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

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

Atomic and itinerant effects at the transition metal x-ray absorption K-pre-edge exemplified in the case of V2_2O3_3

X-ray absorption spectroscopy is a well established tool for obtaining information about orbital and spin degrees of freedom in transition metal- and rare earth-compounds. For this purpose usually the dipole transitions of the L- (2p to 3d) and M- (3d to 4f) edges are employed, whereas higher order transitions such as quadrupolar 1s to 3d in the K-edge are rarely studied in that respect. This is due to the fact that usually such quadrupolar transitions are overshadowed by dipole allowed 1s to 4p transitions and, hence, are visible only as minor features in the pre-edge region. Nonetheless, these features carry a lot of valuable information, similar to the dipole L-edge transition, which is not accessible in experiments under pressure due to the absorption of the diamond anvil pressurecell. We recently performed a theoretical and experimental analysis of such a situation for the metal insulator transition of (V(1-x)Crx)2O3. Since the importance of the orbital degrees of freedom in this transition is widely accepted, a thorough understanding of quadrupole transitions of the vanadium K-pre-edge provides crucial information about the underlying physics. Moreover, the lack of inversion symetry at the vanadium site leads to onsite mixing of vanadium 3d- and 4p- states and related quantum mechanical interferences between dipole and quadrupole transitions. Here we present a theoretical analysis of experimental high resolution x-ray absorption spectroscopy at the V pre-K edge measured in partial fluorescence yield mode for single crystals. We carried out density functional as well as configuration interaction calculations in order to capture effects coming from both, itinerant and atomic limits

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

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

Alteração do Transporte de Ácido Úrico na Glicosúria Renal Familiar e Expressão de SGLT2 no Rim Normal e Patológico

Familial renal glucosuria (FRG) is a rare co -dominantly inherited benign phenotype characterized by the presence of glucose in the urine. It is caused by mutations in the SLC5A2 gene that encodes SGLT2, a Na+ -glucose co -transporter. The purpose of our current work was twofold: to characterize the molecular and phenotype findings of an FRG cohort and, in addition, to detail the SGLT2 expression in the adult human kidney. The phenotype of FRG pedigrees was evaluated using direct sequencing for the identification of sequence variations in the SLC5A2 gene. The expression of SGLT2 in the adult human kidney was studied by immunofluorescence on kidney biopsy specimens. In the absence of renal biopsies from FRG individuals, and in order to evaluate the potential disruption of SGLT2 expression in a glucosuric nephropathy, we have selected cases of nucleoside analogues induced proximal tubular toxicity. We identified six novel SLC5A2 mutations in six FRG pedigrees and described the occurrence of hyperuricosuria associated with hypouricaemia in the two probands with the most severe phenotypes. Histopathological studies proved that SGLT2 is localized to the brush -border of the proximal tubular epithelia cell and that this normal pattern was found to be disrupted in cases of nucleoside analogues induced tubulopathy. We present six novel SLC5A2 mutations, further contributing to the allelic heterogeneity in FRG, and identified hyperuricosuria and hypouricaemia as part of the FRG phenotype. SGLT2 is localized to the brush -border of the proximal tubule in the adult human normal kidney, and aberrant expression of the co -transporter may underlie the glucosuria seen with the use of nucleoside analogues