Base de dados : MEDLINE
Pesquisa : C16.320.565.202.449.448 [Categoria DeCS]
Referências encontradas : 1247 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 125 ir para página                         

  1 / 1247 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29365308
[Au] Autor:Chan YM; Balza R; High FA
[Ad] Endereço:From the Department of Medicine, Boston Children's Hospital (Y.-M.C.), the Departments of Radiology (R.B.) and Pediatrics (F.A.H.), Massachusetts General Hospital, and the Departments of Pediatrics (Y.-M.C., F.A.H.) and Radiology (R.B.), Harvard Medical School - all in Boston.
[Ti] Título:Case 3-2018: A 5-Month-Old Boy with Hypoglycemia.
[So] Source:N Engl J Med;378(4):381-389, 2018 Jan 25.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doença de Depósito de Glicogênio Tipo I/diagnóstico
Hipoglicemia/etiologia
[Mh] Termos MeSH secundário: Diagnóstico Diferencial
Doença de Depósito de Glicogênio Tipo I/complicações
Seres Humanos
Hiperinsulinismo/diagnóstico
Lactente
Rim/diagnóstico por imagem
Rim/patologia
Fígado/diagnóstico por imagem
Fígado/patologia
Masculino
Tamanho do Órgão
Ultrassonografia
[Pt] Tipo de publicação:CASE REPORTS; CLINICAL CONFERENCE; JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMcpc1706107


  2 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28558013
[Au] Autor:Cho JH; Kim GY; Pan CJ; Anduaga J; Choi EJ; Mansfield BC; Chou JY
[Ad] Endereço:Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
[Ti] Título:Downregulation of SIRT1 signaling underlies hepatic autophagy impairment in glycogen storage disease type Ia.
[So] Source:PLoS Genet;13(5):e1006819, 2017 May.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A deficiency in glucose-6-phosphatase-α (G6Pase-α) in glycogen storage disease type Ia (GSD-Ia) leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased glycogen and neutral fat accumulation. A recent report showed that G6Pase-α deficiency causes impairment in autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Here we show that in mice, liver-specific knockout of G6Pase-α (L-G6pc-/-) leads to downregulation of sirtuin 1 (SIRT1) signaling that activates autophagy via deacetylation of autophagy-related (ATG) proteins and forkhead box O (FoxO) family of transcriptional factors which transactivate autophagy genes. Consistently, defective autophagy in G6Pase-α-deficient liver is characterized by attenuated expressions of autophagy components, increased acetylation of ATG5 and ATG7, decreased conjugation of ATG5 and ATG12, and reduced autophagic flux. We further show that hepatic G6Pase-α deficiency results in activation of carbohydrate response element-binding protein, a lipogenic transcription factor, increased expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), a lipid regulator, and suppressed expression of PPAR-α, a master regulator of fatty acid ß-oxidation, all contributing to hepatic steatosis and downregulation of SIRT1 expression. An adenovirus vector-mediated increase in hepatic SIRT1 expression corrects autophagy defects but does not rectify metabolic abnormalities associated with G6Pase-α deficiency. Importantly, a recombinant adeno-associated virus (rAAV) vector-mediated restoration of hepatic G6Pase-α expression corrects metabolic abnormalities, restores SIRT1-FoxO signaling, and normalizes defective autophagy. Taken together, these data show that hepatic G6Pase-α deficiency-mediated down-regulation of SIRT1 signaling underlies defective hepatic autophagy in GSD-Ia.
[Mh] Termos MeSH primário: Autofagia
Doença de Depósito de Glicogênio Tipo I/metabolismo
Transdução de Sinais
Sirtuína 1/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas Relacionadas à Autofagia/genética
Proteínas Relacionadas à Autofagia/metabolismo
Células Cultivadas
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Fatores de Transcrição Forkhead/metabolismo
Glucose-6-Fosfatase/genética
Glucose-6-Fosfatase/metabolismo
Doença de Depósito de Glicogênio Tipo I/genética
Hepatócitos/metabolismo
Camundongos
PPAR gama/genética
PPAR gama/metabolismo
Sirtuína 1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autophagy-Related Proteins); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Forkhead Transcription Factors); 0 (PPAR gamma); EC 3.1.3.9 (Glucose-6-Phosphatase); EC 3.5.1.- (Sirt1 protein, mouse); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006819


  3 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28389590
[Au] Autor:Melis D; Carbone F; Minopoli G; La Rocca C; Perna F; De Rosa V; Galgani M; Andria G; Parenti G; Matarese G
[Ad] Endereço:Sezione di Pediatria, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy; giuseppe.matarese@unina.it daniela.melis@unina.it.
[Ti] Título:Cutting Edge: Increased Autoimmunity Risk in Glycogen Storage Disease Type 1b Is Associated with a Reduced Engagement of Glycolysis in T Cells and an Impaired Regulatory T Cell Function.
[So] Source:J Immunol;198(10):3803-3808, 2017 May 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type 1b (GSD-1b) is an autosomal-recessive disease caused by mutation of glucose-6-phosphate transporter and characterized by altered glycogen/glucose homeostasis. A higher frequency of autoimmune diseases has been observed in GSD-1b patients, but the molecular determinants leading to this phenomenon remain unknown. To address this question, we investigated the effect of glucose-6-phosphate transporter mutation on immune cell homeostasis and CD4 T cell functions. In GSD-1b subjects, we found lymphopenia and a reduced capacity of T cells to engage glycolysis upon TCR stimulation. These phenomena associated with reduced expression of the FOXP3 transcription factor, lower suppressive function in peripheral CD4 CD25 FOXP3 regulatory T cells, and an impaired capacity of CD4 CD25 conventional T cells to induce expression of FOXP3 after suboptimal TCR stimulation. These data unveil the metabolic determinant leading to an increased autoimmunity risk in GSD-1b patients.
[Mh] Termos MeSH primário: Autoimunidade
Doença de Depósito de Glicogênio Tipo I/imunologia
Doença de Depósito de Glicogênio Tipo I/metabolismo
Glicólise
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antiporters/genética
Antiporters/metabolismo
Linfócitos T CD4-Positivos/imunologia
Criança
Pré-Escolar
Feminino
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Doença de Depósito de Glicogênio Tipo I/fisiopatologia
Homeostase
Seres Humanos
Lactente
Linfopenia/imunologia
Linfopenia/fisiopatologia
Masculino
Proteínas de Transporte de Monossacarídeos/genética
Proteínas de Transporte de Monossacarídeos/metabolismo
Mutação
Receptores de Antígenos de Linfócitos T/imunologia
Receptores de Antígenos de Linfócitos T/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiporters); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); 0 (Monosaccharide Transport Proteins); 0 (Receptors, Antigen, T-Cell); 0 (glucose 6-phosphate(transporter))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170409
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601946


  4 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28334808
[Au] Autor:Kim GY; Kwon JH; Cho JH; Zhang L; Mansfield BC; Chou JY
[Ad] Endereço:Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
[Ti] Título:Downregulation of pathways implicated in liver inflammation and tumorigenesis of glycogen storage disease type Ia mice receiving gene therapy.
[So] Source:Hum Mol Genet;26(10):1890-1899, 2017 May 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated. AMPK/sirtuin-1 inhibit the activity of STAT3 (signal transducer and activator of transcription 3) and NFκB (nuclear factor κB), the pro-inflammatory and cancer-promoting transcription factors. Sirtuin-1 also inhibits cancer metastasis via increasing the expression of E-cadherin, a tumor suppressor, and decreasing the expression of mesenchymal markers. Consistently, in AAV-NT mice, hepatic levels of active STAT3 and NFκB-p65 were reduced as were expression of mesenchymal markers, STAT3 targets, NFκB targets and ß-catenin targets, all of which were consistent with the promotion of tumorigenesis. AAV-NT mice also expressed increased levels of E-cadherin and fibroblast growth factor 21 (FGF21), targets of sirtuin-1, and ß-klotho, which can acts as a tumor suppressor. Importantly, treating AAV-NT mice with a sirtuin-1 inhibitor markedly reversed many of the observed anti-inflammatory/anti-tumorigenic signaling pathways. In summary, activation of hepatic AMPK/sirtuin-1 and FGF21/ß-klotho signaling pathways combined with down-regulation of STAT3/NFκB-mediated inflammatory and tumorigenic signaling pathways can explain the absence of hepatic tumors in AAV-NT mice.
[Mh] Termos MeSH primário: Glucose-6-Fosfatase/metabolismo
Fígado/metabolismo
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Caderinas/genética
Carcinogênese/metabolismo
Modelos Animais de Doenças
Regulação para Baixo
Expressão Gênica
Terapia Genética
Vetores Genéticos
Glucose-6-Fosfatase/genética
Doença de Depósito de Glicogênio Tipo I/terapia
Inflamação/metabolismo
Neoplasias Hepáticas/metabolismo
Camundongos
NF-kappa B
Fator de Transcrição STAT3
Transdução de Sinais
Sirtuína 1/metabolismo
beta Catenina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (NF-kappa B); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, mouse); 0 (beta Catenin); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 3.1.3.9 (Glucose-6-Phosphatase); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx097


  5 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28224773
[Au] Autor:Choi R; Park HD; Ko JM; Lee J; Lee DH; Hong SJ; Ki CS; Lee SY; Kim JW; Song J; Choe YH
[Ad] Endereço:Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
[Ti] Título:Novel SLC37A4 Mutations in Korean Patients With Glycogen Storage Disease Ib.
[So] Source:Ann Lab Med;37(3):261-266, 2017 May.
[Is] ISSN:2234-3814
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Molecular techniques are fundamental for establishing an accurate diagnosis and therapeutic approach of glycogen storage diseases (GSDs). We aimed to evaluate SLC37A4 mutation spectrum in Korean GSD Ib patients. METHODS: Nine Korean patients from eight unrelated families with GSD Ib were included. SLC37A4 mutations were detected in all patients with direct sequencing using a PCR method and/or whole-exome sequencing. A comprehensive review of previously reported SLC37A4 mutations was also conducted. RESULTS: Nine different pathogenic SLC37A4 mutations were identified in the nine patients with GSD Ib. Among them, four novel mutations were identified: c.148G>A (pGly50Arg), c.320G>A (p.Trp107*), c.412T>C (p.Trp138Arg), and c.818G>A (p.Gly273Asp). The most common mutation type was missense mutations (66.7%, 6/9), followed by nonsense mutations (22.2%, 2/9) and small deletion mutations (11.1%, 1/9). The most common mutation identified in the Korean population was c.443C>T (p.Ala148Val), which comprised 39.9% (7/18) of all tested alleles. This mutation has not been reported in GSD Ib patients in other ethnic populations. CONCLUSIONS: This study expands knowledge of the SLC37A4 mutation spectrum in Korean patients with GSD Ib.
[Mh] Termos MeSH primário: Antiporters/genética
Grupo com Ancestrais do Continente Asiático/genética
Doença de Depósito de Glicogênio Tipo I/genética
Proteínas de Transporte de Monossacarídeos/genética
[Mh] Termos MeSH secundário: Alelos
Criança
Éxons
Feminino
Genótipo
Doença de Depósito de Glicogênio Tipo I/diagnóstico
Seres Humanos
Lactente
Masculino
Mutação de Sentido Incorreto
Polimorfismo Genético
República da Coreia
Deleção de Sequência
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiporters); 0 (Monosaccharide Transport Proteins); 0 (SLC37A4 protein, human)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.3343/alm.2017.37.3.261


  6 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28126686
[Au] Autor:Letkemann R; Wittkowski H; Antonopoulos A; Podskabi T; Haslam SM; Föll D; Dell A; Marquardt T
[Ad] Endereço:Department of General Pediatrics, Metabolic Diseases, University Children's Hospital Muenster, Germany. Electronic address: r.letkemann@uni-muenster.de.
[Ti] Título:Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib.
[So] Source:Int Immunopharmacol;44:216-225, 2017 Mar.
[Is] ISSN:1878-1705
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type Ib (GSD-Ib) is characterized by impaired glucose homeostasis, neutropenia and neutrophil dysfunction. Mass spectrometric glycomic profiling of GSD-Ib neutrophils showed severely truncated N-glycans, lacking galactose. Experiments indicated the hypoglycosylation of the electron transporting subunit of NADPH oxidase, which is crucial for the defense against bacterial infections. In phosphoglucomutase 1 (PGM1) deficiency, an inherited disorder with an enzymatic defect just one metabolic step ahead, hypogalactosylation can be successfully treated by dietary galactose. We hypothesized the same pathomechanism in GSD-Ib and started a therapeutic trial with oral galactose and uridine. The aim was to improve neutrophil dysfunction through the correction of hypoglycosylation in neutrophils. The GSD-Ib patient was treated for 29weeks. Monitoring included glycomics analysis of the patient's neutrophils and neutrophil function tests including respiratory burst activity, phagocytosis and migration. Although no substantial restoration of neutrophil glycosylation was found, there was partial improvement of respiratory burst activity.
[Mh] Termos MeSH primário: Antiporters/genética
Galactose/uso terapêutico
Glucose/metabolismo
Doença de Depósito de Glicogênio Tipo I/tratamento farmacológico
Hipoglicemia/tratamento farmacológico
Proteínas de Transporte de Monossacarídeos/genética
NADPH Oxidases/metabolismo
Neutrófilos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Administração Oral
Feminino
Genótipo
Doença de Depósito de Glicogênio Tipo I/genética
Glicosilação/efeitos dos fármacos
Seres Humanos
Hipoglicemia/genética
Lactente
Neutrófilos/fisiologia
Estresse Oxidativo/efeitos dos fármacos
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiporters); 0 (Monosaccharide Transport Proteins); 0 (SLC37A4 protein, human); EC 1.6.3.- (NADPH Oxidases); IY9XDZ35W2 (Glucose); X2RN3Q8DNE (Galactose)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE


  7 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28096054
[Au] Autor:Kim GY; Lee YM; Kwon JH; Cho JH; Pan CJ; Starost MF; Mansfield BC; Chou JY
[Ad] Endereço:Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States.
[Ti] Título:Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-α activity restored are at risk of developing hepatic tumors.
[So] Source:Mol Genet Metab;120(3):229-234, 2017 Mar.
[Is] ISSN:1096-7206
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown. In this study, we constructed rAAV-co-G6PC, a rAAV vector expressing a codon-optimized (co) G6Pase-α and showed that rAAV-co-G6PC was more efficacious than rAAV-G6PC in directing hepatic G6Pase-α expression. Over an 88-week study, we showed that both rAAV-G6PC- and rAAV-co-G6PC-treated G6pc-/- mice expressing 3-33% of normal hepatic G6Pase-α activity (AAV mice) maintained glucose homeostasis, lacked HCA/HCC, and were protected against age-related obesity and insulin resistance. Of the eleven rAAV-G6PC/rAAV-co-G6PC-treated G6pc-/- mice harboring 0.9-2.4% of normal hepatic G6Pase-α activity (AAV-low mice), 3 expressing 0.9-1.3% of normal hepatic G6Pase-α activity developed HCA/HCC, while 8 did not (AAV-low-NT). Finally, we showed that the AAV-low-NT mice exhibited a phenotype indistinguishable from that of AAV mice expressing ≥3% of normal hepatic G6Pase-α activity. The results establish the threshold of hepatic G6Pase-α activity required to prevent HCA/HCC and show that GSD-Ia mice harboring <2% of normal hepatic G6Pase-α activity are at risk of tumor development.
[Mh] Termos MeSH primário: Adenoma de Células Hepáticas/prevenção & controle
Carcinoma Hepatocelular/prevenção & controle
Terapia Genética/métodos
Glucose-6-Fosfatase/genética
Doença de Depósito de Glicogênio Tipo I/terapia
Neoplasias Hepáticas/prevenção & controle
[Mh] Termos MeSH secundário: Adenoma de Células Hepáticas/enzimologia
Animais
Carcinoma Hepatocelular/enzimologia
Dependovirus/genética
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Vetores Genéticos/administração & dosagem
Glucose/metabolismo
Glucose-6-Fosfatase/metabolismo
Doença de Depósito de Glicogênio Tipo I/complicações
Doença de Depósito de Glicogênio Tipo I/enzimologia
Homeostase
Seres Humanos
Fígado/enzimologia
Neoplasias Hepáticas/enzimologia
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.3.9 (Glucose-6-Phosphatase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE


  8 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27864142
[Au] Autor:Kim GY; Lee YM; Kwon JH; Jun HS; Chou J
[Ad] Endereço:Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, United States.
[Ti] Título:Glycogen storage disease type Ib neutrophils exhibit impaired cell adhesion and migration.
[So] Source:Biochem Biophys Res Commun;482(4):569-574, 2017 Jan 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is an inherited autosomal recessive disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Neutrophils play an essential role in the defense against invading pathogens. The recruitment of neutrophils towards the inflammation sites in response to inflammatory stimuli is a tightly regulated process involving rolling, adhesion, and transmigration. In this study, we investigated the role of G6PT in neutrophil adhesion and migration using in vivo and in vitro models. We showed that the GSD-Ib (G6pt ) mice manifested severe neutropenia in both blood and bone marrow, and treating G6pt mice with granulocyte colony-stimulating factor (G-CSF) corrected neutropenia. However, upon thioglycolate challenge, neutrophils from both untreated and G-CSF-treated G6pt mice exhibited decreased ability to migrate to the peritoneal cavity. In vitro migration and cell adhesion of G6PT-deficient neutrophils were also significantly impaired. Defects in cell migration were not due to enhanced apoptosis or altered fMLP receptor expression. Remarkably, the expression of the ß2 integrins CD11a and CD11b, which are critical for cell adhesion, was greatly decreased in G6PT-deficient neutrophils. This study suggests that deficiencies in G6PT cause impairment in neutrophil adhesion and migration via aberrant expression of ß2 integrins, and our finding should facilitate the development of novel therapies for GSD-Ib.
[Mh] Termos MeSH primário: Adesão Celular
Movimento Celular
Doença de Depósito de Glicogênio Tipo I/patologia
Neutropenia/patologia
Neutrófilos/patologia
[Mh] Termos MeSH secundário: Animais
Antiporters/genética
Apoptose
Células CACO-2
Células Cultivadas
Deleção de Genes
Doença de Depósito de Glicogênio Tipo I/complicações
Doença de Depósito de Glicogênio Tipo I/genética
Seres Humanos
Camundongos
Proteínas de Transporte de Monossacarídeos/genética
Neutropenia/complicações
Neutropenia/genética
Neutrófilos/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiporters); 0 (Monosaccharide Transport Proteins); 0 (glucose 6-phosphate(transporter))
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161120
[St] Status:MEDLINE


  9 / 1247 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27922231
[Au] Autor:Aydemir Y; Gürakan F; Saltik Temizel IN; Demir H; Oguz KK; Yalnizoglu D; Topçu M; Özen H; Yüce A
[Ad] Endereço:Divisions of Pediatric Gastroenterology and Hepatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
[Ti] Título:Evaluation of central nervous system in patients with glycogen storage disease type 1a.
[So] Source:Turk J Pediatr;58(1):12-18, 2016.
[Is] ISSN:0041-4301
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso Central/fisiopatologia
Sistema Nervoso Central/fisiopatologia
Potenciais Evocados Visuais/fisiologia
Doença de Depósito de Glicogênio Tipo I/fisiopatologia
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Eletroencefalografia
Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia
Feminino
Seres Humanos
Lactente
Imagem por Ressonância Magnética
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161207
[St] Status:MEDLINE


  10 / 1247 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27511118
[Au] Autor:Lu Y; Wang L; Li J; Wu B; Wu H; Luo Y; Jin ZB; Shan X
[Ad] Endereço:Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
[Ti] Título:Molecular genetic analysis and phenotypic characteristics of a consanguineous family with glycogen storage disease type Ia.
[So] Source:Mol Med Rep;14(4):3251-4, 2016 Oct.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Glycogen storage disease type­Ia (GSD­Ia) is a rare autosomal recessive disease caused by a mutation in the gene encoding glucose­6­phosphate­α (G6PC). The present study reported the case of a 3­month­old female Chinese patient with GSD­Ia born to consanguineous parents. The aim of the present study was to identify the precise mutation of the G6PC gene associated with this family and to describe the phenotypic characteristics of the patient. A comprehensive examination was performed on the patient, including physical examination, vein blood gas analysis, abdominal sonography and biochemical analyses. In addition, gene sequencing was performed on the coding region of the G6PC gene to identify the mutation. The patient was diagnosed with GSD­Ia and a G6PC missense mutation of c.518T>C (p.L173P) located in a highly conserved area was identified. The mutation is in a non­helical region of the protein, which previous studies have suggested should result in a lesser effect on G6PC enzymatic activity and milder phenotypic characteristics compared with mutations located in helical regions. However, the severity of the disease phenotype in the subject of the present study was inconsistent with that predicted from her genotype. The patient suffered from serious hypoglycemia, lactic acidosis, increased triglycerides, hepatic dysfunction, clear hepatomegaly and nephromegaly. The incidence of the p.L173P mutation may be relatively high in the Chinese population. Knowledge of the various phenotypic presentations of the p.L173P mutation may beneficial for future investigations.
[Mh] Termos MeSH primário: Glucose-6-Fosfatase/genética
Doença de Depósito de Glicogênio Tipo I/genética
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Grupo com Ancestrais do Continente Asiático/genética
Consanguinidade
Feminino
Genótipo
Doença de Depósito de Glicogênio Tipo I/sangue
Doença de Depósito de Glicogênio Tipo I/diagnóstico
Doença de Depósito de Glicogênio Tipo I/patologia
Homozigoto
Seres Humanos
Lactente
Linhagem
Fenótipo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.3.9 (Glucose-6-Phosphatase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160812
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2016.5617



página 1 de 125 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde