RESUMO
Blau syndrome (BS) is a rare granulomatous inflammatory disease presenting in early childhood as dermatitis, arthritis, and uveitis. Here, we describe a case of hydrocephalus in a patient with sporadic BS. A 36-year-old female, with mutations in the NOD2 gene on chromosome 16, who had been diagnosed with BS at the age of 19 years, had visual impairment and required support when walking for a long time. She was admitted to our hospital due to deterioration in her walking ability and an inability to stand by herself. We diagnosed an obstructive hydrocephalus based on head MRI. The aqueductal stenosis and obstructive hydrocephalus associated with granulomatous lesions were considered in this case. After third ventricle fenestration, her standing movement and walking improved immediately.
Assuntos
Artrite , Hidrocefalia , Uveíte , Adulto , Feminino , Humanos , Hidrocefalia/etiologia , Hidrocefalia/genética , Sarcoidose , Sinovite , CaminhadaRESUMO
BACKGROUND: The effect of cigarette smoking on the onset of nonalcoholic fatty liver disease (NAFLD) is unclear, especially that associated with drinking small amounts of alcohol. We conducted a longitudinal study to investigate the relationship between cigarette smoking and NAFLD onset, which was stratified according to the amount of alcohol consumed. METHODS: We enrolled 7,905 Japanese subjects who had received annual health checkups more than twice between April 2003 and August 2013, 4,045 of whom met at least one of the following exclusion criteria and were excluded: (a) fatty liver at baseline; (b) hepatitis B or hepatitis C; (c) alcohol consumption (men: ≥210 g/wk; women: ≥140 g/wk); (d) change in alcohol drinking status between baseline and the study's endpoint; (e) change in cigarette smoking habits between baseline and the study's endpoint; or (f) current treatment with antidiabetic agents, antihypertensive agents, and/or lipid-lowering agents. The remaining 3,860 subjects (1,512 men, 2,348 women) were divided into two groups based on average alcohol consumption. RESULTS: After adjusting for the variables associated with metabolic disease, smoking was associated with fatty liver disease onset compared with nonsmokers in nondrinkers (adjusted hazard ratio = 1.988, 95% confidence interval 1.057-3.595; p = 0.034). No association was found between smoking and fatty liver disease onset in the low alcohol consumption group (men: <210 g alcohol/week; women: <140 g alcohol/week). The fatty liver disease incidence increased significantly among the nondrinkers as the number of cigarettes smoked increased (p = 0.001). CONCLUSIONS: Cigarette smoking may be a significant risk factor associated with NAFLD onset in nondrinkers. These results may help clinicians to identify patients who are at a high risk of developing NAFLD and to prevent the progression of NAFLD by promoting earlier interventions that help people discontinue unhealthy lifestyle habits.
Assuntos
Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Chorea-acanthocytosis (ChAc) is an autosomal, recessive hereditary disease characterized by striatal neurodegeneration and acanthocytosis, and caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene. VPS13A encodes chorein whose physiological function at the molecular level is poorly understood. In this study, we show that chorein interacts with ß-adducin and ß-actin. We first compare protein expression in human erythrocyte membranes using proteomic analysis. Protein levels of ß-adducin isoform 1 and ß-actin are markedly decreased in erythrocyte membranes from a ChAc patient. Subsequent co-immunoprecipitation (co-IP) and reverse co-IP assays using extracts from chorein-overexpressing human embryonic kidney 293 (HEK293) cells, shows that ß-adducin (isoforms 1 and 2) and ß-actin interact with chorein. Immunocytochemical analysis using chorein-overexpressing HEK293 cells demonstrates co-localization of chorein with ß-adducin and ß-actin. In addition, immunoreactivity of ß-adducin isoform 1 is significantly decreased in the striatum of gene-targeted ChAc-model mice. Adducin and actin are membrane cytoskeletal proteins, involved in synaptic function. Expression of ß-adducin is restricted to the brain and hematopoietic tissues, corresponding to the main pathological lesions of ChAc, and thereby implicating ß-adducin and ß-actin in ChAc pathogenesis.
Assuntos
Actinas/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuroacantocitose/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Membrana Eritrocítica/metabolismo , Células HEK293 , Humanos , Imunoprecipitação , Camundongos , Camundongos Endogâmicos C57BL , Neuroacantocitose/patologia , Ligação Proteica , Transporte ProteicoRESUMO
To understand the domain structure responsible for different enzymatic properties, we constructed chimera cDNAs of the alpha and beta isoforms of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II). The chimera DNAs were expressed in neuroblastoma cells, and the affinity for calmodulin and the subcellular localization of chimera enzymes were investigated. Here, we found that the region in immediately N-terminal of the calmodulin-binding site (exons 10 and 11), including the autophosphorylation site, mainly affected the affinity of each isoform for calmodulin and that the N-terminal region (exons 1 and 2), including the ATP-binding site, modified the affinity for calmodulin of each isoform. It was confirmed that the association of beta CaM kinase II with the particulate fraction was determined by beta-specific insertion, and also found that the association with the particulate fraction was modified by exons 1 and 2 of each isoform. Kinases without beta-specific insertion and chimera kinases consisting of exons 1 and 2 of beta and other regions of alpha appeared reduced in the transport of kinases to neurite. These results indicated that the structure of exons 10 and 11 and exons 1 and 2 modified the properties of CaM kinase II holoenzyme.