RESUMO
Mitochondrial DNA (mtDNA) alterations and their clinical and pathological implications have been analyzed in several human malignancies. A marked decrease in mtDNA copy number along with the increase in malignancy was observed in diffusely infiltrating astrocytomas (24 WHO grade II, 18 grade III, and 78 grade IV or GBM) compared to non-neoplastic brain tissues, being mostly depleted in GBM. Although high relative gene expression levels of mtDNA replication regulators (mitochondrial polymerase catalytic subunit (POLG), transcription factors A (TFAM), B1 (TFB1M) and B2 (TFB2M)) were detected, it cannot successfully revert the mtDNA depletion observed in our samples. On the other hand, a strong correlation among the expression levels of mitochondrial transcription factors corroborates with the TFAM role in the direct control of TFB1M and TFB2M during initiation of mtDNA replication. POLG expression was related to decreased mtDNA copy number, and its overexpression associated with TFAM expression levels also have an impact on long-term survival among GBM patients, interpreted as a potential predictive factor for better prognosis.
Assuntos
Astrocitoma/mortalidade , Astrocitoma/patologia , DNA Mitocondrial/genética , DNA Polimerase Dirigida por DNA/metabolismo , Dosagem de Genes , Fatores de Transcrição/metabolismo , Astrocitoma/genética , DNA Polimerase gama , Replicação do DNA , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , DNA Polimerase Dirigida por DNA/genética , Regulação da Expressão Gênica , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Transcrição/genética , Transcrição GênicaRESUMO
Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5 percent of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature.
O meduloblastoma é o tumor maligno mais frequente do sistema nervoso central na infância, mas também pode ocorrer em adultos. Ele apresenta crescimento altamente invasivo com disseminação de células tumorais ao longo do neuroeixo precocemente no curso da doença. Metástases extraneurais são raras mas frequentemente letais, ocorrendo apenas em 1 a 5 por cento dos pacientes, e estão relacionadas, na maioria dos casos, a presença de derivação ventriculperitoneal. Neste artigo ,apresentamos o perfil de cinco casos de meduloblastoma com disseminção sistêmica das células tumorais, comparando-os com os casos já descritos na literatura.
Assuntos
Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasias Cerebelares/patologia , Meduloblastoma/secundário , Neoplasias Abdominais/secundário , Neoplasias da Medula Óssea/secundário , Seguimentos , Neoplasias Pulmonares/secundário , Neoplasias Pélvicas/secundárioRESUMO
Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.
Assuntos
Biologia Computacional , Proteínas de Membrana/genética , Antígenos de Superfície/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Bases de Dados Genéticas , Epigênese Genética , Variação Genética , Glioblastoma/genética , Humanos , Proteínas de Membrana/metabolismoRESUMO
The objective of this study was to evaluate the presence of anti-C1q antibodies Hospital Israelita Albert Einstein Research Institute, São Paulo, Brazil in 67 juvenile systemic lupus erythematosus (JSLE) patients and 26 healthy controls and to assess the association of these antibodies with disease activity, nephritis, and presence of anti-double-stranded (ds)DNA. Anti-C1q antibodies were detected by ELISA. A higher frequency of anti-C1q antibodies was observed in JSLE patients compared to controls (20% vs. 0%, P = 0.016). Specificity of these antibodies was 100%[95% confidence interval (CI) 86.7-100%] and sensitivity was 19.4% (95% CI 10.7-30.8%) for a lupus diagnosis. The median anti-C1q antibodies was higher in JSLE patients compared to controls [median (range) 9.4 (5.5-127) vs. 7.3 (5-20) units, P = 0.004]. Remarkably, a positive Spearman's coefficient was found between anti-dsDNA and anti-C1q units (r = 0.42, P = 0.0004, 95% CI 0.19-0.60). Our results confirm a low frequency of anti-C1q antibody in our lupus populations, but the presence of anti-Clq antibodies appears to be a good marker for JSLE diagnosis.
Assuntos
Autoanticorpos/sangue , Complemento C1q/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Criança , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Valor Preditivo dos TestesRESUMO
OBJECTIVE: To assess MHC I and II expressions in muscle fibres of juvenile dermatomyositis (JDM) and compare with the expression in polymyositis (PM), dermatomyositis (DM) and dystrophy. PATIENTS AND METHODS: Forty-eight JDM patients and 17 controls (8 PM, 5 DM and 4 dystrophy) were studied. The mean age at disease onset was 7.1+/-3.0 years and the mean duration of weakness before biopsy was 9.4+/-12.9 months. Routinehistochemistry and immunohistochemistry (StreptABComplex/HRP) for MHC I and II (Dakopatts) were performed on serial frozen muscle sections in all patients. Mann-Whitney, Kruskal Wallis, chi-square and Fisher's exact statistical methods were used. RESULTS: MHC I expression was positive in 47 (97.9%) JDM cases. This expression was observed independent of time of disease, corticotherapy previous to muscle biopsy and to the grading of inflammation observed in clinical, laboratorial and histological parameters. The expression of MHC I was similar on JDM, PM and DM, and lower in dystrophy. On the other hand, MHC II expression was positive in just 28.2% of JDM cases and was correlated to histological features as inflammatory infiltrate, increased connective tissue and VAS for global degree of abnormality (p<0.05). MHC II expression was similar in DM/PM and lower in JDM and dystrophy, and it was based on the frequency of positive staining rather than to the degree of the MCH II expression. CONCLUSIONS: MHC I expression in muscle fibres is a premature and late marker of JDM patient independent to corticotherapy, and MHC II expression was lower in JDM than in PM and DM.
Assuntos
Dermatomiosite/metabolismo , Antígenos HLA/metabolismo , Músculo Esquelético/metabolismo , Biomarcadores/metabolismo , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Dermatomiosite/diagnóstico , Dermatomiosite/patologia , Diagnóstico Diferencial , Regulação da Expressão Gênica , Genes MHC Classe I/genética , Genes MHC da Classe II/genética , Humanos , Músculo Esquelético/patologia , Distrofias Musculares/diagnóstico , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Polimiosite/diagnóstico , Polimiosite/metabolismo , Polimiosite/patologiaRESUMO
Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C>A and c.-216G>T) and the c.2073A>T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A>T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A>T polymorphism could play a role in future therapeutic approaches to astrocytoma.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Polimorfismo Genético , Adulto , Idoso , Alelos , Astrocitoma/etnologia , Neoplasias Encefálicas/etnologia , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Resultado do TratamentoRESUMO
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Assuntos
Caderinas/genética , Perfilação da Expressão Gênica , Neoplasias Neuroepiteliomatosas/genética , Adolescente , Adulto , Encéfalo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Diffuse infiltrating gliomas are the most common tumors of the central nervous system. Gliomas are classified by the WHO according to their histopathological and clinical characteristics into four classes: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). Several genes have already been correlated with astrocytomas, but many others are yet to be uncovered. By analyzing the public SAGE data from 21 patients, comprising low malignant grade astrocytomas and glioblastomas, we found COL6A1 to be differentially expressed, confirming this finding by real time RT-PCR in 66 surgical samples. To the best of our knowledge, COL6A1 has never been described in gliomas. The expression of this gene has significantly different means when normal glia is compared with low-grade astrocytomas (grades I and II) and high-grade astrocytomas (grades III and IV), with a tendency to be greater in higher grade samples, thus rendering it a powerful tumor marker.
Assuntos
Astrocitoma/genética , Colágeno Tipo VI/genética , Perfilação da Expressão Gênica , Astrocitoma/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This study aimed to determine the frequency of temporomandibular disorder (TMD) signs in 68 individuals with cerebral palsy, aged between 3 and 23 years. TMD signs were evaluated according to the Research Diagnostic Criteria to assess temporomandibular joint sounds, lateral jaw deviation during opening and closing movements and limitation of maximum mouth opening (>40 mm). The frequency of TMD signs observed in the cerebral palsy group (46/68-67.6%) was higher than in the control group (17/68-25%). The clinical scenario of CP seems to make these individuals more prone to the development of TMD signs.
Assuntos
Paralisia Cerebral/complicações , Transtornos da Articulação Temporomandibular/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prevalência , Transtornos da Articulação Temporomandibular/diagnósticoRESUMO
Diffuse infiltrating gliomas are the most common tumors of the central nervous system. Gliomas are classified by the WHO according to their histopathological and clinical characteristics into four classes: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). Several genes have already been correlated with astrocytomas, but many others are yet to be uncovered. By analyzing the public SAGE data from 21 patients, comprising low malignant grade astrocytomas and glioblastomas, we found COL6A1 to be differentially expressed, confirming this finding by real time RT-PCR in 66 surgical samples. To the best of our knowledge, COL6A1 has never been described in gliomas. The expression of this gene has significantly different means when normal glia is compared with low-grade astrocytomas (grades I and II) and high-grade astrocytomas (grades III and IV), with a tendency to be greater in higher grade samples, thus rendering it a powerful tumor marker.
Assuntos
Humanos , Astrocitoma/genética , Colágeno Tipo VI/genética , Perfilação da Expressão Gênica , Astrocitoma/patologia , Regulação Neoplásica da Expressão Gênica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA NeoplásicoRESUMO
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Caderinas/genética , Perfilação da Expressão Gênica , Neoplasias Neuroepiteliomatosas/genética , Cérebro/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Neuroepiteliomatosas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Cerebral palsy (CP) is one of the most frequent conditions encountered in the daily practice of dentists who treat special-needs patients and it seems that parafunctional oral habits are often present in such individuals. The aim of this study was to investigate the frequency of occurrence of parafunctional habits in individuals with CP. Sixty-five patients with CP were evaluated through a questionnaire and clinical observation, regarding the following habits: pacifier-sucking, finger-sucking, biting objects, tongue interposition, and bruxism. The results showed that nine (13.8%) patients presented with pacifier-sucking, four (6.1%) showed finger-sucking, 12 (18.4%) had the habit of biting objects, 27 (41.5%) presented with tongue interposition, and 24 (36.9%) had eccentric bruxism. The significance of the presence of oral parafunctional habits in individuals with CP, revealed in this study, justifies the need to establish protocols for adequate prevention and clinical intervention in order to minimize the deleterious consequences that may result from such habits.
Assuntos
Paralisia Cerebral/psicologia , Hábitos , Adolescente , Comportamento do Adolescente , Adulto , Bruxismo/fisiopatologia , Criança , Pré-Escolar , Feminino , Sucção de Dedo/efeitos adversos , Sucção de Dedo/psicologia , Humanos , Masculino , Comportamento de Sucção , Hábitos Linguais/efeitos adversos , Hábitos Linguais/psicologiaRESUMO
Myotonic dystrophy is a multisystemic disease with varying symptomatology. The aim of this study was to compare the maximal bite force and handgrip force in patients with molecular diagnosis of myotonic dystrophy with those in a group of healthy individuals. It was hypothesized that these forces were reduced in the patients in comparison with the control subjects. The bite and handgrip forces of 37 patients with molecular diagnosis of myotonic dystrophy and 37 control subjects matched regarding age and gender were measured using an electronic dynamometer. The bite and handgrip forces were significantly lower in the myotonic dystrophy patient group when compared with the healthy controls (P < 0.0001). There were no significant force differences between genders, right- or left-hand side of mastication or hands in the myotonic dystrophy patient group whereas such differences were found among the controls. There were moderate but significant correlations between bite and handgrip force in both groups (r = 0.43-0.59; P < 0.01). It was concluded that there were considerable differences between the myotonic dystrophy group and the control subjects regarding both bite force and handgrip force. The weakness of the masticatory and hand muscles may have various negative consequences for oral function and dental health in patients with myotonic dystrophy.
Assuntos
Força de Mordida , Força da Mão/fisiologia , Distrofia Miotônica/fisiopatologia , Adolescente , Adulto , Criança , Saúde da Família , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Músculos da Mastigação/fisiopatologia , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Fatores SexuaisRESUMO
Clarification of TP53 alterations is important to understand the mechanisms underlying the development of diffuse astrocytomas. It has been suggested that the alleles of TP53 at codon 72 differ in their ability to induce apoptosis in human cancers. The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas. We analyzed 56 surgical specimens of diffuse astrocytomas for alterations of TP53, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) direct sequencing. p53 and cleaved caspase 3 protein expression were assessed by immunohistochemistry. We found TP53 mutations in 19.6% (11 out of 56) of tumors tested, with the lowest mutation rate found in the cases of glioblastomas (8.8%) (p = 0.03). Only 16.1% of tumors tested showed cleaved caspase 3-positive staining, demonstrating that apoptosis is very inhibited in these tumors. All tumors having TP53 mutation and p53 accumulation had no expression of cleaved caspase 3. Additionally, no association was observed in tumors having proline and arginine alleles and expression of cleaved caspase 3. We concluded that clarification of the TP53 alterations allows a better understanding of the mechanisms involved in the progression of diffuse astrocytomas, and the allele status at codon 72 was not associated with apoptosis in these tumors.
Assuntos
Apoptose/genética , Astrocitoma/genética , Genes p53/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Astrocitoma/patologia , Biomarcadores Tumorais/análise , Caspase 3 , Caspases/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético , Proteína Supressora de Tumor p53/biossínteseRESUMO
The congenital muscular dystrophies (CMD) are heterogeneous muscular diseases with early and dystrophic pattern on muscle biopsy. Many different subtypes have been genetically identified and most phenotypes not yet identified belong to the merosin-positive (MP) CMD subgroup. OBJECTIVE: To analyze the immunohistochemical expression of the main proteins of the dystrophin-glycoproteins associated complex in muscle biopsy of patients with different CMD phenotypes, for investigating a possible correlation with clinical and histopathological data. METHOD: Fifty-nine patients with CMD had clinical, histopathological and immunohistochemical data evaluated: 32 had MP-CMD, 23 CMD with merosin deficiency (MD-CMD), one Ullrich phenotype and three Walker-Warburg disease. RESULTS: Dystrophin and dysferlin were normal in all; among the patients with MD-CMD, merosin deficiency was partial in nine who showed the same clinical severity as those with total deficiency; the reduced expression of alpha-sarcoglycan (SG) and alpha-dystroglycan (DG) showed statistically significant correlation with severe MD-CMD phenotype. CONCLUSION: There is a greater relationship between merosin and the former proteins; among MP-CMD patients, no remarkable immunohistochemical/phenotypical correlations were found, although the reduced expression of beta-DG had showed statistically significant correlation with severe phenotype and marked fibrosis on muscular biopsy.
A distrofia muscular congênita (DMC) é doença muscular heterogênea, de início precoce e padrão histopatológico de distrofia. Diversos subtipos foram geneticamente identificados e os fenótipos ainda não identificados pertencem em geral ao subgrupo de DMC merosina-positiva (MP). OBJETIVO: Analisar a expressão imuno-histoquímica das principais proteínas do complexo distrofina-glicoproteínas associadas na biópsia muscular de pacientes com diferentes fenótipos de DMC, a fim de investigar uma eventual correlação com o quadro clínico e histopatológico. MÉTODO: Cinqüenta e nove pacientes com DMC foram avaliados clinicamente e sua biópsia muscular, histopatologica e imuno-histoquimicamente: 32 eram MP, 23 merosina-deficiente (MD), um mostrava fenótipo Ullrich e três síndrome de Walker-Warburg. RESULTADOS: Distrofina e disferlina foram normais em todos; nove pacientes MD apresentavam déficit parcial de merosina, porém com a mesma gravidade clínica daqueles com deficiência total. CONCLUSÃO: A hipoexpressão de a-sarcoglicana (SG) and a-distroglycan (DG) se correlacionou estatisticamente com o grave fenótipo MD, assim indicando maior correlação entre a merosina e as referidas proteínas; entre os pacientes MP, apesar da hipoexpressão de b-DG ter se correlacionado significativamente com fenótipo e histopatologia mais grave, não houve correlação clínica/imuno-histoquímica valorizável.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Complexo de Proteínas Associadas Distrofina/metabolismo , Distrofias Musculares/metabolismo , Laminina/deficiência , Brasil , Distribuição de Qui-Quadrado , Complexo de Proteínas Associadas Distrofina/genética , Distrofias Musculares/congênito , Seguimentos , Fenótipo , Índice de Gravidade de Doença , Sarcoglicanas/metabolismoRESUMO
Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observed. OBJECTIVE: To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen VI immunoreactivity on muscular biopsy. RESULTS: Among 60 patients with CMD, two had no expression of collagen V and their clinical involvement was essentially different: the first (3 years of follow-up) has mild motor difficulty; the second (8 years of follow-up) never acquired walking and depends on ventilatory support. A molecular study, performed by Pan et al. at the Thomas Jefferson University, demonstrated in the first a known mutation of Bethlem myopathy in COL6A1 and in the second the first dominantly acting mutation in UCMD and the first in COL6A1, previously associated only to Bethlem myopathy, with benign course and dominant inheritance. CONCLUSION: Bethlem myopathy should be considered in the differential diagnosis of UCMD, even in patients without fingers contractures; overlap between Ullrich and Bethlem phenotypes can be supposed.
A distrofia muscular congênita (DMC) com hiperextensibilidade articular distal (fenótipo Ullrich) associa-se a mutações nos genes do colágeno VI e corresponde a um grave quadro congênito de herança autossômica recessiva e curso progressivo, ocasionalmente mostrando menor gravidade. OBJETIVO: Avaliar o quadro clínico dos pacientes com DMC tipo Ullrich que apresentam imunoexpressão baixa ou ausente do colágeno VI na biópsia muscular. RESULTADOS: Entre 60 pacientes com DMC, dois mostravam imunomarcação negativa do colágeno VI. Mostravam-se clinicamente essencialmente diferentes: o primeiro, com 8 anos de idade e três de seguimento mostra leve dificuldade motora; o segundo, com 14 anos de idade e 8 de seguimento, não deambula e apresenta insuficiência respiratória. O estudo molecular, realizado na Thomas Jefferson University por Pan et al., revelou no primeiro, no gene COL6A1, mutação típica da miopatia de Bethlem, que tem curso benigno e herança autossômica dominante; e no segundo a primeira mutação de efeito dominante e do gene COL6A1, previamente associado apenas à miopatia de Bethlem. CONCLUSÃO: A miopatia de Bethlem deve constar no diagnóstico diferencial da DMC tipo Ullrich, mesmo na ausência das típicas contraturas dos dedos; pode existir sobreposição dos fenótipos Ullrich e Bethlem.
Assuntos
Adolescente , Criança , Pré-Escolar , Humanos , Masculino , Colágeno Tipo VI/deficiência , Distrofias Musculares/genética , Heterogeneidade Genética , Biópsia , Colágeno Tipo VI/genética , Diagnóstico Diferencial , Distrofias Musculares/congênito , Distrofias Musculares/patologia , Seguimentos , Imuno-Histoquímica , Instabilidade Articular/genética , Instabilidade Articular/patologia , FenótipoRESUMO
BACKGROUND: The presence of 14-3-3 protein in the CSF has been described to have high sensitivity and specificity for Creutzfeldt-Jakob disease (CJD). OBJECTIVE: To relate 14-3-3 protein in the CSF with the clinical diagnoses of diseases causing rapidly progressive dementia. METHODS: The authors studied 46 patients with rapidly progressive dementia that was classified into three diagnostic groups: definitive or probable CJD, possible CJD, and other diagnoses. The definitive or probable CJD group comprised 17 patients (3 definitive sporadic, 1 probable iatrogenic, 3 familial, and 10 probable sporadic CJD cases), the possible CJD group was composed of 7 patients, and the group with other diagnoses had 22 patients. Detection of the 14-3-3 protein was done by the immunoblotting method. RESULTS: In the definitive or probable CJD group, the test for 14-3-3 protein in CSF was positive in 14 (82%) cases, whereas 3 patients (1 probable sporadic and 2 familial cases) had negative results. CSF was positive for 14-3-3 protein in three of seven cases with possible CJD (42%). In the group with other diagnoses, three individuals had false-positive results (13%). Their diagnoses were definitive Alzheimer's disease, hypercalcemia, and multiple intracerebral hemorrhages. CONCLUSIONS: The detection of 14-3-3 protein in CSF is a useful in vivo diagnostic test for CJD and, when used in the appropriate clinical context, shows a good correlation to CJD. The presence of the 14-3-3 protein in the CSF reinforces the CJD clinical diagnosis but may not be able to differentiate CJD from other causes of rapidly progressive dementia in everyday clinical practice.
Assuntos
Demência/líquido cefalorraquidiano , Demência/diagnóstico , Tirosina 3-Mono-Oxigenase/líquido cefalorraquidiano , Proteínas 14-3-3 , Idoso , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Demência/classificação , Diagnóstico Diferencial , Progressão da Doença , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Creutzfeldt-Jakob disease (CJD), the most known human prion disease, is usually sporadic but approximately 15% of the cases are familial. To date, seven CJD cases with codon 210 mutation (GTT to ATT) have been reported in the literature. We describe a case of a 57 year-old woman who presented gait disturbances and rapidly progressive dementia, leading to death four months after onset. Electroencephalogram revealed periodic activity, diffusion-weighted magnetic resonance imaging showed hypersignal in basal ganglia, and test for 14-3-3 protein was strongly positive in the CSF. The complete prion protein gene coding region was sequenced after PCR amplification, showing a point mutation in codon 210. This is the first case of CJD with codon 210 mutation diagnosed in Brazil. We emphasize the role of genetic search for prion protein gene mutation, even in patients presenting clinical features resembling sporadic CJD.
Assuntos
Códon/genética , Síndrome de Creutzfeldt-Jakob/genética , Mutação Puntual/genética , Príons/genética , Evolução Fatal , Feminino , Humanos , Imunoensaio , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Seropositivity of anti-Helicobacter pylori antibody (HP + ) was examined among Japanese Brazilians. The study was announced through 18 Japanese community culture associations in São Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis in 2001. Among 969 participants, 963 individuals aged 33 - 69 years were analyzed. The overall HP + % was 48.1% (95% confidence interval, 44.9 - 51.3%). There was no difference in HP + % between 399 males and 564 females (49.6% and 47.0%, respectively). The HP + % increased with age; 35.3% for those aged 33 - 39 years, 46.2% for those aged 40 - 49 years, 46.5% for those aged 50 - 59 years, and 56.9% for those aged 60 - 69 years, but no differences were observed among the generations (Issei, Nisei, and Sansei) for each 10-year age group. Mogi das Cruzes, a rural area, showed a higher HP + %. Length of education was inversely associated with the positivity; the odds ratio (OR) relative to those with eight years or less of schooling was 0.61 (0.42 - 0.89) for those with 12 years or more. The associations with smoking and alcohol drinking were not significant. Fruit intake was associated with the HP + %; the OR relative to everyday intake was 1.38 (1.05 - 1.83) for less frequent intake, while intake frequencies of green tea, miso soup, and pickled vegetables (tsukemono) were not. Multivariate analysis including sex, 10-year age group, residence, education, and fruit intake showed that all factors except sex were significant. This is the largest study of HP infection among Japanese Brazilians, and the results indicated a similar pattern of age-specific infection rate to that for Japanese in Japan.
Assuntos
Envelhecimento/fisiologia , Povo Asiático , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Estilo de Vida/etnologia , Caracteres Sexuais , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Brasil/epidemiologia , Efeito de Coortes , Comportamento Alimentar , Feminino , Infecções por Helicobacter/etiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , FumarRESUMO
Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.