Biomedical subjects

J A B Chies

Publications and source records attributed to J A B Chies.

10 recordsLinked to original sources

PubMed2006

Frequency of CCR5delta32 in Brazilian populations.

A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59), while blacks and browns (mulattoes) were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively), suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

Alleles↗

PubMed2005

Immunosuppressive therapy for kidney transplant prevents vaso-occlusive crisis in a haemoglobin SC disease patient.

Although the molecular basis of sickle cell disease (SCD) is well established, the wide variability in clinical manifestations still puzzles haematologists and clinicians. Recently, SCD started to be considered by different groups as a chronic inflammatory condition, where the inflammatory tendency of each individual could drive more or less severe clinical features. Here we describe a haemoglobin SC disease patient (heterozygous to both HbS and HbC variants) that experienced several vaso-occlusive crises before underwent a successful kidney transplantation. Since then (16 years ago), she is on uninterruped immunosuppressive therapy, and do not experienced any severe vaso-occlusive crisis. Considering SCD associated morbidity as a result of exacerbated immune responses, we suggest that the immunosuppressive therapy directed to the kidney graft maintenance is actually also helping in the control of the chronic inflammatory responses associated to SCD.

Adult↗

PubMed2005

Induction of fetal haemoglobin expression in erythroid cells--a model based on iron availability signalling.

The K562 cell line has erythroid origin and is used for the study of fetal haemoglobin (HbF) production after treatment with several drugs, such as hydroxyurea, cisplatin and cytosine arabinoside (Ara C). It represents an important tool for the study of cancer differentiation therapy and treatment of thalassaemia and sickle cell disease. Although subject to intense research, the mechanisms involved in the induction of HbF are not fully established, and the regulation of several genes and signalling pathways has been proposed. Using the methodology of differential display, we investigated the changes in gene expression in K562 cells treated with doxorubicin and aclarubicin, which induce HbF expression and cell cycle arrest. Several genes were shown to present differential expression patterns, many of them related to the iron signalling pathway. Particular attention was given to Ndrg1, expressed as early as 24 h after treatment, which can be regulated by iron and is involved with blocking of the cell cycle. A review of the literature shows that, similar to doxorubicin and aclarubicin, most of the drugs used to induce HbF present some kind of effect on the iron signalling pathway, activating in the cells the machinery necessary for the incorporation of extracellular iron. Considering these results, as well as the fact that in erythroid cells the synthesis of haemoglobin is of vital importance, we propose that the production of fetal haemoglobin in erythroid cells is highly dependent on the iron signalling pathway.

Aclarubicin↗

PubMed2005

Immunodominant viral peptides as determinants of cross-reactivity in the immune system--Can we develop wide spectrum viral vaccines?

When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular "viral patterns" seems to be important steps towards the development of wide spectrum viral vaccines.

Animals↗

PubMed2005

Polymorphisms of chemokine receptors and eNOS in Brazilian patients with sickle cell disease.

Sickle cell disease (SCD) is an inherited disorder that presents extremely variable clinical manifestations. For the past few decades, it has been approached as an inflammatory disorder, and several researchers have tried to determine the factors involved in such characteristic. In order to contribute to the identification of the genetic differences underlying this phenotypic diversity in SCD, we proposed to study the distribution of polymorphic variants of the genes encoding the chemokine receptors CCR2 and CCR5, as well as three polymorphisms in the NOS3 gene, in Brazilian SCD patients. These genes are involved in the development of inflammatory immune reactions, a feature believed to be of extreme importance in SCD pathology. Our results indicate that the polymorphisms studied here are not directly associated with severe clinical manifestations in SCD patients. Nevertheless, we observed a tendency for the development of a severe clinical course in carriers of the variant alleles CCR2-64I and CCR5delta32 and in homozygotes for the -786C variant of the NOS3 gene. Further studies should be carried out in order to assess the role of such variants in the clinical picture of SCD.

Adolescent↗

PubMed2005

Relationship between Candida infection and immune cellular response in inflammatory hyperplasia.

OBJECTIVES: To analyze and quantify the CD8(+) and CD4(+) T-lymphocyte populations in inflammatory hyperplasia and to establish the relationship between the frequency and location of these cells and Candida infection. METHODS: Samples of inflammatory hyperplasia were stained with PAS for evidence of Candida sp. and were classified in two groups, infected and control, according to the presence or absence of infection. After immunoreaction with specific anti-CD4 and anti-CD8 monoclonal antibodies, the distribution and frequency of the positive cells were analyzed in 41 cases (19 controls without Candida sp. and 22 infected cases). Lymphocytes were quantified in the three consecutive fields where the inflammatory infiltration was concentrated. RESULTS: There was no relationship between the frequency and location of CD4(+) T cells and Candida sp. infection. The number of CD8(+) cells close to the fungi hyphae as well as the total number of CD8(+) T cells present in inflammatory hyperplasia were higher in the Candida sp. group than in the control noninfected group (P < 0.05). CONCLUSION: Since the CD8(+) T cells were distributed according to the location of Candida sp. hyphae, and since a higher CD8(+)/total lymphocytes ratio was observed in the infected group, we suggest a role for CD8(+) T cells in the defense against Candida in oral infections associated with inflammatory hyperplasia in immunocompetent individuals.

CD4-Positive T-Lymphocytes↗

PubMed2004

T-cell receptor BV gene segment polymorphisms in healthy elderly individuals from the south of Brazil.

The ageing of the immune system (immunosenescence) is believed to be involved in both morbidity and mortality in elderly humans due to a higher incidence of infections, autoimmune diseases, cancers and other pathological situations. As any specific immune response involves recognition of antigens by T cells, the ability to develop a given immune response is also dependent on the T-cell repertoire available at a given time point. Different T-cell receptor beta variable segment (BV) (TCRBV) gene segment alleles have been associated with diseases in various human populations. In the present work we analysed the allelic frequencies of four biallelic polymorphisms in TCRBV gene segments (TCRBV3S1, TCRBV13S5, TCRBV13S6 and TCRBV18) in healthy elderly human subjects (80 years old or more) from the south of Brazil, where life expectancies reach similar levels to those observed in developed countries. Except for allele 2 of the TCRBV13S6 polymorphism, which was more frequent in elderly than in young individuals (P = 0.0105), there were no differences in allele or genotype frequencies between young and elderly individuals. The data suggest that there is no direct correlation between the TCRBV3S1, TCRBV13S5 and TCRBV18 polymorphisms analysed and healthy senescence in this particular group of elderly individuals. The higher frequency of TCRBV13S6 allele 2 in healthy elderly individuals should be confirmed in other samples to establish the significance of this finding.

Adolescent↗

PubMed2003

Copper ions dynamically regulate beta3 integrin subunit expression in Ishikawa cells.

Copper intrauterine device (IUD) users have a reduced expression of beta3 integrin subunit during the implantation window. This integrin has been found to be a uterine marker for implantation. In order to verify if copper ions are involved in this reduction, beta3 integrin subunit expression was assessed in an in vitro model. The beta3 integrin subunit expression was determined by flow cytometry in the presence of copper D-gluconate and/or epidermal growth factor (EGF). The mean percentages of positive beta3 integrin subunit cells under different culture conditions were: 4.7 +/- 0.29 (mean +/- SEM) in controls; 8.6 +/- 0.59 in the presence of copper; 13.4 +/- 0.05 in the presence of EGF and 20.8 +/- 0.36 in the presence of EGF+copper (analysis of variance, p < 0.0001). Copper D-gluconate up-regulates beta3 integrin subunit expression in vitro both in the presence and absence of EGF. The differences between in vivo and in vitro results should be investigated and may represent interference by other factors such as the inflammatory process associated with the presence of IUDs.

Cations↗

PubMed2002

High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia.

Homozygous sickle cell disease (SCD) has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1%) of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3%) with the same ethnic background (Afro-Brazilians). Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

Adolescent↗

PubMed2002

TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black populations.

The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied.

Adult↗