Prognostic impact of RAS mutations in patients with myelodysplastic syndrome

RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10–15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild‐type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol. 88:365–369, 2013. © 2013 Wiley Periodicals, Inc.     

Characteristics and outcome in nonagenarians admitted in general internal medicine and other specialties

SummaryTo describe the characteristics of nonagenarians admitted to the surgical and medical divisions at a tertiary hospital and compare them with nonagenarians admitted to other hospital care services.MethodsA retrospective study of all hospital discharge episodes via the registry of the Basic Minimum Data Set at the Hospital General Universitario de Alicante from January 2007 until December 2011.ResultsOf the 165,870 hospitalizations, 2461 (1.5%) were nonagenarians. The highest number of admitted nonagenarians was in the Division of General Internal Medicine (DGIM) (n = 751), followed by the short stay unit (SSU) (n = 633). The rate of nonagenarians per 100 admissions to the DGIM was 10.2, significantly higher than that of those admitted to the SSU (6.2) (p < 0.001), the service of orthopedic and trauma surgery (2.2) (p < 0.001), and other specialties. Females comprised 64.8% of the nonagenarians. Mortality was 17% for the nonagenarians admitted, while for those admitted to the DGIM it was 27.7%. Those hospitalized in the SSU had a lower risk of death during hospitalization (8.1%) (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.16–0.32) and a greater risk of being admitted for diseases and disorders of the circulatory system (OR: 1.58, 95% CI: 1.22–2.05), particularly for heart failure and shock (OR: 1.82, 95% CI: 1.30–2.53), and being discharged with home hospitalization (OR: 8.05, 95% CI: 5.5–11.8).ConclusionsNonagenarian patients represent a tenth of those admitted to the DGIM. The profile of nonagenarians admitted to the DGIM is different from other hospital services. Hospital mortality for nonagenarians admitted to the DGIM is high and superior to other hospital services.     

Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?

AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential pro     

Tridimensional ultrastructure and glycolipid pattern studies of Trypanosoma dionisii

Trypanosoma (Schizotrypanum) dionisii is a non-pathogenic bat trypanosome closely related to Trypanosoma cruzi, the etiological agent of Chaga's disease. Both kinetoplastids present similar morphological stages and are able to infect mammalian cells in culture. In the present study we examined 3D ultrastructure aspects of the two species by serial sectioning epimastigote and trypomastigote forms, and identified common carbohydrate epitopes expressed in T. dionisii, T. cruzi and Leishmania major. A major difference in 3D morphology was that T. dionisii epimastigote forms present larger multivesicular structures, restricted to the parasite posterior region. These structures could be related to T. cruzi reservosomes and are also rich in cruzipain, the major cysteine-proteinase of T. cruzi. We analyzed the reactivity of two monoclonal antibodies: MEST-1 directed to galactofuranose residues of glycolipids purified from Paracoccidioides brasiliensis, and BST-1 directed to glycolipids purified from T. cruzi epimastigotes. Both antibodies were reactive with T. dionisii epimastigotes by indirect immunofluorescense, but we noted differences in the location and intensity of the epitopes, when compared to T. cruzi. In summary, despite similar features in cellular structure and life cycle of T. dionisii and T. cruzi, we observed a unique morphological characteristic in T. dionisii that deserves to be explored.     

Assessing microleakage on class V composite resin restorations after Er:YAG laser preparation varying the adhesive systems

OBJECTIVE: The aim of this study was to assess the performance of three bonding agents in preventing microleakage of class V cavities prepared and treated by Er:YAG laser associating with acid etching. BACKGROUND DATA: There has been very little research comparing the efficiency of single-component and self-etching adhesive systems in preventing microleakage of cavities prepared and conditioned with Er:YAG laser. MATERIALS AND METHODS: Thirty cavities - with occlusal margin in enamel and cervical in dentin/cementum - were prepared in sound human third molars using a short pulsed Er:YAG laser (500 mJ/5 Hz) The enamel and dentin surfaces were conditioned for 30 sec using lower dosimetries (120 mJ/4 Hz), and the samples were randomly assigned into three groups, according to the adhesive system: (I) Bond-1; (II) Prime & Bond NT; and (III) Etch & Prime 3.0. Groups I and II were acid-etched for 15 sec, and group III did not receive any acid treatment once a self-etching system was employed. Cavities were restored with a light-cured composite resin (JEK-Z250 Filtek-250), and after finishing, the samples were thermocycled, isolated with epoxy resin and nail varnish, immersed in a 0.2% Rhodamine B solution for 24 h, and sectioned longitudinally. The sections obtained were analyzed for leakage using an optical microscope connected to a computer and a video camera. We digitized the images using a special software program that allowed a quantitative evaluation of microleakage in millimeters. RESULTS: Statistical analysis using the Kruskal-Wallis test showed statistically significant difference between both margins, and the occlusal region presented better marginal sealing. Comparing the three resin bonding systems, Prime & Bond NT entirely sealed both margins, while Etch & Prime 3.0 provided the poorest overall results, showing a statistically significant difference (p < 0.01). CONCLUSION: It may be concluded that, for all the tested materials, microleakage values were higher in cervical (dentin/cementum) margins. Additionally, Prime & Bond NT provided a complete elimination of marginal infiltration at both margins, after treating the dental surface with laser irradiation associated with a sequent acid-etching.     

Competence of the human host as a reservoir for Leishmania chagasi

The failure of control programs for visceral leishmaniasis (VL) that depend on elimination of infected dogs suggests that other reservoir hosts may participate in the transmission cycle. To determine whether persons infected with Leishmania chagasi can infect the vector sand fly, laboratory-reared Lutzomyia longipalpis were allowed to feed on Brazilian subjects with active, cured, and asymptomatic VL and on asymptomatic residents of houses of persons with active VL. Of 3747 insects that had fed, 26 acquired infection from 11 of the 44 persons with active VL, but none acquired infection from the 137 asymptomatic persons. Among persons <4 years old with active VL, a history of diarrhea and higher peripheral blood neutrophil counts were independent predictors of infectivity. Further experiments using larger numbers of insects are necessary to evaluate the reservoir competence of persons with asymptomatic infections, who represent a large segment of the population of several Brazilian cities.     

Ischemia/reperfusion is an independent trigger for increasing myocardial content of mRNA B-type natriuretic peptide

This study aims to determine whether a relation exists between ischemia/reperfusion and myocardial B-type natriuretic peptide (BNP) mRNA expression independent of variations in intracavitary diastolic volume and consequently, of cardiomyocyte stretching. Twenty-three rats were subjected to the following conditions: control (C), 15 min of ischemia (I15), or ischemia plus 15 (R15), 30 (R30), or 45 (R45) min of reperfusion in the in situ hearts. Isolated hearts of sixteen additional rats (sham, n = 8; occlusion, n = 8) were perfused for studies in the absence of ventricular distension. All hearts were divided in two segments (ischemic and nonischemic). Ventricular distension was avoided by excluding the atria and mitral valves. In both experiments, BNP mRNA was quantified by real-time polymerase chain reaction in both nonischemic and ischemic regions. In the in situ hearts, myocardial BNP mRNA values at R15 (4.24 ± 0.75) in the ischemic region were higher than in other groups (C: 1.43 ± 0.81, P = 0.044; I15: 3.05 ± 0.62, P = 0.048; R30: 0.76 ± 0.84, P = 0.001; R45: 1.47 ± 0.60, P = 0.046, [analysis of variance]). In isolated hearts without ventricular distension, myocardial BNP mRNA (arbitrary units) content at R15 in ischemic regions (4.54 ± 0.26) was greater than in nonischemic regions in both occlusion (3.51 ± 0.20, P < 0.001) and sham (3.38 ± 0.25, P = 0.0001 and 3.47 ± 0.19, P = 0.0001) groups. The present data show that ischemia/reperfusion is responsible for increased BNP mRNA myocardial content independent of changes of ventricular cavity diastolic volume.     

Regulatory T cells use programmed death 1 ligands to directly suppress autoreactive B cells in vivo

The mechanisms by which regulatory T cells (T(regs)) suppress autoantibody production are unclear. Here we have addressed this question using transgenic mice expressing model antigens in the kidney. We report that T(regs) were essential and sufficient to suppress autoreactive B cells in an antigen-specific manner and to prevent them from producing autoantibodies. Most of this suppression was mediated through the inhibitory cell-surface-molecule programmed death-1 (PD-1). Suppression required PD-1 expression on autoreactive B cells and expression of the two PD-1 ligands on T(regs). PD-1 ligation inhibited activation of autoreactive B cells, suppressed their proliferation, and induced their apoptosis. Intermediate PD-1(+) cells, such as T helper cells, were dispensable for suppression. These findings demonstrate in vivo that T(regs) use PD-1 ligands to directly suppress autoreactive B cells, and they identify a previously undescribed peripheral B-cell tolerance mechanism against tissue autoantigens.