in the lipophilic GS fraction compared to SCM. Liquid PBC was higher in LBSA (24 nmol/g) compared to mature milk types (8-11 nmol/g). Thin-layer chromatography (TLC) and scanning densitometry showed distinct profiles of hydrophilic and lipophilic GS fractions. Lipophilic GS (but importantly not hydrophilic GS) from IBM and its serum decreased prostaglandin series 2 production by 75-80% in cultured human colonic epithelial cells exposed to tumor necrosis factor alpha (TNFalpha). Hydrophilic GD(3) and lipophilic GM(3) selectively bound rotavirus particles prepared from a rhesus strain and its mutant. A GS fraction in IBM showed a GM(1)-specific binding to cholera toxin subunit B (CTB). IBM serum (IBMS) was a rich source of LBSA (420 nmol/g proteins). In summary, improved methodology led to increased LBSA recovery and isolation of additional and bioactive milk GS. Human and Italian buffalo milk had similar CTB binding, and both had increased polysialo-GS compared to cows milk. The toxin binding properties of buffalo milk GS, and the anti-inflammatory activity of the lipophilized GS fraction could be important for developing innovative food applications, as well as the subject of future research.


Assuntos
Gangliosídeos/classificação , Gangliosídeos/metabolismo , Leite/metabolismo , Animais , Búfalos , Linhagem Celular/efeitos dos fármacos , Toxina da Cólera/metabolismo , Cromatografia por Troca Iônica , Cromatografia em Camada Fina/métodos , Gangliosídeos/análise , Gangliosídeos/química , Gangliosídeos/farmacologia , Humanos , Itália , Leite/química , Ácido N-Acetilneuramínico/análise , Paquistão , Rotavirus/metabolismo , Suíça
12.
J Clin Neurosci ; 12(4): 409-15, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15925771

RESUMO

This study was performed to determine whether increased ganglioside-specific T cell reactivity can be detected in the peripheral blood of patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). T cell responsiveness to the gangliosides GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed in peripheral blood mononuclear cells from untreated GBS patients (57), CIDP patients (43), patients with other peripheral neuropathies (55) and healthy control subjects (74) in a standard 6-day proliferation assay. Increased T cell reactivity to GM1 occurred in GBS patients compared to healthy controls and patients with other neuropathies. There was increased reactivity to GM3 in GBS patients compared to patients with other neuropathies but not compared to healthy controls. The frequencies of increased T cell reactivity to GM1 and GM3 in CIDP patients were intermediate between those of GBS patients and controls. We suggest that T cell reactivity to gangliosides might play a contributory role in the pathogenesis of GBS and perhaps CIDP.


Assuntos
Gangliosídeo G(M1)/farmacologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/patologia , Linfócitos T/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/efeitos dos fármacos , Distribuição de Qui-Quadrado , Feminino , Gangliosídeos/classificação , Gangliosídeos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/metabolismo , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Toxoide Tetânico/farmacologia
13.
FEBS Lett ; 260(1): 23-6, 1990 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-2298294

RESUMO

Glucosylceramide, radiolabelled on the glucose residue, was administered to rats and the radioactive gangliosides formed at different time points were chemically characterized. They were identified as GM3, GM1, GD1a and GD1b, each one carrying only radioactive glucose. The time course of each individual ganglioside showed that the simpler gangliosides were formed earlier but were consumed earlier than the more complex ones, resulting in radioactivity patterns that were different at each time point. Only 30 h after injection did it resemble that of endogenous rat liver gangliosides. These results indicate that an extensive precursor-product relationship actually exists in the course of ganglioside biosynthesis.


Assuntos
Cerebrosídeos/farmacocinética , Gangliosídeos/biossíntese , Glucosilceramidas/farmacocinética , Fígado/metabolismo , Animais , Cromatografia Gasosa , Gangliosídeo G(M3)/análise , Gangliosídeo G(M3)/biossíntese , Gangliosídeo G(M3)/classificação , Gangliosídeos/análise , Gangliosídeos/classificação , Glucosilceramidas/análise , Fígado/análise , Masculino , Ratos , Ratos Endogâmicos
14.
Arch Neurol ; 46(4): 398-401, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2705899

RESUMO

Gangliosides GM1, GD1a, GD1b, and GT1b were measured in nine brain regions of five patients, clinically and neuropathologically diagnosed as having dementia of the Alzheimer type (DAT), and of three control patients. Analysis of variance revealed that mean concentrations of all gangliosides analyzed were significantly lower in DAT than in control brains. The areas affected in DAT included the nucleus basalis, and entorhinal, posterior cingulate, visual, and prefrontal cortices. A significant interaction between ganglioside type and brain area indicated unequal ganglioside concentrations. Individual gangliosides had significantly different concentrations in the hippocampal, entorhinal, posterior cingulate, visual, and prefrontal cortices. Analysis of ratios of "a"-ganglioside (GM1 and GD1a) and "b"-ganglioside (GD1b and GT1b) subtypes indicated that DAT preferentially affected "b"-gangliosides. Ganglioside concentrations in nucleus basalis did not correlate with age at disease onset, age at death, or postmortem interval. Changes in gangliosides, observed in this study, were not correlated with classic DAT neuropathology.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Gangliosídeos/metabolismo , Idoso , Análise de Variância , Gangliosídeos/classificação , Humanos , Pessoa de Meia-Idade , Concentração Osmolar
15.
Invest Ophthalmol Vis Sci ; 25(10): 1151-5, 1984 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6480294

RESUMO

Chick corneas from days 9 through 18 of embryonic development were analyzed for phospholipid and glycolipid content, and for phospholipid and ganglioside classes using chromatographic techniques. Little change in phospholipid headgroup classes was detected during this time span, with the exception of a steady increase in the content of phosphatidylserine from 12 to 18% of the total. Changes in glycolipid content also were observed, with a maximum in the sphingolipid/phospholipid ratio at day 14. This increase was correlated with the appearance of highly sialylated gangliosides at days 14 and 15; these ganglioside species then declined in abundance until they were no longer detectable at day 18. These results indicate that gangliosides with high sialic acid content undergo stage-specific developmental cycles in the chick cornea. Furthermore, the data suggest that phosphatidylserine content may be a sensitive biochemical measure of corneal innervation.


Assuntos
Córnea/embriologia , Metabolismo dos Lipídeos , Animais , Embrião de Galinha , Cromatografia em Camada Fina , Córnea/inervação , Córnea/metabolismo , Gangliosídeos/classificação , Gangliosídeos/metabolismo , Glicolipídeos/metabolismo , Glicoesfingolipídeos/metabolismo , Fosfatidilserinas/metabolismo , Fosfolipídeos/classificação , Fosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Fatores de Tempo
16.
J Neurol Sci ; 210(1-2): 99-103, 2003 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-12736097

RESUMO

Anti-ganglioside antibodies frequently are present in sera from patients with Guillain-Barré syndrome (GBS) during the acute phase, but no patients in whom anti-ganglioside antibodies were tested before the onset of the syndrome have been reported. We describe the first case of GBS subsequent to Campylobacter jejuni infection, in which longitudinal changes in anti-ganglioside antibody titers were measured before and after the onset of limb weakness. Serum antibody titers against GM1 (IgM/IgG), GM1b (IgM/IgG), GalNAc-GD1a (IgM/IgG), and GD1b (IgG) were highest on the day of onset, but negative before onset. Anti-C. jejuni IgG and IgA antibody titers paralleled those of the anti-ganglioside antibodies, indicative that C. jejuni infection triggered anti-ganglioside antibody production. Press et al. [J. Neurol. Sci. 190 (2001) 41] reported that anti-ganglioside antibody titers peaked during the recovery phase, but our findings are counter to theirs. We speculate that anti-ganglioside antibodies are the primary effectors of nerve damage in GBS.


Assuntos
Enterite/imunologia , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Anticorpos/imunologia , Campylobacter jejuni/imunologia , Criança , Enterite/complicações , Feminino , Gangliosídeos/classificação , Gangliosídeos/metabolismo , Síndrome de Guillain-Barré/etiologia , Humanos , Isotipos de Imunoglobulinas/metabolismo , Infecções , Síndrome de Miller Fisher/imunologia , Fatores de Tempo
17.
J Neurol Sci ; 210(1-2): 105-8, 2003 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-12736098

RESUMO

Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.


Assuntos
Anticorpos/imunologia , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Proteínas do Líquido Cefalorraquidiano/metabolismo , Terapia Combinada , Gangliosídeos/classificação , Gangliosídeos/metabolismo , Síndrome de Guillain-Barré/terapia , Humanos , Masculino , Debilidade Muscular/fisiopatologia , Debilidade Muscular/terapia , Condução Nervosa/fisiologia , Troca Plasmática/métodos , Plasmaferese/métodos , Prednisolona/uso terapêutico , Recidiva , Extremidade Superior/fisiopatologia , Extremidade Superior/virologia
18.
Life Sci ; 67(15): 1891-9, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11043611

RESUMO

Gangliosides of eye lenses from normal and experimentally induced diabetic rats were investigated by methods including glycolipid-overlay techniques. Adult rat eye lens showed a complex ganglioside pattern that consisted of six major ganglioside components. These gangliosides were identified as GM3, GD3, GD1a, GD1b, GT1b, and GQ1b based upon their reactivity to anti-GM1 antibody after in situ sialidase treatment and mobility on thin-layer chromatography (TLC). Gangliosides in eye lens were further characterized by TLC-immunostaining with A2B5, a specific monoclonal antibody directed toward c-series gangliosides. Eye lens contained GT3 as the main c-series ganglioside component. Unexpectedly, the relative concentration of GT3 in total gangliosides of eye lens was highest among neural and extra-neural tissues examined. Administration of streptozotocin to rats caused a severe reduction in the GT3 content in eye lenses as early as day 3 without apparent changes in the composition of major gangliosides. Alloxan failed to produce such an effect despite producing similar hyperglycemic conditions. These results suggest that rat eye lens probably contains a streptozotocin-susceptible cell type(s), which is highly enriched with c-series gangliosides.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Gangliosídeos/metabolismo , Cristalino/metabolismo , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catarata/induzido quimicamente , Catarata/metabolismo , Cromatografia em Camada Fina , Diabetes Mellitus Experimental/induzido quimicamente , Gangliosídeos/química , Gangliosídeos/classificação , Cristalino/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
19.
Ital J Biochem ; 44(2): 75-88, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7558766

RESUMO

The ganglioside content and pattern have been followed in the different tracts (rectus, convoluted and uterine) of the frog oviduct during the reproductive cycle. The main variations we observed are: a) average higher levels of ganglioside sialic acid in the preovulatory phase, with two peaks in March and April for the convoluted and rectus tract, respectively, and a more homogenous behaviour for the uterine tract; in all three tracts of the oviduct a minimum coincident with the ovulation has been found; b) a balanced presence of sulfolipids and gangliosides in the uterine tract: in fact sulfolipids, whose variations have been determined in a previous work, are higher when gangliosides are lower and vice versa, maintaining nearly constant the total negative charge due to these glycolipids; c) an alternate fluctuation of monosialo- and disialo-gangliosides in the preovulatory phase and a net trend toward the increase of monosialo- and the decrease of disialogangliosides in the postovulatory phase; trisialo-gangliosides are in general less represented and show less marked variations; d) the presence of particular gangliosides in particular moments of the reproductive cycle: Fuc-GM1, a fucosylated ganglioside, is higher than the more represented GM1 during the ovulation, while GD1 alpha, a ganglioside with a sialic acid residue linked to GalNAc, is steadily present in all three tracts after ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Gangliosídeos/metabolismo , Oviductos/metabolismo , Animais , Feminino , Gangliosídeos/química , Gangliosídeos/classificação , Rana esculenta , Reprodução/fisiologia , Estações do Ano , Distribuição Tecidual
20.
Jpn J Ophthalmol ; 30(2): 197-202, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3093739

RESUMO

The amount of gangliosides was determined in normal human lens, cataractous human lens and normal monkey lens. The total gangliosidic sialic acids averaged 176.3 +/- 44.7 (SD) (n = 4) in normal human lenses, and 272.2 +/- 80.6 (n = 14) nmol per gram wet weight in cataractous lenses, respectively; the difference was statistically significant. In monkey lens, the content was 143.8 +/- 32.4 (n = 4) nmol per gram wet weight. The composition of the gangliosides was analyzed by high performance thin-layer chromatography: the components of the a-pathway biosynthesis comprised 78.3% and 70.2%, and those of the b-pathway 13.8% and 20.9%, in the normal and cataractous human lenses, respectively. In the monkey lens, the components of the a-pathway comprised 33.0% and those of the b-pathway were 56.6% of the total gangliosides. Increase in gangliosides was thought to be related with the mechanism underlying formation of cataract.


Assuntos
Gangliosídeos/metabolismo , Cristalino/metabolismo , Animais , Catarata/metabolismo , Gangliosídeos/biossíntese , Gangliosídeos/classificação , Haplorrinos , Humanos , Ácido N-Acetilneuramínico , Ácidos Siálicos/metabolismo
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