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Pathogenic Effects (pathogenic + effects)

Distribution by Scientific Domains
Life Sciences61%
Medical Sciences38%

Selected Abstracts

Getting to the crux of the matter: IL-23 and Th17 cell accumulation in the CNS

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009
Benjamin M. Segal
Abstract IL-23 plays a critical role in EAE induced by the active immunization of C57BL/6 mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein (MOG35,55). It was initially assumed that the pathogenic effects of IL-23 were directly related to the generation, expansion and/or stabilization of autoreactive CD4+ Th17 cells. However, a number of recent studies have uncovered discrepancies between the requirement for IL-23, as opposed to Th17 cells or their products (IL-17A, IL-17F and IL-22), in the development of EAE. In this issue of the European Journal of Immunology, it is demonstrated that impairment of IL-23 signaling does not impede the expansion of myelin-specific CD4+ T cells in peripheral lymphoid tissues but inhibits their accumulation in the CNS. This paper contributes to a growing body of data that implicates IL-23 in the acquisition of CNS homing properties by autoreactive effector cells. [source]

Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic fever

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2001
U.C. Chaturvedi
Abstract During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean±S.D.=36±20 U ml,1) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean±S.D.=5±2 U ml,1; P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the ,cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1,4, 5,8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator. [source]

Pathogenicity of fungi isolated from Quercus suber in Catalonia (NE Spain)

FOREST PATHOLOGY, Issue 5 2000
J. Luque
Summary Thirty-four fungal species isolated from cork oak (Quercus suber) in Catalonia (NE Spain) during 1992,95 were tested for pathogenicity either in stem, leaf or root inoculations. Eleven species were found to be pathogenic on stem: Biscogniauxia mediterranea, Botryosphaeria stevensii, Diatrype cf. stigma, Endothia gyrosa, Fusarium solani, Graphium sp., Ophiostoma quercus, Phomopsis sp., Phytophthora cinnamomi, Sporendocladia bactrospora and an unidentified Coelomycete. Three fungi showed pathogenic effects on leaves: Dendrophoma myriadea, Lembosia quercina and Phomopsis quercella. No clear pathogenic effects were detected in the root inoculation experiment. Trunk pathogens were differentiated into two groups according to the effects induced in the inoculated plants; B. stevensii, Phomopsis sp. and P. cinnamomi caused the death of the inoculated plants and induced the formation of large cankers and vascular necroses. The other pathogenic species also produced severe cankers and vascular lesions, but no significant mortality was detected. Water stress increased the lesions caused by B. mediterranea and Phomopsis sp., but limited those of P. cinnamomi and the rest of the inoculated fungi. However, water stress did not significantly affect the damage caused by B. stevensii, which was the most virulent of the species tested. Leaf pathogens only showed their effects if the leaf cuticle was previously damaged. Lembosia quercina caused small dark lesions whereas D. myriadea and P. quercella produced large necrotic areas in well-watered plants. The lesions caused by the last two fungi were reduced by water stress. Résumé Le pouvoir pathogène de trente-quatre espèces fongiques isolées de chêne liège en Catalogne (nord-est de l'Espagne) de 1992 à 1995 a été testé par inoculation sur tronc, feuilles et racines. Onze espèces se sont montrées pathogènes sur tronc: Biscogniauxia mediterranea, Botryosphaeria stevensii, Diatrype cf. stigma, Endothia gyrosa, Fusarium solani, Graphium sp., Ophiostoma quercus, Phomopsis sp., Phytophthora cinnamomi, Sporendocladia bactrospora et un Coelomycète non identifié. Trois champignons ont eu un effet pathogène sur feuilles: Dendrophoma myriadae, Lembosia quercina et Phomopsis quercella. Aucun effet clair n'a été détecté chez les inoculations de racines. Les pathogènes de tronc se répartissaient en deux groupes selon leurs effets en inoculation; B. stevensii, Phomopsis sp. et P. cinnamomi provoquaient la mort des plants et induisaient le formation de grands chancres et des nécroses vasculaires. Les autres espèces pathogènes produisaient aussi des chancres graves et des lésions vasculaires, mais pas de mortalité significative. Un stress hydrique augmentait les lésions provoquées par B. mediterranea et Phomopsis sp. mais limitait ceux de P. cinnamomi et des autres champignons inoculés. Cependant, le stress hydrique n'affectait pas significativement les dégâts par B. stevensii qui était la plus agressive des espèces testées. Les pathogènes foliaires n'avaient d'effet que si la cuticule foliaire était préalablement endommagée. Lembosia quercina provoquait de petites lésions sombres et D. myriadea et P. quercella provoquaient de grandes plages nécrotiques chez les plants bien arrosés; les lésions causées par ces deux derniers champignons étaient réduites par le stress hydrique. Zusammenfassung Die Pathogenität von 34 Pilzarten, die im Zeitraum 1992,1995 von Korkeichen (Quercus suber) in Katalonien (NO-Spanien) isoliert wurden, wurden mit Hilfe von Trieb-, Blatt- oder Wurzelinokulationen untersucht. Am Stamm erwiesen sich 11 Arten als pathogen: Biscogniauxia mediterranea, Botryosphaeria stevensii, Diatrype cf. stigma, Endothia gyrosa, Fusarium solani, Graphium sp., Ophiostoma quercus, Phomopsis sp., Phytophthora cinnamomi, Sporendocladia bactrospora und ein nicht identifizierter Coelomycet. Drei Arten verursachten Symptome auf Bla¨ttern: Dendrophoma myriadea, Lembosia quercina und Phomopsis quercella. Bei den Wurzelinokulationen wurden keine pathogenen Effekte beobachtet. Bei den Stammpathogenen wurden nach den von ihnen an den inokulierten Pflanzen verursachten Symptomen zwei Gruppen unterschieden: B. stevensii, Phomopsis sp. und P. cinnamomi verursachten den Tod der Pflanzen und induzierten die Bildung von grossen Rinden- und Xylemnekrosen. Die anderen pathogenen Arten verursachten ebenfalls starke Rindennekrosen und Gefa¨ssla¨sionen, es wurde jedoch keine auffallende Mortalita¨t beobachtet. Unter Wasserstress war die durch B. mediterranea und Phomopsis sp. induzierte Nekrosebildung versta¨rkt, dagegen war sie bei P. cinnamomi und den u¨brigen inokulierten Pilzen reduziert. Wasserstress beeinflusst jedoch das Ausmass der Scha¨digung durch B. stevensii, der virulentesten der untersuchten Arten, nicht. Die Blattpathogene verursachten nur dann Symptome, wenn zuvor die Blattcuticula bescha¨digt worden war. Lembosia quercina verursachte kleine dunkle La¨sionen, wa¨hrend D. myriadea und P. quercella bei gut bewa¨sserten Pflanzen grosse Nekrosen verursachten. Diese Symptome waren unter Wasserstress weniger stark ausgepra¨gt. [source]

Soil microorganisms in coastal foredunes control the ectoparasitic root-feeding nematode Tylenchorhynchus ventralis by local interactions

FUNCTIONAL ECOLOGY, Issue 3 2009
Anna M. Pi, kiewicz
Summary 1In natural grassland ecosystems, root-feeding nematodes and insects are the dominant below-ground herbivores. In coastal foredunes, the ectoparasitic nematode Tylenchorhynchus ventralis would be a major root herbivore if not strongly controlled by soil microorganisms. Here, we examined if the suppressive effects of the microbial enemies of T. ventralis act by local interactions such as predation, parasitism or antagonism, or local induction of plant defence, or by non-local interactions, such as systemic effects when microorganisms in one section of the plant roots can affect nematode control in another section of the root system. We show that abundance of T. ventralis in the root zone of the grass Ammophila arenaria is suppressed by local interactions. 2We compared local vs. non-local control of nematodes by a natural community of soil microorganisms in a split-root experiment, where nematodes and microbes were inoculated to the same, or to opposite root compartments. 3The split-root experiment revealed that microorganisms affected T. ventralis numbers only when present in the same root compartment. Therefore, the effects of microorganisms on T. ventralis are due to local interactions and not due to induction of a systemic defence mechanism in the plant host. 4When inoculated together with microorganisms, the nematodes were heavily infected with unknown bacteria and with fungi that resembled the genus Catenaria, suggesting that microorganisms control nematodes through parasitism. However, local defence induction cannot be completely excluded. 5Besides microbial enemies of nematodes, the root zone of A. arenaria also contains plant pathogens. Root biomass was reduced by nematode infection, but also by the combination of nematodes and microorganisms, most likely because the soil pathogens overwhelmed the effects of nematode control on plant production. 6We conclude that there may be a trade-off between beneficial effects of soil microorganisms on the plant host due to nematode control vs. pathogenic effects of soil microorganisms on the plant host. We propose that such trade-offs require more attention when studying below-ground multitrophic interactions. [source]

Fibrosis in heart disease: understanding the role of transforming growth factor-,1 in cardiomyopathy, valvular disease and arrhythmia

IMMUNOLOGY, Issue 1 2006
Razi Khan
Summary The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-,1 (TGF-,1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-,1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-,1. In fact, the pathogenic effects of TGF-,1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-,1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-,1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-,1 is an appropriate target for therapy in a variety of cardiovascular diseases. [source]

Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2007
M. E. VEGA-OSTERTAG
Summary.,Background:,The purpose of this study was to examine whether SB 203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, is effective in reversing the pathogenic effects of antiphospholipid antibodies. Methods:,The adhesion of THP-1 monocytes to cultured endothelial cells (EC) treated with immunoglobulin G (IgG) from a patient with antiphospholipid syndrome (IgG-APS) or control IgG (IgG-NHS) in the presence and absence of SB 203580 was examined. The size of an induced thrombus in the femoral vein, the adhesion of leukocytes to EC of cremaster muscle, tissue factor (TF) activity in carotid artery and in peritoneal macrophages, the ex vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in aorta preparations and platelet aggregation were studied in mice injected with IgG-APS or control IgG-NHS and with or without SB 203580. Results:,SB 203580 significantly reduced the increased adhesion of THP-1 to EC in vitro, the number of leukocytes adhering to EC, the thrombus size, the TF activity in carotid arteries and in peritoneal mononuclear cells, and the expression of VCAM-1 in aorta of mice, and completely abrogated platelet aggregation induced by IgG-APS. Conclusion:,These data suggest that targeting the p38 MAPK pathway may be valuable in designing new therapy modalities for treating thrombosis in patients with APS. [source]

Management measures to control a feline leukemia virus outbreak in the endangered Iberian lynx

ANIMAL CONSERVATION, Issue 3 2009
G. López
Abstract The feline leukemia virus (FeLV) is a retrovirus that affects domestic cats all over the world. Its pathogenic effects generally include anemia, immunosuppression or tumors. Dissemination over populations is linked to cat sociality, because the virus is transmitted by direct contact. Although the domestic cat is its common host, FeLV infection has also been described in some wild felids. In the Iberian lynx Lynx pardinus, some sporadic FeLV infection cases have been reported since 1994, but an outbreak with the involvement of several animals has never been described until now. During spring 2007, an FeLV outbreak hit the Doñana (SW Spain) population. The infection rapidly spread throughout the densest subpopulation throughout Doñana. Infected animals showed very acute anemic disease, most of them dying in <6 months. To avoid FeLV dissemination, a control program was carried out that included removal of viremic lynxes, vaccination of negative individuals and reduction of the feral cat population. The program was implemented both in Doñana and in Sierra Morena populations. In Doñana, around 80% of the total lynx population and 90% of the outbreak focus subpopulation were evaluated. Seven out of the 12 infected individuals found died and two reverted to latency; the remaining viremic animals have been kept in captivity. The outbreak appears to have been successfully confined to the subpopulation where the virus appeared and no more cases have been found since August 2007. In the larger Sierra Morena population, 8% of the lynx population was surveyed. Thirty-four uninfected Iberian lynxes were vaccinated at least once. The FeLV prevalence was found to be 27% in the Doñana population and 0% in the Sierra Morena population. [source]

New Mutations of EXT1 and EXT2 Genes in German Patients with Multiple Osteochondromas

ANNALS OF HUMAN GENETICS, Issue 3 2009
Wolfram Heinritz
Summary Mutations in either the EXT1 or EXT2 genes lead to Multiple Osteochondromas (MO), an autosomal dominantly inherited disorder. This is a report on clinical findings and results of molecular analyses of both genes in 23 German patients affected by MO. Mutation screening was performed by using denaturing high performance liquid chromatography (dHPLC) and automated sequencing. In 17 of 23 patients novel pathogenic mutations have been identified; eleven in the EXT1 and six in the EXT2 gene. Five patients were carriers of recurrent mutations in the EXT2 gene (p.Asp227Asn, p.Gln172X, p.Gln258X) and one patient had no detectable mutation. To demonstrate their pathogenic effect on transcription, two complex mutations in EXT1 and EXT2 and three splice site mutations were characterized by mRNA investigations. The results obtained provide evidence for different aberrant splice effects , usage of new cryptic splice sites and exon skipping. Our study extends the mutational spectrum and understanding of pathogenic effects of mutations in EXT1 and EXT2. [source]

Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, ,-synuclein, and tau

BIOESSAYS, Issue 3 2010
Jean-Marc Taymans
Abstract Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, ,-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA -positive Lewy bodies. Mutations in both proteins are associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins. [source]

Perturbation of retinoic acid (RA)-mediated limb development suggests a role for diminished RA signaling in the teratogenesis of ethanol,,§

BIRTH DEFECTS RESEARCH, Issue 9 2007
Corey S. Johnson
Abstract BACKGROUND: A proposed mechanism for ethanol teratogenicity entails ethanol-mediated reductions in retinoic acid (RA). This premise was investigated utilizing a mouse model, with limb reduction defects as the teratogenic end point. METHODS: Ethanol, Disulfiram, or BMS-189453 was administered to C57BL/6J mice on the 9th day of pregnancy. Forelimb morphology was assessed on gestation day 18 using Alcian blue and Alizarin red staining. Nile blue sulfate or LysoTracker Red (LTR) vital staining identified cell death in the limb bud. The ability of RA to prevent ethanol-induced cell death was assessed by coadministration followed by laser scanning confocal microscopic examination of LTR-staining. In situ hybridization and qPCR were used to examine gene expression in treated limb buds. RESULTS: Ethanol, Disulfiram, and BMS-189453 resulted in postaxial ectrodactyly, intermediate ectrodactyly, and other digital defects. Excessive Nile blue sulfate staining was evident in the presumptive AER following each of the three exposures. Ethanol-induced LTR staining was prevented by RA supplementation. Both in situ hybridization and qPCR illustrated decreases in Shh and Tbx5 in ethanol-exposed embryos as compared to control. CONCLUSIONS: Contrary to studies of prolonged RA deficiency, acute exposure to functional antagonists of RA results in limb defects that are morphologically similar to those caused by ethanol. The rescue of ethanol-induced cell death by RA and similar changes in Shh transcription further suggest that RA contributes to ethanol-induced limb dysmorphology. Moreover, the repression of key mediators of limb development soon after ethanol exposure adds to the existing knowledge of the pathogenic effects of ethanol. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc. [source]

Inhibition of cyclin-dependent kinases by olomoucine and roscovitine reduces lipopolysaccharide-induced inflammatory responses via down-regulation of nuclear factor ,B

CELL PROLIFERATION, Issue 2 2009
R-S. Jhou
Objectives:, Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered. Materials and methods:, Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase,polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-,B) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay. Results:, In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-,B transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-,B activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-,B. Conclusions:, The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via down-regulation of NF-,B. [source]

Do adverse effects of dental materials exist?

CLINICAL ORAL IMPLANTS RESEARCH, Issue 2007
What are the consequences, how can they be diagnosed, treated?
Abstract Objectives: All dental biomaterials release substances into the oral environment to a varying degree. Various preclinical biocompatibility test systems have been introduced, aiming at an evaluation of the potential risks of dental materials. Potential pathogenic effects of released substances from dental materials have been demonstrated. For the biocompatibility of a biomaterial, it is not only important that minimal diffusable substances are released when it is in body contact , the material must also fulfill the function for which it has been designed. This is also very much dependent on the material properties and its handling properties. The aim of this review was to generate an overview of the present status concerning adverse reactions among patients and personnel. Materials and methods: A systematic review was performed using a defined search strategy in order to evaluate all MEDLINE-literature published between 1996 and 2006. Results: The compilation of the literature available has revealed that the majority of studies have been carried out on patients compared with personnel. Adverse reactions towards dental materials do occur, but the prevalence and incidence are difficult to obtain. The results were essentially based on cohort studies. Clinical trials, especially randomized-controlled trials, are in the minority of all studies investigated, with the exception of composite and bonding studies, where clinical trials, but not randomized-controlled trials, represent the majority of studies. Patients and personnel were treated separately in the manuscript. Amalgam studies show the lowest degree of verified material-related diagnosis. Even if objective symptoms related to adverse reactions with polymer resin-based materials have been reported, postoperative sensitivity dominates reports concerning composites/bondings. Verified occupational effects among dental personnel show a low frequency of allergy/toxic reactions. Irritative hand eczema seemed to be more common than in the general population. Conclusions: Patient- and personnel-related studies are of variable quality and can be improved. There is a need for a better description of the content of materials. A registry for adverse effects of dental materials would be useful to detect the occurrence of low-incidence events. [source]