Biomedical subjects

Antonio Ferreira

Publications and source records attributed to Antonio Ferreira.

6 recordsLinked to original sources

PubMed2007

Skin reactivity to thimerosal and phenol-preserved Montenegro antigen in Brazil.

A randomized double-blind trial was performed to determine the frequency of positive reactions to the Montenegro antigen (leishmanin) preserved in thimerosal (Merthiolate) 1:10,000 or phenol 0.4%. The respective products were tested separately in 400 young healthy individuals from a non-endemic area for Leishmaniases. Each volunteer received one of the following reagents: merthiolated antigen, phenolated antigen, merthiolated saline, or phenolated saline. The frequency of positive responses to each reagent after the first application was as follows: 0% (phenolated saline), 9.2% (merthiolated saline), 34.6% (antigen in phenolated saline), and 41.1% (antigen in merthiolated saline). After 1 week, volunteers who had tested positive for merthiolated or phenolated antigen were retested with the respective preservative, while negatives were retested with the preservative they had not received during the first test. In all, 331 volunteers who received merthiolated saline during the study, of whom 41 (12.4%) tested positive. Meanwhile, 326 volunteers who received phenolated saline, 4 (1.2%) tested positive. Positive reactions in each group were similar in relation to gross appearance skin reactions. Considering the high frequency of hypersensitivity to thimerosal in the study population, it is recommended that this compound should be replaced as a preservative of the leishmanin antigen. Almost 30% of positive reactions to Montenegro antigen in what is considered a non-endemic region was surprising and will be the object of future studies.

Adolescent↗

PubMed2006

Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control and family study.

BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. Genetic and environmental factors are suspected to be involved in the development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory activity on immunoglobulin production and it may be an important regulator in IgAD pathogenesis. The IL-10 gene contains several single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers are associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278 patients with IgAD and 573 ethnically matched controls for the microsatellites IL-10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, -819 and -592 in the proximal promoter of the gene. We also included in this study the parents of 194 patients in order to study the IL-10 haplotypes transmitted and not transmitted to the affected offspring. RESULTS: The only allele where a significant difference was observed in the comparison between IgA deficiency patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However, this p value could not withstand a Bonferroni correction. None of the IL-10R or promoter SNP alleles was found at a different frequency when patients were compared with controls. CONCLUSION: Our data do not show any significant difference in IL-10 polymorphism frequencies between control and IgAD patient samples. Their haplotype distribution among patients and controls was also equivalent and therefore these microsatellites and SNPs do not seem to influence IgAD susceptibility.

Case-Control Studies↗

PubMed2006

Bruton's tyrosine kinase is not essential for LPS-induced activation of human monocytes.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by impaired B-cell differentiation caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The natural disease model, the X-linked immunodeficiency mouse, shows a less severe phenotype, indicating a different requirement of Btk in human and mouse B cells. Btk is also expressed in the myeloid line and participates in LPS signaling. Deficient oxidative burst and myeloid differentiation have been reported in the X-linked immunodeficiency mouse, but the precise mechanism and relevance of Btk activity in human monocytes is poorly understood. OBJECTIVE: The apparent absence in XLA of clinical manifestations of myeloid deficiency prompted us to explore the relevance of complete Btk absence in human myeloid cells. METHODS: Seven patients with XLA with BTK mutations conditioning a null protein expression were included in the study. Monocyte LPS-induced mitogen-activated protein kinase activation, TNF-alpha and IL-6 production in monocytes, and oxidative burst in monocytes and granulocytes were analyzed by means of flow cytometry. RESULTS: We show that in response to LPS, Btk-null monocytes from patients with XLA induce early mitogen-activated protein kinase activation and intracellular TNF-alpha and IL-6 production with the same intensity as cells from age- and sex-matched control subjects. In addition, the oxidative burst in response to LPS and other stimulants was completely normal in Btk-null monocytes and neutrophils. CONCLUSION: Our results indicate that Btk is not essential for early LPS signaling in human monocytes and that different Btk dependency might exist between human and mouse myeloid cells. CLINICAL IMPLICATIONS: These findings provide a better understanding of XLA, and they show the differences between human XLA and murine Xid models.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2006

Modeling oligonucleotide microarray signals.

Chemical principles dictate that the specific binding of a target to its complementary probes on a DNA microarray surface, and the nonspecific binding between other nucleotide segments and the same probes, are mutually competitive. We demonstrate that this mechanism can be understood by considering the competitive chemical reaction taking place on the microarray surface. Inspired by the pioneering work of Zhang and Hekstra, we have developed a physical model for microarray signal analysis, based on possible reaction mechanisms, and implemented it with a parallel, generic, simulated-annealing algorithm. Using data supplied by the Affymetrix Latin-square spike-in experiments, our model showed excellent fitting of the data. This correlation between the predicted expression levels and the spike-in concentrations of test transcripts demonstrated good predictive abilities of our model.

Algorithms↗

PubMed2003

[Autoimmune lymphoproliferative syndrome: molecular diagnosis in two families].

BACKGROUND AND OBJECTIVE: The autoimmune lymphoproliferative syndrome (ALPS) is a disorder caused by a defect in lymphocytes' apoptosis and characterized by non malignant lymphoproliferation, autoimmune features and increased TCR alpha + CD4CD8 cells. Most patients have a mutation in the TNFRSF6 gene, which encodes the Fas protein. Our aim was to identify mutations in this gene in two families with possible ALPS cases. PATIENTS AND METHOD: Two patients with suspicion of ALPS, belonging to two unrelated families, were studied. To confirm such a diagnosis, immunoglobulin quantification, cellular phenotypic analysis by flow cytometry, IL-10 quantification, an apoptosis study, and molecular analysis were performed. RESULTS: Both patients showed hypergammaglobulinemia and an increased percentage of TCR alpha + CD4CD8 cells (family A patient: 14%; family B patient: 4.25%). In family A, in vitro Fas-mediated apoptosis was absent in the patient and markedly reduced in his father. In this family, both the patient and his father were heterozygous for the Fas mutation T1045C (Leu 268 Pro). The family B patient and her mother showed the Fas mutation G943T (Arg 234 Leu), both being heterozygous for it too. Both mutations are located in exon 9 of TNFRSF6 gene, affecting the death domain of the Fas protein. CONCLUSIONS: The molecular study of these families confirms a diagnosis of ALPS and suggests that the causing defect of this syndrome is compatible with an autosomal dominant inheritance with incomplete penetrance.

Autoimmune Diseases↗

PubMed2002

MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes.

Familial predisposition to IgA deficiency (IgAD) suggests that genetic factors influence susceptibility. Most studies support a polygenic inheritance with a susceptibility locus (designated IGAD1) in the MHC, but its exact location is still controversial. This study aimed to map the predisposing IGAD1 locus (or loci) within the MHC by investigating the pattern of association of the disease with several markers in the region. DNA-based techniques were used to type individual alleles of four polymorphic HLA genes (HLA-DR, -DQA1, -DQB1, and HLA-B), six microsatellites (all located between HLA-DR and HLA-B), and three single nucleotide polymorphisms on the TNF gene. The frequencies of these alleles were compared among ethnically matched populations comprising 182 patients and 343 controls. Additionally, we investigated parents and siblings of 100 of these patients. All four parental haplotypes were established in each family (n = 400), and transmission disequilibrium tests were performed. Surprisingly, our results did not support the hypothesis of a unique susceptibility gene being shared by all MHC susceptibility haplotypes. On HLA-DR1 and -DR7-positive haplotypes IGAD1 mapped to the class II region, whereas on haplotypes carrying HLA-DR3 the susceptibility locus mapped to the telomeric end of the class III region, as reported previously. Our results show how, in complex diseases, individuals may be affected for different genetic reasons and a single linkage signal to a region of a chromosome may actually be the result of disease-predisposing alleles in different linked genes in different pedigrees.

Alleles↗