Seroprevalence of Chagas disease in Southern Brazilian cardiac patients and their knowledge about the parasitosis and vectors / Soroprevalência da doença de Chagas em pacientes cardíacos do sul do Brasil e seu conhecimento sobre a parasitose e vetores

Abstract Chagas disease (CD) is considered a typical low-income population sickness of the developing countries in Latin America. Given the historical relevance of CD in individuals in southern Rio Grande do Sul (RS) State, Brazil, the aim of this study was to identify the knowledge of the CD and its vectors by cardiac patients, and the prevalence of anti-T cruzi antibodies in these individuals in Pelotas, city located in Rio Grande do Sul (RS) state, Brazil. The subjects with cardiac disease were submitted to a semi-structured questionnaire as well as two serological tests in order to detect anti-T. cruzi IgG antibodies. Of the individuals that born in municipalities showing the highest triatomine infestation rates in recent decades, 81.8% were able to recognize the vector insect (p = 0.0042; OR = 5.9), and 83.3% reported either themselves or someone in their families to have CD (p = 0.043, OR = 5.2). Of the 54 patients submitted to serological analysis, only 01 patient (1.9%) was positive for anti-T. cruzi antibodies, a 55 year old man from the rural area of Canguçu county. This study provides support for the evaluation to be extended to other cardiology centers, given the importance of Chagas disease in Brazil.

Resumo A doença de Chagas (DC) é considerada uma doença típica da população de baixa renda dos países em desenvolvimento da América Latina. Dada a relevância histórica da DC em indivíduos do sul do Estado do Rio Grande do Sul (RS), o objetivo deste estudo foi identificar o conhecimento da doença de Chagas (DC) e seus vetores em pacientes cardíacos, e a prevalência de anticorpos anti-T cruzi nesses indivíduos, em Pelotas, cidade localizada no Rio Grande do Sul (RS), Brasil. Os pacientes cardiopatas foram submetidos a um questionário semiestruturado, e também a dois testes sorológicos para detecção de anticorpos anti-T. cruzi IgG. Dos indivíduos que nasceram em municípios com as maiores taxas de infestação por triatomíneos nas últimas décadas, 81,8% foram capazes de reconhecer o inseto vetor (p = 0,0042; OR = 5,9), e 83,3% relataram que eles próprios ou alguém em suas famílias tem DC (p = 0,043, OR = 5,2). Dos 54 pacientes submetidos à análise sorológica, apenas 01 paciente (1,9%) foi positivo para anticorpos anti-T.cruzi, um homem de 55 anos da área rural do município de Canguçu. Este estudo fornece subsídios para que a avaliação seja estendida a outros centros de cardiologia, devido à importância da doença de Chagas no Brasil.

Seroprevalence of Chagas disease in Southern Brazilian cardiac patients and their knowledge about the parasitosis and vectors.

Chagas disease (CD) is considered a typical low-income population sickness of the developing countries in Latin America. Given the historical relevance of CD in individuals in southern Rio Grande do Sul (RS) State, Brazil, the aim of this study was to identify the knowledge of the CD and its vectors by cardiac patients, and the prevalence of anti-T cruzi antibodies in these individuals in Pelotas, city located in Rio Grande do Sul (RS) state, Brazil. The subjects with cardiac disease were submitted to a semi-structured questionnaire as well as two serological tests in order to detect anti-T. cruzi IgG antibodies. Of the individuals that born in municipalities showing the highest triatomine infestation rates in recent decades, 81.8% were able to recognize the vector insect (p = 0.0042; OR = 5.9), and 83.3% reported either themselves or someone in their families to have CD (p = 0.043, OR = 5.2). Of the 54 patients submitted to serological analysis, only 01 patient (1.9%) was positive for anti-T. cruzi antibodies, a 55 year old man from the rural area of Canguçu county. This study provides support for the evaluation to be extended to other cardiology centers, given the importance of Chagas disease in Brazil.

Seroprevalence of Chagas disease in Southern Brazilian cardiac patients and their knowledge about the parasitosis and vectors

Abstract Chagas disease (CD) is considered a typical low-income population sickness of the developing countries in Latin America. Given the historical relevance of CD in individuals in southern Rio Grande do Sul (RS) State, Brazil, the aim of this study was to identify the knowledge of the CD and its vectors by cardiac patients, and the prevalence of anti-T cruzi antibodies in these individuals in Pelotas, city located in Rio Grande do Sul (RS) state, Brazil. The subjects with cardiac disease were submitted to a semi-structured questionnaire as well as two serological tests in order to detect anti-T. cruzi IgG antibodies. Of the individuals that born in municipalities showing the highest triatomine infestation rates in recent decades, 81.8% were able to recognize the vector insect (p = 0.0042; OR = 5.9), and 83.3% reported either themselves or someone in their families to have CD (p = 0.043, OR = 5.2). Of the 54 patients submitted to serological analysis, only 01 patient (1.9%) was positive for anti-T. cruzi antibodies, a 55 year old man from the rural area of Canguçu county. This study provides support for the evaluation to be extended to other cardiology centers, given the importance of Chagas disease in Brazil.

Resumo A doença de Chagas (DC) é considerada uma doença típica da população de baixa renda dos países em desenvolvimento da América Latina. Dada a relevância histórica da DC em indivíduos do sul do Estado do Rio Grande do Sul (RS), o objetivo deste estudo foi identificar o conhecimento da doença de Chagas (DC) e seus vetores em pacientes cardíacos, e a prevalência de anticorpos anti-T cruzi nesses indivíduos, em Pelotas, cidade localizada no Rio Grande do Sul (RS), Brasil. Os pacientes cardiopatas foram submetidos a um questionário semiestruturado, e também a dois testes sorológicos para detecção de anticorpos anti-T. cruzi IgG. Dos indivíduos que nasceram em municípios com as maiores taxas de infestação por triatomíneos nas últimas décadas, 81,8% foram capazes de reconhecer o inseto vetor (p = 0,0042; OR = 5,9), e 83,3% relataram que eles próprios ou alguém em suas famílias tem DC (p = 0,043, OR = 5,2). Dos 54 pacientes submetidos à análise sorológica, apenas 01 paciente (1,9%) foi positivo para anticorpos anti-T.cruzi, um homem de 55 anos da área rural do município de Canguçu. Este estudo fornece subsídios para que a avaliação seja estendida a outros centros de cardiologia, devido à importância da doença de Chagas no Brasil.

Analphoid marker chromosome in a patient with hyper-IgE syndrome, autism, and mild mental retardation.

Hyper-IgE syndrome with recurrent infections (HIES) is a primary immunodeficiency disease characterized by recurrent skin and lung abscesses and extreme elevations of serum IgE, but also involving dentition, bones, and connective tissue. Although the etiology of HIES is unknown, autosomal dominant inheritance has been observed in multiple kindreds. A 17 year old male with sporadic HIES, autism, and mild mental retardation was found to have a supernumerary marker chromosome in peripheral blood lymphocytes and skin fibroblasts. Microdissection and FISH analysis of the marker chromosome showed that it was derived from a small interstitial deletion of one homologue of chromosome 4q21. Lack of hybridization of probes specific for telomeres and alphoid centromeres, including a centromere 4 specific probe, established that the marker was an analphoid ring chromosome. Comparative genotyping of transformed B-cell subclones with (M+) and without (M-) the marker chromosome showed loss of the maternal alleles in M- cells between markers D4S1569 and D4S3010. FISH using YAC clones from 4q21 confirmed the size and location of the interstitial deletion. Thus our patient's phenotypes were associated with de novo formation of a marker chromosome containing 15-20 cM of DNA deleted from his maternally derived chromosome 4. Proximal chromosome 4q therefore is a candidate region for disease genes for both HIES and autism. Identification of genes disrupted or lost during the formation of the marker chromosome as well as linkage studies in kindreds with HIES or autism may help us to understand the etiology of these complex phenotypes.

Genomic structure and mapping of human FADD, an intracellular mediator of lymphocyte apoptosis.

Fas-associated death domain protein (FADD)/MORT1 is a 23-kDa cytoplasmic protein containing a C-terminal death domain that interacts with the intracellular death domain of the Fas transmembrane receptor. Cross-linking of Fas mediates apoptosis in a variety of cells, primarily peripheral T lymphocytes, for which this pathway plays a major role in mature lymphocyte homeostasis. We report the characterization of the human FADD gene, which spans approximately 3.6 kb and contains two exons (286 and 341 bp) separated by a 2.0-kb intron. FADD was mapped to chromosome 11q13.3 by the independent techniques of PCR screening of somatic cell hybrid mapping panels and fluorescence in situ hybridization. In addition FADD was shown by fluorescence in situ hybridization to be amplified along with other 11q13.3 genes previously studied in the breast cancer cell line MDA-MB-134-VI, raising the possibility that overexpression of mutant FADD could contribute to poor prognosis and increased invasiveness of tumors. Its known role in apoptosis has made FADD a candidate susceptibility gene for autoimmune lymphoproliferative syndrome. Now that it has been colocalized in 11q13.3 with IDDM4, a diabetes susceptibility locus, alterations in FADD should also be considered as potential contributors to insulin-dependent familial diabetes. Elucidation of the map position and gene structure of FADD will make possible linkage and mutation analysis to study the role of this gene in human diseases.

Genomic sequence, organization, and chromosomal localization of human JAK3.

Members of the Janus (JAK) protein tyrosine kinase family including JAK3 have recently emerged as important components in cytokine signal transduction. Mutations of JAK3 have been found in a number of patients who present with severe combined immunodeficiency. To facilitate the further identification of JAK3-SCID patients and to understand the structure of JAK3 better, we undertook the determination of the genomic sequence, organization, and chromosomal localization of the JAK3 gene. The JAK3 gene was found to consist of 19 exons and 18 introns. Interestingly, the organization of the kinase-(JH1) and pseudokinase-(JH2) domains were found to be dissimilar. In addition, the JAK3 gene was localized to human chromosome 19p13.1. These data should facilitate the identification of patients with this new form of immunodeficiency and will provide insight into the structure of this kinase.

Gene localization and syntenic mapping by FISH in the dog.

To begin development of a canine gene map and to define syntenic regions between the canine and human genomes, the technique of fluorescence in situ hybridization (FISH) was adapted to localize specific DNA sequences in canine metaphases. Genomic clones of canine origin as well as human yeast artificial chromosome clones were used to map canine loci. The immunoglobulin heavy-chain region was localized to canine chromosome 4qtel; the canine major histocompatibility locus, DLA, was found to be on chromosome 12qtel. Of particular interest, the canine X chromosome, which morphologically is highly similar to the human X, also showed syntenic localization of the clotting factor VIII (F8C) and factor IX (F9) genes to Xq28 and Xq26.3-->q27.1, respectively.

Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency.

Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly(TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly(CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the gamma chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification.

Localization of the 75-kDa inositol polyphosphate-5-phosphatase (INPP5B) to human chromosome band 1p34.

The 75-kDa (type II) inositol polyphosphate-5-phosphatase, originally described in platelets, is one of at least three known enzymes capable of dephosphorylating inositol-1,4,5-trisphosphate (IP3) to inositol-1,4-bisphosphate (IP2). To further characterize these enzymatic forms, we have mapped the gene (INPP5B) coding for the 75-kDa type II enzyme. Using a combination of human x rodent somatic cell hybrids and fluorescence in situ hybridization, we have determined that this gene maps to human chromosome band 1p34.

The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.

The gene encoding the gamma chain of the lymphocyte interleukin-2 receptor has been cloned and shown to be required to associate with the beta chain in order for IL-2 internalization and cell activation to occur (1). We considered this gene, IL2RG, a candidate for the X-linked form of severe combined immunodeficiency at the SCIDX1 locus, in which affected males have impaired lymphocyte development. Using fluorescence in situ hybridization and PCR amplification of somatic cell hybrid DNAs, we mapped IL2RG to human Xq13.1, a location within the SCIDX1 critical region established by linkage analysis. The 4.2 kb IL2RG gene was sequenced, and its genomic organization was elucidated. Seven of 19 transformed B-lymphocyte cell lines with independent SCIDX1 mutations had absent or minimal IL2RG mRNA. Unique point mutations were documented to be specifically associated with the disease and the carrier state in four unrelated affected males and their family members: one in a boy with no detectable IL2RG mRNA, in which the mutation ablated a splice donor site; one causing premature chain termination; and two causing distinct amino acid changes. The demonstration of impaired IL2RG mRNA expression in males with X-linked SCID and of unique point mutations in SCIDX1 pedigrees constitutes powerful evidence that the SCIDX1 gene is IL2RG. Noguchi et al. (2) have independently published IL2RG mapping to Xq13 and discovery of mutations in three affected males. The specific pathogenesis of IL2RG mutations and approaches to gene therapy can now be addressed in the X-linked form of SCID.