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Increased Production (increased + production)
Selected AbstractsSodium acetate enhances hydrogen peroxide production in Weissella cibariaLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2009A. Endo Abstract Aims:, To investigate hydrogen peroxide production by lactic acid bacteria (LAB) and to determine the key factors involved. Methods and Results:, Six strains of Weissella cibaria produced large amounts (2·2,3·2 mmol l,1) of hydrogen peroxide in GYP broth supplemented with sodium acetate, but very low accumulations in glucose yeast peptone broth without sodium acetate. Increased production of hydrogen peroxide was also recorded when strains of W. cibaria were cultured in the presence of potassium acetate, sodium isocitrate and sodium citrate. Oxidases and peroxidases were not detected, or were present at low levels in W. cibaria. However, strong nicotinamide adenine dinucleotide (NADH) oxidase activity was recorded, suggesting that the enzyme plays a key role in production of hydrogen peroxide by W. cibaria. Conclusions:,Weissella cibaria produces large quantities of hydrogen peroxide in aerated cultures, in a process that is dependent on the presence of acetate in the culture medium. NADH oxidase is likely the key enzyme in this process. Significance and Impact of the Study:, This is the first study showing that sodium acetate, normally present in culture media of LAB, is a key factor for hydrogen peroxide production by W. cibaria. The exact mechanisms involved are not known. [source] DNA damage in children with asthma bronchiale and its association with oxidative and antioxidative measurementsPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2009Dost Zeyrek Increased production of reactive oxygen species leading to an imbalance between the oxidative forces and the antioxidant defense systems favoring an oxidative injury has been implicated in the pathogenesis of asthma. The aim of the study was to investigate the peripheral DNA damage, and its association with oxidative and antioxidative measurements in children with asthma bronchiale. The study population contained 42 children with asthma bronchiale and 32 healthy controls. DNA damage was assessed by alkaline comet assay in peripheral lymphocytes. Plasma levels of total antioxidant status (TAS), total peroxide concentration (LOOHs), and total oxidant status (TOS) were determined. In asthma bronchiale patients, DNA damage was significantly higher than in controls (17.9 ± 11.8 AU vs. 1.2 ± 2.0 AU, p < 0.001). Plasma TOS and LOOHs were higher in patients than in healthy controls (13.4 ± 7.0 vs. 9.0 ± 3.5, p = 0.002; 9.9 ± 3.4 vs. 4.4 ± 1.5, p < 0.001, respectively). Plasma TAS level in patients was higher than in healthy controls (5.5 ± 2.5 vs. 1.0 ± 0.6, p < 0.001). DNA damage was correlated with TOS (r = 0,616, p < 0.001). The findings indicated that lymphocyte DNA damage level increases in children with asthma bronchiale. Elevated DNA damage may be related to increased oxidative stress. However, the mechanism of this association, and whether it is direct or indirect, remains to be explored. [source] Increased production of serum IgA-class antibody to lipid A in Kawasaki diseasePEDIATRICS INTERNATIONAL, Issue 1 2002Seiichiro Takeshita Abstract Background:,The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). Methods:,We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. Results:,The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. Conclusion:,These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD. [source] Association between parasite infection and immune responses in multiple sclerosisANNALS OF NEUROLOGY, Issue 2 2007Jorge Correale MD Objective To assess whether parasite infection is correlated with a reduced number of exacerbations and altered immune reactivity in multiple sclerosis (MS). Methods A prospective, double-cohort study was performed to assess the clinical course and radiological findings in 12 MS patients presenting associated eosinophilia. All patients presented parasitic infections with positive stool specimens. In all parasite-infected MS patients, the eosinophilia was not present during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month intervals. When counts became elevated, patients were enrolled in the study. Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-,, and interferon-, production by myelin basic protein,specific peripheral blood mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3 and Smad7 expression were studied by reverse-transcriptase polymerase chain reaction. Results During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein,specific responses in peripheral blood showed a significant increase in IL-10 and TGF-, and a decrease in IL-12 and interferon-,,secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein,specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-, secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-,. Interpretation Increased production of IL-10 and TGF-,, together with induction of CD25+CD4+ FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS. Ann Neurol 2007 [source] Role of ,1-adrenoceptor in increased lipolysis in cancer cachexiaCANCER SCIENCE, Issue 7 2010Dong-xing Cao Increased production of hormone-sensitive lipase (HSL) protein has been demonstrated to be the major cause behind enhanced lipolysis in cancer cachexia. The mechanism governing this alteration is unknown and was presently investigated. This study was conducted to detect the expression of relevant receptors in the adipocytes of cancer cachexia patients, and to elucidate their implication in the increased lipolysis. Gene expressions of ,1-adrenoceptor (ADRB1), ,2-adrenoceptor (ADRB2), ,3-adrenoceptor (ADRB3), ,2C-adrenoceptor (ADRA2C), natriuretic peptide receptor A (NPRA), insulin receptor (INSR), and HSL were determined in adipose tissues of 34 patients by real-time PCR. Protein levels of ADRB1 and HSL were determined by western blot analysis. ,1-Adrenoceptor (ADRB1) was also detected by immunofluorescence staining. mRNA expressions of both ADRB1 and HSL were approximately 50% elevated selectively in the cachexia group, whereas mRNA levels of the other receptors were unchanged. ,1-Adrenoceptor (ADRB1) protein expression was 1.5-fold increased in cachexia as compared with the cancer controls, and 3-fold increased as compared with nonmalignant controls, and was confirmed as a membrane protein in adipocytes by immunofluorescence. Hormone-sensitive lipase (HSL) protein expression was 2,2.5-fold increased selectively in cachectic patients. There was a positive correlation between the protein expressions of ADRB1 and HSL. As much as approximately 50% of the variations in HSL protein expression could be explained by variations in ADRB1 protein expression. There was a link between ADRB1 protein level and lipolytic rate. Increased ADRB1 expression may account for some of the functional changes of HSL in patients with cancer cachexia. (Cancer Sci 2010) [source] Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P-glycoprotein substrates in multidrug resistant breast cancer cellsCANCER SCIENCE, Issue 11 2007Qing-Quan Li Treatment of animals bearing multidrug resistant (MDR) tumor cells with P-glycoprotein (P-gp) substrates could worsen host survival. It is assumed that this is due to increased tumor metastasis. To clarify the mechanism(s) underlying this observation, the MDR human breast cancer cell line, MCF-7/AdrR, and its sensitive parental line, MCF-7, was treated with various concentrations of P-gp substrate drugs (vincristine, paclitoxel, adriamycin) and a P-gp non-substrate drug (bleomycin) in serum-free media. Increased production of CD147, and matrix metalloproteinases (MMP)-2, -9 was observed only in MDR cancer cells exposed to P-gp substrates, as determined using real-time polymerase chain reaction, western blotting and zymography. Correspondingly, P-gp substrates significantly enhanced the in vitro invasion abilities of MCF-7/Adr cells. It was also found that the drug-induced promotion of CD147, and MMP-2, -9 was consistent with increased expression of epidermal growth factor receptor (EGFR) and that inhibition of either EGFR or P-gp activity could significantly interrupt the downstream effects, and so inhibit in vitro invasion abilities motivated by P-gp substrates. These results imply that treatment of MDR tumors with P-gp substrates could adversely affect therapeutic outcomes through modulating the production of CD147, MMP-2, -9, and EGFR, and suggest that this effect may be initiated by the transporter function of P-gp. (Cancer Sci 2007; 98: 1767,1774) [source] Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxisCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009E. Ono Abstract Background Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient. Objective The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis. Methods We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphlaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9,, 11,-prostaglandin F2 (9,, 11,-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits. Results Significantly higher concentrations of urinary LTE4 and 9,, 11,-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9,, 11,-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock. Conclusions This is a report on the significant increase in urinary LTE4 and 9,, 11,-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9,, 11,-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis. [source] Analysis of N-cadherin function in limb mesenchymal chondrogenesis in vitro,DEVELOPMENTAL DYNAMICS, Issue 2 2002Anthony M. Delise Abstract During embryonic limb development, cartilage formation is presaged by a crucial mesenchymal cell condensation phase. N-Cadherin, a Ca2+ -dependent cell,cell adhesion molecule, is expressed in embryonic chick limb buds in a spatiotemporal pattern suggestive of its involvement during cellular condensation; functional blocking of N-cadherin homotypic binding, by using a neutralizing monoclonal antibody, results in perturbed chondrogenesis in vitro and in vivo. In high-density micromass cultures of embryonic limb mesenchymal cells, N-cadherin expression level is high during days 1 and 2, coincident with active cellular condensation, and decreases upon overt chondrogenic differentiation from day 3 on. In this study, we have used a transfection approach to evaluate the effects of gain- and loss-of-function expression of N-cadherin constructs on mesenchymal condensation and chondrogenesis in vitro. Chick limb mesenchymal cells were transfected by electroporation with recombinant expression plasmids encoding wild-type or two mutant extracellular/cytoplasmic deletion forms of N-cadherin. Expression of the transfected N-cadherin forms showed a transient profile, being high on days 1,2 of culture, and decreasing by day 3, fortuitously coincident with the temporal profile of endogenous N-cadherin gene expression. Examined by means of peanut agglutinin (PNA) staining for condensing precartilage mesenchymal cells, cultures overexpressing wild-type N-cadherin showed enhanced cellular condensation on culture days 2 and 3, whereas expression of the deletion mutant forms (extracellular/cytoplasmic) of N-cadherin resulted in a decrease in PNA staining, suggesting that a complete N-cadherin protein is required for normal cellular condensation to occur. Subsequent chondrogenesis was also affected. Cultures overexpressing the wild-type N-cadherin protein showed enhanced chondrogenesis, indicated by increased production of cartilage matrix (sulfated proteoglycans, collagen type II, and cartilage proteoglycan link protein), as well as increased cartilage nodule number and size of individual nodules, compared with control cultures and cultures transfected with either of the two mutant N-cadherin constructs. These results demonstrate that complete N-cadherin function, at the levels of both extracellular homotypic binding and cytoplasmic linkage to the cytoskeleton by means of the catenin complex, is required for chondrogenesis by mediating functional mesenchymal cell condensation. © 2002 Wiley-Liss, Inc. [source] Effects of dietary fatty acids on insulin sensitivity and secretionDIABETES OBESITY & METABOLISM, Issue 6 2004Melania Manco Globalization and global market have contributed to increased consumption of high-fat, energy-dense diets, particularly rich in saturated fatty acids( SFAs). Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells by inducing their own oxidation through the reduction of lipogenic gene expression and the enhancement of the expression of those genes controlling lipid oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in non-adipocyte cells as triglycerides (TG) leading to cellular damage as a sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle cells (IMTG) derives from increased FA uptake coupled with deficient FA oxidation. High levels of circulating FAs enhance the expression of FA translocase the FA transport proteins within the myocites. The biochemical mechanisms responsible for lower fatty acid oxidation involve reduced carnitine palmitoyl transferase (CPT) activity, as a likely consequence of increased intracellular concentrations of malonyl-CoA; reduced glycogen synthase activity; and impairment of insulin signalling and glucose transport. The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG accumulation causes impairment of insulin secretion. In rat models, ,-cell dysfunction is related to increased triacylglycerol content in islets, increased production of nitric oxide, ceramide synthesis and ,-cell apoptosis. The decreased insulin gene promoter activity and binding of the pancreas-duodenum homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG effect in islets. In humans, acute and prolonged effects of FAs on glucose-stimulated insulin secretion have been widely investigated as well as the effect of high-fat diets on insulin sensitivity and secretion and on the development of type 2 diabetes. [source] Conspicuous extra-floral nectaries are inducible in Vicia fabaECOLOGY LETTERS, Issue 6 2003Edward B. Mondor Abstract Mutualistic interactions are dynamic associations that vary depending on the costs and benefits to each of the interacting parties. Phenotypic plasticity in mutualistic interactions allows organisms to produce rewards to attract mutualists when the benefits of their presence outweigh the costs of producing the rewards. In ant,plant defensive mutualisms, defences are indirect as plants produce extra-floral nectaries (EFN) to attract predatory ants to deter herbivores. Here we demonstrate that in broad bean, Vicia faba, the overall number of EFNs on a plant increases dramatically following leaf damage. In two damage treatments, removal of: (1) one-third of one leaf in a single leaf pair or (2) one-third of both halves of a single leaf pair, resulted in a 59 and 106% increase in the number of EFNs on the plants, respectively, over 1 week. We suggest that the increased production of visually conspicuous EFNs is an adaptive inducible response, to attract predatory arthropods when risk of herbivory increases. [source] Evidence of oxidative stress in bluegill sunfish (Lepomis macrochirus) liver microsomes simultaneously exposed to solar ultraviolet radiation and anthraceneENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2000Jonghoon Choi Abstract Many polycyclic aromatic hydrocarbons (PAHs) are acutely toxic to fish and other aquatic organisms in the presence of environmentally realistic intensities of solar ultraviolet radiation (SUVR). However, the biochemical mechanism of this toxicity is not well established. In this study, increased levels of both reactive oxygen species production and lipid peroxidation were hypothesized as a toxic mechanism. To test this hypothesis, the production of superoxide anion and of a lipid peroxidation product (malondialdehyde) was measured in bluegill sunfish (Lepomis machrochirus) liver microsomes. These microsomes were exposed to a representative phototoxic PAH (anthracene [ANT]) and to SUVR and normal laboratory fluorescent light (FLU) in four different combinations: FLU + no ANT, FLU + ANT, SUVR + no ANT, and SUVR + ANT. The highest mean levels of both superoxide anion and malondialdehyde production were observed in the SUVR + ANT group, and these levels were significantly different (p < 0.05) from those in all other treatment groups. We conclude that the photoinduced toxicity of ANT, and possibly of other phototoxic PAHs, manifests at least in part through lipid peroxidation after increased production of reactive oxygen species. [source] Expression of angiogenic factors in chronic myeloid leukaemia: role of the bcr/abl oncogene, biochemical mechanisms, and potential clinical implicationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2004C. Sillaber Abstract Chronic myeloid leukaemia (CML) is a stem cell disease characterized by an increased production and accumulation of clonal BCR/ABL,positive cells in haematopoietic tissues. The chronic phase of CML is inevitably followed by an accelerated phase of the disease, with consecutive blast crisis. However, depending on genetic stability, epigenetic events, and several other factors, the clinical course and survival appear to vary among patients. Recent data suggest that angiogenic cytokines such as vascular endothelial growth factor (VEGF), are up-regulated in CML, and play a role in the pathogenesis of the disease. These factors appear to be produced and released in leukaemic cells in patients with CML. In line with this notion, increased serum-levels of angiogenic growth factors are measurable in CML patients. In this study we provide an overview of angiogenic growth factors expressed in CML cells, discuss the possible pathogenetic role of these cytokines, the biochemical basis of their production in leukaemic cells, and their potential clinical implications. [source] The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory responseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2010Rossella Baggetta Abstract The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-,B is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation. [source] The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkersEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. Khademi Background:, Natalizumab affects systemic cytokine expressions and clinical course in relapsing,remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP)-9 and osteopontin (OPN) in CSF, and clinical outcome measures in 22 natalizumab-treated RRMS patients. Methods:, mRNA levels of cytokines in cells were detected with real-time RT-PCR. Protein levels of OPN and MMP-9 were measured by ELISA. Results:, Natalizumab reduced CSF cell counts (P < 0.0001). Tumor necrosis factor (TNF) and interferon-, (IFN-,) mRNAs were significantly increased in PBMCs. In contrast, expressions of IFN-, and interleukin (IL)-23 were decreased but IL-10 increased in the CSF cells. OPN and MMP-9 were reduced in the CSF. Patients being in remission at baseline showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. Conclusions:, Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow increased production of the anti-inflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy. [source] Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2007Sachin Patil Abstract A high-fat diet has been shown to significantly increase the risk of the development of Alzheimer's disease (AD), a neurodegenerative disease histochemically characterized by the accumulation of amyloid beta (A,) protein in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Previously, we have shown that saturated free fatty acids (FFAs), palmitic and stearic acids, caused increased amyloidogenesis and tau hyperphosphorylaion in primary rat cortical neurons. These FFA-induced effects observed in neurons were found to be mediated by astroglial FFA metabolism. Therefore, in the present study we investigated the basic mechanism relating astroglial FFA metabolism and AD-like changes observed in neurons. We found that palmitic acid significantly increased de-novo synthesis of ceramide in astroglia, which in turn was involved in inducing both increased production of the A, protein and hyperphosphorylation of the tau protein. Increased amyloidogenesis and hyperphoshorylation of tau lead to formation of the two most important pathophysiological characteristics associated with AD, A, or senile plaques and neurofibrillary tangles, respectively. In addition to these pathophysiological changes, AD is also characterized by certain metabolic changes; abnormal cerebral glucose metabolism is one of the distinct characteristics of AD. In this context, we found that palmitic acid significantly decreased the levels of astroglial glucose transporter (GLUT1) and down-regulated glucose uptake and lactate release by astroglia. Our present data establish an underlying mechanism by which saturated fatty acids induce AD-associated pathophysiological as well as metabolic changes, placing ,astroglial fatty acid metabolism' at the center of the pathogenic cascade in AD. [source] Heat shock in the developmentally sensitive period of butterfly eyespots fails to increase fluctuating asymmetryEVOLUTION AND DEVELOPMENT, Issue 3 2003Casper J. Breuker SUMMARY Fluctuating asymmetry (FA) is considered to provide a means of evaluating developmental stability and to reflect an individual's quality or the stress experienced during development. Stress is predicted to increase the phenotypic variation of both FA and trait size. In this study we examined the effect of a particular heat shock on both FA and size of eyespots in the butterfly, Bicyclus anynana. We also examined whether those eyespots thought to be involved in partner choice and sexual selection were particularly sensitive to stress. We applied a heat shock of 39.5°C for 3 h before, during, and after a sensitive period in eyespot development. We examined the FA, variation in FA, size, and variation in size of five eyespots, two on the dorsal forewing (sexually selected traits), two on the ventral forewing, and one on the ventral hindwing (nonsexually selected traits). For each sex and treatment, the heat shock did not result in significant changes in mean trait size and FA nor in the variation of size and FA. There were no differences in the response to the heat shock between sexually and nonsexually selected traits. We discuss how the increased production of heat shock proteins, including HSP60, may have stabilized development and how this might explain the results. [source] Granulomatous rosacea and Crohn's disease in a patient homozygous for the Crohn-associated NOD2/CARD15 polymorphism R702WEXPERIMENTAL DERMATOLOGY, Issue 12 2008M. A. M. Van Steensel Abstract:, NOD2/CARD15 belongs to the N-terminal caspase recruitment domain family of proteins involved in regulating NF-kB activation in response to inflammatory stimuli transduced through Toll-like receptors. Mutations and polymorphisms in the NOD2/CARD15 gene reduce antibacterial responses and are associated with granulomatous inflammatory conditions such as Blau syndrome and early-onset sarcoidosis. The polymorphism R702W (arginine to tryptophan) is strongly associated with susceptibility to Crohn's disease in Caucasian populations. Skin abnormalities (other than cutaneous manifestations of Crohn's disease) have not been previously associated with R702W. We report on a female patient homozygous for R702W who developed granulomatous rosacea at the age of 12 years old. From the occurrence in the context of Crohn associated with R702W, we speculate that granulomatous rosacea may be an entity distinct from other forms of rosacea, which are associated with increased production of antibacterial proteins such as cathelicidin. [source] Effects of ,-aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010Karima Begriche Abstract ,-Aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this ,-amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin-independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti-inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals. [source] The effect of additives in silages of pure timothy and timothy mixed with red clover on chemical composition and in vitro rumen fermentation characteristicsGRASS & FORAGE SCIENCE, Issue 3 2003M. Hetta Abstract The aim was to compare the effects of additives on direct cut silages of pure timothy and timothy mixed with tetraploid red clover. First and second growth cuts were ensiled during three consecutive years, 1994, 1995 and 1996, either without any additive or with the addition of formic acid, or lactic acid bacteria in combination with molasses. Effects of the additives on the degradation characteristics of the herbage and the silages were analysed using an automatic in vitro gas production (GP) technique. At the end of the in vitro procedures, organic matter and neutral-detergent fibre (NDF) degradabilities were determined. The tetraploid red clover persisted in the leys during the 3 years and was the dominant species at the second growth in the mixed leys. The herbage from the mixed crops had lower dry-matter contents, higher crude protein concentrations and higher buffering capacity compared with the pure timothy at both cuts. In general, the additives reduced pH, and the concentrations of ammonium-N and acetic acid in the silages. The treated silages had a more rapid faster GP in both crops. The silages from the mixed crop benefited more from the additives compared with the grass silages. The additives affected the soluble fractions as well as the NDF degradability of the silages of the mixed crop more than those fractions of the grass silages. The addition of molasses in combination with a commercial inocula resulted in increased production of lactic acid and ethanol in silages from both crops. The silages without additives could not meet the requirements for good silages according to the standards of the Swedish dairy industry. [source] CCR5 deficiency exacerbates T-cell,mediated hepatitis in mice,HEPATOLOGY, Issue 4 2005Christophe Moreno Experimental T-cell,mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A,induced liver injury. Serum levels of CCR5 ligands and their hepatic transcript levels were significantly increased after Con A injection, whereas CCR5+ liver mononuclear cells were recruited to the liver. CCR5-deficient (CCR5,/,) mice disclosed increased mortality and liver injury following Con A administration compared with wild-type mice. CCR5,/, mice also exhibited increased production of interleukin 4, tumor necrosis factor ,, CCL3, CCL4, and CCL5, and a prominent liver mononuclear cell infiltrate, among which many cells were CCR1+. In vivo neutralization of CCR5 ligands in CCR5,/, mice afforded a protection against hepatitis only when CCL5 was neutralized. In conclusion, CCR5 deficiency exacerbates T-cell,mediated hepatitis, and leads to increased levels of CCR5 ligands and a more pronounced liver mononuclear infiltrate, suggesting that CCR5 expression can modulate severity of immunomediated liver injury. (HEPATOLOGY 2005;42:854,862.) [source] IL-6 levels decrease with SSRI treatment in patients with major depressionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2005Ayse Devrim Basterzi Abstract Objective Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression. The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors (SSRI). Method Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study. The severity of depression was measured with the Hamilton rating scale for depression. Blood samples for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase sandwich enzyme immunoassay. All patients were treated with an SSRI. Results The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline. However, IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls. Conclusion The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effect of immune serum and role of individual Fc, receptors on the intracellular distribution and survival of Salmonella enterica serovar Typhimurium in murine macrophagesIMMUNOLOGY, Issue 2 2006Hazel Uppington Summary Immune serum has a protective role against Salmonella infections in mice, domestic animals and humans. In this study, the effect of antibody on the interaction between murine macrophages and S. enterica serovar Typhimurium was examined. Detailed analysis at the single-cell level demonstrated that opsonization of the bacteria with immune serum enhanced bacterial uptake and altered bacterial distribution within individual phagocytic cells. Using gene-targeted mice deficient in individual Fc gamma receptors it was shown that immune serum enhanced bacterial internalization by macrophages via the high-affinity immunoglobulin G (IgG) receptor, Fc gamma receptor I. Exposure of murine macrophages to S. enterica serovar Typhimurium opsonized with immune serum resulted in increased production of superoxide, leading to enhanced antibacterial functions of the infected cells. However, opsonization of bacteria with immune serum did not increase either nitric oxide production in response to S. enterica serovar Typhimurium or fusion of phagosomes with lysosomes. [source] The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytesIMMUNOLOGY, Issue 1 2003J. Wan Summary BNIP3 is a recently described pro-apoptotic member of the Bcl-2 family and in BNIP3 cDNA-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (,,m). However, its expression or function in physiologic cell types is not known. Our results using the T-cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl-2 family pro-apoptotic molecules, BNIP3 is transcriptionally highly up-regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation-induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3-induced cell death. AICD of CTL was caspase-independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3-induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased ,,m. Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T-cell homeostasis by regulating effector CTL numbers. [source] Influence of oestrogen receptor , and , on the immune system in aged female miceIMMUNOLOGY, Issue 1 2003U. Islander Summary Oestrogen has a dichotomous effect on the immune system. T and B lymphopoiesis in thymus and bone marrow is suppressed, whereas antibody production is stimulated by oestrogen. In this study the importance of the oestrogen receptors (ER) ER-, and ER-, in the aged immune system was investigated in 18 months old-wild type (WT), ER-, (ERKO), ER-, (BERKO) and double ER-, and ER-, (DERKO) knock-out mice, and compared with 4 months old WT mice. Cell phenotypes in bone marrow, spleen and thymus, and the frequency of immunoglobulin (Ig) spot forming cells (SFC) were determined. We show here that the 17-,-oestradiol (E2)-induced downregulation of B lymphopoietic cells in bone marrow of young ovariectomized mice can be mediated through both ER-, and ER-,. However, only ER-, is required for the age-related increased frequency of immunoglobulin M (IgM) SFC in the bone marrow, as well as for the increased production of interleukin-10 (IL-10) from cultured splenocytes in aged mice. Furthermore, increased age in WT mice resulted in lower levels of both pro- and pre-B cells but increased frequency of IgM SFC in the bone marrow, as well as increased frequency of both IgM and IgA SFC in the spleen. Results from this study provide valuable information regarding the specific functions of ER-, and ER-, in the aged immune system. [source] Prospective evaluation of intestinal homing memory T cells in ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 5 2004A. L. Hart Abstract Background: Intestinal homing (,7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (,7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. Methods: Twelve patients with frequently relapsing ulcerative colitis (,2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify ,7+ cells and ,7, populations within CD3+CD45RA, leukocytes. Production of cytokines (IFN-,, TNF-,, IL-2, IL-10, TGF-,, and IL-4) was determined by intracellular labeling. Results: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of ,7+:,7, memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing ,7+ memory T cells produced IL-4 (p < 0.02) and TNF-, (p < 0.05) at disease relapse compared with remission. Non-intestinal homing ,7,memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. Conclusions: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-, and TH2 (IL-4) cytokines by intestinal homing ,7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis. [source] Evidence of active cytomegalovirus infection and increased production of IL-6 in tissue specimens obtained from patients with inflammatory bowel diseasesINFLAMMATORY BOWEL DISEASES, Issue 3 2003Afsar Rahbar Abstract Recent reports have focused interest on human cytomegalovirus (HCMV) in inflammatory bowel diseases (IBD). Our aim in this study was to examine the frequency of HCMV-infected intestinal cells in tissue sections obtained from patients with IBD, and to investigate if HCMV-infected intestinal cells produce the proinflammatory cytokine IL-6. We studied intestinal tissue sections from 13 patients with ulcerative colitis, 10 with Crohn's disease, 10 cancer patients without intestinal inflammation, and 10 samples from HCMV-infected AIDS patients. HCMV-DNA was detected by in situ hybridization in sections obtained from 12/13 patients with ulcerative colitis, in 10 with Crohn's disease, in 10/10 samples from HCMV-infected AIDS patients, but not in any of the 10 samples that were obtained from uninflamed tissues. HCMV-specific antigens were detected in samples from all HCMV-infected AIDS patients, in 11/13 sections from patients with ulcerative colitis, in 10/10 samples from patients with Crohn's disease, but not in sections from uninflamed tissues. Cells were double positive for an HCMV early antigen and IL-6 in 10/13 sections from patients with ulcerative colitis, in all patients with Crohn's disease, and in 4/10 samples from AIDS patients. In conclusion, these results suggest that active HCMV infection in the intestine is very frequent in patients with IBD, and may contribute to the inflammatory process through an increased production of IL-6. [source] Very high conservation between Cyp6a2 from Drosophila melanogaster and its ortholog Cyp6a26 from D. simulansINSECT SCIENCE, Issue 1 2007SOPHIE TARÈS Abstract Although Drosophila simulans is closely related to D. melanogaster, very few cytochrome P450 genes have been studied in this species until now. As Cyp6a2 from D. melanogaster is a major gene implicated in the detoxification of xenobiotic molecules, we decided to look for its ortholog in D. simulans. The isolated gene, Cyp6a26, presents structural characteristics very similar to those of Cyp6a2: an identical size of 1 590-bp comprising two exons separated by a 69-bp intron and a nucleotide sequence homology of 95%. Many putative transcriptionally important motifs were identified in the upstream DNAs of the two genes but only 16 elements are in common positions. Treatment of flies with phenobarbital leads to an increased production of Cyp6a26 mRNAs. The expression of Cyp6a26 mRNAs varies following developmental stages in the same manner as Cyp6a2. Immunohistochemistry experiments of phenobarbital-treated adult drosophila show that the spatial expression pattern of the two proteins is also conserved between the two species. All these data argue in favor of the conservation of the function of these homologous genes between the two Drosophila species. [source] Association between a common IL10 distal promoter haplotype and IgE production in individuals with atopic dermatitisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2009K. Lacy Summary Atopic dermatitis (AD) is a genetically determined inflammatory skin disease characterized by abnormal cytokine production, including increased production of interleukin 10 (IL10). Single nucleotide polymorphisms (SNP) and haplotypes in the IL10 gene promoter region on chromosome 1q31-32 have been implicated in several inflammatory diseases, but generally, only SNPs proximal to the transcription start site (TSS) have been investigated. The aim of this study was to identify proximal, distal and combined haplotype sets in the IL10 promoter region and to study their association with clinical phenotypes in atopic dermatitis. SNPs at positions ,3575, ,2849, ,2779, ,2763, ,1082, ,851, ,819 and ,592 in the IL10 promoter region were genotyped in individuals with atopic dermatitis (n= 47) and nonatopic control subjects (n= 40) using polymerase chain reaction-based techniques and induced heteroduplex generator (IHG) analysis. Pan-promoter, TSS-proximal and TSS-distal haplotypes were reconstructed using phase analysis. Fifteen haplotypes representing all eight SNPs were identified. Subgrouping identified four 4-locus and three 3-locus TSS-proximal haplotypes; and nine 4-locus TSS-distal haplotypes. No difference was found in haplotype or SNP frequencies between the AD and control groups, or between patients with mild or severe disease. However, a common 4-locus TSS-distal haplotype (TGAC) was significantly increased in patients with IgE levels over 1000 kIU L,1. This study is the first to analyse the association between haplotype groups in the IL10 promoter region and clinical phenotypes in AD. We have demonstrated a significant association between the TSS-distal haplotype TGAC, and IgE levels in AD patients. It remains to be shown if there is an association between the TGAC haplotype and IL10 production, which might account for the stimulation of IgE production. [source] Uptake of Calcium by Mitochondria: Transport and Possible FunctionIUBMB LIFE, Issue 3-5 2001Thomas E. Gunter Abstract Vertebrate mitochondria contain a complex system for transport of Ca 2+ and related ions, consisting of two saturable modes of Ca 2+ influx and two separate, saturable mechanisms of Ca 2+ efflux. The characteristics of the mechanisms of Ca 2+ uptake, the uniporter and the RaM, are discussed here and suggestions are made about how the mechanisms may work together and separately to mediate the two physiological roles with which they are most commonly associated - control of the rate of cellular ATP production and induction of the permeability transition and apoptosis. It is argued that more subtlety of control of intramitochondrial free Ca 2+ concentration ([Ca 2+ ] m ) must be used by the uniporter and the RaM to fulfill their physiological roles than has been commonly recognized. This is because an increase in [Ca 2+ ] m is associated with both increased production of ATP which supports the continued life of the cell and with induction of the permeability transition and possibly apoptosis, which leads to cell death. The saturable mechanisms of mitochondrial Ca 2+ efflux and the Ca 2+ -induced mitochondrial permeability transition, which can transport Ca 2+ as well as other ions and molecules and is often considered as a Ca 2+ transport mechanism, are being reviewed separately. [source] Wheat Cellular Membrane Thermotolerance Under Heat StressJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2010A. S. Dias Abstract Four genotypes of Triticum aestivum L. and Triticum turgidum subsp. durum chosen according to their genetic background diversity were subjected to heat stress after anthesis. Membrane permeability, lipid peroxidation and fatty acids (C14:0, C16:0, C16:1c, C16:1t, C18:0, C18:1, C18:2 and C18:3) were quantified. The estimation of the quantum yield of non-cyclic photosynthetic electron transport was used as well as a test system to further evaluate the implications on thylakoid functioning. It was found differences within bread and durum wheat species concerning the capability to cope with high temperatures at the stage of grain filling. The genotype Sever showed high thermal sensitivity concerning membrane lipid peroxidation and membrane permeability, as evaluated by the increased production of ethylene and MDA, as well as by the impact on TFA (at the middle term of grain filling). In the durum wheat genotypes, differences were also found, with TE 9306 displaying high membrane stability, with no increases on membrane permeability, MDA and ethylene content. In this way, the observed changes on TFA in this genotype might have constituted a mechanism to allow qualitative lipid changes, reflected in lower unsaturation level of membrane FAs which is a positive trait under high temperatures. 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