bluuebunny/crossref_metadata_2025_split huggingface dataset:
B cells capable of spontaneous IgG secretion in cerebrospinal fluid from patients with multiple sclerosis: dependency on local IL-6 production
Authors: Perez L , Alvarez-CermeÑO J C , Rodriguez C , RoldÁN E , Brieva J A 
Published: July 2010

SUMMARYCerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains B cells capable of spontaneous IgG secretion in vitro. This study analyses the function and regulation of these cells. CSF cells obtained from nine MS patients actively produced IgG during 2–3 days in culture, and the activity decreased when CSF cells were cultured in serum-free medium. CSF cells from four controls did not secrete detectable IgG in vitro. Further experiments revealed that IL-6 played a role on MS CSF IgG-secreting cells, as can be deduced from the following findings: (i) the addition of exogenous IL-6, but not of other cytokines, to serum-free cultures restored missing CSF cell IgG secretion; (ii) the inclusion of anti-IL-6, but not of control, blocking MoAb reduced IgG secretion by CSF cells in fetal calf serum (FCS)-containing cultures; and (iii) CSF cells were capable of active IL-6 production in the presence of FCS. These results suggest that endogenous IL-6 production by MS CSF cells seems to be responsible for inducing CSF IgG-secreting B cells to reach terminal differentiation.
In vitroanalysis of metabolic predisposition to drug hypersensitivity reactions
Authors: Riley R J , Leeder J S 
Published: July 2010

SUMMARYIdiosyncratic hypersensitivity reactions may account for up to 25% of all adverse drug reactions, and pose a constant problem to physicians because of their unpredictable nature, potentially fatal outcome and resemblance to other disease processes. Current understanding of how drug allergy arises is based largely on the hapten hypothesis: since most drugs are not chemically reactive per se, they must be activated metabolically to reactive species which may become immunogenic through interactions with cellular macromolecules. The role of drug metabolism is thus pivotal to the hapten hypothesis both in activation of the parent compound and detoxification of the reactive species. Although conjugation reactions may occasionally produce potential immunogens (for example, the generation of acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac), bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The multifactorial nature of hypersensitivity reactions, particularly the role of often unidentified, reactive drug metabolites in antigen generation, has hampered the routine diagnosis of these disorders by classical immunological methods designed to detect circulating antibodies or sensitized T cells. Similarly, species differences in drug metabolism and immune system regulation have largely precluded the establishment of appropriate animal models with which to examine the immunopathological mechanisms of these toxicities. However, the combined use of in vitro toxicity assays incorporating human tissues and in vivo phenotyping (or, ultimately, in vitro genotyping) methods for drug detoxification pathways may provide the metabolic basis for hypersensitivity reactions to several drugs. This brief review highlights recent efforts to unravel the bases for hypersensitivity reactions to these therapeutic agents (which include anticonvulsants and sulphonamides) using drug metabolism and Immunochemical approaches. In particular, examples are provided which illustrate breakthroughs in the identification of the chemical nature of the reactive metabolites which become bound to cellular macromolecules, the enzyme systems responsible for their generation and (possibly) detoxification, and the target proteins implicated in the subsequent immune response.
Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus erythematosus
Authors: Monestier M , Novick K E , Karam E T , Chabanne L , Monier J-C , Rigal D 
Published: July 2010

SUMMARYDogs can develop systemic lupus erythematosus syndromes that are clinically similar to those seen in humans. In contrast, previous observations suggest differences in their autoantibody reactivity patterns against histones and DNA which are components of the nucleosome in chromatin. The objective of this study was to assess comprehensively the levels of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus and control dog sera were determined using IgM- and IgG-specific reagents in an ELISA against a variety of chromatin antigens. When compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosomes in lupus dogs. There was no significant increase in any of the IgM specificities tested. Therefore, the reactivity pattern to nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands In contrast with human and murine lupus, where autoantibodies are directed against a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in canine lupus. The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA antibodies are not required for the development of this complication, whereas IgG anti-histone antibodies may be relevant to its pathogenesis.
Analysis of γδ region usage in normal and diseased human intestinal biopsies and peripheral blood by polymerase chain reaction (PCR) and flow cytometry
Authors: Bucht A , SÖDerstrÖM K , Esin S , Grunewald J , Hagelberg S , Magnusson I , Wigzell H , GrÖNberg A , Kiessling R 
Published: July 2010

SUMMARYThe intestinal population of γδ T cell receptor (TCR)-bearing cells was characterized with regard to Vδ and Vγ subtype expression. For this purpose, we utilized V gene-specific PCR of mRNA prepared from intestinal biopsies. Predominant expression of the Vδ1 subtype was demonstrated in the small intestine of patients with coeliac disease and in the inflamed colon of patients with inflammatory bowel diseases (IBD: ulcerative colitis and Crohn's disease) as well as in colon biopsies taken from macroscopically normal areas of colon. Although intestinal γδ T cells preferentially expressed Vδ1, other Vδ transcripts could be detected, of which Vδ2 and Vδ5 were commonly expressed. Analysis of biopsies from mesenteric lymph nodes demonstrated a Vδ repertoire similar to the mucosa. In peripheral blood on the other hand, high expression of both Vδ2 and Vδ1 was found. The predominant expression of Vδ1 transcripts in the intestinal mucosa of IBD patients correlated well with protein cell surface expression as analysed by flow cytometry using Vδ1- and Vδ2-specific antibodies. Selective expansion of γδ T cells could not be demonstrated within the inflamed mucosa as shown by mRNA analysis and flow cytometry. Instead, IBD patients demonstrated a decreased proportion of TCR 76-carrying T cells in the inflamed mucosa compared with macroscopically normal area of colon. On the other hand, a significantly increased percentage of T cells bearing the γδ TCR was found in peripheral blood of patients with Crohn's disease compared with healthy individuals, indicating that local mucosal inflammation may influence the circulating γδ T cell population.
In vitroandin vivoT cell responses in mice during bronchopulmonary infection with mucoidPseudomonas aeruginosa
Authors: Stevenson M M , Kondratieva T K , Apt A S , Tam M F , Skamene E 
Published: July 2010

SUMMARYIn vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57B1/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57B1/6 mice through 20 days post-intratracheal infection with 104 colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 105 CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57B1/6 mice infected with 104 CFU Ps. aeruginosa and in BALB/c mice infected with 105 CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57B1/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.
Enhanced production of transforming growth factor-beta (TGF-β) during autologous mixed lymphocyte reaction of systemic sclerosis patients
Authors: OTA H , KUMAGAI S , MORINOBU A , YANAGIDA H , NAKAO K 
Published: July 2010

SUMMARYSystemic sclerosis (SSc) is characterized by systemic fibrosis and microvascular lesions. As TGF-β is suggested to be related to skin fibrosis, we examined the production of TGF-β from peripheral mononuclear cells (MNC) of SSc patients. Since anti-TGF-β neutralizing antibody improved the defective proliferative response in autologous mixed lymphocyte reaction (AMLR) of SSc patients, TGF-β was thought to participate in the decreased AMLR of SSc patients. Greater amounts of TGF-β in the active as well as in the latent forms were produced during AMLR of SSc patients than that of normal subjects. It was suggested that TGF-β excessively produced from the MNC of SSc patients might play a major role in the fibrosis of the patients during AMLR-like in vivo responses.
Selective recruitment of lymphocyte subsets to the inflamed appendix
Authors: SOO K S , MICHIE C A , BAKER S R , WYLLIE J H , BEVERLEY P C L 
Published: July 2010

SUMMARYTotal lymphocyte counts and the distribution of lymphocyte subsets were determined in peripheral venous blood and appendiceal mononuclear cells from 60 patients who underwent appendicectomy for the clinical diagnosis of appendicitis. A significant peripheral lymphopenia was observed in the 46 patients with histologically confirmed acute appendicitis which was accompanied by an increase in the appendiceal lymphocyte concentration. There was an even greater depletion of CD45RO+ (memory) T lymphocytes in peripheral blood and an increase in the inflamed appendix. Reciprocal changes were observed in the CD45RA+ (naive) T lymphocyte subset. These changes were reflected in the local arterial and venous CD45RA and CD45RO T lymphocyte subsets. Proliferation studies showed an expanded functional repertoire of T lymphocytes in the inflamed appendix. Selective recruitment of memory T lymphocytes from the peripheral blood to the inflamed appendix was demonstrated.
Cell-mediated autoimmunity in patients with Wegener's granulomatosis (WG)
Authors: BALLIEUX B E P B , VAN DER BURG S H , HAGEN E C , VAN DER WOUDE F J , MELIEF C J M , DAHA M R 
Published: July 2010

SUMMARY
Despite the well described infiltration of cells of the cellular immune system in vasculitic lesions and the granuloma formation in patients with WG, the role of T cell-mediated autoimmunity in WG is not clear. Reports of T cell proliferation in response to neutrophil azurophilic granule proteins are contradictory. In this study we have assessed the proliferation of T cells of WG patients to purified proteinase 3 (PR3) and to total azurophilic granule proteins in two different assays. In addition to the classical proliferation assay with isolated peripheral blood mononuclear cells, we have used a whole blood proliferation assay. In both assays we found proliferative responses to PR3 in patients with WG. The number of patients reacting to the azurophilic granule extract was higher than the patients reacting to the purified PR3, suggesting that other autoantigens may also be involved. We have identified epitopes of PR3 that may be potential targets of class I-restricted T cell responses in the context of HLA-A*0201, the most common MHC class I molecule. These epitopes were determined by the binding of synthetic PR3 peptides to HLA-A*0201 on the antigen-processing defective cell line, T2. In addition, T cell lines were established from tissue biopsies, obtained from WG patients, and assessed for cytolytic reactivity against T2 cells, preloaded with synthetic PR3 peptides. We conclude that T lymphocytes of WG patients have increased proliferative responses to purified PR3 and to a larger extent to non-fractionated proteins of azurophilic granules of polymorphonuclear neutrophilic leucocytes (PMN).
Autoantibodies against eukaryotic protein L7 in patients suffering from systemic lupus erythematosus and progressive systemic sclerosis: frequency and correlation with clinical, serological and genetic parameters
Authors: NEU E , VON MIKECZ A H , HEMMERICH P H , PETER H-H , FRICKE M , DEICHER H , GENTH E , KRAWINKEL U 
Published: July 2010

SUMMARYRecent studies have shown that sera of patients suffering from systemic autoimmune diseases contain autoantibodies directed against the eukaryotic ribosomal protein L7 [1]. In the present study we screened a large panel of sera from patients with systemic lupus erythematosus (SLE) for the presence of anti-L7 autoantibodies and their relationship to clinical, serological and genetic parameters of SLE. By means of an ELISA employing recombinant protein L7 as antigen we detected anti-L7 autoantibodies in 172 of 506 SLE sera (34%). Negative correlations were observed between the presence of anti-L7 autoantibodies, serum IgG levels and proteinuria; a potentially positive relationship existed with lung fibrosis. In order to analyse further this possibility we screened sera of 129 patients suffering from progressive systemic sclerosis (PSS) for anti-L7 reactivity; 45 of these patients had lung fibrosis. Of the PSS patients, 41% exhibited anti-L7 autoantibodies, but positive reactions were evenly distributed among patients with and without lung fibrosis. Protein L7 thus represents a major autoantigen of systemic autoimmune diseases, but does not so far define a distinct subpopulation of patients.
The level of the serum opsonin, mannan-binding protein in HIV-1 antibody-positive patients
Authors: NIELSEN S L , ANDERSEN P L , KOCH C , JENSENIUS J C , THIEL S 
Published: July 2010

SUMMARYThe concentrations of mannan-binding protein (MBP) in consecutive samples from 10 HIV+ persons were estimated using an ELISA based on polyclonal rabbit anti-MBP. The changes in MBP with time were similar in HIV+ and HIV− persons, and did not appear to be of clinical significance. MBP was determined in a further 70 persons found HIV-1+ during a period af 2·5 years (1984–1986). Out of the total of 80 patients, 32 have by now died from AIDS. According to the serum level of MBP the HIV-infected persons were grouped into high (&gt; 650 ng MBP/ml). intermediate (101–650 ng/ml), and low MBP (&lt; 101 ng/ml). At the termination of the study the frequency of deaths/total in each of the groups were: high MBP, 14/39 (36%); intermediate MBP, 12/26 (46%); and low MBP, 6/14 (43%). There was no association between the MBP level of the individual and the progressive loss of CD4+ T cells, and the level of MBP was not predictive for the length of time between the detection of HIV antibodies and development of AIDS, nor for the duration of AIDS before death occurred. The number of HIV+ persons without detectable MBP (10%) was significantly higher than previously reported for healthy persons (2·4%, P= 0·027). The course of HIV infection does not seem to be influenced by the level of MBP, nor does the antimicrobial activity of MBP appear to affect the progression of AIDS. Further studies are required to substantiate the significance of absence of MBP in the susceptibility to HIV.
Inhibition ofex vivoproinflammatory cytokine secretion in fatalMycobacterium tuberculosisinfection
Authors: FRIEDLAND J S , HARTLEY J C , HARTLEY C G C , SHATTOCK R J , GRIFFIN G E 
Published: July 2010

SUMMARYTuberculosis is characterized by fever, weight loss, a prolonged acute-phase protein response and granuloma formation. These characteristics may partly be due to action of proinflammatory cytokines tumour necrosis factor (TNF), IL-6 and IL-8. We investigated plasma concentrations of these cytokines before and after ex vivo lipopolysaccharide stimulation of whole blood leucocytes from 41 Zambian patients with tuberculosis, 32 of whom were also HIV+. Although patients had a reduced weight, were more anaemic and had higher erythrocyte sedimentation rate compared with controls (all P &lt; 0·0005), clinical and laboratory measurements of disease state were similar in those who died and survivors. In contrast, plasma IL-6 and IL-8 concentrations were higher in patients who died (P &lt; 0·05). There was no detectable cytokine mRNA in unstimulated leucocytes. There was reduced secretion of TNF (P &lt; 0·005 at 2h), IL-6 (P &lt; 0·005 at 8 h) and IL-8 (P &lt; 0·005 at 24 h) after ex vivo stimulation of whole blood leucocytes from patients who died compared with survivors. This was partly due to a soluble inhibitory factor present in plasma. The only additional effect of concurrent infection by HIV with Myco. tuberculosis was decreased IL-6 secretion following ex vivo stimulation of leucocytes. Reduced proinflammatory cytokine release may represent a critical impairment of host immune defences important in determining outcome in tuberculosis.
Synthesis and regulation of accessory/proinflammatory cytokines by intestinal epithelial cells
Authors: PANJA A , SIDEN E , MAYER L 
Published: July 2010

SUMMARYIntestinal epithelial cells (IEC) have been shown to act as antigen-presenting cells (APC) in vitro and may have this capacity in vivo. In order to determine whether IEC, like other APC, are able to produce accessory cytokines which may play a role in T cell activation, we assessed the accessory cytokine profile of IEC constitutively or after stimulation. We measured expression, production and regulation of accessory cytokines (IL-1β, IL-6, tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) by the presence of mRNA as well as secreted protein. Freshly isolated IEC from surgical specimens were cultured in the presence or absence of lipopolysaccharide (LPS), interferon-gamma (IFN-γ), IL-1β or TNF-α. mRNA was assessed by a specific RNAse protection assay which controlled for contaminating cell populations while protein secretion was measured by ELISA (IL-1) or bioassay (TNF and IL-6). Neither IL-1β nor TNF-α were detectable in cultured IEC supernatants, supporting the lack of macrophage contamination. All IEC spontaneously secreted IL-6 at levels comparable to those of macro-phages. IEC IL-6 mRNA also increased approximately 200-fold during the first 24 h of culture. LPS, IFN-γ or TNF-α had no effect on spontaneous IL-6 production, and neither resulted in the secretion of IL-1β or TNF-α. However, IL-1β up-regulated IL-6 synthesis by 6–7-fold. IEC express a profile of cytokine mRNAs distinct from conventional APC (low level constitutive IL-6 expression but no detectable IL-1β, TGF-β or TNF-α), adding to their uniqueness as APC.
IL-1 receptor antagonist (IL-1Ra) does not inhibit the production of C-reactive protein or serum amyloid A protein by human primary hepatocytes. Differential regulation in normal and tumour cells
Authors: GABAY C , GENIN B , MENTHA G , IYNEDJIAN P B , ROUX-LOMBARD P , GUERNE P-A 
Published: July 2010

SUMMARYThe synthesis of some class 1 acute-phase proteins (APP), including C-reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL-1 receptor antagonist (IL-1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL-1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cylokine inhibitors in connective tissues diseases suggested that IL-1 and tumour necrosis factor-alpha (TNF-α) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL-1β, IL-6, and TNF-α and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL-1β and/or TNF-α had synergistic effects with IL-6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL-6 and decreased by IL-1 (and TNF-α) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine-rich mononuclear cell-conditioned medium was totally unaffected by IL-1Ra or anti-TNF-α antibodies. In contrast, the addition of IL-1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell-conditioned medium. We therefore conclude that IL-1β and TNF-α do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.
Immune responsiveness to inhaled antigens: local antibody production in the respiratory tract in health and lung diseases
Authors: YOSHIZAWA Y , OHTANI Y , INOUE T , MIYAKE S , IKEDA A , TANBA M , KURUP V P , MIYAMOTO K 
Published: July 2010

SUMMARYThe pulmonary defence mechanism in summer type hypersensitivity pneumonitis induced by Trichosporon cutaneum was investigated. We have studied the antibody response to fungal antigens in sera and bronchoalveolar lavage (BAL) fluids from patients with summer type hypersensitivity pneumonitis, bird fancier's lung, interstitial pneumonia associated with collagen vascular disease (INT-PNE), and from normal volunteers. Antigens extracted from fungi frequently isolated from home environments were used in ELISA to detect IgG and IgA antibodies in sera and BAL fluids. The results of the present study show that antibody titre in the respiratory tract to a variety of fungi from home environments is modulated by ongoing pulmonary inflammation, and that antibody production against inhaled antigens is altered by pulmonary inflammation resulting from diverse pathogenesis. This study concludes that the preexisting pulmonary inflammatory disease alters antibody production in the respiratory tract in response to inhaled fungi, and that the type of alteration depends in part on the etiology of the preexisting disease.
The inhibitory effects ofMycobacterium tuberculosison MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants
Authors: WADEE A A , KUSCHKE R H , DOOMS T G 
Published: July 2010

SUMMARYThe expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell HLISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-γ) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function.