bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis
Authors: Leon M P , Spickett G , Jones D E J , Bassendine M F 
Published: July 2010

SUMMARY
Primary biliary cirrhosis (PBC) is an autoimmune condition characterized by destruction of the intrahepatic bile ducts. Autoreactive CD4+ T cells have been reported both in the peripheral circulation and in the mononuclear cell infiltrate in the affected portal tracts. In this large study we have used two- and three-colour flow cytometry to determine the phenotypes of the CD4+ T cell subsets in the peripheral blood and liver-infiltrating lymphocytes of PBC patients (n= 43), normal controls (n= 19) and patients with alcoholic cirrhosis (n= 15), according to a novel classification based on the simultaneous expression of different isoforms of CD45. In PBC patients the proportion of peripheral blood CD4+Cells possessing the CD45ROhigh RA−‘memory’ phenotype was significantly increased, and the CD45RO− RAhigh‘naive’ population was significantly decreased, compared with the two control groups. No significant differences in peripheral blood CD4+ T cell subsets were seen between patients with pre-cirrhotic and cirrhotic PBC. A similar, but more marked, shift towards the CD45ROhigh RA−‘memory’ phenotype was seen in the liver-infiltrating CD4+ T cells in PBC patients compared with alcoholic cirrhotics. Cells within the CD4+ memory subpopulation were further subgrouped according to expression of CD45RB, the level of expression of which has been associated with functional differences in the memory subset. In peripheral blood no differences were seen between PBC patients and controls with respect to the proportion of CD45ROhigh RBhigh and CD45ROhigh RBdim memory subsets. A statistically significant difference in the distribution of these memory subsets, with an increased memory-2/ memory-1 ratio was observed in the liver-infiltrating CD4+ T cells of PBC patients compared with those from alcoholic cirrhotic patients. The potential implications of this observation are discussed.
Immunogenetics of epitopes of the carboxyl terminus of the human 60-kD Ro autoantigen
Authors: Scofield R H , Dickey W D , Hardgrave K L , Neas B R , Horowitz R M , Mcarthur R A , Fujisak A , Frank M B , Harley J B 
Published: July 2010

SUMMARYSystemic lupus erythematosus is associated with the presence of autoantibodies which bind several ribonucleoproteins, including Ro (or SS-A). We have explored the relationship of the HLA-DQ and T cell receptor alleles in patients producing autoantibodies binding the 13-kD carboxyl terminus fragment of the 60-kD Ro and with autoantibodies binding a peptide epitope within this fragment (amino acid residues 480 494). Antibodies binding the 13-kD fragment are more likely to be found in the sera of patients with particular DQA1 and DQB1 alleles, while antibodies binding the epitope at 480–494 are found almost exclusively in the sera of patients with a Bg/II 9–8-kb polymorphism of the T cell receptor β gene. Meanwhile, in these same patient sera the level of autoantibodies binding the complete 60-kD Ro particle is associated with a distinct pattern of alleles at these same immunoregulatory loci. These data demonstrate that component parts of autoantibody responses may be under genetic control which can be distinguished from the HLA associations characteristic of the response to the intact, complete autoantigen.
A vridine-induced arthritis in rats; a T cell-dependent chronic disease influenced both by MHC genes and by non-MHC genes
Authors: Vingsbo C , Jonsson R , Holmdahl R 
Published: July 2010

SUMMARY
Avridine is a potent synthetic adjuvant that can induce arthritis in most rat strains. The clinical appearance and histopathology of avridine-induced arthritis show great similarity to other arthritis models such as collagen-induced arthritis. In LEW and DA rats the avridine-induced arthritis is severe and long lasting. To investigate a possible genetic influence on the disease we compared LEW, DA and E3 rats, which are of different genetic origins, for their ability to develop arthritis after injection of a low dose of avridine (1.5mg/rat). The E3 rat was shown to be resistant, whereas ail of the DA rats developed arthritis. Recombinant inbred strains derived from DA and E3 parentals varied in susceptibility to avridine. Only strains sharing RT1av1 with DA developed arthritis, indicating a role for the MHC genes. The MHC association was further analysed in a series of Lewis congenic strains using the l-5mg avridine dose. All strains developed arthritis. LEW.1C and LEW.1W developed only acute arthritis, whereas LEW.1A, LEW, LEW.1D, LEW.1N and LEW.1F developed chronic arthritis. In particular, the LEW.1F rats developed a chronic severe arthritis of high incidence. The chronic arthritis showed an active, erosive joint inflammation several months after induction. Nude rats are resistant to avridine-induced arthritis, indicating a T cell dependence of the disease which supports the importance of MHC. However, non-MHC genes are also crucial to arthritis development. Recombinants between DA and E3, sharing RT1av1 with DA, showed either a lower incidence or a lower severity of disease than the DA rats. The E3 rat and the recombinants with RT1u were completely resistant, whereas LEW.1W, also RT1u, were highly susceptible.
Oligoclonal activation of CD4+ T lymphocytes in posterior uveitis
Authors: Feron E J , Calder V L , Lightman S L 
Published: July 2010

SUMMARYSeveral lines of evidence support an important role for activated T lymphocytes in the perpetuation of autoimmune intraocular inflammatory disease (posterior uveitis). In this study peripheral blood lymphocytes (PBL) were examined by three-colour flow cytometry to assess the distribution of IL-2 receptors (IL-2R) among CD4+ and CD8+ T cell subsets in patients with active posterior uveitis and control subjects. Patients with uveitis (n= 70) showed a significant increase in PBL expressing the α-chain (Tac) of the IL-2R compared with controls (n= 28) (34·2%versus 29·6%) (P &lt; 0·05). This increased Tac expression was present on both the CD4+ subset (25·7%versus 20·9%) (P &lt; 0·05) and the CD8+ subset (2·5%versus 1·8%) (P &lt; 0·05) of lymphocytes. We also examined whether the activated CD4+ PBL from uveitis patients (n= 30) showed a dominant pattern of T cell receptor (TCR) gene rearrangement, suggestive of an oligoclonal response to a small number of antigenic peptides. A significant increase in the usage of the Vα2.3 TCR family by activated but not by non-activated CD4+ PBL was detected in patients (3·9%versus 3·4%) (P &lt; 0·05) compared with controls. There was evidence of oligoclonal activation of CD4+ PBL in 11/30 patients (36·7%) but in none of the controls (n= 10). However, different Vα or Vβ TCR families were selectively activated among and even within individual patients. The heterogeneity in TCR expression among patients with active intraocular inflammatory disease is discussed.
Blood-Stage malaria infection in diabetic mice
Authors: Elased K , De Souza J B , Playfair J H L 
Published: July 2010

SUMMARYInfection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice.
Activated CD4+ T cells preferentially take up lipid microspheres, but resting cells do not
Authors: Suzuki K 
Published: July 2010

SUMMARYLipid microspheres (LM) used as drug carriers increase the effectiveness and reduce the toxicity of incorporated drugs. The present study is designed to determine whether or not activated T lymphocytes, which were the cells chosen first from the ‘inflammatory cells’, can take up LM in vitro. LM were labelled with a fluorescent probe, DiI (Dil-LM), to examine the kinetics. Flow cytometric analysis demonstrated that in freshly isolated peripheral blood mononuclear cells (PBMC), monocytes principally took up Dil-LM, while lymphocytes and granulocytes did not. When PBMC were stimulated with immobilized anti-CD3 MoAb and IL-2, cells expressing CD3, CD4, CD8 and CD 16 incorporated Dil-LM. Purified CD4+ T cells, obtained by positive panning selection, were stimulated with this system. They were CD25, CD71, LFA-1-positive, and also showed an ability to take up Dil-LM, which resting cells did not. The findings were confirmed by flow cytometry and quantitative analysis of Dil. Confocal micrographs showed fluorescent granules from the probe in the cytoplasm of stimulated CD4+ T cells after incubation with DiI-LM. These results suggest that immunomodulatory agents incorporated into LM might selectively regulate the function of CD4+ or CD8+ T cells when these are activated.
Screening for anti-neutrophil cytoplasmic antibodies (ANCA): is indirect immunofluorescence the method of choice?
Authors: Baslund B , Segelmark M , Wiik A , Szpirt W , Petersen J , Wieslander J 
Published: July 2010

SUMMARYDetection of ANCA has become an important tool for the diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG). Unfortunately, a group of sera positive by the standard method for ANCA detection, indirect immunofluorescence (IIF). are negative when more specific tests with purified proteins are used. In order to examine this discrepancy we examined groups of sera selected for being (i) C-ANCA-positive by IIF; (ii) positive in proteinase 3 (PR3)-ANCA ELISA; and (iii) from 24 patients with WG. The following assays were used: IIF, PR3-ANCA ELISA and capture PR3-ANCA ELISA using MoAbs against PR3. Furthermore, since granule enzymes are released during coagulation, we also measured ANCA in complex with PR3. To test if granule enzyme release had any influence on ANCA detection, both serum and EDTA-plasma were collected from a patient with active WG. No difference, however, was found. In the IIF-positive group (n= 60) 68% of the sera were positive in PR3-ANCA ELISA. 86% in capture PR3-ANCA ELISA and 80% were positive for the PR3 IgG-ANCA complex. In the PR3-ANCA ELISA group (n= 105) 88% of the sera were positive by IIF, 98% in capture PR3-ANCA ELISA and 53% in the PR3/IgG-ANCA assay. To evaluate the tests clinically sera from 24 patients with WG were examined. In the remission group (n= 10) two patients were positive by IIF, four in the PR3-ANCA ELISA, and five in the capture PR3-ANCA ELISA. Fourteen had active disease, and in this group 11/14 were positive by IIF, 10/14 in PR3-ANCA ELISA and 12/14 by capture-ELISA. The correlation between IIF and capture PR3-ANCA ELISA titre (r= 0·72, P= 0·0095) was better than between PR3-ANCA ELISA and IIF (r= 0·56. P= 0·043). It is concluded that the capture PR3-ANCA ELISA is more sensitive than PR3-ANCA ELISA, and that the capture ELISA can be used for screening of PR3-ANCA.
Inhibition of tumour necrosis factor-alpha (TNF-α) release from mast cells by the anti-inflammatory drugs, sodium cromoglycate and nedocromil sodium
Authors: Bissonnette E Y , Enciso J A , Befus A D 
Published: July 2010

SUMMARYTNF-α is a cytokine thought to be involved in the pathogenesis of asthma and in several other inflammatory conditions. Given recent evidence that mast cells (MC) are an important source of TNF-α, we investigated the effects of two anti-inflammatory drugs, nedocromil sodium (NED) and sodium cromoglycate (SCG). on rat MC-derived TNF-α. We established that at least 2h pretreatment with NED or SCG followed by washing was required to inhibit TNF-α-dependent cytotoxicity by rat peritoneal MC (PMC). A maximum inhibition of TNF-α occurred after 6h treatment. The inhibitory effect of NED and SCG (10−5 10−3 M) was concentration-dependent (20-37% for NED and 16-37% for SCG). The time-course analysis and the use of cycloheximide, an inhibitor of protein synthesis, provided strong evidence that new protein synthesis by the MC is required for this inhibitory effect. Furthermore, 24h treatment with I mM NED inhibited the levels of mRNA for TNF-α by 59-83%. In addition to the effect on TNF-α-dependent cytotoxicity by MC, 20min pretreatment with 10−4M NED and SCG inhibited antigen-stimulated TNF-α release (6h) by 42% and 48%, respectively. Interestingly, the functionally distinct intestinal mucosal MC (IMMC) is unresponsive to these drugs with regard to histamine secretion. However, as with PMC, 2h pretreatment with NED or SCG inhibited TNF-α-dependent cytotoxicity by IMMC. These effects may be important in the action of these drugs in vivo in the late phase reaction in asthma or other inflammatory conditions.
Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis
Authors: Shijubo N , Imai K , Shigehara K , Hirasawa M , Tsujisaki M , Hinoda Y , Abe S 
Published: July 2010

SUMMARYICAM-1 plays AN important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-l) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar marcrophages, and significantly increased values of circulating and BAL fluid sICAM-l in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients. sICAM-l values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-l values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.
Epitope mapping of anti-proteinase 3 and anti-myeloperoxidase antibodies
Authors: Chang L , Binos S , Savige J 
Published: July 2010

SUMMARYAnti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) autoantibodies are present in many patients with Wegener's granulomatosis (WG) and microscopic polyarteritis. The aim of this study was to determine whether these antibodies bound to linear peptide sequences on their target antigens. If common linear epitopes were demonstrated, then these could be manufactured and used in diagnostic ELISAs for anti-PR3 and anti-MPO antibodies. In addition, any homology between these epitopes and bacterial or viral sequences might implicate those microorganisms in the development of these antibodies and the pathogenesis of the associated diseases. The presence of linear epitopes on PR3 and MPO was suggested by the binding of the corresponding autoantibodies to these proteins after they had been reduced with beta-mercaptoethanol (β-ME) and denatured with SDS or boiling, and digested with proteases. Four of the 22 sera with anli-PR3 antibodies bound to PR3 in Western blots after treatment with SDS. β-ME and boiling for 5 min. Thermal denaturation reduced the amount of binding more than other forms of denaturation. One serum with anti-PR3 antibodies bound to Lys-C and Glu-C-digested PR3 in dot blots. Linear epitopes could not be further defined by their binding in an EL ISA using overlapping peptides corresponding to the PR3 molecule because of non-specific binding. Three of the five sera with anti-MPO antibodies bound to MPO in Western blots after treatment with SDS, 5-MEand boiling for 5 min. One serum with anti-MPO antibodies bound to Lys-C and Glu-C-digested MPO in dot blots. Again, linear epitopes could not be further defined using an ELISA with overlapping peptides because of non-specific binding. Sotne anti-PR3 and anti-MPO antibodies are likely to recognize linear epitopes. but these cannot be defined by use of a PIN ELISA system.
Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration
Authors: Blank M , Tomer Y , Stein M , Kopolovic J , Wiik A , Meroni P L , Conforti G , Shoenfeld Y 
Published: July 2010

SUMMARY
Wegener's granulomatosis (WG) is a granuiomatous necrotizing vasculitis associated with the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLF) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin. respectively. The mice developed first anti-autoantibodies and, alter about 4 months anti-anti-autoantibodies (Ab3. simulating autoantibodies (Ab1) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of the human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purified IgG fraction (ANCA) from the sera of two patients with untreated WG. emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In the first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after S 15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity both to PR3 and to myeloper-oxidase, as well as anti-endothelial autoantibodies (AECA), as shown by radioimmunoprecipitation, Pathologically, the immunized mice developed proteinuria hut not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while dif fuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.
Progressive renal lesions induced by administration of monoclonal antibody 1-22-3 to unilaterally nephrectomized rats
Authors: Cheng QL , Orikasa M , Morioka T , Kawachi H , Chen XM , Oite T , Shimizu F 
Published: July 2010

SUMMARYA new animal model of progressive glomerulosclerosis was developed by administering a single i.v., injection of MoAb 1–22–3 to unilaterally nephrectomized rats. Renal morphological analysis revealed that glomerular lesions characterized by mesangial cell proliferation and mesangial matrix expansion were induced in about 95% of the glomeruli. Approximately 20% of the glomeruli of the unilaterally nephrectomized rats showed sclerosis or segmental sclerosis by week 6 after MoAb injection and crescent formation was observed in some glomeruli (ca 4%). Cellular infiltration was also noted in some parts of the interstitium. Increased expression of transforming growth factor–beta (TGF-β) was observed in the unilaterally nephrectomized rats treated with MoAb 1-22-3, but we could not demonstrate pathological involvement of platelet-derived growth factor (PDGF). even though early-stage mesangial cell proliferation was observed. The mechanism of mesangial cell proliferation in this model remains to be elucidated. The relatively short period of time needed to induce the sclerotic changes is considered to be a great advantage of this model for clarifying the mechanisms involved in the chronic progression of mesangial proliferative glomerulonephritis.
Proteomic analysis of peripheral T lymphocytes, suitable circulating biosensors of strictly related diseases
Authors: Borro M , Gentile G , Stigliano A , Misiti S , Toscano V , Simmaco M 
Published: July 2010

Summary
T lymphocytes and/or their subpopulations from peripheral blood may represent molecular sensors to be used for the evaluation of gene expression modification in physiological and pathological conditions, providing a unique and easily available biological model for integrated studies of gene expression in humans. In this study, a proteomic approach was applied to evaluate the association between changes in T cell protein expression patterns and specific diseased conditions. In particular, two hyperandrogenic syndromes were studied, sharing many clinical and biochemical signs: polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH). Comparison of proteomic maps of T lymphocytes derived from patients affected by PCOS or CAH with those derived from healthy subjects showed that 14 proteins are expressed differentially in both PCOS and CAH, 15 exclusively in PCOS and 35 exclusively in CAH. Seventeen of these proteins have been identified by mass spectrometry analysis. Furthermore, proteomic data mining by hierarchical clustering was performed, highlighting T lymphocytes competence as a living biosensor system.
Tumour necrosis factor-α blockade suppresses murine allergic airways inflammation
Authors: Hutchison S , Choo-Kang B S W , Bundick R V , Leishman A J , Brewer J M , McInnes I B , Garside P 
Published: July 2010

SummaryAsthma is a heterogeneous disease that has been increasing in incidence throughout western societies and cytokines, including proinflammatory tumour necrosis factor alpha (TNF-α), have been implicated in the pathogenesis of asthma. Anti-TNF-α therapies have been established successfully in the clinic for diseases such as rheumatoid arthritis and Crohn's disease. TNF-α-blocking strategies are now being trialled in asthma; however, their mode of action is poorly understood. Based on the observation that TNF-α induces lymph node hypertrophy we have attempted to investigate this as a mechanism of action of TNF-α in airway inflammation by employing two models of murine airway inflammation, that we have termed short and long models, representing severe and mild/moderate asthma, respectively. The models differ by their immunization schedules. In the short model, characterized by eosinophilic and neutrophilic airway inflammation the effect of TNF-α blockade was a reduction in draining lymph node (DLN) hypertrophy, eosinophilia, interleukin (IL)-5 production and immunoglobulin E (IgE) production. In the long model, characterized by eosinophilic inflammation, TNF-α blockade produced a reduction in DLN hypertrophy and IL-5 production but had limited effects on eosinophilia and IgE production. These results indicate that anti-TNF-α can suppress DLN hypertrophy and decrease airway inflammation. Further investigations showed that anti-TNF-α-induced inhibition of DLN hypertrophy cannot be explained by preventing l-selectin-dependent capture of lymphocytes into the DLN. Given that overall TNF blockade was able to suppress the short model (severe) more effectively than the long model (mild/moderate), the results suggest that TNF-α blocking therapies may be more effective in the treatment of severe asthma.