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Search Results: 1 - 10 of 371157 matches for " Chella S David "
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Association of MHC and rheumatoid arthritis: Regulatory role of HLA class II molecules in animal models of RA - studies on transgenic/knockout mice
Veena Taneja, Chella S David
Arthritis Research & Therapy , 2000, DOI: 10.1186/ar88
Abstract: Over a period of nearly two decades, several studies have shown the association of various HLA class II molecules to autoimmune diseases. Since the antigens are presented as a MHC-peptide complex by antigen presenting cells, a crucial role of HLA molecules is indicated in distinguishing self and nonself. However, the pathophysiological role of the HLA associations is poorly understood, although a break in peripheral tolerance to distinguish self from nonself has been suggested to be a critical step for development of autoimmune disease. RA is an autoimmune disorder, leading to pathological damage to joints. Although etiology and candidate antigen for RA is unknown, type II collagen is a potential candidate since it is a major component of joint articular cartilage, and both anti-type II collagen antibodies and T cells specific for type II collagen have also been detected in patients. Extensive documentation exists linking HLA-DR molecules that share the HV3 region with the DRB1*0401 'shared epitope' to susceptibility to RA, although the mechanism is not clear. Recently, it has been proposed that shared epitope might function by determining the charge in peptide binding pockets [1]. Alternatively, this epitope might be responsible for shaping the T cell repertoire in thymus, thereby determining the outcome of disease when the relevant antigen is presented in periphery [2]. However, since DRB1 genes occur in linkage with DQB1, it is difficult to rule out the role of DQ molecule in disease development. Studies in certain ethnic populations do suggest that DQ genes play an important role in the disease process. Recent insights into structure and function of MHC has enabled us to better understand the interaction between MHC-peptide complexes and T cell receptor along with other T cell surface molecules. Since immune response to a particular antigen depends on the specificity and affinity of binding to MHC and T cell recognition, it is important to define the causative a
Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneously
Jennifer L Lamoureux, Jane Buckner, Chella S David, David S Bradley
Arthritis Research & Therapy , 2006, DOI: 10.1186/ar2023
Abstract: We present evidence here that transgenic strains expressing the DQ6α8β transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5–6 months and 40–50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis – three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however – more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis.This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis.Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology. RP is relatively rare, affecting 3.5–4/1,000,000 people, with a slight female preponderance [1]. Typical onset occurs during mid-life years with a median age of diagnosis at 46.6 years, although cases have been reported in newborns and in individuals over the age of 80 [2]. The most prominent manifestations of RP are auricular chondritis, polyarthritis and saddle nose deformation, with
Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome
Ashenafi Y. Tilahun,Marah Holz,Tsung-Teh Wu,Chella S. David,Govindarajan Rajagopalan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016764
Abstract: Toxic shock syndrome (TSS) caused by the superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes is characterized by robust T cell activation, profound elevation in systemic levels of multiple cytokines, including interferon-γ (IFN-γ), followed by multiple organ dysfunction and often death. As IFN-γ possesses pro- as well as anti-inflammatory properties, we delineated its role in the pathogenesis of TSS. Antibody-mediated in vivo neutralization of IFN-γ or targeted disruption of IFN-γ gene conferred significant protection from lethal TSS in HLA-DR3 transgenic mice. Following systemic high dose SEB challenge, whereas the HLA-DR3.IFN-γ+/+ mice became sick and succumbed to TSS, HLA-DR3.IFN-γ?/? mice appeared healthy and were significantly protected from SEB-induced lethality. SEB-induced systemic cytokine storm was significantly blunted in HLA-DR3.IFN-γ?/? transgenic mice. Serum concentrations of several cytokines (IL-4, IL-10, IL-12p40 and IL-17) and chemokines (KC, rantes, eotaxin and MCP-1) were significantly lower in HLA-DR3.IFN-γ?/? transgenic mice. However, SEB-induced T cell expansion in the spleens was unaffected and expansion of SEB-reactive TCR Vβ8+ CD4+ and CD8+ T cells was even more pronounced in HLA-DR3.IFN-γ?/? transgenic mice when compared to HLA-DR3.IFN-γ+/+ mice. A systematic histopathological examination of several vital organs revealed that both HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ?/? transgenic mice displayed comparable severe inflammatory changes in lungs, and liver during TSS. Remarkably, whereas the small intestines from HLA-DR3.IFN-γ+/+ transgenic mice displayed significant pathological changes during TSS, the architecture of small intestines in HLA-DR3.IFN-γ?/? transgenic mice was preserved. In concordance with these histopathological changes, the gut permeability to macromolecules was dramatically increased in HLA-DR3.IFN-γ+/+ but not HLA-DR3.IFN-γ?/? mice during TSS. Overall, IFN-γ seemed to play a lethal role in the immunopathogenesis of TSS by inflicting fatal small bowel pathology. Our study thus identifies the important role for IFN-γ in TSS.
DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP)
Nathali Kaushansky, Daniel M Altmann, Chella S David, Hans Lassmann, Avraham Ben-Nun
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-29
Abstract: The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II-/-), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile.PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice.While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.Multiple sclerosis (MS) is a disease of the human central nervous system (CNS), characterized by perivascular inflammation, accompanied by primary demyelination and axonal damage. It is believed to result from autoimmune mechanisms leading to destruction of myelin, presumably initiated by abnormally activated T cells that recognize CNS components in MS patients. The pathogenic autoimmunity in MS appears to be associa
Nonequivalence of Classical MHC Class I Loci in Ability to Direct Effective Antiviral Immunity
Kevin D. Pavelko equal contributor,Yanice Mendez-Fernandez equal contributor,Michael P. Bell,Michael J. Hansen,Aaron J. Johnson,Chella S. David,Moses Rodriguez,Larry R. Pease
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002541
Abstract: Structural diversity in the peptide binding sites of the redundant classical MHC antigen presenting molecules is strongly selected in humans and mice. Although the encoded antigen presenting molecules overlap in antigen presenting function, differences in polymorphism at the MHC I A, B and C loci in humans and higher primates indicate these loci are not functionally equivalent. The structural basis of these differences is not known. We hypothesize that classical class I loci differ in their ability to direct effective immunity against intracellular pathogens. Using a picornavirus infection model and chimeric H-2 transgenes, we examined locus specific functional determinants distinguishing the ability of class I sister genes to direct effective anti viral immunity. Whereas, parental FVB and transgenic FVB mice expressing the H-2Kb gene are highly susceptible to persisting Theiler's virus infection within the CNS and subsequent demyelination, mice expressing the Db transgene clear the virus and are protected from demyelination. Remarkably, animals expressing a chimeric transgene, comprised primarily of Kb but encoding the peptide binding domain of Db, develop a robust anti viral CTL response yet fail to clear virus and develop significant demyelination. Differences in expression of the chimeric Kbα1α2Db gene (low) and Db (high) in the CNS of infected mice mirror expression levels of their endogenous H-2q counterparts in FVB mice. These findings demonstrate that locus specific elements other than those specifying peptide binding and T cell receptor interaction can determine ability to clear virus infection. This finding provides a basis for understanding locus-specific differences in MHC polymorphism, characterized best in human populations.
The role of the outdoor space in the containment of the energy consumption of the building
Michele Lepore,Fabrizio Chella
Techne : Journal of Technology for Architecture and Environment , 2012,
Abstract: In most of the contemporary urban spaces built in recent decades in Italy little attention is evident on the creation of environmental niches that are able to mitigate the microclimate. The following research aims to verify how the physical design of the outer space affects either the immaterial dimension of the space itself (livability, comfort), and the environmental performances of the surrounding buildings. The research supports the definition of the energetic-environmental requalification techniques to be used in the recovery phase of buildings. The analysis of the microclimatic features in the outdoor urban spaces, together with the implications in terms of comfort for those people who use them, opens new possibilities for the development of urban areas for what concerns both the new design and the requalification of the existing built-up area. Because of the complexity in terms of space-time variability of such parameters and of the wide set of activities in which people are committed, there have been so far very few attempts to understand the external comfort conditions, but mainly of how the external climatic effects could have an impact on the internal comfort conditions of the inhabited area.
Analysis of flow pattern between hill and lake
Devatha Chella,Arun Kumar Thalla
Journal of Engineering and Applied Sciences , 2009,
Abstract: The demand for water is increasing rapidly with the increased population, industries and irrigation which lead to the scarcity of water. In order to avoid such a scarcity, which will hamper the development of the country, water resources projects should be planned and managed effectively. The south part of the Chennai metropolitan in India consists of hills and lakes. Due to the rapid urbanization, all the lakes in this zone are being encroached thus hindering the contribution of lake for ground water resulting in the depletion of ground water. For this enhancing situation, a microlevel study has been carried out on the surface water estimation and analysis of sub-surface flow pattern. This paper mainly emphasize on ground water modeling using VISUAL MODFLOW. Groundwater flow models are used to calculate the rate and direction of movement of groundwater through aquifers. Estimation of surface runoff using Soil Conservation Service (SCS) shows that only in the year 2004, there is a high runoff which leads to over flow from the lakes and for the other years (2001-2003) average runoff contribution to the lakes is from 17% to 45%. The ground water analysis was done for six years (2001 to 2006) and the results indicate that for the monsoon period the velocity ranges from 0.02 to 0.05m/sec and for the non-monsoon period it ranges from 3.21*10-2m/sec to 8.75*10-2m/sec. which implies that there is a rapid increase in the radius of influence due to urbanization.
On Various Parameters of $Z_q$-Simplex codes for an even integer q
P. Chella Pandian,C. Durairajan
Mathematics , 2015,
Abstract: In this paper, we defined the $Z_q$-linear codes and discussed its various parameters. We constructed $Z_q$-Simplex code and $Z_q$-MacDonald code and found its parameters. We have given a lower and an upper bounds of its covering radius for q is an even integer.
Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice
Jane M. Natividad, Xianxi Huang, Emma Slack, Jennifer Jury, Yolanda Sanz, Chella David, Emmanuel Denou, Pinchang Yang, Joseph Murray, Kathy D. McCoy, Elena F. Verdú
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006472
Abstract: Background and Aims Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. Methodology/Principal Findings HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-γ in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. Conclusion Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-γ production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota.
Multiphase, Multicomponent Fluid Flow in Homogeneous and Heterogeneous Porous Media écoulement de fluides multiconstituants polyphasiques dans des milieux poreux homogènes et hétérogènes
Chella R.,Lasseux D.,Quintard M.
Oil & Gas Science and Technology , 2006, DOI: 10.2516/ogst:1998029
Abstract: The flow of several components and several phases through a porous medium is generally described by introducing macroscopic mass-balance equations under the form of generalized dispersion equations. This model raises several questions that are discussed in this paper on the basis of results obtained from the volume averaging method, coupled with pore-scale simulations of the multiphase flow. The study is limited to a binary, two-phase system, and we assume that the momentum equations can be solved independently from the diffusion/advection equations. The assumption of local-equilibrium is discussed and several length-scale and time-scale constraints are provided. A key issue concerns the impact on the dispersion tensors of the pore-scale equilibrium condition at the interface between the different phases. Our results show that this phenomenon may lead to significant variations of the dispersion coefficients with respect to passive dispersion, i. e. , dispersion without interfacial mass fluxes. Macroscopic equations are then obtained in the general case, and several local closure problems are provided that allow one to calculate the dispersion tensors and others properties, from the pore-scale geometry, velocities, and fluid characteristics. Examples of solutions of these closure problems are given in the case of two-dimensional representative unit cells. The two-phase flow equations are solved in two different ways : a boundary element technique, or a modified lattice Boltzmann approach. Solutions of the closure problems associated with the dispersion equations are then given using a finite volume element formulation of the partial differential equations. The results show the influence of velocity and saturation on the effective parameters. They emphasize the importance of geometry on the behavior of the dispersion tensor. Extension of these results to a larger-scale including the effect of heterogeneities is proposed in a limited case corresponding to the flow of one phase, the other phase being at residual saturation. A new large-scale dispersion equation is provided, which features a large-scale dispersion tensor that can be determined from the heterogeneity characteristics through a set of closure problems. Results are extended to a more general two-phase flow problem, when the large-scale two-phase flow can be assumed to be quasi-static. Indications are given on the difficulties associated with flow under large-scale dynamic conditions, with abnormal dispersion. L'écoulement polyphasique de plusieurs constituants à travers un milieu poreux est génér
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