RESUMO
We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21_{stat}±0.20_{syst} (1.62±0.15_{stat}±0.22_{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.
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BACKGROUND AND PURPOSE: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. METHODS: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. RESULTS: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations. CONCLUSIONS: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.
Assuntos
Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Axônios/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Heterozigoto , Humanos , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Mutação/genética , Neuroglia/patologia , Penetrância , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Caracteres Sexuais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto JovemRESUMO
We report on a clear solar-cycle variation of the Sun's shadow in the 10 TeV cosmic-ray flux observed by the Tibet air shower array during a full solar cycle from 1996 to 2009. In order to clarify the physical implications of the observed solar cycle variation, we develop numerical simulations of the Sun's shadow, using the potential field source surface model and the current sheet source surface (CSSS) model for the coronal magnetic field. We find that the intensity deficit in the simulated Sun's shadow is very sensitive to the coronal magnetic field structure, and the observed variation of the Sun's shadow is better reproduced by the CSSS model. This is the first successful attempt to evaluate the coronal magnetic field models by using the Sun's shadow observed in the TeV cosmic-ray flux.
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Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Zmax = 9.719).
Assuntos
Cromossomos Humanos Par 14 , Degenerações Espinocerebelares/genética , Mapeamento Cromossômico , DNA Satélite/genética , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Desequilíbrio de Ligação , Masculino , Linhagem , Polimorfismo GenéticoRESUMO
Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.
Assuntos
Apraxias/genética , Ataxia/genética , Proteínas de Ligação a DNA/genética , Mutação , Proteínas Nucleares/genética , Músculos Oculomotores/fisiopatologia , Albumina Sérica/metabolismo , Sequência de Aminoácidos , Animais , Apraxias/complicações , Ataxia/complicações , Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Proteínas de Ligação a DNA/química , Feminino , Ligação Genética , Humanos , Masculino , Dados de Sequência Molecular , Proteínas Nucleares/química , Linhagem , Filogenia , Homologia de Sequência de AminoácidosRESUMO
At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded polyQ stretches preferentially bind to TAFII130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAFII130. Our results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Peptídeos/metabolismo , Fatores Associados à Proteína de Ligação a TATA , Fator de Transcrição TFIID , Fatores de Transcrição/metabolismo , Transcrição Gênica , Idoso , Idoso de 80 Anos ou mais , Animais , Atrofia/genética , Atrofia/patologia , Western Blotting , Encéfalo/metabolismo , Células COS , Morte Celular , Linhagem Celular , Nucléolo Celular/metabolismo , Núcleo Celular/metabolismo , Clonagem Molecular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Giro Denteado/metabolismo , Giro Denteado/patologia , Eletroforese em Gel de Poliacrilamida , Feminino , Globo Pálido/metabolismo , Globo Pálido/patologia , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Peptídeos/genética , Plasmídeos/metabolismo , Testes de Precipitina , Ligação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ativação Transcricional , Transfecção , Expansão das Repetições de Trinucleotídeos , Técnicas do Sistema de Duplo-Híbrido , beta-Galactosidase/metabolismoRESUMO
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.
Assuntos
Clonagem Molecular/métodos , Proteínas/genética , Degenerações Espinocerebelares/genética , Repetições de Trinucleotídeos , Sequência de Aminoácidos , Ataxinas , Sequência de Bases , Sondas de DNA , Feminino , Humanos , Hibridização In Situ/métodos , Masculino , Dados de Sequência Molecular , Proteínas do Tecido Nervoso , Linhagem , Análise de Sequência de DNA , Degenerações Espinocerebelares/classificaçãoRESUMO
BACKGROUND/AIMS: Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver-protective effect. METHODS: Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured hepatocytes were treated with interleukin-1ß in the presence or absence of AHCC-sugar fraction (AHCC-SF). RESULTS AND CONCLUSION: AHCC-SF inhibited the production of NO and reduced expressions of iNOS mRNA and its protein. AHCC-SF had no effects on either IκB degradation or nuclear factor-κB (NF-κB) activation. In contrast, AHCC-SF inhibited the upregulation of type I interleukin-1 receptor (IL-1RI) through the inhibition of Akt phosphorylation. Transfection experiments with iNOS promoter-luciferase constructs revealed that AHCC-SF reduced the levels of iNOS mRNA at both promoter transactivation and mRNA stabilization steps. AHCC-SF inhibited the expression of iNOS gene antisense transcript, which is involved in iNOS mRNA stabilization. These findings demonstrate that AHCC-SF suppresses iNOS gene expression through a IκB/NF-κB-independent but Akt/IL-1RI-dependent pathway, resulting in the reduction of NO production. AHCC-SF may have therapeutic potential for various liver injuries.
Assuntos
Hepatócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/farmacologia , Animais , Biomarcadores/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-1beta , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Regulação para CimaRESUMO
OBJECTIVE: This study aimed to determine the spectrum of pathological involvement of the striatonigral (StrN) and olivopontocerebellar (OPC) systems in Japanese patients with multiple system atrophy (MSA). This study also aimed to compare the pathological spectrum of Japanese MSA patients with the previously reported results in British MSA patients. METHODS: A semiquantitative pathological analysis of 50 MSA patients' brains that were referred to the Brain Research Institute, Niigata University, Japan, was performed. The severity of neuronal cell loss was determined as previously described by the study from the Queen Square Brain Bank (QSBB), UK. RESULTS: The mean neuronal cell loss score was significantly higher in the OPC area than in the basal ganglia sites examined, except the dorsolateral putamen. The relative prevalence of pathological phenotypes showed that 40% of cases had OPC-predominant pathology, 18% had StrN-predominant pathology and the remaining (42%) had equivalent StrN and OPC pathology. None of the MSA cases had coexistent Lewy bodies in the dorsal motor nucleus of the vagus and the substantia nigra. CONCLUSIONS: In contrast to the previously reported results involving British patients' brains from the QSBB (OPC-predominant pathology 17%, StrN-predominant pathology 34%, equivalent StrN and OPC pathology 49%), the results of the present study showed more pathological involvement of the OPC system than of the StrN system. The rarity of Lewy bodies may underlie the phenotypic expression of Japanese MSA. The present observations reflect the disequilibrium in the phenotype distribution between the two populations.
Assuntos
Povo Asiático/estatística & dados numéricos , Encéfalo/patologia , Atrofia de Múltiplos Sistemas/etnologia , Atrofia de Múltiplos Sistemas/patologia , Adulto , Idoso , Contagem de Células , Cerebelo/patologia , Feminino , Humanos , Japão/epidemiologia , Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/genética , Núcleo Olivar/patologia , Fenótipo , Prevalência , Substância Negra/patologia , Nervo Vago/patologiaRESUMO
BACKGROUND: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined. METHODS: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients. RESULTS: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls. CONCLUSIONS: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.
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Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Duplicação Gênica , Idade de Início , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Atrofia , Encéfalo/patologia , Estudos de Coortes , DNA/genética , Feminino , Dosagem de Genes , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Linhagem , RNA Mensageiro/sangue , Proteínas tau/líquido cefalorraquidianoRESUMO
Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. Recent data show that normal and malignant epithelial cells deficient in K8/18 are nearly 100 times more sensitive to tumor necrosis factor (TNF)-induced cell death. We have now identified human TNF receptor type 1 (TNFR1)-associated death domain protein (TRADD) to be the K18-interacting protein. Among IF proteins tested in two-hybrid systems, TRADD specifically bound K18 and K14, type I (acidic) keratins. The COOH-terminal region of TRADD interacted with the coil Ia of the rod domain of K18. Endogenous TRADD coimmunoprecipitated with K18, and colocalized with K8/18 filaments in human mammary epithelial cells. Overexpression of the NH2 terminus (amino acids 1-270) of K18 containing the TRADD-binding domain as well as overexpression of K8/18 in SW13 cells, which are devoid of keratins, rendered the cells more resistant to killing by TNF. We also showed that overexpressed NH2 termini of K18 and K8/18 were associated with endogenous TRADD in SW13 cells, resulting in the inhibition of caspase-8 activation. These results indicate that K18 may sequester TRADD to attenuate interactions between TRADD and activated TNFR1 and moderate TNF-induced apoptosis in simple epithelial cells.
Assuntos
Apoptose , Queratinas/metabolismo , Proteínas/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Aclarubicina/farmacologia , Animais , Linhagem Celular , Cães , Relação Dose-Resposta a Droga , Expressão Gênica , Células HeLa , Humanos , Filamentos Intermediários/metabolismo , Queratinas/genética , Paclitaxel/farmacologia , Proteínas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores do Fator de Necrose Tumoral/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fator 1 Associado a Receptor de TNF , Células Tumorais Cultivadas , Zinostatina/farmacologiaRESUMO
Membranes containing cylindrical metal nanotubules that span the complete thickness of the membrane are described. The inside radius of the nanotubules can be varied at will; nanotubule radii as small as 0.8 nanometer are reported. These membranes show selective ion transport analogous to that observed in ion-exchange polymers. Ion permselectivity occurs because excess charge density can be present on the inner walls of the metal tubules. The membranes reject ions with the same sign as the excess charge and transport ions of the opposite sign. Because the sign of the excess charge on the tubule can be changed potentiostatically, a metal nanotubule membrane can be either cation selective or anion selective, depending on the potential applied to the membrane.
RESUMO
Analysis of DNA from human embryo fibroblasts showed that ten Eco RI fragments were hybridizable with the Yamaguchi sarcoma virus oncogene (v-yes). Four of the Eco RI fragments were assigned to chromosome 18 and one to chromosome 6. There was evidence for multiple copies of yes-related genes in the human genome; however, only a single RNA species, 4.8 kilobases in length, was related to yes in various cells.
Assuntos
Mapeamento Cromossômico , Oncogenes , Animais , Vírus do Sarcoma Aviário/genética , Sequência de Bases , Cromossomos Humanos 16-18 , Cromossomos Humanos 6-12 e X , DNA/genética , Humanos , Células Híbridas/metabolismo , Camundongos , Hibridização de Ácido Nucleico , Transdução GenéticaRESUMO
We have found that interleukin 3 (IL-3), a growth factor for hematopoietic cells, is a novel trophic factor for mouse and rat central cholinergic neurons. It enhanced neurite outgrowth and elevated choline acetyltransferase activity. The effect seems to be specific for cholinergic neurons, since somatostatin release and glutamic acid decarboxylase and 2',3'-cyclic nucleotide 3'-phosphodiesterase activities were not significantly influenced by IL-3. In vivo, IL-3 was infused into the lateral ventricles of rats after unilateral axotomy of the septohippocampal pathways. Two weeks later, the IL-3-treated animals showed significant numbers of acetylcholinesterase-positive neurons remaining in the septal region.
Assuntos
Acetilcolinesterase/metabolismo , Encéfalo/citologia , Colina O-Acetiltransferase/metabolismo , Interleucina-3/farmacologia , Neurônios/citologia , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Animais , Axônios/ultraestrutura , Fatores Biológicos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Linhagem Celular , Células Cultivadas , Citocinas , Replicação do DNA/efeitos dos fármacos , Glutamato Descarboxilase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Endogâmicos , Timidina/metabolismoAssuntos
Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/metabolismo , Corpos de Inclusão/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , beta Carioferinas/metabolismo , Idoso , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Atrofia , Encéfalo/patologia , Feminino , Humanos , Corpos de Inclusão/patologia , Mutação , Proteína FUS de Ligação a RNA/genética , beta Carioferinas/genéticaRESUMO
Sudden death has been reported in patients with multiple system atrophy (MSA), although the frequency of this event has not been well delineated. We investigated the frequency and potential causes of sudden death in patients with MSA. During the 5-year observation period, 10 of 45 patients with probable MSA died. The causes of death included sudden death of unknown etiology (seven patients), aspiration pneumonia (one patient), asphyxia after vomiting (one patient), and lung cancer (one patient). The mean survival time of patients with sudden death was 63.0 +/- 24.7 months (range, 39-116 months). Among seven patients who experienced sudden death, six were found to have died during sleep. Among these patients, two had been treated with tracheostomy and three with continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) during sleep, suggesting that these treatments do not always prevent sudden death in patients with MSA. Nocturnal sudden death should be recognized as the most common mechanism of death in patients with MSA.
Assuntos
Morte Súbita , Atrofia de Múltiplos Sistemas/mortalidade , Adulto , Idoso , Causas de Morte , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/fisiopatologia , Respiração com Pressão Positiva , Sono , Taxa de Sobrevida , TraqueostomiaRESUMO
BACKGROUND: In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified. METHODS: Because Yakuts are considered as a population isolate and the disease is rare in other populations, genomewide homozygosity mapping was performed using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut. RESULTS: All families shared an identical haplotype in the same region as the identical loci responsible for 3-M and gloomy face syndromes and a novel homozygous 4582insT mutation in Cullin 7 (CUL7) was found, which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 (Q1553X). Yakut patients with short stature syndrome have unique features such as a high frequency of neonatal respiratory distress and few bone abnormalities, whereas the clinical features of the other Yakut patients were similar to those of 3-M syndrome. Furthermore, abnormal vascularisation was present in the fetal placenta and an abnormal development of cartilage tissue in the bronchus of a fetus with CUL7 mutation. CONCLUSION: These findings may provide a new understanding of the clinical diversity and pathogenesis of short stature syndrome with CUL7 mutation.
Assuntos
Códon sem Sentido , Proteínas Culina/genética , Nanismo/genética , Etnicidade/genética , Face/anormalidades , Retardo do Crescimento Fetal/genética , Mutagênese Insercional , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Adolescente , Adulto , Brônquios/embriologia , Brônquios/patologia , Criança , Pré-Escolar , Nanismo/classificação , Nanismo/etnologia , Etnicidade/etnologia , Feminino , Retardo do Crescimento Fetal/etnologia , Retardo do Crescimento Fetal/patologia , Efeito Fundador , Genes Recessivos , Haplótipos/genética , Humanos , Recém-Nascido , Masculino , Fenótipo , Placenta/irrigação sanguínea , Placenta/patologia , Síndrome do Desconforto Respiratório do Recém-Nascido/etnologia , Sibéria/epidemiologia , SíndromeRESUMO
We investigated the incidence and clinical features of patients with myasthenia gravis (MG) associated with autoimmune diseases. Associated autoimmune diseases were found in 28 of 142 consecutive Japanese MG patients (19.7%), amongst which Graves' disease (7.7%) and Hashimoto's thyroiditis (4.2%) were predominant. The clinical features of MG patients with Graves' disease were different from those of MG patients without autoimmune diseases in terms of age at onset of MG symptoms (35.5 +/- 4.0 years and 49.0 +/- 1.7 years; P < 0.05), positivity for the anti-acetylcholine receptor antibody (44.4% and 89.8%; P < 0.05), and association with thymic hyperplasia (72.7 and 17.9%; P < 0.05). The therapeutic outcome of MG patients with Graves' disease and that of those without autoimmune diseases were not significantly different. Further studies should be performed to investigate whether MG associated with Graves' disease is a distinct subtype of MG.
Assuntos
Doenças Autoimunes/epidemiologia , Miastenia Gravis/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Criança , Comorbidade , Feminino , Doença de Graves/epidemiologia , Doença de Graves/imunologia , Doença de Graves/fisiopatologia , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/imunologia , Doença de Hashimoto/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Miastenia Gravis/fisiopatologia , Prevalência , Receptores Colinérgicos/imunologia , Hiperplasia do Timo/epidemiologia , Hiperplasia do Timo/imunologia , Hiperplasia do Timo/fisiopatologia , Resultado do TratamentoRESUMO
Granulocyte colony-stimulating factor (G-CSF) plays an essential role in granulopoiesis during bacterial infection. Macrophages produce G-CSF in response to bacterial endotoxins such as lipopolysaccharide (LPS). To elucidate the mechanism of the induction of G-CSF gene in macrophages or macrophage-monocytes, we have examined regulatory cis elements in the promoter of mouse G-CSF gene. Analyses of linker-scanning and internal deletion mutants of the G-CSF promoter by the chloramphenicol acetyltransferase assay have indicated that at least three regulatory elements are indispensable for the LPS-induced expression of the G-CSF gene in macrophages. When one of the three elements was reiterated and placed upstream of the TATA box of the G-CSF promoter, it mediated inducibility as a tissue-specific and orientation-independent enhancer. Although this element contains a conserved NF-kappa B-like binding site, the gel retardation assay and DNA footprint analysis with nuclear extracts from macrophage cell lines demonstrated that nuclear proteins bind to the DNA sequence downstream of the NF-kappa B-like element, but not to the conserved element itself. The DNA sequence of the binding site was found to have some similarities to the LPS-responsive element which was recently identified in the promoter of the mouse class II major histocompatibility gene.