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Biomedical subjects

Ana Coelho

Publications and source records attributed to Ana Coelho.

10 recordsLinked to original sources

A functional polymorphism in the promoter region of leptin gene increases susceptibility for non-small cell lung cancer.

Leptin hormone and receptor have been associated to cancer development and were identified in lung tissue. In this study, a functional polymorphism in the 5' flanking region of the leptin gene (LEP -2548 G/A) was found to increase susceptibility for non-small cell lung cancer [odds ratio (OR), 1.97; 95% confidence interval (CI), 1.13-3.43]. Age-adjusted logistic regression analysis in men indicated an association of AA genotype with adenocarcinoma (OR, 4.29; CI, 1.64-11.72) and squamous cell carcinoma (OR, 3.19; CI, 1.26-8.13). Logistic regression analysis confirmed the AA genotype as an independent risk factor for lung cancer after adjustment for age and gender (OR, 2.57; CI, 1.34-4.92). The AA genotype was overrepresented only in patients with non-metastatic disease (OR, 1.86; CI, 1.13-3.04). Kaplan-Meier analysis demonstrated an earlier age of onset for lung cancer in AA carriers (P=0.023). Results suggest the existence of genetic susceptibility for lung cancer in carriers of this LEP functional polymorphism. Further studies are warranted to extend knowledge of leptin involvement in lung cancer.

Adult↗

Identification and characterization of merozoite antigens of a Theileria species highly pathogenic for small ruminants in China.

A new pathogenic Theileria species transmitted by Haemaphysalis qinghaiensis was identified in the Northwestern part of China and was shown to be highly pathogenic for small ruminants. The present article aimed at identifying merozoite antigens that might be suitable for developing diagnostic methods and designing a potential vaccine. Absence of other theilerial or babesial infections was confirmed by reverse line blot in all antigen samples used. Extensive Western blot analyses using serum from infected and noninfected animals led to the identification of four potential merozoite immunoreactive proteins at different molecular weights. Further protein characterization using peptide mass mapping by matrix-assisted laser desorption/ionization (MALDI) followed by database searching resulted in two significant hits that identified two proteins of parasite origin, one homologous to a possible MO25-family protein from Cryptosporidium parvum and the other with an HSP70 from Theileria annulata. Another protein was also identified as a parasite protein but without significant homology. Immunization of rabbits with selected proteins produced antisera that reacted specifically on Western blots with merozoite antigens of the corresponding sizes. This article represents the first identification and characterization of potential antigenic proteins of Theileria sp. (China) for veterinary purposes.

Animals↗

Cervical cancer and CYP2E1 polymorphisms: implications for molecular epidemiology.

INTRODUCTION: Besides human papillomavirus (HPV) infection, several cofactors are considered important for the development of cervical cancer (CC). Among these, tobacco smoke, other sexually transmitted diseases, inflammation and nutritional factors have been intensively described. CYP2E1 polymorphisms have been associated with the metabolization of several carcinogens, some of them considered risk factors for CC development, such as tobacco smoke. The aim of this study was to evaluate the role of CYP2E1 polymorphisms in the susceptibility to cervical cancer in a Portuguese population. PATIENTS AND METHODS: The genotypic analysis was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, using peripheral blood samples of 454 individuals: 122 presented invasive squamous cell carcinoma (ICC), 59 presented squamous intraepithelial lesions (SIL), and the control population was composed of 274 healthy individuals. RESULTS: Concerning the DraI polymorphism, we observed a decreased risk for the development of squamous cervical lesions in the presence of the C allele [odds ratio (OR)=0.600; 0.378<OR<0.952; p=0.029]. In the stratification of the analysis according to the mean age, we observed an increased risk for the development of SIL, for women older than 39 years of age, in the presence of the D allele (OR=0.087; 0.012<OR<0.651; p=0.003). Regarding the RsaI polymorphism, we did not find any significant differences. CONCLUSION: The decreased risk observed for the development of SIL and not ICC in the presence of the D allele may indicate that CYP2E1 interferes with the initial steps of the carcinogenic process, probably due to its involvement in the action of immunological mediators, expressed during cervical inflammation. These aspects may help to define new therapeutic strategies for chemoprevention.

Adult↗

The neuraminidase gene is present in the non-toxigenic Vibrio cholerae Amazonia strain: a different allele in comparison to the pandemic strains.

The neuraminidase gene, nanH, is present in the O1, non-toxigenic Vibrio cholerae Amazonia strain. Its location has been assigned to a 150 kb NotI DNA fragment, with the use of pulsed-field gel electrophoresis and DNA hybridization. This NotI fragment is positioned inside 630 kb SfiI and 1900 kb I-CeuI fragments of chromosome 1. Association of the pathogenicity island VPI-2, carrying nanH and other genes, with toxigenic strains has been described by other authors. The presence of nanH in a non-toxigenic strain is an exception to this rule. The Amazonia strain nanH was sequenced (Genbank accession No. AY825932) and compared to available V. cholerae sequences. The sequence is different from those of pandemic strains, with 72 nucleotide substitutions. This is the first description of an O1 strain with a different nanH allele. The most variable domain of the Amazonia NanH is the second lectin wing, comprising 13 out of 17 amino acid substitutions. Based on the presence of nanH in the same region of the genome, and similarity of the adjacent sequences to VPI-2 sequences, it is proposed that the pathogenicity island VPI-2 is present in this strain.

Alleles↗

Protective role of the polymorphism CCR2-64I in the progression from squamous intraepithelial lesions to invasive cervical carcinoma.

OBJECTIVE: Invasive cervical cancer (ICC) is one of the most common malignant diseases among women, representing almost 10% of all the cancers in the female population. The aim of this study was to explore the association of the CCR2-64I polymorphism with the risk of developing invasive cervical cancer (ICC) from squamous intraepithelial lesions (SILs). METHODS: DNA samples were extracted from peripheral blood cells of 109 patients with squamous intraepithelial lesions (28 low-grade and 81 high-grade cases) and 217 patients with ICC. The CCR2-64I polymorphism was analyzed through polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) (BseJI). The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between CCR2-64I genotypes and cervical cancer risk. RESULTS: The frequency of the G/A genotype was significantly higher in SIL patients (n = 109) than ICC patients (n = 217) (P = 0.005; OR = 0.42; 95% CI: 0.22-0.83). Furthermore, no association was found when we analyzed the influence of the A allele in the progression from low-grade SIL (LSIL) to high-grade SIL (HSIL) (OR = 1.05; 95% CI = 0.370-2.98; P = 0.930), but a statistically significant association was found in the progression from high-grade SIL to ICC (OR = 0.435; 95% CI = 0.222-0.854; P = 0.014). CONCLUSION: These findings suggest that CCR2-64I polymorphism might have a protective role in the evolution from high-grade SIL to ICC.

Adult↗

Proton-assisted two-electron transfer in natural variants of tetraheme cytochromes from Desulfomicrobium Sp.

The tetraheme cytochrome c3 isolated from Desulfomicrobium baculatum (DSM 1743)(Dsmb) was cloned, and the sequence analysis showed that this cytochrome differs in just three amino acid residues from the cytochrome c3 isolated from Desulfomicrobium norvegicum (Dsmn): (DsmnXXDsmb) Thr-37 --> Ser, Val-45 --> Ala, and Phe-88 --> Tyr. X-ray crystallography was used to determine the structure of cytochrome c3 from Dsmb, showing that it is very similar to the published structure of cytochrome c3 from Dsmn. A detailed thermodynamic and kinetic characterization of these two tetraheme cytochromes c3 was performed by using NMR and visible spectroscopy. The results obtained show that the network of cooperativities between the redox and protonic centers is consistent with a synergetic process to stimulate the hydrogen uptake activity of hydrogenase. This is achieved by increasing the affinity of the cytochrome for protons through binding electrons and, reciprocally, by favoring a concerted two-electron transfer assisted by the binding of proton(s). The data were analyzed within the framework of the differences in the primary and tertiary structures of the two proteins, showing that residue 88, close to heme I, is the main cause for the differences in the microscopic thermodynamic parameters obtained for these two cytochromes c3. This comparison reveals how replacement of a single amino acid can tune the functional properties of energy-transducing proteins, so that they can be optimized to suit the bioenergetic constraints of specific habitats.

Bacterial Proteins↗

A proteome reference map for Vibrio cholerae El Tor.

A proteome reference map has been constructed for Vibrio cholerae El Tor, in the pI range of 4.0 to 7.0. The map is based on two-dimensional gels (2-D) and the identification, by peptide mass fingerprint, of proteins in 94 spots, corresponding to 80 abundant proteins. Two strains are compared, strain N16961 and a Latin American El Tor strain C3294. The consensus map contains 340 spots consistently seen with both strains grown in Luria-Bertani broth (LB) or minimal M9 medium. The results were obtained from nine gels run with 18 cm immobilized pH gradient strips and precast gels. The 2-D gels were anchored to real N16961 proteins identified by mass spectrometry. Various energy metabolism components and periplasmic ATP-binding cassette (ABC) transporter proteins were identified among the abundant proteins. Two isoforms of OmpU were found. Five operons are proposed and seven hypothetical proteins were experimentally confirmed. Comparisons are made with protein 2-D gels for a classical strain and to microarray analysis available for the N16961 El Tor strain. New results were obtained from the proteome analysis, indicating an abundance of periplasmic ABC transporter proteins not found in microarray studies.

Bacterial Proteins↗

Failure of eruption of first and second permanent molars.

Failure of eruption of permanent molars is an uncommon condition with a range of possible causative factors. This retrospective study of 35 pediatric subjects assesses the influence of these factors in the prognosis. The study aims to broaden our understanding of an abnormality, which has a considerable clinical impact, and proposes a treatment protocol for the management of these patients.

Adolescent↗

The Vibrio cholerae haemolysin anion channel is required for cell vacuolation and death.

Several strains of Vibrio cholerae secrete a haemolytic toxin of 63 kDa, termed V. cholerae cytolysin (VCC). This toxin causes extensive vacuolation and death of cells in culture and forms an anion-selective channel in planar lipid bilayers and in cells. Here, we identify inhibitors of the VCC anion channel and show that the formation of the anion channel is necessary for the development of the vacuoles and for the cell death induced by this toxin. Using markers of cell organelles, we show that vacuoles derive from different intracellular compartments and we identify the contribution of late endosomes and of the trans-Golgi network in vacuole biogenesis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗