bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benznidazole, a drug employed in the treatment of Chagas’ disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages
Authors: Revelli S , LE. Page C L E , Piaggio E , Wietzerbin J , Bottasso O 
Published: March 2003

SUMMARYBenznidazole (BZL) is a nitroheterocyclic drug employed in the chemotherapy of Chagas’ disease, a protozoan disease caused by Trypanosoma cruzi. Because this parasite mostly replicates in macrophages, we investigated whether BZL was likely to modify the synthesis of macrophage mediators such as nitrite, tumour necrosis factor-alpha (TNF-α), IL-1β, IL-6 and IL-10. Control and stimulated murine macrophages (lipopolysaccharide (LPS) and/or interferon-gamma (IFN-γ)) were treated with BZL and measurements were carried out in culture supernatants collected 24 h later. Synthesis of nitrite, IL-6 and IL-10 was maximal upon combined stimulation with LPS + IFN-γ, whereas lower amounts of the three mediators were detected when both stimuli were given alone. BZL treatment significantly reduced nitrite, IL-6 and IL-10 production, to undetectable levels in some cases, particularly IL-6 and IL-10. LPS was the most potent stimulus of IL-1β and TNF-α production, followed by LPS + IFN-γ and IFN-γ in decreasing order. BZL partly inhibited TNF-α synthesis, but this effect was smaller than that observed for nitrite, IL-6 and IL-10. LPS-induced production of IL-1β was also affected by BZL. Semiquantification of gene expression for inducible nitric oxide synthase (iNOS) showed that BZL completely inhibited iNOS gene induction by IFN-γ, and resulted in respective inhibitions of 30% and 50% with LPS- and LPS + IFN-γ-stimulated cells. BZL was not cytotoxic on macrophage cultures, as shown by the lactate dehydrogenase activity. Besides its trypanocidal activity, BZL may also alter the balance between pro- and anti-inflammatory mediators with important consequences for the course of T. cruzi infection.
Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant
Authors: O’Toole E A , Mak L L , Guitart J , Woodley D T , Hashimoto T , Amagai M , Chan L S 
Published: March 2003

SUMMARYA subset of pemphigus herpetiformis, a rare pemphigus variant, is characterized histopathologically by subcorneal acantholysis and neutrophilic infiltration. The mechanism of neutrophil infiltration is unknown, but chemokines such as IL-8 may play a role. We investigated the possible role of IL-8 in two such cases. Direct and indirect immunofluorescence studies demonstrated in vivo-bound and circulating IgG epithelial cell surface-binding autoantibodies, both predominated by IgG4 subclass. ELISA and immunoblotting studies revealed that the patients’ IgG autoantibodies recognized recombinant desmoglein 1 but not desmoglein 3. Preadsorption of the patients’ sera with recombinant desmoglein 1 completely removed the epidermal cell surface immunostaining. Significantly, immunohistochemistry demonstrated intense expression of IL-8, co-localized with in vivo-bound IgG, in the upper epidermis, where the acantholysis took place. Affinity-purified sera IgG from these two patients, a normal individual, and a pemphigus vulgaris patient containing desmoglein 1 autoantibodies, were incubated with normal human keratinocytes in vitro. Cells treated with these patients’ IgG secreted a seven-to-nine-fold increase of IL-8 (30–37 pg/ml) compared with the controls (2–4 pg/ml) and expressed a higher intensity of cytoplasmic IL-8 staining. These data demonstrate a novel functional role for IL-8 in the pathogenesis of the neutrophil-dominant subset of pemphigus herpetiformis. The autoantibody-induced epidermal cell IL-8 expression may represent a novel mechanism of epidermal neutrophil recruitment.
Induction of microthrombotic thrombocytopenia in normal mice by transferring a platelet-reactive, monoclonal anti-gp70 autoantibody established from MRL/lprmice: an autoimmune model of thrombotic thrombocytopenic purpura
Authors: Hashimoto K , Tabata N , Fujisawa R , Matsumura H , Miyazawa M 
Published: March 2003

SUMMARYMRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop immune complex-mediated glomerulonephritis and thrombocytopenia. Although the presence of cross-reactive anti-phospholipid antibodies in sera of MRL/lpr mice has been demonstrated, possible relationships between detected autoantibodies and the development of thrombocytopenia have not been elucidated. Recent genetic analyses in a few different strains of lupus-prone mice have pointed out a close correlation between autoantibodies reactive with endogenous retroviral env gene product, gp70, and the development and severity of glomerulonephritis. In the process of establishing possibly nephritogenic anti-gp70 autoantibody-producing hybridoma cells from MRL/lpr mice, we identified an IgG2a-producing anti-gp70 hybridoma clone that induced microvascular intraluminal platelet aggregation, thrombocytopenia, and amenia upon transplantation into syngeneic non-autoimmune mice. This and two other anti-gp70 antibodies bound onto the surface of mouse platelets, and purified IgG2a of the anti-gp70 autoantibody induced glomerular lesions with characteristics of thrombotic thrombocytopenic purpura when injected into non-autoimmune mice. The pathogenic anti-gp70 autoantibody specifically precipitated a platelet protein with an approximate relative molecular mass of 40 000.
Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus
Authors: Byleveld M , Pang G T , Clancy R L , Roberts D C K 
Published: March 2003

SUMMARYThe effect of a fish oil diet on virus-specific cytotoxicity and lymphocyte proliferation was investigated. Mice were fed fish oil (17 g fish oil and 3 g sunflower/100 g) or beef tallow (17 g tallow and 3 g sunflower/100 g) diets for 14 days before intranasal challenge with influenza virus. At day 5 after infection, lung virus-specific T lymphocyte, but not macrophage or natural killer (NK) cell, cytotoxicity was significantly lower in mice fed fish oil, while bronchial lymph node cell proliferation to virus was significantly higher. In mice fed fish oil, spleen cell proliferation to virus was also significantly higher following immunization. The results showed that, despite improved lymphocyte proliferation, fish oil impairs primary virus-specific T lymphocyte cytotoxicity. This impairment may explain the delayed virus clearance that we have previously reported in infected mice fed the fish oil diet.
PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis
Authors: Tay G K , Hui J , Gaudieri S , Schmitt-Egenolf M , Martinez O P , Leelayuwat C , Williamson J F , Eiermann T H , Dawkins R L 
Published: March 2003

SUMMARY
The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis.
Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice
Authors: Verdù E F , Bercik P , Cukrowska B , Farre-castany M A , Bouzourene H , Saraga E , Blum A L , Corthésy-Theulaz I , Tlaskalova-Hogenova H , Michetti P 
Published: March 2003

SUMMARYHomeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)-induced colitis. Sonicates of Gram-positive, Gram-negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1 mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1–14); median (range)) compared with PBS-fed control animals (15 (7–19); P &lt; 0·05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6–11); P &lt; 0·05 versus control), but not in mice fed a pool of Gram-positive and -negative sonicates (16 (12–16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS-fed control animals. DSS-induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.
Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener’s granulomatosis?
Authors: Brons R H , Bakker H I , Van Wijk R T , Van Dijk N W , Muller Kobold A C , Limburg P C , Manson W L , Kallenberg C G M , Cohen Tervaert J W 
Published: March 2003

SUMMARY
The majority of patients with Wegener’s granulomatosis (WG) are chronic nasal carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus is associated with an increased risk of developing a relapse of the disease. The mechanism by which this occurs is still unknown. We hypothesized that a cationic protein of S. aureus, staphylococcal acid phosphatase (SAcP), acts as a planted antigen and initiates glomerulonephritis and vasculitis in patients with WG. In order to test the hypothesis that SAcP can act as a planted antigen in WG, we studied the ability of SAcP to bind to human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells. We also studied whether this binding can be prevented by preincubation with an anionic protein, and whether binding of SAcP activates endothelial cells. We also evaluated whether antibodies in sera of patients with WG are able to bind to endothelial cell-bound SAcP. The results show that SAcP can act as a planted antigen by binding to both types of endothelial cells in a concentration-dependent manner. Binding of concentrations as low as 4 μg/ml can be detected on HUVEC within 5 min of incubation. Binding of SAcP to endothelial cells was charge-dependent but did not activate endothelial cells. Finally, endothelial cell-bound SAcP was recognized by sera of patients with WG. The data suggest a possible pathogenic role for SAcP by acting as a planted antigen thereby initiating glomerulonephritis and vasculitis in patients with WG.
Impact of highly active anti-retroviral therapy (HAART) on cytokine production and monocyte subsets in HIV-infected patients
Authors: Amirayan-Chevillard N , Tissot-dupont H , Capo C , Brunet C , Dignat-George F , Obadia Y , Gallais H , Mege J-L 
Published: March 2003

SUMMARYHIV infection is associated with cytokine production by monocytes and expansion of a monocyte subset that expresses high levels of CD16. Our study was designed to investigate the effects of anti-retroviral therapies on these immune parameters. Four groups of HIV+ patients were included in the study. The first group comprised drug-naive patients (n = 20); the second included patients who received two inhibitors of HIV reverse transcriptase (n = 45); the third group received a therapy combining these two inhibitors and one inhibitor of HIV protease (HAART) (n = 35); the fourth consisted of patients who had stopped their treatment (n = 20). The release of inflammatory cytokines (tumour necrosis factor, IL-1β, IL-6) and immunoregulatory cytokines such as IL-10 by monocytes was determined by ELISA. The monocyte subsets expressing low or high levels of CD16 were studied by flow cytometry. Monocytes from patients naive of treatment released higher amounts of inflammatory cytokines and IL-10 than HIV− individuals. Each anti-retroviral therapy restored a normal pattern of cytokine secretion. Nevertheless, the release of cytokines increased again after the arrest of the treatment. The expansion of the monocyte subset that expresses high levels of CD16 was significantly decreased by HAART but not by the treatment including two inhibitors of reverse transcriptase. These results suggest that only HAART controls monocyte activation in the treatment of HIV infection.
Kinase mutant Btk results in atypical X-linked agammaglobulinaemia phenotype
Authors: Gaspar H B , Ferrando M , Caragol I , Hernandez M , Bertran J M , De gracia X , Lester T , Kinnon C , Ashton E , Espanol T 
Published: March 2003

SUMMARY
X-linked agammaglobulinaemia (XLA) is a B cell humoral abnormality arising from mutations in the gene encoding Bruton’s tyrosine kinase (Btk). The phenotype of XLA can be variable, with some individuals having a less severe immunophenotype, although in most cases this cannot be correlated with the Btk mutation or expression of Btk protein. In this study we describe clinical and immunological heterogeneity within the same pedigree. Analysis of the genetic defect identified a missense mutation in the kinase domain of Btk which, unusually, preserved Btk protein expression but at reduced levels, and also considerably diminished autophosphorylation activity. Structural analysis of the effect of this mutation on the kinase domain suggests that this mutation is not an integral part of the ATP or substrate binding domains but may affect the interaction of the kinase domain with its own kinase domain and other substrates. Together, these data may provide an explanation for the variable XLA phenotype.
Elevated serum concentrations of soluble CD14 in HIV− and HIV+ patients with tuberculosis in Africa: prolonged elevation during anti-tuberculosis treatment
Authors: Lawn S D , Labeta M O , Arias M , Acheampong J W , Griffin G E 
Published: March 2003

SUMMARYData are limited regarding serum concentrations of soluble CD14 (sCD14), a marker of macrophage activation, in patients with active tuberculosis (TB) and during drug treatment. In this study, concentrations of sCD14 were measured in serum samples obtained from 105 African subjects who were categorized into one of four groups: persons with pulmonary TB alone (TB+HIV−, n = 30), pulmonary TB and HIV co-infection (TB+HIV+, n = 20), or HIV infection alone (TB−HIV+, n = 25), and healthy controls (TB−HIV−, n = 30). Mean total sCD14 was significantly increased in serum of patients with newly diagnosed pulmonary TB (mean = 6·6 g/ml, s.d. = 1·6 g/ml) compared with healthy controls (mean = 3·1 g/ml, s.d. = 0·6 g/ml; P &lt; 0·0001), and this elevation comprised proportionate increases in the α (2·1-fold greater, P &lt; 0·0001) and β (2·0-fold greater, P &lt; 0·0001) forms of sCD14. Total sCD14 was also increased in serum of HIV-infected patients (mean = 4·1 g/ml, s.d. = 1·9 g/ml; P &lt; 0·01), but the highest concentrations were observed in patients with pulmonary TB and HIV co-infection (mean = 8·7 g/ml, s.d. = 3·1 g/ml; P &lt; 0·0001). Analysis of serum samples prospectively collected from TB+HIV−patients during the first 3 months of successful anti-TB treatment demonstrated steep reductions in mean concentrations of the acute-phase protein, C-reactive protein, and the soluble lymphocyte activation marker, sCD25. In contrast, levels of sCD14 increased during the first month of treatment and slowly declined thereafter. These data indicate that the serum concentration of sCD14 is not a sensitive index of response to anti-TB treatment and suggest that cellular activation resolves more slowly in the macrophage pool compared with the lymphocyte pool during anti-TB treatment.
Peptide T does not ameliorate experimental autoimmune encephalomyelitis (EAE) in Lewis rats
Authors: Sáez-Torres I , Espejo C , Pérez J J , Acarín N , Montalban X , Martínez-Cáceres E M 
Published: March 2003

SUMMARYPeptide T has been shown to inhibit T cell activation and cytokine production and function. Moreover, it has been reported to be a safe treatment in humans. We have studied the ability of peptide T to prevent or ameliorate EAE in Lewis rats. Peptide T was administered subcutaneously at different doses and phases of the disease according to several treatment protocols, but we could not observe a consistent effect of peptide T ameliorating the disease. Lymph node cell proliferation and IL-4 and interferon-gamma production were also studied. We conclude that peptide T neither prevents nor ameliorates EAE in Lewis rats.
Differences in regulatory pathways identify subgroups of T cell-derived Th2 cytokines
Authors: Rafiq K , Bullens D M A , Kasran A , Lorré K , Ceuppens J L , Van gool S W 
Published: March 2003

SUMMARYWe analysed regulatory mechanisms involved in the production of Th2 cytokines by freshly isolated human T cells. We used an in vitro culture system in which the primary signal was provided by a cross-linking anti-CD3 MoAb presented on the Fc receptors of P815 cells. Both CD80 and CD86, expressed on transfected P815 cells, were able to provide efficient costimulation for the production of IL-4, IL-5 and IL-13. IL-2 was also highly important for induction of all three Th2 cytokines. However, differences between IL-4 on the one hand and IL-5 and IL-13 on the other hand were observed when sensitivity to cyclosporin A (CsA) was studied. CsA (an inhibitor of calcineurin phosphatase activity) strongly inhibited IL-4 production, but it did either not affect or even increased IL-5 and IL-13 production. In accordance with this, CD80 and phorbol myristate acetate (PMA) (without anti-CD3 or calcium ionophore) were sufficient to induce production of IL-5 and IL-13, but not of IL-4. The subgrouping of Th2 cytokines was further confirmed at another level on the basis of differences in cell sources: IL-4 was predominantly produced by CD4+ T cells, while IL-5 and IL-13 were produced by both CD4+ and CD8+ T cells. Thus, differences in cell sources and in the requirement of the calcium/calcineurin-signalling pathway allowed us to identify two subgroups (IL-4 and IL-5/IL-13) among human Th2-type T cell cytokines.
Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis
Authors: Costa M , Rodríguez-Sánchez J L , Czaja A J , Gelpí C 
Published: March 2003

SUMMARY
We previously described autoantibodies against a UGA serine tRNA–protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec antibodies was highly specific for type-1 autoimmune hepatitis, as 47·5% of patients were positive compared with none of the control subjects. To characterize the antigenic protein(s), we immunoscreened a human cDNA library with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone 19 encodes a protein with a predicted molecular mass of 48·8 kD. Clone 13 is a shorter cDNA, almost identical to clone 19, which encodes a 35·9-kD protein. Expression of both cDNAs was accomplished in Escherichia coli as His-tagged recombinant proteins. Antibodies eluted from both purified recombinant proteins were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract, demonstrating their cross-reactivity with the mammalian antigenic complex. Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec.
Resistance/susceptibility toEchinococcus multilocularisinfection and cytokine profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype
Authors: Godot V , Harraga S , Beurton I , Tiberghien P , Sarciron E , Gottstein B , Vuitton D A 
Published: March 2003

SUMMARYDifferences have been shown between HLA characteristics of patients with different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2 haplotype was associated with more severe forms of this granulomatous parasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-γ) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA-DR3+, DQ2+, B8+ AE patients and from 10 HLA-DR3−, DQ2−, B8− patients after non-specific mitogenic and specific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3+, DQ2+, B8+ healthy subjects and nine HLA-DR3−, DQ2−, B8− subjects were also studied as controls. PBMC from AE patients with HLA DR3+, DQ2+ haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients without this haplotype. Higher levels of IL-5 and IFN-γ were also produced by these patients' PBMC after stimulation with non-purified parasitic antigenic preparations; however, the specific alkaline phosphatase antigen extracted from E. multilocularis induced only Th2-type cytokine secretion. A spontaneous secretion of TNF by HLA DR3+, DQ2+ B8+ AE patients was also found. These results suggest that HLA characteristics of the host can influence immune-mediated mechanisms, and thus the course of AE in humans; specific antigenic components of E. multilocularis could contribute to the preferential Th2-type cytokine production favoured by the genetic background of the host.