Role of microRNAs in the predisposition to gastrointestinal malignancies

MicroRNAs(miRNAs)are highly deregulated in cancer and play a role in the initiation of tumorigenesis.Recently,miRNAs have attracted attention in gastrointestinal(GI)cancers.Single nucleotide polymorphisms(SNPs)could affect the genes involved in each step of miRNA biosynthesis.Several metaanalyses of case-control studies have assessed the association between miRNA“pathway”gene-SNPs(including biosynthesis regulators and binding sites)and susceptibility to GI cancers.We present in this mini-review the current knowledge on the association between miRNAs“pathway”genes and GI cancer predisposition.The interaction between miRNA/regulators/binding site-SNPs and environmental as well as genomic factors is an interesting field that should be exploited in future studies.     

Roles of Amino Acids 161 to 179 in the PSE-4 Ω Loop in Substrate Specificity and in Resistance to Ceftazidime

The PSE-4 enzyme is a prototype carbenicillin-hydrolyzing enzyme exhibiting high activity against penicillins and early cephalosporins. To understand the mechanism that modulates substrate profiles and to verify the ability of PSE-4 to extend its substrate specificity toward expanded-spectrum cephalosporins, we used random replacement mutagenesis to generate six random libraries from amino acids 162 to 179 in the Ω loop. This region is known from studies with TEM-1 to be implicated in substrate specificity. It was found that the mechanism modulating ceftazidime hydrolysis in PSE-4 was different from that in TEM-1. The specificity of class 2c carbenicillin-hydrolyzing enzymes could not be assigned to the Ω loop of PSE-4. Analysis of the percentage of functional enzymes revealed that the hydrolysis of ampicillin was more affected than hydrolysis of carbenicillin by amino acid substitutions at positions 162 to 164 and 165 to 167.β-Lactam hydrolysis by the ubiquitous bacterial β-lactamases represents the most common biochemical mechanism of resistance engineered by bacteria to protect themselves against the bactericidal effect of β-lactam antibiotics. Based upon amino acid sequence alignments, four distinct classes of β-lactamases can be distinguished (2, 3, 5, 16). Classes A, C, and D are serine β-lactamases, which undergo acylation by the substrate β-lactam ring. Those in class B are zinc-catalyzed β-lactamases.TEM-1-derived extended-spectrum β-lactamases are numerous and widespread (6) because of the intensive usage of expanded-spectrum cephalosporins and other compounds resistant to the usual β-lactamases. The capacity of TEM-1 to modify its substrate specificity represents a major clinical problem, and work to understand the mechanisms modulating this specificity was done previously with this enzyme (4, 11, 18, 19, 21, 26–28). Amino acid substitutions and pentapeptide insertion in the Ω loop of TEM-1 (residues 162–179) were found to increase the level of activity toward ceftazidime and subsequently to increase the level of ceftazidime resistance (9, 18, 19, 21). The Ω loop is a secondary structural element having a small distance between segment termini and is known to form a part of the active site; it also contains the catalytic residue Glu166, which is implicated in the deacylation step.Studies of the capacity of other related class A β-lactamase mutants to appear with modifications in substrate specificity have been poorly characterized. Because resistance to expanded-spectrum cephalosporins is still developing with the identification of newer β-lactamases, it is important to understand how substrate specificity can be modified in other class A β-lactamases and to determine if the genetic mechanism modulating substrate specificity could be generalized to all other members of this class.PSE-4 is a class A β-lactamase classified in the group 2c of Bush et al. (3). The particularity of these enzymes is the ability to hydrolyze carbenicillin as efficiently or better than benzylpenicillin. To investigate the potential of PSE-4 to extend its substrate specificity toward expanded-spectrum cephalosporins and to identify potential determinants of substrate specificity for ampicillin and carbenicillin, we used random replacement mutagenesis to randomize all of the amino acids of the Ω loop. Screening of the libraries with penicillins and the expanded-spectrum cephalosporin ceftazidime permitted the identification of subtle differences between ampicillin and carbenicillin hydrolysis, the former activity being more affected by amino acid substitution. It was also found that the mechanisms modulating ceftazidime hydrolysis were different in PSE-4 from those in TEM-1.     

Value of deanxit in the treatment of anxiety and depression due to pharyngeal paraesthesia

Background：Alotoffactorsmaycontributetothedevelop－mentofpharyngealparaesthesiawhichischaracterizedbypharyngealsymptomsandabnormalmentalmanifestations．InHilger＇sopinion，mentalstressproducedvegetativenervedisorderbyaffectingcentralvegetativenervesystem，lowerthalam．Inthecurrentstudy，weconcludedthatanxietyanddepressionweremanifestedbypharyn－gealparaesthesia．Itcontainstwoingredients：flupentixolandmelitracen，andfunctionsbyregulatingcentralnervesystemandsignificantlyimprovedanxiety，depr…     

Decreasing the minimal duration of the attack to 1 hour: is this sufficient to increase the sensitivity of the ICHD-II diagnostic criteria for migraine in childhood?

Abstract We applied the second edition of the International Classification of Headache Disorders (ICHD-II) in 417 children (age range, 2–12 years) with chronic headaches attending a pediatric headache clinic. The initial diagnosis was made according to the ICHD-II while the final diagnosis was, based on the longitudinal intuitive clinical diagnosis (LICD), deemed to be the gold standard. The diagnosis of migraine without aura had a sensitivity of 52%, a specificity of 100% and a positive predictive value of 100%; for the diagnosis of migraine (at the one-digit level) these values were 87%, 100% and 100%, respectively. The ICHD-II criteria for migraine without aura have high specificity but low sensitivity in childhood, even considering the minimal duration of the attacks to be 1 hour. Other factors, such as the existence of subgroup 2.4 (probable tension-type headache), are responsible for the low sensitivity of ICHD-II criteria for the diagnosis of migraine without aura in patients of this age group.     

Implication of γδ T cells in the human immune response to cytomegalovirus

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.     

Quality of the Live Birth Information System in the state of Paraná, from 2000 to 2005

This study analyzed the quality of the Live Birth Information System in the State of (SINAC) Paraná, Brazil, from 2000 to 2005, through the percentage of undeclared variables, using a database provided by the State Health Department. Quality was analyzed using the following scale: excellent, undeclared percentage<1%; good between 1% and 2.99%; regular between 3% and 6.99%; and poor>7%. The quality in completing the SINAC in Paraná was excellent, especially as of year 2003. The mothers' occupation, classified as regular and poor, was the variable with the lowest quality in all Regional Health Departments. Live births, stillbirths, and race/color varied between poor and excellent quality. There is a need to improve the quality of the variables marital status and stillbirths in all Regional Health Departments. The excellence of the SINAC demonstrated its potential as a source of health information in Paraná.     

Foreword to “the girl in the raindrop”

The issue of whether suicide can be a good death was separated into two different questions: (1) can suicide be an appropriate death, and (2) can suicide be a rational death? Several definitions of an “appropriate” death were proposed, and suicide was seen as potentially appropriate. Similarly, several criteria for rationality were proposed and suicide was seen as sometimes meeting these criteria. Thus, suicide can be sometimes conceptualized as a “good” death.