bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of CD14 promoter polymorphism andH. pyloriinfection and its clinical outcomes on circulating CD14
Authors: KARHUKORPI J , YAN Y , NIEMELÄ S , VALTONEN J , KOISTINEN P , JOENSUU T , SAIKKU P , KARTTUNEN R 
Published: March 2003

SUMMARYCD14 is a pattern recognition receptor on the membranes of monocytes and macrophages for several microbial products, of which lipopolysaccharide (LPS) is the best known. A shed form of CD14 is present in serum. As the CD14 gene promoter polymorphism –159C/T and some bacterial infections may affect the sCD14 levels, we compared the impact of both the CD14 promoter polymorphism and Helicobacter pylori infection on serum sCD14 levels in 201 dyspeptic patients (group 1) who had undergone gastroscopy, and 127 staff members (group 2) with no endoscopy. sCD14 was measured from the sera by a commercial enzyme immunoassay (EIA), and CD14 genotyping was carried out with PCR. Helicobacter pylori infection was detected by serology and/or culture or PCR. sCD14 levels were elevated in the subjects carrying the T allele (CT or TT genotype) in both groups when compared with subjects with the CC genotype. Overall, H. pylori-positive subjects tended to have higher sCD14 levels compared with H. pylori-negative subjects. In group 1 consisting of dyspeptic patients, those with gastric ulcer, gastric erosion or duodenal ulcer had significantly elevated levels of sCD14 compared with the patients with normal endoscopic findings or macroscopic gastritis. The recent use of NSAIDs was also associated with enhanced sCD14. Thus, we were able to show several factors, one genetic and the other environmental (H. pylori infection and mucosal lesion), to have an impact on sCD14.
Macrophage Inflammatory Protein 3α–CC chemokine receptor 6 interactions play an important role in CD4+T-cell accumulation in periodontal diseased tissu
Authors: HOSOKAWA Y , NAKANISHI T , YAMAGUCHI D , TAKAHASHI K , YUMOTO H , OZAKI K , MATSUO T 
Published: March 2003

SUMMARYThe regulatory role of chemokines and chemokine receptors on specific lymphocyte recruitment into periodontal diseased tissue is poorly characterized. We observed that lymphocytes infiltrating inflamed gingival tissue expressed marked levels of CCR6. In periodontal diseased tissue, the expression of MIP-3α mRNA was detected by RT-PCR and further, MIP-3α was distributed in the basal layer of gingival epithelial cells, microvascular endothelial cells and the areas of inflammatory cells as shown by immunohistochemistry. Moreover, CCR6-expressing cells infiltrated into periodontal diseased tissue, and the proportion of CCR6-positive CD4+ T cells was significantly elevated in periodontal diseased tissue compared with peripheral blood in the same patients. Furthermore, gingival lymphocytes isolated from patients showed migration toward MIP-3α in an in vitro chemotaxis assay in which migration was abrogated by specific antibody to CCR6. Thus, these findings suggested that CCR6 and the corresponding chemokine, MIP-3α may have an important regulatory role in specific lymphocyte migration into inflamed periodontal tissue.
Generation of a recombinant Fab antibody reactive with the Alzheimer's disease-related Aβ peptide
Authors: TAMMER A H , COIA G , CAPPAI R , FULLER S , MASTERS C L , HUDSON P , UNDERWOOD J R 
Published: March 2003

SUMMARY
A recombinant Fab antibody, designated 1E8–4b, which reacts with the Alzheimer's disease (AD)-related Aβ peptides, Aβ[1–40], Aβ[1–42] and Aβ[1–43] has been developed. The 1E8–4b Fab was constructed by cloning the VHCH1 and VLCL domains from the parent hybridoma 1E8 antibody, reported previously to recognize these Aβ peptides. Briefly, a C-terminal Flag tag sequence was incorporated into this construct, which was ligated into the vector pHFA2 and expressed in Escherichia coli. Following purification on an M2 anti-Flag affinity column, the 1E8–4b recombinant Fab antibody was shown to bind plaques within sections of brain tissue from CERAD-defined AD patients by immunohistochemistry. ELISA, epitope mapping and immunoblotting confirmed the recognition of the Aβ1–40/42/43] peptides by the 1E8–4b Fab. The 1E8–4b Fab did not recognize APP695 or APP770 which contain the Aβ sequence. The Aβ specificity of the recombinant 1E8–4b Fab antibody was identical to the parent 1E8 monoclonal antibody.
Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion
Authors: CHAKRAVORTY S J , COCKWELL P , GIRDLESTONE J , BROOKS C J , SAVAGE C O S 
Published: March 2003

SUMMARYFractalkine (CX3CL1) is a transmembrane molecule with a CX3C chemokine domain attached to an extracellular mucin stalk which can induce both adhesion and migration of leucocytes. Mononuclear cell infiltration at renal tubular sites and associated tubular epithelial cell damage are key events during acute renal inflammation following renal allograft transplantation. Using northern and Western blot analysis, we have demonstrated the expression of fractalkine message and protein by renal tubular epithelial cells in vitro. The expression was up-regulated by TNF-α, a key proinflammatory cytokine in acute rejection. Investigation of surface expression of fractalkine on cultured proximal tubular epithelial cells revealed only a subpopulation of positively staining cells. Immunohistochemistry revealed that only a proportion of tubules in renal allograft biopsies showed induction of fractalkine expression. Studies using a static model of adhesion demonstrated CX3CR1/fractalkine interactions accounted for 26% of monocytic THP-1 cell and 17% of peripheral blood natural killer cell adhesion to tubular epithelial cells, suggesting that fractalkine may have a functional role in leucocyte adhesion and retention, at selected tubular sites in acute renal inflammation. Thus, fractalkine blockade strategies could reduce mononuclear cell mediated tubular damage and improve graft survival following kidney transplantation.
Respiratory syncytial virus induces prostaglandin E2, IL-10 and IL-11 generation in antigen presenting cells
Authors: BARTZ H , BÜNING-PFAUE F , TÜRKEL Ö , SCHAUER U 
Published: March 2003

SUMMARYBronchiolitis caused by respiratory syncytial virus (RSV) infection is a major cause of hospitalization in children under 1 years of age. The disease characteristically does not induce protective immunity. However, a mononuclear peribronchiolar and perivascular infiltrate during RSV infection is suggestive of an immune-mediated pathogenesis. Macrophages and dendritic cells (DCs) play an essential role in the initiation and maintenance of immune response to pathogens. To analyse interactions of RSV and immune cells, human cord blood derived macrophages and dendritic cells were infected with RSV. Both cells were found to be infected with RSV resulting in the activation of macrophages and maturation of dendritic cells as reflected by enhanced expression of several surface antigens. In the next set of experiments, generation of mediators was compared between cells infected with RSV, parainfluenza (PIV3) and influenza virus as well as ultracentrifuged virus free supernatant. Whereas the supernatant did not induce release of mediators, all three live virus infections induced IL-6 production from macrophages and DC. Influenza virus infection induced predominantly IL-12 p75 generation in DC. In contrast, RSV induced strong IL-11 and prostaglandin E2 release from both macrophages and DCs. In addition, RSV but not influenza and parainfluenza virus induced a strong IL-10 generation particularly from macrophages. Since IL-10, IL-11 and PGE2 are known to act immunosuppressive rather than proinflammatory, these mediators might be responsible for the delayed protective RSV specific immune response.
Treatment of oral pemphigoid with intravenous immunoglobulin as monotherapy. Long-term follow-up: influence of treatment on antibody titres to human α6 integrin
Authors: SAMI N , BHOL K C , AHMED A R 
Published: March 2003

Summary
Oral pemphigoid (OP) is a chronic autoimmune disease, involving the oral cavity, characterized by a homogenous linear deposition of immunoglobulins, complement, or both along the basement membrane zone (BMZ) and a subepithelial blister formation. The α6/β4 heterodimer is an integrin family of adhesion receptors, which mediates basal cell to matrix interactions. Recent evidence suggests a pathophysiologic role for antibodies against human α6 integrin in blister formation in OP, in organ culture studies. Fifty percent of OP patients have been reported to experience disease progression to involve other mucosal tissues, including the eye and larynx. To prevent this extension of disease, systemic therapy with systemic corticosteroids, dapsone, and immunosuppressive agents has been recommended. The use of intravenous immunoglobulin (IVIg) in the treatment of pemphigoid has been recently described. In this study, we present the use of IVIg, in a group of seven patients, with severe OP, in whom systemic conventional treatment was contraindicated. To determine the influence of treatment on antibodies to human α6 integrin in OP, seven patients with OP treated with IVIg therapy and a comparable control group of seven patients with OP, treated with conventional therapy, were evaluated at monthly intervals, for a 12 consecutive month treatment period. An effective clinical response was observed in all seven patients treated with IVIg therapy, after a mean treatment period of 4·5 months. IVIg therapy induced a prolonged and sustained clinical remission in all seven patients after a mean treatment period of 26·9 months. A statistically significant difference was observed in the quality of life pre- and post-IVIg therapy (P &lt; 0·001). Both the study and the control groups had a very similar initial serological response to treatment. A statistically significant reduction in the antibody titres was observed after four months of treatment, in both groups (P = 0·015). Thereafter, patients treated with IVIg therapy had a faster rate of decline in the antibody titres, and the difference in the rate of decline between the study and control groups became statistically significant after six months of treatment (P = 0·03). The use of IVIg therapy resulted in reduction of antiα6 antibody titres and in inducing and maintaining both a sustained, clinical and serological remission.
Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B – restoration by exogenous interleukin-12
Authors: LÖHR H F , PINGEL S , BÖCHER W O , BERNHARD H , HERZOG-HAUFF S , ROSE-JOHN S , GALLE P R 
Published: March 2003

SUMMARYInsufficient stimulatory capacities of autologous dendritic cells (DC) may contribute in part to impaired T cell stimulation and therefore viral persistence in patients with chronic hepatitis B virus (HBV) infection. In order to characterize the antigen presenting functions of DC from chronic HBV carriers and controls antigen specific T cell responses were analysed. CD34+ peripheral blood progenitor cells were differentiated to immature DC in the presence of GM-CSF, IL-6/IL-6R fusion protein and stem cell factor. Proliferative CD4+ T cell responses and specific cytokine release were analysed in co-cultures of DC pulsed with HBV surface and core antigens or tetanus toxoid and autologous CD4+ T cells. Cultured under identical conditions DC from chronic HBV carriers, individuals with acute resolved hepatitis B and healthy controls expressed similar phenotypical markers but chronic HBV carriers showed less frequent and weaker HBV antigen specific proliferative T helper cell responses and secreted less interferon-γ while responses to the tetanus toxoid control antigen was not affected. Preincubation with recombinant IL-12 enhanced the HBV specific immune reactivities in chronic HBV patients and controls. In conclusion, the weak antiviral immune responses observed in chronic hepatitis B may result in part from insufficient T cell stimulating capacities of DC. Immunostimulation by IL-12 restored the HBV antigen specific T cell responses and could have some therapeutical benefit to overcome viral persistence.
Exposure to Mycobacterium avium primes the immune system of calves for vaccination with Mycobacterium bovis BCG
Authors: HOWARD C J , KWONG L S , VILLARREAL-RAMOS B , SOPP P , HOPE J C 
Published: March 2003

Summary
The objective of the investigation was to provide data on how a prior exposure of cattle to Mycobacterium avium, used here as a model of exposure to an environmental mycobacterium, affected the cellular immune response that follows vaccination with Mycobacterium bovis BCG. The assessment of cellular immune responses included lymphocyte proliferation assays, the delayed hypersensitivity skin test and IFN-γ synthesis in whole blood cultures. One group of calves was inoculated subcutaneously with M. avium followed 12 weeks later by M. bovis-BCG. The other group was vaccinated subcutaneously with BCG alone. Calves previously exposed to M. avium responded more rapidly, as assessed in the in vitro assays, to purified protein derivative (PPD) from M. avium (PPD-A) or M. bovis (PPD-B) than did calves inoculated with BCG only, indicating that the exposure to M. avium had primed the immune response in these calves. Following inoculation of BCG the intensity of the in vitro responses and the delayed hypersensitivity skin test to PPD-A was higher for the M. avium-primed animals while the responses to PPD-B were similar in the M. avium-primed and BCG-only groups. The results are consistent with a model in which prior exposure to environmental mycobacteria does not necessarily inhibit the immune response to the vaccine strain, BCG. They suggest that M. avium infection primes the immune system of calves and that the detection of an immune response specific for M. bovis BCG is masked by reactivity to antigens also present in M. avium.
Autoantibodies against small nucleolar ribonucleoprotein complexes and their clinical associations
Authors: VAN EENENNAAM H , VOGELZANGS J H P , BISSCHOPS L , TE BOOME L C J , SEELIG H P , RENZ M , DE ROOIJ D-J , BROUWER R , PLUK H , PRUIJN G J M , VAN VENROOIJ W J , VAN DEN HOOGEN F H J 
Published: March 2003

Summary
Sera from patients suffering from systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) have been shown to contain reactivities to nuclear components. Autoantibodies specifically targeting nucleolar antigens are found most frequently in patients suffering from SSc or SSc overlap syndromes. We determined the prevalence and clinical significance of autoantibodies directed to nucleolar RNA-protein complexes, the so-called small nucleolar ribonucleoprotein complexes (snoRNPs). A total of 172 patient sera with antinucleolar antibodies were analysed by immunoprecipitation. From 100 of these patients clinical information was obtained by chart review. Autoantibodies directed to snoRNPs were detected not only in patients suffering from SSc and primary Raynaud's phenomenon (RP), but also in patients suffering from SLE, rheumatoid arthritis (RA) and myositis (PM/DM). Antibodies against box C/D small snoRNPs can be subdivided in antifibrillarin positive and antifibrillarin negative reactivity. Antifibrillarin-positive patient sera were associated with a poor prognosis in comparison with antifibrillarin negative (reactivity with U3 or U8 snoRNP only) patient sera. Anti-Th/To autoantibodies were associated with SSc, primary RP and SLE and were found predominantly in patients suffering from decreased co-diffusion and oesophagus motility and xerophthalmia. For the first time autoantibodies that recognize box H/ACA snoRNPs are described, identifying this class of snoRNPs as a novel autoantigenic activity. Taken together, our data show that antinucleolar patient sera directed to small nucleolar ribonucleoprotein complexes are found frequently in other diseases than SSc and that categorization of diagnoses and clinical manifestations based on autoantibody profiles seems particularly informative in patient sera recognizing box C/D snoRNPs.
Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum-mediated but complement-independent mechanisms
Authors: CORTES-HERNANDEZ J , FOSSATI-JIMACK L , CARUGATI A , POTTER P K , WALPORT M J , COOK H T , BOTTO M 
Published: March 2003

SummaryAn increased number of apoptotic bodies have been detected in glomeruli of non-nephritic kidneys of C1q-deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro clearance of apoptotic cells by glomerular mesangial cells. Phagocytosis was assessed using a novel flow cytometric assay that was validated by immunofluorescence studies. The uptake of apoptotic cells by mesangial cells, measured as percentage of mesangial cells ingesting apoptotic cells, was ∼25%, 10% and 10% for a T cell lymphoma line (RMA), thymocytes and neutrophils, respectively. The uptake reached a plateau phase after 3 h, was specific for apoptotic cells and was mediated by serum but not by complement components C1q or C3. The phagocytosis of apoptotic cells was significantly inhibited by Arg-Gly-Asp-Ser (RGDS), a peptide capable of blocking the interaction of thrombospondin with CD36 or the vitronectin receptor. Pretreatment of the mesangial cells with dexamethasone (200 nm) but not with LPS increased the uptake markedly. These findings indicate that murine mesangial cells are capable of taking up syngeneic apoptotic cells, although much less efficiently than professional phagocytic cells. They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.
Butyrate modulates intestinal epithelial cell-mediated neutrophil migration
Authors: BÖCKER U , NEBE T , HERWECK F , HOLT L , PANJA A , JOBIN C , ROSSOL S , SARTOR R B , SINGER M V 
Published: March 2003

SUMMARYButyrate, a short-chain fatty acid released by colonic bacteria and administered therapeutically in inflammatory bowel diseases, exerts immunomodulatory properties. The aim of the study was to determine the functional consequences of butyrate exposure on the proinflammatory responsiveness of human intestinal epithelial cells (IEC). IL-8 promoter activity in IEC pretreated with butyrate then exposed to proinflammatory stimuli was assayed by transfection of luciferase constructs. IL-8 secretion was determined by ELISA and neutrophil migration by flow cytometry. Receptor mRNA was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR). Butyrate modulated proinflammatory IL-8 secretion differentially in Caco-2 and HT-29 cells on the transcriptional level. Pointing to the potentially underlying mechanism of increased IL-1β-stimulated IL-8 secretion in HT-29 cells, butyrate up-regulated IL-1RI mRNA but not IL-1RII. Butyrate pretreatment of IEC lines stimulated by IL-1β modulated neutrophil migration significantly: reduction towards Caco-2 and enhancement towards HT-29/p cells. Pharmacological inhibition of protein tyrosine phosphatases or treatment with mesalamine or sulphasalazine diminished IL-1β-stimulated IL-8 secretion by butyrate-exposed HT-29 cells substantially. Immunomodulatory effects of butyrate on IEC are functionally relevant for neutrophil migration. Pharmacological inhibition of enhanced IL-1β-mediated IL-8 secretion in a subpopulation of IEC may improve the clinical efficacy of butyrate.
Decreases in plasma TNF-αlevel and IFN-γmRNA level in peripheral blood mononuclear cells (PBMC) and an increase in IL-2 mRNA level in PBMC are associated with effective highly active antiretroviral therapy in HIV-infected patients
Authors: BRAZILLE P , DEREUDDRE-BOSQUET N , LEPORT C , CLAYETTE P , BOYER O , VILDÉ J-L , DORMONT D , BENVENISTE O 
Published: March 2003

SUMMARYIn this study, we investigated the cytokine profiles of 14 treatment-naive HIV-infected patients on the initiation of highly active antiretroviral therapy (HAART). At baseline, plasma levels of TNF-α and its mRNA in peripheral blood mononuclear cells (PBMC) were highest in the most severely immunocompromised patients (&lt;200 CD4+ cells/mm3). After 12 months of HAART, the virus was undetectable in the plasma of all patients (&lt;200 copies/ml), and median CD4 T cell counts had increased (+164 cells/mm3). We also observed a gradual decrease in the number of proviral DNA copies in PBMC and in immune activation, with lower levels of IFN-γ mRNA in PBMC associated with weaker activation of CD8+ T cells and lower levels of plasma TNF-α. IL-2 mRNA levels in PBMC were found to increase in parallel. The decrease in TNF-α and IFN-γ levels and the increase in IL-2 production appear to be correlated with the efficacy of HAART in naive immunocompromised HIV-infected individuals.
Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission
Authors: OHLSSON S , WIESLANDER J , SEGELMARK M 
Published: March 2003

SummaryIn systemic small vessel vasculitides, patients form autoantibodies against neutrophil granular proteins, anti-neutrophilic cytoplasmic autoantibodies (ANCA). Some correlation is seen between ANCA titre and disease activity, but whether this is cause or effect is still unknown. It has been reported that levels of proteinase 3 (PR3), one of the main ANCA antigens, are increased in patients with active disease. An increased level of circulating antigen could mean a predisposition to autoimmunity. In order to explore this we measured PR3 levels in patients with stable disease. In addition we measured neutrophil gelatinase-associated lipocalin (NGAL) as a specific marker of neutrophil degranulation, cystatin C as a marker of renal function as well as C-reactive protein (CRP), IL-6 and sTNFr1 as markers of inflammation. PR3, NGAL, IL-6 and sTNFr1 were measured in plasma by the ELISA technique. In the PR3 ELISA, we used anti-PR3 monoclonal antibodies as capture-antibodies and affinity-purified rabbit-anti-PR3 antibodies for detection. PR3-ANCA, myeloperoxidase (MPO)-ANCA, CRP and cystatin C were measured by routine methods. PR3 was significantly raised (P &lt; 0·0001) in vasculitis patients (median 560 µg/l, range 110–3940, n = 59) compared with healthy blood donors (350 µg/l, 110–580, n = 30) as well as disease controls (360, 110–580, n = 46). No correlation was seen with disease activity, inflammation or renal function. The raised NGAL levels correlated strongly with decreased renal function (r = 0·8, P &lt; 0·001). After correcting for this, slightly increased levels (110, 42–340, n = 59) were observed compared with healthy blood donors (81, 38–130, n = 25), but not compared with the disease controls (120, 57–260, n = 48). In the disease controls, there was a significant correlation between NGAL and proteinase 3 (r = 0·3, p &lt; 0·05), but this was not the case in the vasculitis patients. Whether patients had PR3-ANCA or MPO-ANCA was of no significance. In our measurements, we found significantly raised levels of PR3 in plasma from patients with small vessel vasculitis, regardless of ANCA specificity. This was not due to decreased renal function, ongoing inflammation or neutrophil activation. Plausible mechanisms for this include defects in the reticuloendothelial system, genetic factors and selective neutrophil degranulation or leakage.