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Disease Development (disease + development)
Selected AbstractsIdentification of Critical Stage for Disease Development and Biocontrol of Alternaria Blight of Indian Mustard (Brassica juncea)JOURNAL OF PHYTOPATHOLOGY, Issue 4 2004P. D. Meena Abstract Fungicides mancozeb and carbendazim caused 100% reduction in mycelial growth of Alternaria brassicae over control in vitro while 1% (w/v) aqueous bulb extract of Allium sativum and leaf extract of Acacia nilotica caused significant reductions. In dual culture, GR isolate of Trichoderma viride performed the best among the test isolates of Trichoderma, causing 81%, 82% reduction in mycelial growth of A. brassicae over control. Performance of isolates SI-2, P and SI-1 of T. viride were at par (P < 0.01) with that of GR isolate. Spraying of A. brassicae at different ages of the mustard host plant identified 75 days after sowing (d.a.s.) as the most critical age of the mustard plant for development of Alternaria blight severity on the crop with 45 d.a.s. being the next most important one. Mancozeb was the best among all the treatments, resulting in the lowest disease severity on leaves of mustard at both Sewar and Ludhavai as also the lowest A-value (area under disease progress curve). Performance of bulb extract of A. sativum in checking the disease severity on leaves and pods was at par (P,<,0.05) with mancozeb. The GR isolate of T. viride was at par with mancozeb in checking blight severity on mustard leaves at Sewar while performance of the bioagent was significantly (P,<,0.05) inferior to the chemical fungicide at Ludhavai. Performance of the bioagent isolate GR of T. viride in checking the disease severity on pods was at par (P < 0.05) with mancozeb at both Sewar and Ludhavai, the treatment recording the lowest A-value on pods. While application of bulb extract of A. sativum resulted in highest seed yield at Sewar in 2001,2002, the bioagent isolate GR of T. viride did so at Ludhavai, both the treatments being at par (P < 0.05) with mancozeb and significantly higher than control. Application of bulb extract of A. sativum at 45 and 75 d.a.s. resulted in lowest blight severity on leaves and pods as also in highest seed yield among the different single and combination of treatments. Although disease severity in the treatment was at par (P < 0.05) with that in mancozeb, application of the plant extract at the two stages of crop growth resulted in significantly higher seed yield compared with the two applications of the chemical fungicide. However, application of the treatments singly only at 75 d.a.s., GR isolate of T. viride at 45 and 75 d.a.s., A. sativum 45 d.a.s. + T. viride 75 d.a.s., and T. viride 45 d.a.s. + A. sativum 75 d.a.s. resulted in seed yield at par (P < 0.05) with application of bulb extract of A. sativum at 45 and 75 d.a.s. [source] Inhibition of Obliterative Airway Disease Development in Murine Tracheal Allografts by Matrix Metalloproteinase-9 DeficiencyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2005Félix G. Fernández This study was designed to define the roles of matrix metalloproteinase (MMP)-2 and MMP-9 in obliterative airway disease (OAD) in heterotopic murine tracheal allografts, considered a suitable animal model for chronic lung allograft rejection. BALB/c tracheal allografts were transplanted into MMP-2-deficient (,/,) and MMP-9,/, mice. Also, wild-type recipients were treated with doxycycline, a nonspecific MMP inhibitor. After 10, 20 and 30 days, allografts were analyzed for OAD development, intragraft levels of MMP-2 and MMP-9 and the frequency and cytokine/chemokine production profile of alloreactive T cells. Allografts transplanted into wild-type mice developed OAD lesions within 30 days. These allografts revealed significant upregulation of both MMP-2 and MMP-9. Allografts transplanted into MMP-9,/, and doxycycline-treated recipients did not develop OAD. In contrast, allografts transplanted into MMP-2,/, mice developed OAD lesions with normal kinetics. Interestingly, MMP-9,/, recipients showed an enhanced T cell alloreactivity associated with an abnormal profile of cytokine/chemokine production. The enhanced T cell alloreactivity in MMP-9,/, mice was mediated by enhanced dendritic cell stimulatory capacity as well as enhanced T cell responsive capacity. These results suggest that MMP-9 plays an important role in the pathogenesis of OAD and may represent a target for the therapeutic intervention of chronic lung allograft rejection. [source] Susceptibility of invasive taxa of European blackberry to rust disease caused by the uredinial stage of Phragmidium violaceum under field conditions in AustraliaPLANT PATHOLOGY, Issue 3 2005K. J. Evans European blackberry (Rubus fruticosus agg.) is an aggregate of closely related taxa, with at least 15 taxa naturalized in Australia. Biological control of this Weed of National Significance, using the nonindigenous rust fungus Phragmidium violaceum, is effective when the weather is conducive to multiple cycles of infection, but some blackberry taxa escape severe disease. Thirty-one taxa of naturalized R. fruticosus agg. from southeastern Australia were isolated, their DNA phenotype determined and clones of each taxon inoculated with P. violaceum isolate SA1. Disease development was monitored for at least four generations of uredinia on large potted plants under field conditions. Although variation in mean disease severity appeared continuous over the range of Rubus clones tested, counts of uredinia and telia enabled identification of eight resistant taxa. Fine scale variation in susceptibility to rust disease was observed when different clones of R. leucostachys with the same DNA phenotype were found to express either resistance or susceptibility to P. violaceum (SA1). There were significant differences among 23 Rubus taxa rated as susceptible to rust disease in the mean number of leaves emerging per latent period of uredinia (LELPU). Mean LELPU appeared to account for some of the variation in two measures of mean disease severity observed among susceptible Rubus clones, although the correlation was insignificant (0·10 < P > 0·05). [source] Epidemiology of Plum pox virus strain M in GreeceEPPO BULLETIN, Issue 2 2006C. Varveri Plum pox virus has been endemic in Greece since 1967 causing important losses in apricot and to a lesser extent in peach crops. A survey undertaken in 1992 in public and private mother-tree plantations to estimate its incidence revealed that the virus was absent in isolated areas far from commercial stone-fruit crops. Virus titers decrease significantly during the hot months in the infected trees but re-increase in October,November permitting reliable detection. It is virulent M-type isolates which are effectively transmitted by aphids that are mostly recovered. Aphis gossypii and Hyalopterus pruni were the most abundant virus vectors captured during the small scale monitoring undertaken in apricot orchards in 1999 and 2000. Virus spread was monitored in two apricot orchards from 1996 to 2000 and analysed. Initial infections followed a completely random spatial pattern, while loose clusters appeared in succeeding years, to finally reach a uniform distribution representing high infection levels. The nearby ecological conditions greatly affected the rate of disease development. [source] Lymphotoxin,, receptor-Ig fusion protein treatment blocks actively induced, but not adoptively transferred, uveitis in Lewis ratsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Hui Shao Abstract Previous studies have shown that treatment of rodents with a lymphotoxin (LT),, receptor-Ig fusion protein (LT,R-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T,cells. Interestingly, LT,R-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LT,R-Ig-treated R16-injected rats had a significantly decreased T,cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease. [source] Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseasesEXPERIMENTAL DERMATOLOGY, Issue 2 2007Takashi Matsushita Abstract:, Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma. [source] Actin mutations in hypertrophic and dilated cardiomyopathy cause inefficient protein folding and perturbed filament formationFEBS JOURNAL, Issue 8 2005Søren Vang Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common hereditary cardiac conditions. Both are frequent causes of sudden death and are often associated with an adverse disease course. Alpha-cardiac actin is one of the disease genes where different missense mutations have been found to cause either HCM or DCM. We have tested the hypothesis that the protein-folding pathway plays a role in disease development for two actin variants associated with DCM and six associated with HCM. Based on a cell-free coupled translation assay the actin variants could be graded by their tendency to associate with the chaperonin TCP-1 ring complex/chaperonin containing TCP-1 (TRiC/CCT) as well as their propensity to acquire their native conformation. Some variant proteins are completely stalled in a complex with TRiC and fail to fold into mature globular actin and some appear to fold as efficiently as the wild-type protein. A fraction of the translated polypeptide became ubiquitinated and detergent insoluble. Variant actin proteins overexpressed in mammalian cell lines fail to incorporate into actin filaments in a manner correlating with the degree of misfolding observed in the cell-free assay; ranging from incorporation comparable to wild-type actin to little or no incorporation. We propose that effects of mutations on folding and fiber assembly may play a role in the molecular disease mechanism. [source] Structural determination of the O-chain polysaccharide from Agrobacterium tumefaciens, strain DSM 30205FEBS JOURNAL, Issue 12 2002Cristina De Castro Agrobacterium tumefaciens is a Gram-negative, phytopathogenic bacterium and is characterized by an unique mode of action on dicotyledonous plants: it is able to genetically modify the host, and because of this feature, it is used as a tool for transgenic plants. Many experiments have demonstrated that lipopolysaccharides (LPSs) play an important role for the disease development, as they are involved in the adhesion process of the bacterium on the plant cell wall. Despite the wealth of information on the role of LPS on phytopathogenesis, the present paper appears as the first report on the molecular primary structure of the O-chain produced from Agrobacterium. Its repeating unit was determined by means of chemical and spectroscopical analysis, and has the following structure: (3)-,- d -Araf -(1,3)-,- l -Fucp -(1,. [source] Rust severity in bioenergy willow plantations treated with additional nutrientsFOREST PATHOLOGY, Issue 1 2009M. Toome Summary A 3-year field study was carried out to determine the effect of wastewater irrigation and previous differences in mineral fertilization on the occurrence of willow leaf rust (Melampsora epitea). The experiment was conducted in two energy forest plantations: one designed for wastewater purification and the other as a mineral fertilization experiment. The severity of leaf rust on different clones and sites with different treatments was assessed by counting the number of uredinia per leaf unit area. Generally, plants irrigated with wastewater consistently had more leaf rust, irrespective of the study years or willow clones. Previous mineral fertilization had mixed effects on different clones 2 years after the last application. Three years after the last fertilizer application, however, no impact of the treatment on rust disease development was detected. In general, the rust levels differed from year to year probably due to climate. In this study, no correlation was detected between shoot age and rust severity, whereas climate and treatments strongly influenced leaf rust levels on some willow clones. [source] Seasonal resin canal formation and necroses expansion in resinous stem canker-affected Chamaecyparis obtusaFOREST PATHOLOGY, Issue 4-5 2002T. YAMADA Summary The season of disease development on the basis of two major internal symptoms, resin canal formation and necrotic lesion expansion in phloem, were anatomically determined in Chamaecyparis obtusa (Hinoki cypress) affected by resinous stem canker. Newly formed resin canals were mostly observed at first from July to August in samples of the canker-affected C. obtusa phloem. This result indicates the occurrence of stimuli causing resin canal formation and the beginning of the formation from May to July of the same year. This and the beginning of resin exudation observed in May or June indicated that resin, exuded at least before August, originated from resin canals formed in the previous year(s). The expansion of phloem necrotic lesions began in June and continued until October, and was conspicuous in the August samples. Stimuli causing necrotic lesion development were also suggested to occur from May to August of the same year. It is hypothesized that excess resin production induces lesion development and that expansion of necrotic lesion induces both resin exudation from previously formed resin canals and new resin canal formation. The causal agent of the disease could be activated in the late spring or summer season. Résumé Formation saisonnière de canaux résinifères et extension des nécroses chez Chamaecyparis obtusa atteint par le chancre résineux du tronc Chez Chamaecyparis obtusa affecté par le chancre résineux du tronc, la saison de développement de la maladie a été déterminée anatomiquement en se basant sur deux symptômes internes majeurs: la formation de canaux résinifères et l'extension des nécroses au niveau du phloème. Des canaux résinifères récemment formés ont surtout été observés à partir de juillet et en août dans le phloème de C. obtusa atteint par la maladie. Ce résultat montre l'existence de stimuli de la formation de canaux résinifères, ceux-ci commençant à se former en mai jusqu'en juillet. Jointe au fait que l'exsudation de résine a lieu en mai ou juin, cette observation montre que la résine (au moins celle exsudée avant août) provient des canaux formés au cours de la ou des années précédentes. L'extension de la nécrose du phloème débutait en juin, était forte en août et se poursuivait jusqu'en octobre. Il est suggéré que les stimuli du développement de la nécrose ont lieu entre mai et août de la même année. Il est supposé, d'une part que la production excessive de résine induit le développement des lésions, et d'autre part que l'extension des nécroses induit l'exsudation de résine à partir des canaux antérieurement formés ainsi que la formation de nouveaux canaux. L'agent causal de la maladie pourrait être activéà la fin du printemps ou en été. Zusammenfassung Saisonale Harzkanalbildung und Entwicklung der Nekrosen bei Chamaecyparis obtusa mit ,HarzigemStammkrebs' Bei Chamaecyparis obtusa mit Befall durch den ,Harzigen Stammkrebs' wurde die Phänologie der Krankheitsentwicklung anhand der Harzkanalbildung und der Ausbreitung der Nekrosen im Phloem anatomisch erfasst. Im krebsbefallenen Phloem wurden neu gebildete Harzkanäle zuerst im Juli und August beobachtet. Dies weist darauf hin, dass die Stimulation für die Harzkanalbildung und die Entwicklung der Harzkanäle in der Zeit von Mai bis Juli des laufenden Jahres erfolgt. Diese Beobachtung und der Beginn des Harzflusses, welcher im Mai und Juni auftritt, deuten darauf hin, dass der Harzfluss vor dem August aus Harzkanälen stammt, die bereits im Vorjahr oder noch früher angelegt worden waren. Die Expansion der Phloem-Nekrosen begann im Juni und hielt bis Oktober an, im August war sie besonders stark ausgeprägt. Der Reiz für die Ausdehnung der Nekrosen dürfte somit von Mai bis August des laufenden Jahres vorhanden sein. Es wird die Hypothese aufgestellt, dass die stark gesteigerte Harzproduktion die Nekrosenentwicklung fördert und dass die Expansion der Nekrosen sowohl den Harzfluss aus den früher gebildeten Harzkanälen anregt als auch die Bildung neuer Harzkanäle induziert. Der ursächliche Faktor für diese Krankheit dürfte im späten Frühjahr oder im Sommer aktiv sein. [source] Pathogenesis of Helicobacter pylori InfectionHELICOBACTER, Issue 2004Paul Hofman ABSTRACT Research in the last year has provided new insights into the function of the the cag -associated type IV secretion system and the vacuolating toxin VacA. A quite new aspect was disclosed by the finding that Helicobacter pylori in Mongolian gerbils colonizes a very distinct topology in the gastric mucous layer, obviously providing optimal conditions for long-term survival. Further research activities focused on H. pylori ammonia and metal metabolism as well as on bacterial stress defence mechanisms. Differential expression of approximately 7% of the bacterial genome was found at low pH suggesting that H. pylori has evolved a multitude of acid-adaptive mechanisms. VacA was shown to interrupt phagosome maturation in macrophage cell lines as well as to modulate and interfere with T lymphocyte immunological functions. Gastric mucosa as well as the H. pylori -infected epithelial cell line AGS strongly express IL-8 receptor A and B, which might contribute to the augmentation of the inflammatory response. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. The chronic imbalance between apoptosis and cell proliferation is the first step of gastric carcinogenesis. In this regard, it was demonstrated that coexpression of two H. pylori proteins, CagA and HspB, in AGS cells, caused an increase in E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein. Taken together, we now have a better understanding of the role of different virulence factors of H. pylori. There is still a lot to be learned, but the promising discoveries summarized here, demonstrate that the investigation of the bacterial survival strategies will give novel insights into pathogenesis and disease development. [source] Antibodies to citrullinated proteins: molecular interactions and arthritogenicityIMMUNOLOGICAL REVIEWS, Issue 1 2010Hüseyin Uysal Summary:, The discovery of antibodies specific for citrullinated protein epitopes [anti-citrullinated protein antibodies (ACPAs)] is a hallmark for the diagnosis and prognosis of rheumatoid arthritis (RA) and will also be a useful tool for understanding the fundamental pathologic processes. There are several essential questions pertaining to ACPA that remain to be explored, such as understanding the early specificity of the underlying T-cell recognition, whether the production of ACPA is a primary or secondary process, and in the event of such antibodies being arthritogenic, whether they could possibly regulate the disease development. To answer these questions, animal models are needed, but unfortunately ACPA is not a prominent feature of any of the classical animal models of RA. However, we showed recently that ACPA can be isolated from animals susceptible to collagen-induced arthritis that are specific for citrullinated type II collagen (CII). The citrulline specificity could be visualized, and the specificity is determined primarily by a direct interaction with citrulline. We also demonstrated that these antibodies are specific for the citrullinated epitopes and are pathogenic in vivo. A new hypothesis to explain how inflammation in RA can be directed to cartilaginous joints and be self-perpetuating is suggested, which involves recognition of post-translational modifications (glycosylation and citrullination) on CII by T and B cells that can have both arthritogenic and regulatory consequences. [source] Role of pathogenic T cells and autoantibodies in relapse and progression of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in LEW.1AV1 ratsIMMUNOLOGY, Issue 1pt2 2009Yoh Matsumoto Summary Accumulating evidence suggests that T cells and autoantibodies reactive with myelin oligodendrocyte glycoprotein (MOG) play a critical role in the pathogenesis of multiple sclerosis (MS). In the present study, we have tried to elucidate the pathomechanisms of development and progression of the disease by analysing T cells and autoantibodies in MOG-induced rat experimental autoimmune encephalomyelitis (EAE), which exhibits various clinical subtypes mimicking MS. Analysis using overlapping peptides revealed that encephalitogenic epitopes resided in peptide 7 (P7, residue 91,108) and P8 (residue 103,125) of MOG. Immunization with MOGP7 and MOGP8 induced relapsing,remitting or secondary progressive EAE. T cells taken from MOG-immunized and MOGP7-immunized rats responded to MOG and MOGP7 and sera from MOG-immunized rats reacted to MOG and MOGP1. Significant epitope spreading was not observed at either T-cell or antibody levels. Interestingly, sera from MOGP7-immunized rats with clinical signs did not react to MOG and MOG peptides throughout the observation period, suggesting that disease development and relapse in MOGP7-induced EAE occur without autoantibodies. However, MOGP7 immunization with adoptive transfer of anti-MOG antibodies aggravated the clinical course of EAE only slightly. Analysis of antibodies against conformational epitope (cme) suggests that anti-MOGcme may play a role in the pathogenicity of anti-MOG antibodies. Collectively, these findings demonstrated that relapse of a certain type of MOG-induced EAE occurs without autoantibodies but that autoantibodies may play a role in disease progression. Relapses and the progression of MS-mimicking EAE are differently immunoregulated so immunotherapy should be designed appropriately on the basis of precise information. [source] Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivoIMMUNOLOGY, Issue 4 2004Monika Gad Summary Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4+ T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4+ CD25, T cells. The DC-induced Treg cells are a mixture of CD25+ (10,20%) and CD25, (80,90%) T cells. However, all the suppressor activity in vitro and in vivo resides in the CD25+ T-cell subset. The CD25+ DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25+ Treg cells display a naïve phenotype, expressing high levels of CD45RB and l -selectin (CD62L). In addition, the DC-induced Treg cells mediate a stronger suppressive activity than prototype CD25+ regulatory T cells. The DC-induced Treg cells, and hereof purified CD25+ and CD25, T-cell fractions, were co-injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4+ CD25, T cells. Both unfractionated CD4+ and purified CD25+ Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25, T cells offered no protection against disease development. Enterobacterial antigen-exposed CD4+ T cells of the protected mice secreted higher levels of interleukin-10 and lower levels of interferon-, than the unprotected mice. The present data demonstrate DC-induced CD4+ CD25+ Treg cells, which phenotypically and functionally differ from the generally accepted prototype of CD25+ Treg cells. These data may initiate new procedures for the expansion of Treg cells for clinical use. [source] Blockage of the neurokinin 1 receptor and capsaicin-induced ablation of the enteric afferent nerves protect SCID mice against T-cell-induced chronic colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2009Monika Gad PhD Abstract Background: The neurotransmitter substance P (SP) released by, and the transient receptor potential vanilloid (TRPV1), expressed by afferent nerves, have been implicated in mucosal neuro-immune-regulation. To test if enteric afferent nerves are of importance for the development of chronic colitis, we examined antagonists for the high-affinity neurokinin 1 (NK-1) SP receptor and the TRPV1 receptor agonist capsaicin in a T-cell transfer model for chronic colitis. Methods: Chronic colitis was induced in SCID mice by injection of CD4+CD25, T cells. The importance of NK-1 signaling and TRPV1 expressing afferent nerves for disease development was studied in recipient SCID mice systemically treated with either high-affinity NK-1 receptor antagonists or neurotoxic doses of capsaicin. In addition, we studied the colitis-inducing effect of NK-1 receptor deleted CD4+CD25, T cells. Results: Treatment with the NK-1 receptor antagonist CAM 4092 reduced the severity of colitis, but colitis was induced by NK-1 receptor-deleted T cells, suggesting that SP in colitis targets the recipient mouse cells and not the colitogenic donor T cells. Capsaicin-induced depletion of nociceptive afferent nerves prior to CD4+CD25, T-cell transfer completely inhibited the development of colitis. Conclusions: Our data demonstrate the importance of an intact enteric afferent nerve system and NK-1 signaling in mucosal inflammation and may suggest new treatment modalities for patients suffering from inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] Mucosal NOD2 expression and NF-,B activation in pediatric Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2008Laura Stronati PhD Abstract Background: Recent advances in the pathogenesis of Crohn's disease (CD) have suggested that an aberrant innate immune response initiates the cascade of events leading to T-cell activation and to disease development. NOD2 protein, which is mainly expressed by innate immunity cells, appears to play a key role against bacteria by triggering a host defense response through the activation of the transcriptor factor NF-,B and a consequent proinflammatory cytokine production. The present study was aimed at investigating the expression and activity of NOD2, NF-,B, and of 2 proinflammatory cytokines, TNF, and IL-1,, in mucosal biopsies of CD affected children compared to healthy controls. Methods: In all, 22 children with active CD and 10 matched controls were entered in the study. mRNA and protein expressions were detected using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot; NF-,B binding activity was assessed by electromobility gel shift assay (EMSA). Results: NOD2 and IL-1, mRNAs were upregulated in CD children. Protein levels of NOD2, TNF,, and nuclear NF-,B, as well as the binding activity of NF-,B to a consensus DNA sequence, were significantly increased in inflamed mucosa of patients as compared to controls. Moreover, NF-,B activity was strongly upregulated in patients also when bound to the NOD2 promoter site. No difference was seen between patients and controls when NF-,B binding activity was determined in the uninflamed tissue. Conclusions: This study suggests that altered mechanisms regulating NOD2 induction, NF-,B activation and cytokine production may contribute to dysregulate the innate immune response underlying pediatric CD. (Inflamm Bowel Dis 2007) [source] MDM2 SNP309 T>G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patientsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Bente A. Talseth Abstract Disease expression in hereditary nonpolyposis colorectal cancer (HNPCC) cannot be readily explained by mutation site in the respective DNA mismatch repair genes associated with this disorder. One explanation is the role of modifying genes that can either promote or prevent disease development on a background of increased risk. Two single nucleotide polymorphisms in MDM2 and TP53 have been shown to be associated with younger ages of disease onset in HNPCC (TP53) and Li-Fraumeni syndrome (MDM2). In this study 220 HNPCC patients were examined, from Australia and Poland, all characterized at the molecular level to determine the frequency of the MDM2 SNP309 T>G and to assess its influence on disease expression. The results were then pooled with the results of a previous study to assess the combined influence of the MDM2 SNP309 T>G and TP53 SNP R72P. A significant difference was observed between CRC patients and unaffected MMR gene mutation carriers over the age of 45 years (p = 0.01). The unaffected MMR gene mutation carriers over the age of 45 years who carry the G allele have a reduced risk of developing CRC. The results indicate that the MDM2 SNP309, alone or in combination with TP53 R72P, does not influence age of diagnosis of CRC in individuals with HNPCC. In conclusion, the data indicates the G allele of MDM2 SNP309 might have a protective effect on disease development in HNPCC patients and that age of diagnosis of CRC is not associated with MDM2 SNP309 or TP53 R72P either as single SNPs or combined. © 2006 Wiley-Liss, Inc. [source] Etiopathogenic role of HLA-B27 alleles in ankylosing spondylitisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005Nurullah AKKOC Abstract HLA-B27 is the major genetic susceptibility factor for ankylosing spondylitis (AS). However, its precise role in the pathogenesis of AS still remains unclear, even though its gene has been cloned and sequenced, and its crystallographic structure has been defined. Arthritogenic peptide and molecular mimicry hypotheses propose mechanisms related to an antigen-presenting function of HLA-B27 to be responsible for disease development. However, peculiar aspects of its immunobiology, such as its misfolding and heavy chain dimerization raise the possibility of involvement of pathogenic mechanisms unrelated to its physiological function. Moreover, HLA-B27 is not a single allele, but a family of 31 different alleles, named HLA-B*2701 to HLA-B*2727. Studies worldwide indicate that the relatively common alleles (subtypes) HLA-B*2705, B*2704, and B*2702 are strongly associated with AS, whereas HLA-B*2706 which is prevalent in South-east Asia and HLA-B*2709 which is prevalent on the Italian island of Sardinia, seem to lack such an association. The distinction between the disease-associated subtypes and those that are not associated, may provide clues to the actual role of HLA-B27 in disease pathogenesis. B*2706 differs from B*2704 by only two residues, and B*2709 differs from B*2705 by only one residue. Moreover, both B*2706 and B*2709 bind an endogenous peptide (derived from vasoactive intestinal peptide type 1 receptor) and also an exogenous peptide (latent membrane protein 2 of Epstein-Barr virus) but in two drastically diverse conformations. These recent X-ray diffraction studies of individual peptides in the context of different HLA-B27 alleles broaden our perception of the possible pathogenetic role of this molecule in the development of AS and related spondyloarthopathies. In summary, the pathogenetic role of HLA-B27 in AS seem to be quite heterogenous, and cannot be explained by a single mechanism, and new ideas have been raised based on the aberrant immunobiologic features of HLA-B27. [source] Approaching risk assessment of complex disease development in horse chestnut trees: a chemical ecologist's perspectiveJOURNAL OF APPLIED ENTOMOLOGY, Issue 5 2008A. B. Johne Abstract The chemo-ecological predispositions were investigated for the development of a complex disease on the basis of an insect,fungus mutualism using the system of horse chestnuts (Aesculus hippocastanum and Aesculus x carnea), the horse chestnut leaf miner (Cameraria ohridella) and the biotrophic powdery mildew (Erysiphe flexuosa). Both C. ohridella and E. flexuosa can appear on the same horse chestnut leaf tissue simultaneously. The olfactory detection of fungal infection by the insect, its ability to discriminate the potentially mutualistic fungus from other fungi and the impact of fungal infection on insect oviposition were examined. Gas chromatography coupled with mass spectroscopic and electroantennographic detection by C. ohridella (GC-MS/EAD) was used to assess the olfactory detection of fungal-infected A. hippocastanum and A. x carnea leaves by C. ohridella. Infection-related compounds, such as benzyl alcohol, dodecane, tridecane and methyl salicylate as well as fungus-related C8 compounds, are perceived by C. ohridella. The discrimination of E. flexuosa from another phytopathogenic fungus, such as Guignardia aesculi, is based primarily on the differing pattern of C8 compounds of these fungi. Oviposition on fungal-infected leaves of A. hippocastanum and leaves treated with fungal-related compounds showed that C. ohridella is able to respond to the modifications in the leaf volatile profiles of horse chestnuts caused by the different fungal infections. Thus, from the perception point of view, the necessary predispositions for the development of a close insect,fungus relation between the biotrophic fungus E. flexuosa and the leaf-mining insect C. ohridella are fulfilled. However, decreased oviposition on infected leaves does not enhance the selective contact between the species. As a consequence, an important predisposition for forming an insect,fungus mutualism is not fulfilled by these two species and, according to this approach, the risk of forming a complex disease can be assessed as low. [source] Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditionsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2009Lorena Perrone Chronic hyperglycemia and activation of receptor for advanced glycation end products (RAGE) are known risk factors for microvascular disease development in diabetic retinopathy. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of antioxidant thioredoxin (TRX), plays a causative role in diabetes and its vascular complications. Herein we investigate whether HG and RAGE induce inflammation in rat retinal endothelial cells (EC) under diabetic conditions in culture through TXNIP activation and whether epigenetic mechanisms play a role in inflammatory gene expression. We show that RAGE activation by its ligand S100B or HG treatment of retinal EC induces the expression of TXNIP and inflammatory genes such as Cox2, VEGF-A, and ICAM1. TXNIP silencing by siRNA impedes RAGE and HG effects while stable over-expression of a cDNA for human TXNIP in EC elevates inflammation. p38 MAPK-NF-,B signaling pathway and histone H3 lysine (K) nine modifications are involved in TXNIP-induced inflammation. Chromatin immunoprecipitation (ChIP) assays reveal that TXNIP over-expression in EC abolishes H3K9 tri-methylation, a marker for gene inactivation, and increases H3K9 acetylation, an indicator of gene induction, at proximal Cox2 promoter bearing the NF-,B-binding site. These findings have important implications toward understanding the molecular mechanisms of ocular inflammation and endothelial dysfunction in diabetic retinopathy. J. Cell. Physiol. 221: 262,272, 2009. © 2009 Wiley-Liss, Inc [source] EFFECT OF OXYGEN CONCENTRATION ON THE BIOCHEMICAL AND CHEMICAL CHANGES OF STORED LONGAN FRUITJOURNAL OF FOOD QUALITY, Issue 1 2009G. CHENG ABSTRACT Longan fruits were stored for 6 days in atmosphere of 5, 21 (air) or 60% O2 (balance N2) at 28C and 90,95% relative humidity to examine effects of low and high O2 concentration on enzymatic browning and quality attributes of the fruit. Changes in pericarp browning, pulp breakdown, disease development, total phenol content, activities of phenol metabolism-associated enzymes, relative leakage rate, ,,, -diphenyl- , -picrylhydrazy (DPPH) radical scavenging activity, and contents of total soluble solids, titratable acidity and ascorbic acid were evaluated. Storage of fruit in a 5% O2 atmosphere markedly delayed pericarp browning in association with maintenance of high total phenolic content and reduced activities of polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia lyase. Moreover, the fruit stored in a 5% O2 atmosphere exhibited a lower relative leakage rate and higher DPPH radical scavenging activity than fruit stored in air. This presumably was beneficial in maintaining compartmentation of enzymes and substrates, and thus, reducing pericarp browning. Pulp breakdown and disease development were also reduced by exposure to a 5% oxygenatmosphere. On the contrary, exposure of longan fruit to a 60% O2 atmosphere accelerated pericarp browning, pulp breakdown and decay development. PPO and POD activities and relative leakage rate were similar for control and 60% O2 -treated fruit after 4 and 6 days of storage. Furthermore, treatment with 60% O2 significantly decreased the phenolic content and DPPH scavenging activity of fruit. In addition, exposure to 5 or 60% O2 resulted in a higher level of total soluble solids, but a lower level of ascorbic acid of longan fruit flesh. In conclusion, exposure to a 5% O2 atmosphere showed great potential to reduce pericarp browning and extend shelf life of longan fruit. PRACTICAL APPLICATIONS Pericarp browning and pulp breakdown are the major causes of deterioration in postharvest longan. Conventional controlled atmosphere with low O2 and high CO2 is effective in maintaining quality and extending shelf life of fruits and vegetables, including inhibition of tissue browning. In this study, 5%-controlled atmosphere reduced significantly pericarp browning, pulp breakdown and rot development. It could potentially be useful as a postharvest technology of longan fruit for reducing or replacing the use of chemicals such as SO2 and fungicides, but it requires further investigation. [source] Comparison of dietary fat and fatty acid intake estimated by the duplicate diet collection technique and estimated dietary recordsJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 6 2003L. M. Brady Abstract Introduction A high saturated fatty acid intake is a well recognized risk factor for coronary heart disease development. More recently a high intake of n-6 polyunsaturated fatty acids (PUFA) in combination with a low intake of the long chain n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid has also been implicated as an important risk factor. Aim To compare total dietary fat and fatty acid intake measured by chemical analysis of duplicate diets with nutritional database analysis of estimated dietary records, collected over the same 3-day study period. Methods Total fat was analysed using soxhlet extraction and subsequently the individual fatty acid content of the diet was determined by gas chromatography. Estimated dietary records were analysed using a nutrient database which was supplemented with a selection of dishes commonly consumed by study participants. Results Bland & Altman statistical analysis demonstrated a lack of agreement between the two dietary assessment techniques for determining dietary fat and fatty acid intake. Conclusion The lack of agreement observed between dietary evaluation techniques may be attributed to inadequacies in either or both assessment techniques. This study highlights the difficulties that may be encountered when attempting to accurately evaluate dietary fat intake among the population. [source] Is susceptibility to tuberculosis acquired or inherited?JOURNAL OF INTERNAL MEDICINE, Issue 2 2007E. Schurr Abstract. Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well-established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non-genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene,environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis. [source] Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?JOURNAL OF INTERNAL MEDICINE, Issue 3 2006C. SÖDERBERG-NAUCLÉR Abstract. Human cytomegalovirus (HCMV) is a herpes virus that infects and is carried by 70,100% of the world's population. During its evolution, this virus has developed mechanisms that allow it to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen, as it appeared to cause only rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted for survival in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients and in patients undergoing immunosuppressive therapy following organ or bone marrow transplantation. HCMV-mediated disease in such patients has highlighted the possible role of this virus in the development of other diseases, in particular inflammatory diseases such as vascular diseases, autoimmune diseases and, more recently, with certain forms of cancers. Current research is focused on determining whether HCMV plays a causative role in these diseases or is merely an epiphenomenon of inflammation. Inflammation plays a central role in the pathogenesis of HCMV. This virus has developed a number of mechanisms that enable it to hide from the cells of the immune system and, at the same time, reactivation of a latent infection requires immune activation. Numerous products of the HCMV genome are devoted to control central functions of the innate and adaptive immune responses. By influencing the regulation of various cellular processes including the cell cycle, apoptosis and migration as well as tumour invasiveness and angiogenesis, HCMV may participate in disease development. Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases. [source] End-stage renal disease , not an equal opportunity disease: the role of genetic polymorphismsJOURNAL OF INTERNAL MEDICINE, Issue 1 2005L. NORDFORS Abstract. Despite several decades of development in renal replacement therapy, end-stage renal disease (ESRD) patients continue to have markedly increased morbidity and mortality especially caused by cardiovascular disease (CVD). This shows that current strategies, e.g. the focus on dialysis adequacy, to improve the clinical outcome in ESRD patients have to be complemented by novel approaches. Although traditional risk factors are common in dialysis patients they cannot alone explain the unacceptably high prevalence of CVD in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, vascular calcification and oxidative stress. Recent studies show that genetic factors, such as DNA single nucleotide polymorphisms, may significantly influence the immune response, the levels of inflammatory markers, as well as the prevalence of atherosclerosis in this patient group. To elucidate the respective roles of DNA polymorphisms in genes that encode inflammatory markers (such as IL-10, IL-6 and TNF- ,) and other factors that may affect the development of atherosclerosis (such as apolipoprotein E, transforming growth factor and fetuin-A), sufficiently powered studies are needed in which genotype, the protein product and the specific phenotype all are analysed in relation to outcome. The recent developments in the field of genetics have opened up entirely new possibilities to understand the impact of genotype on disease development and progress and thus offer new options and strategies for treatment. It seems conceivable that in the near future, prognostic or predictive multigene DNA assays will provide the nephrological community with a more precise approach for the identification of ,high-risk' ESRD patients and the development of accurate individual treatment strategies. For this purpose, integrative studies on genotype,phenotype associations and impact on clinical outcome are needed. [source] Preclinical AIDS vaccine research: survey of SIV, SHIV, and HIV challenge studies in vaccinated nonhuman primatesJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2002Jon WarrenArticle first published online: 21 AUG 200 Abstract: This current supplementary and systematic survey of 237 preclinical AIDS vaccine challenge/protection studies in nonhuman primates enumerates and broadly describes the recent status of different vaccine strategies in macaque and chimpanzee experimental models. Published studies since the previous survey were compiled and categorized by their vaccine types, challenge parameters, and challenge results. These models have supportively verified that some prophylactic vaccine approaches, though rarely preventing infection (which is observed in these models with some passively administered antibody-based vaccines), can control to some degree primate lentivirus replication and disease development, and this is encouraging because it places more potentially effective immunogens on the precipice for early clinical studies. Many of these promising approaches may benefit from more testing in mucosal challenge models, and resources will be needed to follow more of these partially protected vaccinees for longer periods. [source] Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanismsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008Mario Bermúdez de León Abstract Myotonic dystrophy type 1 (DM1) is a dominant neuromuscular disorder caused by the expansion of trinucleotide CTG repeats in the 3,-untranslated region (3,-UTR) of the DMPK gene. Prominent features of classical DM1 are muscle wasting and myotonia, whereas mental retardation is distinctive for congenital DM1. The main nervous system symptoms of DM1 are cognitive impairment, neuroendocrine dysfunction, and personality and behavior abnormalities. It is thought that expansion of CTG repeats causes DM1 pathology through different molecular mechanisms; however, a growing body of evidence indicates that an RNA gain-of-function mechanism plays a major role in the disease development. At the skeletal muscle level, three main molecular events can be distinguished in this model: 1) formation of nuclear foci that are composed at least of mutant DMPK mRNA and recruited RNA-binding proteins, such as splicing regulators and transcription factors; 2) disturbance of alternative splicing of specific genes; and 3) impairment of cell differentiation. Contrasting with the substantial advances in understanding DM1 muscle pathology, the molecular basis of DM1 in the nervous system has just started to be revealed. This review focuses in the DM1 nervous system pathology and provides an overview of the genetic and molecular studies analyzing the effects of the DMPK gene CUG expanded repeats on cell function in neuronal systems. A comparison between the molecular mechanisms of DM1 in the skeletal muscle and those identified in DM1 nervous system models is provided. Finally, future directions in the study of DM1 in the nervous system are discussed. © 2007 Wiley-Liss, Inc. [source] 24S-hydroxycholesterol in relation to disease manifestations of acute experimental autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2007C.E. Teunissen Abstract Levels of the brain-specific cholesterol metabolite 24S-hydroxycholesterol are proposed as possible biomarkers for multiple sclerosis (MS). It is not yet clear for which aspect of the MS disease manifestations 24S-hydroxycholesterol is a reflection. We studied the relation of serum levels of 24S-hydroxycholesterol and other sterols to the disease characteristics of acute experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Serum was analyzed for cholesterol precursors, oxysterols, and plant sterols during the course of disease development. Significantly increased levels of the cholesterol metabolites 24S-hydroxycholesterol and 27-hydroxycholesterol were observed on day 9, before the onset of clinical signs. The serum levels of these oxysterols gradually increased up to 193% and 415%, respectively, at day 17, when clinical symptoms had recovered. Total cholesterol levels were slightly but significantly decreased on day 9 and day 17 in treated animals. Serum levels of cholesterol precursors and plant sterols decreased gradually from day 11 and day 14, respectively. Immunostaining of the 24S-hydroxycholesterol-forming enzyme Cyp46 was shown in macrophage infiltrates. In vitro experiments confirmed the presence of Cyp46 in macrophages and showed a decreased expression after LPS treatment. The data indicate that changes in serum oxysterols occur early in EAE and can be formed by macrophages. These early changes indicate an important role for oxysterols in the development of EAE. © 2007 Wiley-Liss, Inc. [source] Kinematics of the ACL-deficient canine knee during gait: Serial changes over two yearsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Scott Tashman Abstract The ACL-deficient dog is a model for investigating the development and progression of mechanically driven osteoarthrosis of the knee. ACL loss creates dynamic instability in the ACL-deficient knee which presumably leads to progressive joint degeneration, but the nature of this instability over the time course of disease development is not well understood. The goal of this study was to characterize three-dimensional motion of the canine knee during gait, before and serially for two years after ACL transection. Canine tibial-femoral kinematics were assessed during treadmill gait before and serially for two years after ACL transection (ACL-D group; 18 dogs) or sham transection (ACL-I group; five dogs). Kinematic data was collected at 250 frames/s using a biplane video-radiographic system. Six degree-of-freedom motions of the tibia relative to the femur were calculated, and values immediately prior to pawstrike as well as the maximum, minimum, midpoint and range of motion during early/mid stance were extracted. Between-group differences relative to baseline (pre-transection) values, as well as changes over time post-transection, were determined with a repeated-measures ANCOVA. In the ACL-D group, peak anterior tibial translation (ATT) increased by 10 mm (p < 0.001), and did not change over time (p = 0.76). Pre-pawstrike ATT was similar to ACL-intact values early on (2,4 months) but then increased significantly over time, by 3.5 mm (p < 0.001). The range of ab/adduction motion nearly doubled after ACL loss (from 3.3° to 6.1°). The magnitude (midpoint) of knee adduction also increased significantly over time (mean increase 3.0°; p = 0.036). All changes occurred primarily between 6 and 12 months. There were no significant differences between groups in the transverse plane, and no significant changes over time in the ACL-I group. In summary, peak anterior tibial translation and coronal-plane instability increased immediately after ACL loss, and did not improve with time. ATT just prior to pawstrike and mean knee adduction throughout stance became progressively more abnormal with time, with the greatest changes occurring between 6 and 12 months after ACL transection. This may be due to overload failure of secondary restraints such as the medial meniscus, which has been reported to fail in a similar timeframe in the ACL-deficient dog. The relationships between these complex mechanical alterations and the rate of OA development/progression are currently under investigation. © 2004 Published by Elsevier Ltd. on behalf of Orthopaedic Research Society. [source] Genetic Variability Analysis and Molecular Detection of Fusarium oxysporum f.sp. eustomae Isolated from Eustoma grandiflorum in Northern ItalyJOURNAL OF PHYTOPATHOLOGY, Issue 7-8 2010Yuan Li Abstract A total of 35 isolates of Fusarium oxysporum f.sp. eustomae obtained from diseased Eustoma grandiflorum plants in northern Italy, showing typical Fusarium wilt symptoms, were analysed for their genetic variability and molecular identification. Genetic diversity of the isolates was studied by using random amplified polymorphic DNA (RAPD). This analysis clustered the isolates into three groups at a genetic similarity of 69%. Sequence analysis of RAPD fragments led to the design of a pair of specific primers that amplify a 505-bp SCAR (sequence characterized amplified region) marker (SCAR505) which was used to rapidly detect F. oxysporum f.sp. eustomae on Eustoma grandiflorum plants. In a temperature-controlled chamber, detection of the pathogen by PCR was 100% successful in root and stem samples of infected but still symptomless plants. The diagnostic procedure could be completed in 1 day and allowed rapid and reliable detection of the pathogen in asymptomatic plants in the early stages of disease development. [source] | |||||||||||||||||||||||||||||||