bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell receptor repertoire and mitotic responses of lamina propria T lymphocytes in inflammatory bowel disease
Authors: QIAO L , GOLLING M , AUTSCHBACH F , SCHURMANN G , MEUER S C 
Published: July 2010

SUMMARYHuman intestinal lamina propria T lymphocytes (LPL-T) physiologically exhibit minimal proliferation in response to antigen receptor stimulation in vitro. This is thought to occur as a consequence of regulatory influences which are exerted by the mucosal microenvironment. The present study is aimed at investigating whether proliferative responses of intestinal LPL-T to antigen receptor stimulation are altered in patients with inflammatory bowel disease. Accordingly, proliferative responses of LPL-T in patients with Crohn's disease and ulcerative colitis to stimulation with CD3 MoAb plus IL-2 were examined and compared with controls. In addition, T cell receptor (TCR) repertoires of LPL-T and peripheral blood T lymphocytes were determined by indirect immunofluorescenee using a panel of 11 TCR Vβ specific antibodies. In most patients with inflammatory bowel disease, LPL-T showed enhanced proliferation to antigen receptor stimulation compared with controls. Moreover, perhaps as a consequence, an enhanced frequency of in vivo preactivated T cells was seen as judged from an increased spontaneous proliferative response to low concentrations of exogenous IL-2. LPL-T and peripheral blood T lymphocytes exhibited similar percentages of TCR Vβ gene usage both in controls and in patients. In summary, polyclonal activation of LPL-T due to impairment of local adjustment, i.e. insufficient down-regulation of TCR/CD3-dependent signalling processes, may contribute to the pathogenesis of inflammatory bowel disease.
Combined effect of fluconazole and thymosin α1 on systemic candidiasis in mice immunosuppressed by morphine treatments
Authors: DI FRANCESCO P , GAZIANO R , CASALINUOVO I A , BELOGI L , PALAMARA A T , FAVALLI C , GARACI F 
Published: July 2010

SUMMARYTreatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin α1 (Tα1)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 106 C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and Tal prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with Tα1 or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of Tα1 and fluconazole is due lo a direct antifungal action and activation of the immunocompetence.
Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study
Authors: SPRONK P E , BOOTSMA H , HUITEMA M G , LIMBURG P C , KALLENBERG C G M 
Published: July 2010

SUMMARYActive SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-l (sVCAM-1). soluble intercellular adhesion molecule-l (slCAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI). and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P &lt; 0.0001), levels in patients with renal involvement being higher than in those without (P &lt; 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P &lt; 005) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P &lt; 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-l were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P &lt; 0.02). Levels of sICAM-l and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-l are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.
Cytotoxic effects of antibodies to proteinase 3 (C-ANCA) on human endothelial cells
Authors: MAYET W-J , SCHWARTING A , MEYER ZUM BÜSCHENFELDE K-H 
Published: July 2010

SUMMARYAutoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially those with specificity for proteinase 3 (PR-3) and myeloperoxidase, are valuable markers for differential diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG) and other vasculitides. Till now, several concepts concerning a direct role of antibodies against PR-3 in the pathogenesis of WG have been discussed. Recently we were able to show that these antibodies recognize PR-3 translocated into the membrane of human endothelial cells. The aim of this study was to investigate putative cytotoxic effects of antibodies to PR-3 on human endothelial cells. Antibodies were obtained by affinity purification of sera from patients with active WG, Purified antibodies to Ro (SS-A), La (SS-B) and RNP served as controls. Purified antibodies to PR-3 displayed a lytic activity against endothelial cells treated with tumour necrosis factor-alpha (TNF-α) with the help of cytokine-primed neutrophils as measured in a Cr-release assay. About 100% specific cytotoxicity occurred after 4 h and was independent of complement, Cytotoxic effects were inhibited by coincubation with unprimed ncutrophils or preincubation of PR-3 antibodies with purified antigen. Antibodies to Ro (SS-A), La (SS-B) or RNP had no cytotoxic effect. In summary, PR-3 antibody-induced cytotoxicity required (i) expression of PR-3 on the surface of TNF-α-treated endothelial cells: and (ii) co-cultivation of cytokine-primed neutrophils. This is to the best of our knowledge the first report on direct cytotoxic effects of PR-3 antibodies on vascular endothelium. Our data give a hint at a PR-3 antibody-mediated mechanism of endothelial injury via antibody-dependent cellular cytotoxicity in WG and other ANCA-related vasculitides.
Reduced interferon-gamma (IFN-γ) secretion with increased IFN-γ mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect
Authors: TANG M L K , VARIGOS G , KEMP A S 
Published: July 2010

SUMMARYReduced secretion of IFN-γ in atopic individuals has been implicated in the pathogenesis of disease, though the mechanisms leading to this reduced secretion have not been elucidated. As production of IFN-γ has been shown to be predominantly regulated by its rate of transcription, expression of IFN-γ mRNA was examined in atopic children and in age-matched, non-atopic controls by polymerase chain reaction (PCR)-assisted mRNA amplification. Children with atopic dermatitis were found to have constitutive expression of IFN-γ mRNA in freshly isolated peripheral blood mononuclear cells (PBMC) and in unstimulated PBMC cultures which increased further following stimulation with phorbol myristate acetate (PMA)/Ca in vitro. In contrast, expression of IFN-γ mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate that circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of the inflammatory process in atopic dermatitis. Although expression of IFN-γ mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(s) underlying reduced IFN-γ secretion in these individuals lie post-transcriptionally.
Analysis of lymphocyte cell death and apoptosis in HIV-2-infected patients
Authors: JALECO A C , COVAS M J , VICTORINO R M M 
Published: July 2010

SUMMARYRecent evidence suggests that T cell apoptosis could be involved in the pathogenesis of HIV-1 infection. As the progression of HIV-2 associated disease appears to be slower than that of HIV-1, we investigated whether there were differences in the degree of T cell death and apoptosis in peripheral blood mononuclear cell (PBMC) cultures from patients with HIV-1 or HIV-2 infection. PBMC from healthy controls (n = 28) and patients infected with HIV-1 (n = 26: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL). w = 16; and AlDS-related complex (ARC)AIDS n = 10) or HIV-2 (n = 30: ASY/PGL, n = 16: ARC/ AIDS, n = 14) were cultured in the absence or presence of mitogens (PHA, PWM) or superantigen (SEB). After 48 h, cell death (CD) was assessed by trypan blue exclusion and in some patients programmed cell death (PCD) was quantified in flow cytometry by measuring the percentage of hypodiploid nuclei corresponding to fragmented DNA, after treating the cells with a propidium iodide hypotonic solution. HlV-1 and HlV-2 ARC/AIDS patients and ASY/PGL HIV-1+ patients had significant increases in cell death percentages compared with controls, both in unstimulated and stimulated lymphocyte cultures. However, HIV-2+ ASY/FGL patients did not exhibit significant increases of cell death in unstimutated cultures. In addition, the comparison between HIV-l and HIV-2 infected subjects in similar stages of disease, showed no significant differences in CD in the ARC AIDS patients, although ASY/PGL HIV-2-infected subjects had lower levels of CD than the HIV-1+ ASY/PGL (3.4%± 0.6 s.e.m. versus 6.8%± M s.e.m., P &lt; 0.01). PCD was significantly increased both in ASY/PGL (14.3%± 2.2 s.e.m., n = 8, P&lt; 0.005) and m ARC/AIDS (25.3%± 4.5 s.e.m., n = 9, P &lt; 0.001) HIV-1+ patients compared with healthy controls (5.8%± l.7 s.e.m., n = 11). This contrasts with HIV-2 infected subjects where the ASY/PGL patients (10.0%± 2.8 s.e.m., n = 6) did not differ significantly from healthy controls, although ARC/AIDS patients (27.2%± 4.2 s.e.m., n = 9. P &lt; 0.001) had significantly increased levels of PCD. In conclusion, this is the first report describing the occurrence of spontaneous and activation-induced lymphocyte death by apoptosis in HlV-2 infected subjects. The lower levels of PCD in ASY/PGL HlV-2 infected patients compared with HIV-T patients at a similar stage justify further investigation to define whether these differences have any rote in the putative slower progression of HlV-2 disease.
Pneumocystis carinii-induced activation of the respiratory burst in human monocytes and macrophages
Authors: LAURSEN A L , MØLLER B , RUNGBY J , PETERSEN C M , ANDERSEN P L 
Published: July 2010

SUMMARYHuman monocytes and monocyte-derived macrophages were studied for their ability to phagocytose Pneumocystis carinii and produce superoxide (O−2) during the process. One × 106 freshly isolated monocytes. incubated with 0.1 – 3.75 × 106P. carinii cysts, increased O−2 production in a dose-related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O−2 production significantly above the response obtained by lung tissue from rats (10.7 and 4.9 versus 30 fmol/cell per 90 min). The difference between pneumocysts opsonized in untreated versus complement-depleted serum was not significant (10.7 versus 12.6 fmol/cell per 90 min). Monocyte-derived macrophages also activated the respiratory burst when stimulated with pneumocysts, and this effect could be significantly increased, from 4.2 to 8.8 fmol/cell per 90 min, when cells were primed with interferon-gamma (IEN-γ). Cells primed with IL-3 also increased O2 production, though to a lesser extent. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) had only a small effect on the respiratory burst in cells stimulated with P. carinii. Priming with IEN-γ increased the rate of phagocytosis in macrophages. After incubation for 90 min or more, however, the percentage of cells with phagocytic vacuoles was only slightly higher in IFN-γ-primed cells. When examined by electron microscopy (EM), most vacuoles contained partially or totally degraded pneumocysts. In conclusion, we have demonstrated the ability of monocytes and monocyte-derived macrophages to ingest and degrade pneumocysts. activating the respiratory burst during the process.
Induction in vitro of 72-kD heat shock protein in a continuous culture of rat thyroid cells, FRTL5
Authors: MISAKI T , TAKEUCHI R , MIYAMOTO S , HIRANO A , KASAGI K , KONISHI J 
Published: July 2010

SUMMARY
In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been healed at 425 C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retroocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.
Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis
Authors: COERS W , BROUWER L , VOS J T W M , CHAND A , HUITEMA S , HEERINGA P , KALLENBERG C G M , WEENING J J 
Published: July 2010

SUMMARYWe examined immunopathological changes of podocytes in vivo which, based on in vitro studies, are thought to be relevant for the pathogenesis of renal diseases. We investigated the alterations of podocytes in local inflammation in a recently developed model of pauci-immune necrotizing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plastic embedded kidney sections at different time points of the disease were incubated with antibodies directed to MHC class I, MHC class II, ICAM-1 and to relevant cytokines. Strong glomerular expression of MHC class I. II and ICAM-1 was found within 4 days, and plastic embedded sections clearly demonstrated increased cell membrane staining of podocytes. Increased glomerular interferon-gamma (IFN-γ) was detected within 24 h of induction of NCGN. and IL-IβT and tumour necrosis factor-alpha (TNF-α) were found from day 4. The potency of these cytokines to induce adhesion molecules on podocytes was investigated on rat glomerular epithelial cells in vitro. By using IACS analysis and electron microscopical techniques, we found that the in vivo expression of MHC class I, II and ICAM-I by podocytes could in vivo be simulated by IFN-γ IFN-α weakly induced MHC class I. while IL-Iβ and TNF-α were ineffective. We hypothesize that podocytes in this in vivo model are important to maintain the local inflammatory process in the glomerulus by expression of relevant adhesion molecules and MHC molecules upon stimulation with specific cytokines.
Influence of an established acute phase response on the severity of experimental nephritis
Authors: KARKAR A M , REES A J 
Published: July 2010

SUMMARYSmall doses of lipopolysaccharide (LPS) induce an acute phase response (APR), and a number of studies have also shown that this greatly enhances the severity of glomerular injury in the heterologous phase of nephrotoxic nephritis (hNTN), an experimental model of anuglomerular basement membrane (GBM) disease. Here, we examined the influence of pre-existing subclinical infection and raised APR assessed by plasma α2-macrogiobulin (α2-M) concentration, on the degree of injury in this model of nephritis. Studies were initially performed to determine the normal range of α2-M in rats and its modulation by IL-6 and different doses of LPS. Plasma concentration of α2-M was found to be variable and dependent on the weight of the rats. Single injections of either LPS or IL-6 had a comparable effect and continuous perfusions of LPS caused a progressive increase in α2-M which peaked al 4S h and declined gradually over 1 week. Following induction of nephritis with long of anti-GBM antibody, rats with raised α2-M had 14 ± 3 mg 24 h albuminuria compared with 4 ± 1 mg 24 h in rats with normal α2-M (P &lt; 0.0.001, Wilcoxon). Injection of 20 mg anti-GBM antibody caused 36 ± 11 mg 24 h albuminuria compared with 16 ± 4 mg/24h (P &lt; 0001), respectively. However, all these rats remained active and none of them died, hi contrast, injection of 0.25 μg LPS before induction of nephritis with 10 mg anti-(IBM antibody, in rats with raised a,-M, caused severe albuminuria (115 ± 23 mg 24 h) compared wilh rats having normal levels of α2-M (72 ± 15 mg 24h. P &lt; 005), Furthermore, rats with raised α2-M also had severe systemic manifestations characterized by pulmonary haemorrhage and extensive glomerular thrombosis, and many of them died. These results demonstrate the potential effect of pre-existing subclinical infection and raised APR on severity of glomerular injury which may affect the outcome of experimental studies.
Reactive oxygen product formation by human neutrophils as an early marker for biocompatibility of dialysis membranes
Authors: ROSENKRANZ A R , TEMPL E , TRAINDL O , HEINZL H , ZLABINGER G J 
Published: July 2010

SUMMARYProduction of reactive oxygen intermediates (ROI) by neutrophils (PMN) in vivo was examined by a whole blood assay using dichlorofluorescein-diacetate (DCFH-DA) in 10 patients each dialyser consecutively with two different dialyser membranes. Haemodialysis (HD) with cuprophan membrane (CM) led to a significantly (P &lt; 0001) more pronounced ROI production by PMN (2.4 ± 0.5-fold increase in Intracellular oxidation of DCFH-DA) compared with HD with polysulfone membranes (PM; 1.5 ± 0.2-fold). HD with CM induced a decrease in PMN count by about 90%, whereas PM induced a decrease by only 25% (P &lt; 0.001). In CM patients maximal ROI production coincided with the nadir in PMN count. All patients dialysed with CM showed a clear increase in serum levels of Bb fragments. whereas PM-dialysed patients did not. In this respect however, no clear time relationship was seen to the kinetics of ROI production, nor to the disappearance of neutrophils from the circulation valuating a direct effect of the dialysis membranes on PMN demonstrated that incubation of neutrophils with hollow fibres of the CM but not of the PM in the absence of plasma induces significant ROI production by PMN. Our study thus indicates that ROI production by PMN during HD correlates to membrane biocompatibility. Furthermore, one might speculate that also independently from but perhaps in addition to complement activation, reactive oxygen products arc critically involved in the generation of haemodialysis-associated neutrophil emigration.
Cellular mRNA expression of interferon-gamma, IL-4 and transforming growth factor-beta (TGF-β) by rat mononuclear cells stimulated with peripheral nerve myelin antigens in experimental allergic neuritis
Authors: ZHU J , MIX E , OLSSON T , LINK H 
Published: July 2010

SUMMARYExperimental allergic neuritis (EAN) serves as a useful model for inflammation in the peripheral nervous system. To study the potential role of important immunoregulatory and effector cytokines in EAN, we examined the expression of mRNA for interferon-gamma (IFN-γ), IL-4 and JGF-β by in situ hybridization in lymph node and splenic cells cultured with bovine peripheral nerve myelin (BFM), P2 and P0 during the course of EAN in Lewis rats. Levels of IFN-γ mRNA-expressing mononuclear cells (MNC) from lymph nodes and spleens roughly correlated with clinical status, consistent with a disease-promoting role for IFN-γ. BPM, P0 and P2-rcactive IFN-γ mRNA-expressing T cells appeared in lymph nodes and spleen before onset of the disease, whereas a significant TGF-β response to BPM, P2 and PO was observed at lower levels than the IFN-γ response and at onset of recovery, consistent with a disease down-regulating role of TGF-β. IL-4 mRNA-expressing cells were found at levels similar to TGF-β mRNA-expressing cells, and with the latest peak of the three cytokines examined. This result suggests that IL-4 may also suppress IFN-γ expression at late recovery phase of EAN.
Transforming growth factor-beta 1 (TGF-β1)- and β2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer
Authors: MAEDA J , UEKI N , OHKAWA T , IWAHASHI N , NAKANO T , HADA T , HIGASHINO K 
Published: July 2010

SUMMARY
We investigated the levels of TGF-β in malignant pleural effusions (MPE) caused by malignant mesothelioma (MESO) or primary lung cancer. TGF-β levels in MPE caused by MESO were 283.9 ± 219.2pM (mean plusmn; s.d.) and were three to six times higher than those due to primary lung cancers (P &lt; 0.01 or P &lt; 0.05). We also evaluated TGF-β1- and β2-like activities in MPE using specific polyclonal antibodies. Although TGF-β1-like activity could be detected in all cases, TGF-β2-like activities were detected in five of seven in MESO and in a few cases with primary lung cancer. These results demonstrate that the levels of total TGF-β and TGF-β2-like activity may be clinically useful to differentiate MESO from primary lung cancer. Our data also suggest that TGF-β may help further characterize the clinical features of MESO.