bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients
Authors: Etienne‐Grimaldi Marie‐Christine , Milano Gérard , Maindrault‐Gœbel Frédérique , Chibaudel Benoist , Formento Jean‐Louis , Francoual Mireille , Lledo Gérard , André Thierry , Mabro May , Mineur Laurent , Flesch Michel , Carola Elisabeth , De Gramont Aimery 
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics. WHAT THIS STUDY ADDS • This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C→T and 1298A→C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively.• Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTπ 105Ile→Val and XPD 751Ly→Gln) influenced progression‐free survival.• These results corroborate the observation that response was related to the cumulative FU dose, whereas progression‐free survival was related to the cumulative oxaliplatin dose.AIMS To test prospectively the predictive value of germinal gene polymorphisms related to fluorouracil (FU) and oxaliplatin (Oxa) pharmacodynamics on toxicity and responsiveness of colorectal cancer (CRC) patients receiving FOLFOX therapy.METHODS Advanced CRC patients (n= 117) receiving FOLFOX 7 therapy were enrolled. Gene polymorphisms relevant for FU [thymidylate synthase (TYMS, 28 bp repeats including the G→C mutation + 6 bp deletion in 3'UTR), methylenetetrahydrofolate reductase (MTHFR, 677C→T, 1298A→C), dihydropyrimidine deshydrogenase (IVS14+1G→A) and Oxa: glutathione S‐transferase (GST) π (105Ile→Val, 114Ala→Val), excision repair cross‐complementing group 1 (ERCC1) (118AAT→AAC), ERCC2 (XPD, 751Lys→Gln) and XRCC1 (399Arg→Gln)] were determined (blood mononuclear cells).RESULTS None of the genotypes was predictive of toxicity. Response rate (54.7% complete response + partial response) was related to FU pharmacogenetics, with both 677C→T (P= 0.042) and 1298A→C (P= 0.004) MTHFR genotypes linked to clinical response. Importantly, the score of favourable MTHFR alleles (677T and 1298C) was positively linked to response, with response rates of 37.1, 53.3, 62.5 and 80.0% in patients bearing no, one, two or three favourable alleles, respectively (P= 0.040). Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression‐free survival, with a better outcome in patients bearing GSTπ 105 Val/Val genotype or XPD 751Lys‐containing genotype (P= 0.054).CONCLUSIONS These results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms.
The fundamental contribution of William Bate Hardy to shape the concept of mast cell heterogeneity
Authors: Crivellato Enrico , Ribatti Domenico 
Published: October 2009

SummaryThis review article acknowledges the pioneering contribution of William Bate Hardy in shaping the concept of mast cell heterogeneity. In two outstanding papers, published in 1894 and 1895, he focussed on the ‘wandering cells’ (the modern leucocytes) in different mammalian species and distinguished two types of granular basophil cells, i.e., the coarsely granular basophil cells and the splanchnic basophil cells. These corresponded to the populations of connective tissue‐type and mucosal mast cells, respectively, described 70 years later by Enerbäck in rodents. Among the coarsely granular basophil cells, he also differentiated those cells which populated the serosal cavities – the so‐called coelomic coarsely granular basophil cells – from the common coarsely granular basophil cells, which were localized in the connective tissues. He stated that the granular basophil cells presented with different morphological and histochemical characteristics in diverse animal species as well as at different anatomical sites. Remarkably, he performed a series of functional experiments on the basophil cells as well as the other wandering cells, and suggested the view that different granular basophil cells might express functional specializations.
Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans
Authors: De Roock S. , Van Elk M. , Van Dijk M. E. A. , Timmerman H. M. , Rijkers G. T. , Prakken B. J. , Hoekstra M. O. , De Kleer I. M. 
Published: October 2009

SummaryBackground
Trials with probiotic lactic acid bacteria have yielded different results, which may be due to the strains used. Lactobacilli and bifidobacteria are known to be potent modulators of the immune system. The capacity of these bacteria used as probiotics to influence both T helper type 1 (Th1)‐ and Th2‐mediated diseases has been shown before. However, the ability of strains to induce forkhead box P3 (FOXP3+) expressing regulatory T cells has not yet been investigated.Objective
Test the inherent differences between strains in their capacity to induce functional regulatory T cells in human peripheral blood mononuclear cells (PBMC).Methods
Human PBMC were co‐cultured in vitro with either Bifidobacterium lactis W51, Lactobacillus acidophilus W55 or Lactobacillus plantarum W62 or an Escherichia coli control strain. The percentage of FOXP3+ cells, the origin of the induced cells and the functionality of these cells were assessed.Results
Probiotic strains differ in their capacity to induce regulatory T cells. FOXP3+ cells were induced from CD25− cells and were able to suppress effector T cells. Naturally occurring regulatory T cells were not affected by co‐culture with lactobacilli. IL‐10 concentrations found in the supernatant showed a trend towards the same differences between strains. Blockade of IL‐10 did not influence the up‐regulation of FOXP3. No differences between lactic acid bacteria were found in IL‐17, IFN‐γ or IL‐13.Conclusions
Some probiotic strains are potent inducers of regulatory cells, while others are not. The clear differences between strains imply that an in vitro characterization of probiotic strains before application is recommended. Cite this as: S. de Roock, M. van Elk, M. E. A. van Dijk, H. M. Timmerman, G. T. Rijkers, B. J. Prakken, M. O. Hoekstra and I. M. de Kleer, Clinical & Experimental Allergy, 2010 (40) 103–110.
The effect of oral steroids with and without vitamin D3 on early efficacy of immunotherapy in asthmatic children
Authors: Majak P. , Rychlik B. , Stelmach I. 
Published: October 2009

SummaryBackground
The possibility of additional strategies to enhance the effectiveness of specific immunotherapy (SIT) is highly attractive.Aim
The aim of our study was to assess the influence of oral corticosteroids and oral corticosteroids combined with vitamin D3 on the early clinical and immunological effects of SIT.Methods
It was a randomized, double‐blind, placebo‐controlled trial conducted in 54 asthmatic children allergic to house dust mites. Intervention was based on receiving a single dose of oral steroid, with or without vitamin D3, or placebo only on the day of the build‐up phase of SIT.Results
After 12 months of SIT, the median daily inhaled corticosteroid (ICS) dose, which controls the symptoms of asthma, was reduced by 25% in the steroid group. However, a 50% reduction of the median daily ICS dose was observed in the control group. The clinical effects of SIT were not affected in the steroid+D3 group. Concomitantly, we found that intervention with prednisone significantly impaired the induction of T regulatory lymphocytes. Importantly, the clinical and immunological effects of SIT were not affected by intervention with steroids administered with vitamin D3.Conclusions
Our study failed to show a beneficial effect of oral corticosteroids on allergen‐specific immunotherapy. We observed that the combined administration of a corticosteroid drug and allergen extract suppressed the early clinical and immunological effects of SIT and that vitamin D3 prevented this ‘adverse’ influence of steroids.
Suppression of gastric acid increases the risk of developing Immunoglobulin E‐mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model
Authors: Riemer A. B. , Gruber S. , Pali‐Schöll I. , Kinaciyan T. , Untersmayr E. , Jensen‐Jarolim E. 
Published: October 2009

SummaryBackground
Hypersensitivity reactions towards non‐steroidal anti‐inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac‐specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti‐acid medication as a risk factor for sensitization against food proteins.Objective
Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm.Methods
We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays.Results
Only mice receiving albumin‐coupled diclofenac under gastric acid suppression developed anti‐diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti‐diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo.Conclusion
Gastric acid suppression was found to be a causative mechanism in the induction of IgE‐mediated diclofenac allergy. Cite this as: A. B. Riemer, S. Gruber, I. Pali‐Schöll, T. Kinaciyan, E. Untersmayr and E. Jensen‐Jarolim, Clinical & Experimental Allergy, 2010 (40) 486–493.
The effect of ultrasonic removal of various root‐end filling materials
Authors: Pirani C. , Iacono F. , Chersoni S. , Sword J. , Pashley D. H. , Tay F. R. , Looney S. , Gandolfi M. G. , Prati C. 
Published: October 2009

AbstractAim  To compare residual root‐end filling material in apical root‐end cavities following their removal with ultrasonic retrotips.Methodology  Thirty single‐rooted teeth were filled with Thermafil and AH Plus sealer. Root‐ends were resected at 90°, 3 mm from the apex. Root‐end cavities were prepared with diamond burs and ultrasonic retrotips and filled with one of three filling materials: group I: Retro‐TC (calcium silicate‐based cement), group II: IRM (Dentsply, Germany), group III: Vitrebond (3M ESPE, USA). After 30 days of storage, ultrasonic retrotips were used to remove materials from the root‐end cavities. The ultrasonic application time was fixed at 60 s. Polyether impressions and replicas of the root‐ends were made. Root apices and replicas were examined by one operator under a scanning electron microscope. Remnants of residual materials were evaluated using a four‐level scoring system; fractures, smear layer and exposed dentinal tubules were also examined.Results  Forty per cent of the specimens filled with Retro‐TC revealed complete removal of the material with exposure of dentinal tubules, whilst 60% contained residual cement. Twenty per cent of specimens filled with IRM were completely devoid of material, whereas 80% had retained material. Ten per cent of specimens filled with Vitrebond retained a moderate amount of material whilst 90% had substantial retention of the material. Statistically significant differences were found (P < 0.05) amongst the three groups of materials.Conclusions  Retro‐TC was successfully removed in 40% of cases using ultrasonics retrotips for 60 s, whereas IRM and Vitrebond specimens had evidence of retained material in 80% and 90% of all specimens respectively.
An in vivo comparison of working length determination of two frequency‐based electronic apex locators
Authors: Pascon E. A. , Marrelli M. , Congi O. , Ciancio R. , Miceli F. , Versiani M. A. 
Published: October 2009

AbstractAim  To compare in vivo the accuracy of two electronic apex locators (EALs) by means of digital radiographic imaging system.Methodology  Electronic working lengths of 831 canals were determined with the DentaPort ZX and Raypex 5 apex locators and confirmed radiographically. The radiographic images acquired with the aid of a digital radiographic imaging system (VisualiX eHD; Gendex Dental Systems, Des Plaines, IL, USA) were blindly analysed by two independent evaluators. The distance between the file tip and the radiographic apex was measured using dedicated software (VixWin Pro, Gendex Dental Systems, Des Plaines, IL, USA) and the mean distance achieved between different tooth type and EALs were compared statistically. Statistical analyses were performed using the t‐test for independent samples and one‐way anova with the null hypothesis set as 5%. Positive or negative values were recorded when the file tip was detected beyond or short of the radiographic apex, respectively.Results  The mean distance between file tip and radiographic apex were −1.08 ± 0.73 and −1.0 ± 0.67 mm considering DentaPort ZX and Raypex 5 groups, respectively, with no significant differences (P > 0.05). No statistically significant differences were found amongst the same tooth type when comparing both groups (P > 0.05) or amongst different teeth type in the same group (P > 0.05).Conclusions  Within the limitations of this in vivo study, the DentaPort ZX and Raypex 5 were similar in terms of accuracy.
Identification of a novel FAM83H mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta
Authors: Hyun H.‐K. , Lee S.‐K. , Lee K.‐E. , Kang H.‐Y. , Kim E.‐J. , Choung P.‐H. , Kim J.‐W. 
Published: October 2009

AbstractAim  To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known FAM83H mutation.Methodology  Mutational screening of the FAM83H on the basis of candidate gene approach was performed. All exons and exon–intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value.Results  A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of FAM83H, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control.Conclusions  Mutational analysis revealed a novel mutation in FAM83H gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.
Investigation of the root canal configuration of mandibular first molars in a Taiwan Chinese population
Authors: Chen G. , Yao H. , Tong C. 
Published: October 2009

AbstractAim  To investigate the root form and canal morphology of mandibular first molar teeth in a Taiwan Chinese population.Methodology  A total of 183 mandibular first molars were collected and examined visually through a dissecting microscope after rendering the teeth transparent. The number of roots, number of canals and canal configuration were recorded. The root canal morphology was categorized and compared according to Vertucci (1984).Results  Overall 46% of the mandibular first molars had four canals and 20% had extra‐distal roots (distolingual root). In addition, 97% of the specimens had two mesial canals and 46% had two distal canals. In total, 68% of teeth with two mesial canals had two separated apical foramina, and 33% of teeth with two distal canals had two apical foramina. The most common canal configurations (Vertucci, 1984) of mesial roots were type 4 (46%) and type 2 (23%). Type 1 was encountered in 54% of the distal roots.Conclusions  The frequency of the extra‐distal root on the mandibular first molar was 20%, and the incidence of three canals (Vertucci’s type 8 classification) with separate apical foramina at the apex of the mesial root was 6%. The three‐rooted variation of the mandibular first molar appears to be a genetic characteristic of an Asiatic racial background.
Bridging the gap between community ecology and historical biogeography: niche conservatism and community structure in emydid turtles
Authors: STEPHENS P. R. , WIENS J. J. 
Published: October 2009

AbstractHistorical (phylogenetic) biogeography and community ecology were once integrated as part of the broader study of organismal diversity, but in recent decades have become largely separate disciplines. This is unfortunate because many patterns studied by community ecologists may originate through processes studied by historical biogeographers and vice versa. In this study, we explore the causes of a geographic pattern of community structure (habitat use) in the emydid turtle assemblages of eastern North America, with more semi‐terrestrial species of the subfamily Emydinae in the north and more aquatic species of Deirochelyinae in the south. Specifically, we address the factors that prevent northern emydines from invading southern communities. We test for competitive exclusion by examining patterns of range overlap, and test for the role of niche conservatism using analyses of climatic and physiological data based on a multilocus molecular phylogeny. We find no support for competitive exclusion, whereas several lines of evidence support the idea that niche conservatism has prevented northern emydines from dispersing into southern communities. Our results show how understanding the causes of patterns of historical biogeography may help explain patterns of community structure.
Bacterial chemoattraction towards jasmonate plays a role in the entry of Dickeya dadantii through wounded tissues
Authors: Antunez‐Lamas Maria , Cabrera Ezequiel , Lopez‐Solanilla Emilia , Solano Roberto , González‐Melendi Pablo , Chico Jose Manuel , Toth Ian , Birch Paul , Pritchard Leighton , Liu Hui , Rodriguez‐Palenzuela Pablo 
Published: October 2009

SummaryJasmonate is a key signalling compound in plant defence that is synthesized in wounded tissues. In this work, we have found that this molecule is also a strong chemoattractant for the phythopathogenic bacteria Dickeya dadantii (ex‐Erwinia chysanthemi). Jasmonic acid induced the expression of a subset of bacterial genes possibly involved in virulence/survival in the plant apoplast and bacterial cells pre‐treated with jasmonate showed increased virulence in chicory and Saintpaulia leaves. We also showed that tissue wounding induced bacterial spread through the leaf surface. Moreover, the jasmonate‐deficient aos1 Arabidopsis thaliana mutant was more resistant to bacterial invasion by D. dadantii than wild‐type plants. These results are consistent with the hypothesis that sensing jasmonic acid by this bacterium helps the pathogen to ingress inside plant tissues.
SpoIIIE and a novel type of DNA translocase, SftA, couple chromosome segregation with cell division in Bacillus subtilis
Authors: Kaimer Christine , González‐Pastor José Eduardo , Graumann Peter L. 
Published: October 2009

SummaryCell division must only occur once daughter chromosomes have been fully separated. However, the initiating event of bacterial cell division, assembly of the FtsZ ring, occurs while chromosome segregation is still ongoing. We show that a two‐step DNA translocase system exists in Bacillus subtilis that couples chromosome segregation and cell division. The membrane‐bound DNA translocase SpoIIIE assembled very late at the division septum, and only upon entrapment of DNA, while its orthologue, SftA (YtpST), assembled at each septum in B. subtilis soon after FtsZ. Lack of SftA resulted in a moderate segregation defect at a late stage in the cell cycle. Like the loss of SpoIIIE, the absence of SftA was deleterious for the cells during conditions of defective chromosome segregation, or after induction of DNA damage. Lack of both proteins exacerbated all phenotypes. SftA forms soluble hexamers in solution, binds to DNA and has DNA‐dependent ATPase activity, which is essential for its function in vivo. Our data suggest that SftA aids in moving DNA away from the closing septum, while SpoIIIE translocates septum‐entrapped DNA only when septum closure precedes complete segregation of chromosomes.
Streptococcus mutans autolysin AtlA is a fibronectin‐binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis
Authors: Jung Chiau‐Jing , Zheng Quan‐Hau , Shieh Ya‐Hsiung , Lin Chi‐Shuan , Chia Jean‐San 
Published: October 2009

SummaryStreptococcus mutans, a commensal of the human oral cavity, can survive in the bloodstream and cause infective endocarditis (IE). However, the virulence factors associated with this manifestation of disease are not known. Here, we demonstrate that AtlA, an autolysin of S. mutans is a newly identified fibronectin (Fn) binding protein and contributes to bacterial resistance to phagocytosis and survival in the bloodstream. Interestingly, prior exposure to plasma at low concentrations was sufficient to enhance bacterial survival in the circulation. Calcium ions at physiological plasma concentrations induced maturation of AtlA from the 104–90 kDa isoform resulting in increased Fn binding and resistance to phagocytosis. An isogenic mutant strain defective in AtlA expression exhibited reduced survival and virulence when tested in a rat model of IE compared with the wild‐type and complemented strains. The data presented suggest that plasma components utilized by S. mutans enhanced survival in the circulation and AtlA is a virulence factor associated with infective endocarditis.
The γ‐glutamylcysteine synthetase gene of Leishmania is essential and involved in response to oxidants
Authors: Mukherjee Angana , Roy Gaétan , Guimond Chantal , Ouellette Marc 
Published: October 2009

SummaryGamma‐glutamylcysteine synthetase, encoded by the GSH1 gene, is the rate‐limiting enzyme in the biosynthesis of glutathione and of trypanothione in Leishmania. The importance of GSH1 was assessed by generating GSH1 null mutants in Leishmania infantum. Removal of even a single wild‐type allelic copy of GSH1 invariably led to the generation of an extra copy of GSH1, maintaining two intact wild‐type alleles. However, by first supplementing the parasites with a rescue plasmid, we succeeded in obtaining both a single and null chromosomal GSH1 mutants. Parasites with one intact GSH1 chromosomal allele lost the rescuing plasmid but not the double knockout, when grown in the absence of antibiotic, indicating the essentiality of the GSH1 gene in Leishmania. Heterozygous mutants with one allele‐inactivated transcribed less GSH1 mRNA and synthesized less glutathione and trypanothione. These mutants were more susceptible to oxidative stresses in vitro as promastigotes and showed decreased survival inside activated macrophages producing reactive oxygen or nitrogen species. These mutants showed a significant decreased survival in the presence of antimony (SbV) compared with control cells. All phenotypes were reverted in the add‐back mutant, thus proving the importance of thiols in dealing with oxidants including the action of antimonials.