Fatal anaphylactic sting reaction in a patient with mastocytosis

We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a `prophylactic' VIT. Copyright (C) 2008 S. Karger AG, Basel

Polymorphisms in base excision repair genes and thyroid cancer risk

We wish to thank Luisa Manso Oliveira, Lylliane Luz, Silvia Morgado Amaro and Maria Catarina Soveral for technical support. This study was supported by the Center for Research in Human Molecular Genetics (CIGMH), Projects PTDC/SAU-OSM/105572/2008, PTDC/SAU-ESA/102367/2008 and PTDC/QUI/67522/2006 from Fundacao para a Ciencia e Tecnologia (FCT) and Fundacao Calouste Gulbenkian (Grant 76438/2006). The grants to M. Pingarilho (SFRH/BD/22612/2005) from FCT are also acknowledgedThyroid cancer (TC) is the most frequent endocrine malignancy, accounting however for only 1-2\% of all human cancers, and tilt: best-established risk factor for TC is radiation exposure, particularly during childhood. Since the BER pathway seems to play an important role in the repair of DNA damage induced by IR and other genotoxicants, we carried out a hospital-based case-control study in order to evaluate the potential modifying role of 6 BER polymorphisms on the individual susceptibility to non-familial TC in 109 TC patients receiving iodine-131, and 217 controls matched for age ( 2 years), gender and ethnicity. Our results do not reveal a significant involvement of XRCCI Arg194Trp and Arg399Gln, OGGI Ser326Cys, APEXI Asp148Glu, MUTYH Gln335His and,PARPI Val762Ala polymorphisms on the individual susceptibility towards TC, mostly in aggreement with the limited available evidence. By histological stratification analyis, we observed that the association between the presence of heterozygozity in the MUTYH Gln335His polymorphism and TC risk almost reached significance for the papillary subtype of TC. This was the first time that the putative association between this polymorphism and TC susceptibility was evaluated. However, since the sample size was modest, the possibility of a type I error should not be excluded and this result should, therefore, be interpreted with caution. More in depth studies involving larger populations should be pursued in order to further clarify the potential usefulness of the MUTYH Gln335His genotype as a predictive biomarker of susceptibility to TC and the role of the remaining BER polymorphisms on TC susceptibility.publishersversionpublishe

Temperature and pressure-induced spin-state transitions in LaCoO3

We report the continuous variation of the spin moment of cobalt in LaCoO3 across its temperature and pressure-induced spin transitions evidenced with K\beta emission spectra. The first thermal transition is best described by a transition to an orbitally nondegenerate intermediate spin (S=1) state. In parallel, continuous redistribution of the 3d electrons is also indicated by partial fluorescence yield X-ray absorption spectra. At high pressure, our study confirms that the material becomes low spin between 40 and 70 kbar at room temperature

MX100, a new Escherichia coli tester strain for use in genotoxicity studies

The development of a new Escherichia coli tester strain for use in metabolic and mechanistic studies of genotoxins, strain MR2101/pKR11, has recently been reported. This strain, a derivative of the E.coli K12 laboratory strain AB1157, has sensitivity towards the detection of base-substitution mutagenesis, monitored by the reversion of arginine auxotrophy [argE3, (ochre)]. Besides arginine, MR2101/pKR11 is auxotrophic for histidine (hisG4), leucine (leuB6), proline (ΔproA) and threonine (thr-1). MX100 was developed to overcome the auxotrophy for four amino acids of MR2101/pKR11 which are non-essential for the mutagenic responsiveness of the strain. We restored the biosynthesis for these four amino acids in MR2101/pKR11, resulting in strain MX100. This strain showed an almost 2-fold increase in mutagenic activity relative to MR2101/pKR11 with a set of diagnostic mutagens (aflatoxin B1, benzo[α]pyrene, 4-nitroquinoline-1-oxide, 2,7-dimethyl-benz[a]anthracene and others) and was further characterized with other types of mutagens in which it showed sensitivity towards the detection of oxidative (H2O2, t-butyl-hydroperoxide, cumene-hydroperoxide, KO2) and carbonyl mutagens (methylglyoxal, malondialdehyde). As MX100 seems to have the right characteristics of a versatile genotoxicity tester strain and due to the extensive genetic and physiological knowledge of E.coli K12 in general and AB1157 in particular, we propose that MX100 could serve as mother strain for the development of specialized tester strains, of interest in studies of metabolism and/or mechanism of action of genotoxic carcinogens.publishersversionpublishe

The role of GSTA2 polymorphisms and haplotypes in breast cancer susceptibility: A case-control study in the Portuguese population

We wish to thank Luisa Manso Oliveira, Lylliane Luz, Silvia Morgado Amaro and Maria Catarina Soveral for technical support. Center for Research in Human Molecular Genetics (CIGMH), Projects POCTI/QUI/57110/2004 from Fundacao da Ciencia e Tecnologia (FCT) and Fundacao Calouste Gulbenkian (Grant 69405) support our current research. The PhD grant SFRH/BD/17828/2004 from FCT is also acknowledged.Glutathione-S-transferases (GSTs) are a superfamily of phase II metabolizing enzymes that catalyse the detoxification of a large range of endogenous and exogenous toxic compounds, playing an important role in protecting cells against damage, through glutathione conjugation with electrophilic substances. Polymorphic variation in these enzymes that affect its activity seems to be related to individual susceptibility to various human diseases, including cancer. Of the GST super-family, the alpha class GSTs have commonly been described as one of the most versatile class, since it is responsible for detoxification of compounds such as bilirubin, bile acids and penicillin, thyroid and steroid hormones, allowing its solubilization and storage in the liver. Among the alpha class, GSTA1 and GSTA2 isoforms are the most widely expressed in human tissues. Additionally, these enzymes can catalyse conjugation of the nitrogen mustard group of alkylating anticancer drugs, some heterocyclic amines and alpha,beta-unsaturated aldehydes. Since some risk factors for increased breast cancer risk could be related to high production of reactive oxygen species during the metabolism of estrogens by catechol estrogens, or to the exposure to genotoxic compounds, and some of these toxic compounds are usually metabolized by GSTA2, we carried out a hospital based case-control study in a Caucasian Portuguese population (291 breast cancer patients without familiar history of breast cancer and 547 controls matched for age, sex and ethnicity) in order to evaluate the potential modifying role of three non-synonymous polymorphisms in the GSTA2 gene (P110S Ex 5+56C>T;, rs2234951; S112T Ex5+63G>C, rs2180314 and E210A Ex7+83A>C, rs6577) on the individual susceptibility to breast cancer. Our data show that the Studied polymorphisms are in strong linkage disequilibrium, but no association was observed between individual GSTA2 polymorphisms and haplotypes and individual susceptibility to breast cancer.publishersversionpublishe

Identification of genetic determinants associated with susceptibility and therapeutic efficacy in Philadelphia-negative Myeloproliferative Neoplasms

Poster presented at the Scientific Toxomics Meeting, 28 September 2015, Lisbon, Portugal

Resonant inelastic x-ray scattering in single-crystal superconducting PrFeAsO0.7

Resonant inelastic x-ray scattering (RIXS) spectra at the Fe K-edge were measured for a single crystal of the iron oxypnictide superconductor PrFeAsO0.7 (Tc=42 K). They disclose a weak, broad feature centered around 4.5 eV energy loss, which is slightly resonantly enhanced when the incident energy is tuned in the vicinity of the 4p white line. We tentatively ascribe it to the charge-transfer excitation between As 4p and Fe 3d.Comment: 2 pages, 2 figure

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: the role of base excision repair genes polymorphisms

Sob uma licença CC-BY-NC-ND - http://creativecommons.org/licenses/by-nc-nd/4.0/The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8‑oxoguanine DNA glycosylase 1, poly (ADP‑ribose) polymerase (PARP) 1, PARP4 and X‑ray repair cross‑complementing 1 (XRCC1)] in a case‑control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN‑MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single‑nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2‑positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN‑MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.info:eu-repo/semantics/publishedVersio