bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some alterations of the leucoeyte β2‐adrenoceptor/cAMP‐system in patients with seasonal allergic rhinoconjunctivitis are related to disease activity
Authors: HAEN E. , BLEISE U. , PRZYBILLA B. 
Published: November 2003

SummaryBackground
Disturbances of β2‐adrenoceptors are discussed as a pathogenic factor in atopic diseases.Methods
In this study tbe expression and function of β2‐adrenoceptors on peripheral blood leucocytes (PBL) of seven atopic patients with seasonal rhinoconjunctivitis and their seven healthy controls was evaluated in relation to disease activity. Earlier reported data during pollen. season were now compared with data obtained from the same subjects after their allergic symptoms had subsided.Results
The variables that had indicated a β2‐adrenoceptor subsensitivity in tbe patients during pollen season returned to control values, i.e. the reduced β2‐adrenoceptor affinity, the reduced β2‐adrenoceptor sensitivity, the reduced increase of intracellular cyclic adenosine monophosphate (cAMP) content upon stimulation with isoproterenol, and the reduced cAMP plasma concentration (values no longer significantly different from those of controls). However, the variable that had suggested an increase in activity of the cAMP degrading enzyme phosphodiesterase (PDE), i.e. the reduced basal intracellular cAMP content of the patients, remained reduced after the pollen season (4.9 ± 1.1 pmol/lO6’cells in patients vs 8.2 ± 0.9pmol/106 cells in controls: P < 0.05). There were no significant differences in β2‐adrenoceptor density between patients and controls at both investigations.Conclusions
Atopic seasonal rhinoconjunctivitis is associated with various alterations in the PBL β2‐adrenoceptor/cAMP system that depend on disease activity. The reversible β2‐adrenoceptor subsensitivity is likely to be a consequence of the disease, whereas the irreversibly decreased basal intracellular cAMP content, suggested an elevated PDE activity, might be a basic trait of atopy.
Analysis of rearranged T cell receptor (TCR) Vβ transcripts in livers of primary biliary cirrhosis: preferential Vβ usage suggests antigen-driven selection
Authors: Tsai S L , Lai M Y , Chen D S 
Published: November 2003

SUMMARY
The presence of autoantibodies to mitochondrial pyruvate dehydrogenase complex-E2 (PDC-E2) and self-reactive T cells to PDC suggests that autoimmune mechanisms may be involved in the pathogenesis of primary biliary cirrhosis (PBC). Molecular analysis of intrahepatic TCR repertoire may provide valuable information on a T cell mechanism for PBC immunopathogenesis. We therefore analysed the TCR Vβ usage in different regions of the livers removed during transplantation from two PBC patients. Using reverse transcription and polymerase chain reaction (RT-PCR), a limited heterogeneity of rearranged TCR Vβ transcripts was demonstrated in different locations of the same liver. Sequence analysis of Vβ–Dβ–Jβ (CDR3: the third complementarity determining region) showed the presence of conserved residues, no random N additions, and a common motif within CDR3. These results suggest that T cells homing to PBC liver may be antigen-driven. To elucidate further whether an immune deviation related to T helper 1 cell (Th1) or Th2 responses may exist in PBC, intrahepatic mRNA expression of IL-2, IL-4 and interferon-gamma (IFN-γ) was examined by the RT-PCR method. IL-2 and IFN-γ could be amplified, whereas IL-4 was virtually undetectable in the livers from the two patients with PBC. The findings suggest that polarization of intrahepatic lymphokine expression toward the Th1-dominant pattern may be significant in the immunopathogenesis of PBC.
Detection of bilayer phospholipid-binding antibodies using flow cytometry
Authors: Eschwège V , Laude I , Toti F , Pasquali J-L , Freyssinet J-M 
Published: November 2003

SUMMARY
Antiphospholipid antibodies (APL) are usually detected using solid-phase immunoassays, where cardiolipin is the most common capture antigen. Phosholipids are believed to adopt a monolayer organization when coated onto polystyrene after evaporation of the solvent. However, bilayer phospholipids are probably those evidenced as microparticles or cell fragments circulating in vivo under various pathological circumstances. The surface density of monolayer phospholipids on polystyrene is six times lower than that of bilayer phospholipids. In order to assess the influence of phospholipid organization on the detection of APL, we prepared glass microspheres coated with bilayer phospholipids (cardiolipin, phosphatidylcholine, cholesterol). Such lipospheres enabled us to study the binding of antibodies in 1:100 diluted plasma samples from patients with anti-cardiolipin antibodies of IgG isotype previously diagnosed by ELISA. Among the 39 plasma samples analysed by flow cytometry, 17 showed positive IgG binding to lipospheres. Only four additional samples became positive when adding 20 μg/ml apolipoprotein H. The specificity of the binding was demonstrated by complete reversibility with 1.4 μm annexin V and with a large excess of liposomes of the same composition. The absence of correlation between liposphere and ELISA results suggests that different subgroups of antibodies are detected depending on the method. The detection of APL using bilayer phospholipids is an original assay and may represent a more physiopathological approach to the specificity of APL.
Ultraviolet B irradiation and cytomegalovirus infection synergize to induce the cell surface expression of 52-kD/Ro antigen
Authors: Zhu J 
Published: November 2003

SUMMARY
Cultured human fibroblasts (MRC-5) have been previously demonstrated to express calreticulin, but not Ro autoantigen, on their surface after human cytomegalovirus (CMV) infection. The present study addresses the question of whether other stimuli, alone or in combination with CMV, can induce the surface expression of Ro autoantigens on human fibroblasts. Using a fixed-cell ELISA to detect autoantigen expression, a synergistic effect between ultraviolet B (UVB) exposure and CMV infection on the surface expression of 52-kD/Ro antigen, but not 60-kD/Ro or calreticulin, was observed. The enhanced expression of 52-kD/Ro antigen was significant and specific, compared with untreated cells, cells infected with CMV alone or irradiated with UVB only, and cells subjected to other treatments, such as low pH. Immunofluorescence studies confirmed these findings and indicated that cells expressed 52-kD/Ro protein on their surface at 24 h after a combined UVB and CMV treatment. These studies provide evidence that synergy between UVB irradiation and CMV infection may play a role in the induction of cell surface expression of the human autoantigen, 52-kD/Ro.
T and B lymphocytes reacting with the extracellular loop of the β2-adrenergic receptor (β2AR) are present in the peripheral blood of patients with myasthenia gravis
Authors: Yi Q , He W , Matell G , Pirskanen R , Magnusson Y , Eng H , Lefvert A K 
Published: November 2003

SUMMARY
Eighteen percent of patients with myasthenia gravis (MG) have serum antibodies against a synthetic peptide corresponding to the second extracellular loop of the human β2AR (residues 172–197). In this study we examined T and B cell responses to the peptide, using assays to detect individual cells secreting interferon-gamma (IFN-γ) and IL-4 or antibodies against the peptide, and by measuring thymidine incorporation in response to the peptide. The peptide from the β2AR induced cytokine secretion from blood mononuclear cells in 67% of MG patients, compared with 14–28% of the control groups. Cells secreting antibodies binding to the peptide were present in 54% of MG patients and in 19–28% of controls. The numbers of β2AR-reactive cells were higher in MG patients than in controls. Peptide-induced increase in thymidine incorporation in cells was also more frequently demonstrated in patients (26%) compared with controls (about 10%). Activation of cells was dependent on monocytes and on MHC class II DR antigen. Based on the pattern of the cytokine secretion induced, β2AR-reactive T cells comprise both T helper type-1 and type-2 subsets. In addition, control peptide-reactive T and B cells were much less frequently demonstrated in the patients, and the number of such cells did not differ between the groups. Our results show that β2AR-reactive cells are present in most patients with MG. Such autoreactive antibodies and cells might play a role in the pathogenesis of the disease by influencing the function of skeletal muscle and immune systems.
Down-modulation of mycobacterial-induced IL-1β production in human mononuclear cells by IL-4
Authors: Méndez-Samperio P , Hernandez-Garay M , Badillo-Flores A , Nuñez-Vazquez A 
Published: November 2003

SUMMARY
Tuberculosis is characterized by a cellular immune response mediated by various cytokines, including IL-1β released by stimulated mononuclear cells. It is now well established that IL-1β plays an important role in local and systemic inflammatory response in tuberculosis. Here we have demonstrated, for the first time, that addition of IL-4 to human mononuclear cells obtained from 11 healthy bacille Calmette–Guérin (BCG)-vaccinated donors reduced BCG-induced production of IL-1β by 91.46 ± 2.2%. This inhibitory effect was found highly significant (P &lt; 0.001) and was dose-dependent. The effect of IL-4 on the secretion of IL-1β was specific, since a complete reversion was obtained with a neutralizing MoAb to human IL-4. In addition, this inhibitory effect was not attributed to a cytotoxic effect, since trypan blue exclusion studies indicated no loss of cell viability in response to IL-4. Interestingly, the induction of IL-1β was regulated by IL-4, at least in part, by a direct mechanism mediated through the 130 extracellular domain of the IL-4 receptor, as demonstrated by incubation of the mononuclear cells with the neutralizing anti-IL-4 receptor MoAb. Finally, a significant down-regulation of IL-1β secretion was observed in hsp70-stimulated mononuclear cells cultured with IL-4. Further experimental work is needed to establish the relevance of IL-4 in human mycobacterial infection in vivo. However, an understanding of the mechanisms that control IL-1β secretion in human mycobacterial infections is essential to understand the pathogenesis of tuberculosis.
A malaria parasite toxin associated with Plasmodium vivax paroxysms
Authors: Wijesekera S K , Carter R , Rathnayaka L , Mendis K N 
Published: November 2003

SUMMARY
We have previously demonstrated a correlation between clinical paroxysms in Plasmodium vivax malarial infections and the appearance in patients' plasma of factors that kill blood stage parasites (gametocytes). This activity was, as previously shown, dependent on the presence in paroxysm plasma of tumour necrosis factor-alpha (TNF-α), which acts in conjunction with other ‘complementary' factors. Here we have identified a parasite component which is essential for this activity and functions as a ‘complementary' factor together with TNF, and a third component of unknown origin. The P. vivax parasite component present in paroxysm plasma can be substituted for by a blood-stage schizont extract of either P. vivax or P. falciparum. This was demonstrated by restoring the parasite-killing activity to post-paroxysm plasma (from which it was absent) with the addition of the extracts together with TNF. The active materials in these extracts, however, are different from the natural components in P. vivax paroxysm plasma, i.e. while the schizont extracts are immunologically cross-reactive between species, the activity of the natural P. vivax toxin(s) in patients' plasma is neutralized only by the homologous antisera. Plasmodium falciparum infections have neither distinct paroxysms nor parasite-killing activity in plasma. The pronounced paroxysms of P. vivax infections may thus be due in part to a species-specific toxin(s).
Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC)
Authors: Ueki T , Mizuno M , Uesu T , Kiso T , Nasu J , Inaba T , Kihara Y , Matsuoka Y , Okada H , Fujita T , Tsuji T 
Published: November 2003

SUMMARY
The third component of complement (C3) is central to both the classical and alternative pathways in complement activation. In this study, involvement of C3 activation in the mucosal injury of UC was investigated. We examined the distribution of activated (C3b) and degraded fragments (iC3b/C3dg) of C3, terminal complement complex (TCC), and complement regulatory proteins in normal and diseased colonic mucosa including UC and other types of colitis using immunohistochemical techniques at the level of light and electron microscopy. While C3b and iC3b/C3dg staining was negligible in the normal mucosa, iC3b/C3dg and, to a lesser extent, C3b were deposited in UC mucosa along the epithelial basement membrane. The deposition was enhanced in relation to the severity of mucosal inflammation (C3b, P &lt; 0.05; iC3b/C3dg, P &lt; 0.01). Epithelial deposition of TCC was not observed in most UC mucosa. Immunoelectron microscopy showed that C3b and iC3b/C3dg were distributed mainly along the epithelial basement membrane and the underlying connective tissue in a granular, studded manner, and weakly present along the basolateral surface of epithelial cells. These C3 fragments were also deposited in inflammatory control mucosa such as ischaemic and infectious colitis. Our findings suggest that deposition of the C3 fragments occurs in inflamed colonic mucosa of diverse etiologies, including UC, but to define a role of the deposition in the development of mucosal injury in UC awaits direct study.
Macrophage nitric oxide synthase (NOS) activation by Nocardia opaca fractions and 15- and 56-kD isolated antigens
Authors: Tučková L , Zídek Z , Hanikýřová M , Cukrowska B , TlaskalovÁ-Hogenová H , Barot-Ciorbaru R 
Published: November 2003

SUMMARY
The Gram-positive bacterium, Nocardia opaca, is a source of substances with adjuvant effect, ability to stimulate macrophages and natural killer cells for enhanced cytotoxity and cytokine production and B lymphocytes for polyclonal immunoglobulin secretion. We determined the immunogenicity of isolated N. opaca fractions and prepared MoAbs against immunogenic water-soluble mitogen (NWSM). Two main proteins of molecular mass 15 and 56 kD were detected in Western blot analysis and isolated by affinity chromatography using anti-NWSM MoAb B7/7. Both these isolated nocardial antigens were found to stimulate mouse peritoneal macrophage NOS. The effect of 5 μg NWSM was comparable to that of 5 μg lipopolysaccharide (LPS) or 20 U of interferon-gamma (IFN-γ) added to cell cultures. The MoAb B7/7 decreased NO−2 production induced by NWSM or by isolated nocardial antigens, but did not significantly influence the production elicited by LPS or IFN-γ. On the other hand, NOS activation by NWSM was not affected by anti-IFN-γ MoAb. The possible independent pathway for IFN-γ and NWSM macrophage activation is discussed.
Dynamics of HIV-1 replication following influenza vaccination of HIV+ individuals
Authors: Røsok B , Voltersvik P , Bjerknes R , Axelsson M , Haaheim L R , Åsjö B 
Published: November 2003

SUMMARY
Levels of HIV-1 have been reported to increase in peripheral blood after influenza vaccination of HIV+ individuals. In this study we have evaluated the dynamics of these changes. Ten HIV-1+ individuals classified in revised CDC clinical categories B and C as well as five seronegative healthy controls were vaccinated with the recommended influenza strains. HIV viral RNA and proviral DNA were sequentially quantified in serum and blood lymphocytes, respectively. Nine of the 10 HIV+ individuals had an increase in the frequency of infected CD4 cells 2 weeks after influenza vaccination. Individuals with low viral load had a rapid increase in viraemia and a small increase in frequency of infected cells in peripheral blood. In contrast, individuals with high viral load had a small drop in viraemia followed by a significant rise in the rate of infected cells. The observed changes may resemble those taking place during intercurrent infections in HIV+ individuals. The effects of the relative increases in infectious virus after the transient viraemic phase should be further investigated to evaluate potential risks of vaccination.
Immunoregulatory properties of IL-13 in patients with inflammatory bowel disease; comparison with IL-4 and IL-10
Authors: Kucharzik T , Lügering N , Weigelt H , Adolf M , Domschke W , Stoll R 
Published: November 2003

SUMMARY
Activated monocytes with increased expression of proinflammatory cytokines play a major role in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4 and IL-10 can effectively suppress the proinflammatory response of activated monocytes. IL-13 is a recently described antiinflammatory agent in vitro. The aim of our study was to determine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL-10 in patients with IBD. Peripheral blood monocytes were isolated from 27 patients with ulcerative colitis (UC), 27 patients with Crohn’s disease (CD) and 16 healthy controls. Cells were stimulated with pokeweed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secretion of IL-1β, tumour necrosis factor-alpha (TNF-α) and IL-6 was assessed using sandwich ELISA systems. Peripheral blood monocytes secreted significantly increased amounts of TNF-α and IL-6 under stimulation with PWM in patients with CD, while UC patients showed significantly elevated levels of IL-1β. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretion of IL-1β in a dose-dependent manner. With regard to IL-13 and IL-4, there was no significant suppression of TNF-α and IL-6 in patients with active IBD. By contrast, IL-10 was able to down-regulate all proinflammatory cytokines in active IBD as well as in controls. Proinflammatory cytokines from patients with inactive IBD could be significantly down-regulated by all three immunoregulatory cytokines. The inhibitory effect of IL-13 on TNF-α and IL-6 production in differentiated macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-α and IL-6 after treatment with IL-13. In conclusion, the antiinflammatory activity of IL-13 is partially reduced in patients with active IBD. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.
90K (Mac-2 BP) in human milk
Authors: D’Ostilio N , Sabatino G , Natoli C , Ullrich A , Iacobelli S 
Published: November 2003

SUMMARY
Human 90K, also known as Mac-2 binding protein (Mac-2 BP), is a secreted glycoprotein which is widely expressed, binds to the human macrophage-associated lectin Mac-2, and may have a role in host defence. We have measured the concentrations of 90K in human breast milk from eight healthy mothers delivering mature healthy infants after full-term pregnancy using a specific immunoenzymatic assay. Maximal 90K concentrations were observed on days 2–3 post-partum, and ranged from 13.4 to 79.2 μg/ml. The concentrations of 90K in the milk had no correlation with those in the maternal blood.
Anti-dsDNA production coincides with concurrent B and T cell activation during development of active disease in systemic lupus erythematosus (SLE)
Authors: Spronk P E , Horst G , van der Gun B T F , Limburg P C , Kallenberg C G M 
Published: November 2003

SUMMARY
The objective was to serially analyse T and B cell activation in relation to autoantibody production during the development of relapses in SLE. In a prospective study we serially analysed, by flow cytometry, T cell activation in relation to B cell activation and anti-dsDNA production in quiescent SLE and during the development of a clinical relapse. In addition, we related changes in T and B cell activation to changes in levels of anti-dsDNA and total IgG. During periods with clinically quiescent disease, the expression of activation markers on T cells (IL-2R and HLA-DR) and B cells (CD38) was persistently higher in SLE than in healthy controls (P &lt; 0.001). Percentages of CD20+CD38+ B cells were related to levels of total IgG (P &lt; 0.02), but not to levels of anti-dsDNA. Development of disease activity was paralleled by an increase in the percentages of CD4+ T cells (P &lt; 0.005) and CD20+CD38+ B cells (P &lt; 0.001), which were interrelated. Increases in B cell activation were related to increases in levels of anti-dsDNA (P &lt; 0.005), but not to changes in total IgG levels. B cells expressing high levels of CD38 spontaneously produced IgG class anti-dsDNA in vitro. Persistence of activated B cells during periods with clinically quiescent disease in SLE seems to underly hypergammaglobulinaemia but not anti-dsDNA production. Prior to clinical disease activity, further activation of T and B cells occurs, which is paralleled by rises of anti-dsDNA but not of total IgG. This suggests that the production of anti-dsDNA is a T cell-dependent antigen-driven process, which is independent of the polyclonal activation of the immune system inherent to the disease.
CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease
Authors: Claesson M H , Rudolphi A , Kofoed S , Poulsen S S , Reimann J 
Published: November 2003

SUMMARY
Transfer of 2 × 105 congenic or semiallogenic purified TCRαβ+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients. In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression of epithelial nuclear proliferation antigen, and elongation of the crypts. Later on, massive mononuclear cell infiltration, hypertrophy of all layers of the colon and occasional epithelial ulcerations were observed. At this stage, accumulations of IgA, IgM and small numbers of IgG1-, IgG2-and IgG3-secreting plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages, neutrophils and plasma cells secreting IgA, IgM, and to a lesser degree IgG antibodies which might play an accessory role in the pathogenesis of IBD.