RESUMO
Recent studies demonstrated that the expression of coxsackievirus and adenovirus receptor (CAR) is implicated in the pathophysiology of myocarditis. The aim of the present study was to assess the association between active and borderline myocarditis and CAR expression in endomyocardial tissues, and analyze the association between CAR expression and treatment response. An analytic, crosssectional, retrospective study was performed in 26 patients with myocarditis and 10 control subjects without heart disease. Myocardial biopsies were obtained and CAR transcription was measured by reverse transcriptionquantitative polymerase chain reaction analysis. The association between CAR mRNA levels and the response to immunosuppressive or conventional therapy (treatment responders, n=17; nonresponders, n=9) or with the type of histological myocarditis (active myocarditis, n=16; borderline myocarditis, n=10) was analyzed. CAR transcription levels were significantly lower (P=0.012) in patients with myocarditis compared with controls, and a significant decrease was observed (P=0.023) in CAR mRNA levels among patients with borderline myocarditis compared with the no myocarditis group. Patients responding to therapy exhibited higher CAR mRNA levels (P=0.036) compared with patients not responding to treatment, as evaluated based on clinical and echocardiographic criteria (immunosuppressive therapy, n=8; conventional therapy, n=1). Myocarditis in nonresponders was associated with fewer clinical manifestations and lower CAR mRNA levels. A significant difference was only found regarding the use of oral steroids in patients with active myocarditis who responded to treatment (P=0.02), with no difference in borderline myocarditis. In conclusion, the transcriptional level of CAR is low in the endomyocardial tissue of patients with myocarditis, and it is lower in borderline myocarditis and in nonresponder patients. These findings may enable early identification of patients who may benefit from treatment and timely determination of prognosis.
Assuntos
Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Miocardite/genética , Miocárdio/patologia , Adulto , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocárdio/metabolismo , RNA Mensageiro/genética , Adulto JovemRESUMO
PURPOSE: Here we describe LifePrint, a sequence alignment-independent k-tuple distance method to estimate relatedness between complete genomes. METHODS: We designed a representative sample of all possible DNA tuples of length 9 (9-tuples). The final sample comprises 1878 tuples (called the LifePrint set of 9-tuples; LPS9) that are distinct from each other by at least two internal and noncontiguous nucleotide differences. For validation of our k-tuple distance method, we analyzed several real and simulated viroid genomes. Using different distance metrics, we scrutinized diverse viroid genomes to estimate the k-tuple distances between these genomic sequences. Then we used the estimated genomic k-tuple distances to construct phylogenetic trees using the neighbor-joining algorithm. A comparison of the accuracy of LPS9 and the previously reported 5-tuple method was made using symmetric differences between the trees estimated from each method and a simulated "true" phylogenetic tree. RESULTS: The identified optimal search scheme for LPS9 allows only up to two nucleotide differences between each 9-tuple and the scrutinized genome. Similarity search results of simulated viroid genomes indicate that, in most cases, LPS9 is able to detect single-base substitutions between genomes efficiently. Analysis of simulated genomic variants with a high proportion of base substitutions indicates that LPS9 is able to discern relationships between genomic variants with up to 40% of nucleotide substitution. CONCLUSION: Our LPS9 method generates more accurate phylogenetic reconstructions than the previously proposed 5-tuples strategy. LPS9-reconstructed trees show higher bootstrap proportion values than distance trees derived from the 5-tuple method.