bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatoid factor production by mononuclear cells derived from different sites of patients with rheumatoid arthritis
Authors: OTTEN H G , DAHA M R , DOLHAIN R J E M , de ROOY H H , BREEDVELD F C 
Published: July 2010

SUMMARY
To investigate the origin of circulating rheumatoid factor (RF) and the relation between RF production at different sites in patients with rheumatoid arthritis (RA), mononuclear cells derived from bone marrow, synovium and peripheral blood of patients with RA were examined for the presence of plasma cells and for their capacity to produce RF and other immunoglobulins in vitro. Analysis of culture supernatants for the presence of immunoglobulins demonstrated that cells derived from bone marrow, synovium and peripheral blood were all found to be capable of producing every immunoglobuiin and RF isotype investigated. No significant correlations were found between concentrations of immunoglobulin isotypes produced by cells derived from different sites of one individual. Significant correlations were found, however, between concentrations of RF isotypes produced by cells derived from the three sites. These results indicate that the production of RF in the different compartments is not an autonomously regulated process. Mononuclear cells derived from bone marrow were found to be able to produce RF in similar quantities to cells dissociated from synovial tissue. In combination with the fact that circulating immunoglobulins are produced mainly in the bone marrow, this observation suggests that bone marrow is also a major source of circulating RF.
Synthesis of the third component of complement (C3) by human gastric cancer-derived cell lines
Authors: KITANO E , KITAMURA H 
Published: July 2010

SUMMARYThis is a study of complement components secreted by gastric cancer-derived cell lines (MKN28. MKN45, MKN74 and KATO-III), each of which has a different histological origin. Haemolytic activity of complement component was detected only in the culture supernatant of KATO-III (C2 activity) and in that of MKN45 (C5 activity). However, the third component of complement, C3, was detected by an ELISA assay in the supernatants of all cell lines. In our studies focusing on C3 production by these cell lines, we have found that: (i) tumour necrosis factor (TNF) induced an increase in the amount of secreted C3 in a dose- and time-dependent fashion; (ii) TNF (10 U/ml) stimulated C3 secretion by these cell lines to levels of 25.4–62.9 ng C3/106cells per 24 hours; (iii) C3 haemolytic activity was detected in supernatants of TNF-stimulated cell lines. The mean specific activities of C3 by TNF (10 U/ml)-stimulated cell lines were 1.2–5.6 × 10- effective molecules/ng (e.m./ng), when that of C3 in normal human serum (NHS) was 1.7 × 106 e.m./ng; (iv) de novo synthesis of C3 by these cell lines was demonstrated by the effect of cycloheximide and by the incorporation of 35S-methionine into secreted C3; (v) immunoblot analysis of culture supernatants indicated that secreted C3 was mainly composed of C3α and C3β chains, but pro-C3 was also present. These results, which show the de novo synthesis and secretion of C3 by all the tested gastric cancer-derived cell lines in response to TNF, suggest the possibility that C3 may be secreted in the gastric wall as part of its normal physiology, or as a result of tumour pathology, and thereby participate in local immune or inflammatory responses.
Evaluation ofin vivoimmune complex formation and complement activation in patients receiving intravenous Streptokinase
Authors: FREYSDOTTIR J , ORMARSDOTTIR S , SIGFUSSON A 
Published: July 2010

SUMMARYThe usefulness of several different methods for delecting immune complex formation and complement activation in the circulation were applied to samples from patients receiving intravenous Streptokinase therapy for myocardial infarction. Streptokinase is a foreign antigen and can cause immune reactions. We collected samples from 13 patients, before Streptokinase administration (baseline), at the end of infusion (I h), 12 h later and on day 7. We measured IgG containing immune complexes (IgG-IC), free C3d and antibodies to Streptokinase by ELISA. and CR1. C3d and C4d on erythrocytes by flow cytometric assay. Antibodies to Streptokinase are common, as all but two of the patients had measurable antibody levels. During Streptokinase treatment there was a drop in antibody levels, most prominent in those patients who had high baseline levels. At the same time increased levels of free C3d and erythrocyte-bound C3d were observed. After 12 h free C3d was usually back to baseline level, but C3d on erythrocytes was still raised. These data indicate the formation of Streptokinase immune complexes in patients with high Streptokinase antibody levels, and show that these complexes are cleared rapidly from the circulation, leaving more persistent signs of complement activation. We conclude that free C3d is a good indicator of ongoing complement activation, whereas C3d on erythrocytes indicates that complement activation has recently taken place.
Systemic immunization against IgA in immunoglobulin deficiency
Authors: MOCHIZUKI S , SMITH C I E , HÅLLGREN R , HAMMARSTRÖM L 
Published: July 2010

SUMMARY
The presence of scrum IgM and IgG antibodies against IgA is common among individuals with IgA deficiency. The route of immunization is still unknown, but it is possible that immunization occurs through the gut. We analysed anti-IgA antibody production in gastrointestinal lavage, saliva and breast milk from patients with IgA deficiency. In no case was there any evidence of local production of anti-IgA antibodies. Immunization may thus be due to exposure to endogenous IgA and therefore represent a ‘true’ autoimmune phenomenon which may possibly be involved in the pathogenesis of the disease.
Multifunctional effects of anticomplementary agent K-76 on carrageenan-induced colitis in the rabbit
Authors: KITANO A , MATSUMOTO T , NAKAMURA S , OSHITANI N , OBATA A , OKAWA K , INOUE Y , KOBAYASHI K , NAKURA H 
Published: July 2010

SUMMARYIn this study the effect of K-76. a sesquiterpcne compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochcmical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotcin concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.
Expression of adhesion molecules on infiltrating T cells in thyroid glands from patients with Graves' disease
Authors: ISHIKAWA N , EGUCHI K , UEKI Y , NAKASHIMA M , SHIMADA H , ITO K , NAGATAKI S 
Published: July 2010

SUMMARYThe present study was performed to elucidate the role of adhesion molecules in the pathogenesrs of Graves'disease. Peripheral blood and intrathyroidal mononuclear cells were obtained from 14 patients with Graves'disease. The expression of adhesion molecules and HLA-DR antigen on CD4+ cells and CD4+ cell subpopulations was analysed by the two- or three-colour immunofluorescence method. The expression of adhesion molecules including LFA-1α, LFA-l/β, CD2, VLA-4α and VLA-5α on CD4+ cells in the thyroid gland was markedly higher than that in peripheral blood. In peripheral blood CD4+ cell subsets, the CD4+CD45RO+ cell population had an enhanced expression of the adhesion molecules compared with the CD4+ CD45RA+ cell population. However, there was no significant difference in the expression of adhesion molecules by CD4+ cell populations and subsets between Graves'disease and healthy subjects. The thyroid gland from Graves'disease contained a higher percentage of CD4+ CD45RO+ cells and a lower percentage of CD4+ CD45RA+ cells. In intrathyroidal CD4+ cell subsets, the CD4+CD45RO+ cell population had an increased expression of LFA-1 and CD2 compared with the CD4+CD45RA+ cell population, but there was no significant difference in VLA-4 and VLA-5 expression between the two cell subsets. Furthermore, the expression of LFA-1 and CD2 on the CD4+CD45RO+ cell population in the thyroid was significantly higher than that in matched peripheral blood. A similar finding was also observed for the CD4+CD45RA+ cell population. The thyroid gland had an increased percentage of CD4+HLA-DR+ cells compared with matched or healthy peripheral blood. However, there was no significant difference in the percentage of HLA-DR+ cells in the thyroid gland between CD4+CD45RO+ cell and CD4+CD45RA+ cell populations. These results suggest that increased expression of adhesion molecules on CD4+ cells may be responsible for the migration of these cells into thyroid glands and cellular interactions between these cells and thyroid epithelial cells.
Characterization of a human monoclonal autoantibody directed to cardiolipin/β2 glycoprotein I produced by chronic lymphocytic leukaemia B cells
Authors: MARIETTE X , LEVY Y , DUBREUIL M-L , INTRATOR L , DANON F , BROUET J-C 
Published: July 2010

SUMMARYWe determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Helerohybrids obtained by fusion of CLL cells with the mouse X63-Ag 8.653 myeloma produced IgMλ MoAbs directed to the cardiolipin/β2 glycoprotein I (β2GPI) complex and ssDNA. They were devoid of polyreactivity. Nuclcotide sequence analysis of the variable domain of the μ chain indicated the utilization of the VH4 71.2 gene or one allotypic variant, DXp4 and JH3 segments. The λ light chain used the single gene from the Vλ8 subfamily, Jλ3 and Cλ3 genes. The VH gene displayed 11 nucleotide changes in comparison with its putative germline counterpart. However, these nucleotide changes correspond to variations observed in other published VH4 sequences, suggesting gene polymorphism ralher than somatic mutation. Dxp4 and Jh3 were also in germline configuration. The Vl gene exhibited a single replacement mutation in CDRl. These data suggest that the monoclonal CLLB cells in this patient retained VH and VL genes in germline configuration although they secreted a pathogenic anti-cardiolipin antibody associated with clinical symptoms, vasculitis and thrombosis, which may be provoked by antibodies to the phospholipid/β2GPI complex.
Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin
Authors: NICOLETTI F , BORGHI M O , MERONI P L , BARCELLINI W , FAIN C , DI MARCO R , MENTA R , SCHORLEMMER H U , BRUNO G , MAGRO G , GRASSO S 
Published: July 2010

SUMMARYTen out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2–5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented. Moreover, DSP-treated animals showed reduced signs of pancreatic insulitis, had lower percentages of splenic lymphoid cells (SLC) expressing IL-2 receptors and Ly-6C antigens on their surfaces, and these cells released lower amounts of interferon-gamma (IFN) when stimulated in vitro. These data, providing evidence for the capacity of DSP to protect NOD/WEHI mice from experimental autoimmune diabetes and to modulate histo-immunological pathogenic pathways, indicate DSP as a drug of potential interest in the treatment of human insulin-dependent diabetes mellitus.
Immunization of mice with baculovirus-derived recombinant SV40 large tumour antigen induces protective tumour immunity to a lethal challenge with SV40-transformed cells
Authors: SHEARER M H , BRIGHT R K , LANFORD R E , KENNEDY R C 
Published: July 2010

SUMMARYIn this study, we examine the humoral immune responses and in vivo tumour immunity induced by baeulovirus reeombinant simian virus 40 (SV40) large tumour antigen (rSV40 T-ag). BALB/c mice immunized with rSV40 T-ag produced antibody responses that recognized SV40 large tumour antigen (T-ag) by ELISA. Analysis of these anti-SV40 T-ag responses indicated that the antibodies recognized epitopes associated with both the carboxy and amino terminus of SV40 T-ag. This pattern of SV40 T-ag epitope recognition was similar to that observed in anti-SV40 T-ag responses induced by inoculation with irradiated SV40-transformed cells. Mice immunized with either rSV40 T-ag or with the inactivated transformed cells were protected from a subsequent in vivo lethal tumour challenge with live SV40-transformed cells. These studies suggest that humoral immune responses induced by rSV40 T-ag are similar in epitope specificity to that induced by inactivated SV40-transformed cells. In addition, recombinant tumour-specific antigens from papovaviruses, such as SV40, can be used to induce tumour immunity which protects from a subsequent lethal tumour challenge. This study may provide insight into the use of recombinant tumour antigens as putative tumour vaccines and in the development of active immunotherapeutic strategies for treating virus-induced eancers.
Phenotypic analysis of cells in bronchoalveolar lavage fluid and peripheral blood of maedi visna-infected sheep
Authors: LUJÁN L , BEGARA I , COLLIE D D S , WATT N J 
Published: July 2010

SUMMARYA phenolypic analysis of bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) cells in maedi visna virus (MVVVinlecled sheep has been performed. The differential cell eount in BALF from MVV-infeeted animals was characterized by a significant increase (P &lt; 0±05) i n lymphocytes and neutrophils. Lymphocyte phenotyping in BALF from MVV-infeeted sheep showed a significant decrease (P &lt; 0·05) or CD4+ cells, a significant increase (P &lt; 0·05) of CD8+ eells and a significant inversion (P&lt;0·001) of the CD4+/CD8+ ratio. CD5+ lymphocytes were also significantly decreased (P &lt; 0·05). γδ T cells and B cells did not differ significantly when compared with the controls. No correlation was observed between BALF and PB lymphocyte phenotypes. BALF macrophages from MVV-infeeted animals showed inereased MHC class II expression and BALF lymphocytes from the same animals demonstrated up-regulation of LFA-1 and LFA-3 expression. These findings and their relationship with lentiviral pathogenesis are discussed.
Differential mechanisms of intracellular killing ofMycobacterium aviumandListeria monocytogenesby activated human and murine macrophages. The role of nitric oxide
Authors: BERMUDEZ L E 
Published: July 2010

SUMMARYMurine peritoneal macrophages activated with interferon-gamma (IFN-γ) produce large quantities of nitric oxide and are efficient in the killing of certain intracellular pathogens. To examine the role of this mechanism in the killing of Mycobacterium avium by murine and human macrophages, we infected mouse peritoneal macrophages and human monocyte-derived macrophages with M. avium and Listeria monocytogenes and stimulated the cells with recombinant tumour necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) or IFN-γ, in the presence or absence of N-monomethyl-L-arginine (NMA) or arginase. Neither competitive inhibition with NMA nor depletion of arginine by arginase had any effect on the inhibition of growth/intracellular killing of M. avium by activated human and murine macrophages. In contrast, activation of murine but not human macrophages infected with L. monocytogenes by IFN-γ was significantly inhibited by the addition of NMA/arginase. Furthermore, murine macrophages produced large concentrations of nitric oxide following stimulation with recombinant cytokines, although no significant increase of nitric oxide production was observed with human monocyte-derived macrophages.
Direct evidence that human follicular dendritic cells (FDC) rescue germinal centre B cells from death by apoptosis
Authors: LINDHOUT E , MEVISSEN M L C M , KWEKKEBOOM J , TAGER J M , de GROOT C 
Published: July 2010

SUMMARYIt is supposed that FDC have a pivotal role in the rescue of gcrminal centre (GC) B lymphocytes from apoptosis. However, formal proof for this hypothesis has not as yet been presented. In the present study FDC and GCB cells were isolated from humati tonsils and cultured. When brought into culture FDC and B cells rapidly formed spherical clusters. T cells were not observed inside these clusters. At dilTerent time points cultures of FDC and B cells were siipravitally stained with Hoechst 33258 or aeridine orange and examined by direct observation tising fluorescence microscopy. Viable B cells appeared to be profoundly restricted to clusters, whereas cells not taking part in clusters all had an apoptotic appearance. The formation of clusters could be prevented by addition of MoAbs against CD11a (LFA-1α) or CD49d (VLA-4α). resulting in an apoptotic appearance of virtually al B lymphocytes. The present data demonstrate that a physical interaetion between FDC and germinal centre B lymphocytes is able to rescue the latter from apoptotic cell death.
Percentile ranges for serum IgG subclass concentrations in healthy Chinese children
Authors: LAU Y L , JONES B M , NG K W , YEUNG C Y 
Published: July 2010

SUMMARYIn order to establish normal reference ranges of serum immunoglobulin G subclasses for different age groups in Chinese, we measured the four IgG subclasses by radial immunodiffusion using poiyclonal antisera in 350 normal healthy subjects (148 males and 202 females) recruited Irom ihe community. There was no signifieant sex difference for all the four IgG subclasses. Using Box-Cox transformation, we constructed smooth age-dependent percentile curves lor the four IgG subclasses. For the 50th percentile values, the plateaus Tor IgGl lo lgG4 are respectively 970 mg/dl at 13 years old. 481 mg/dl al 18. 48 mg/dl at 17 and 80 mg/dl at 13. Methodology, reagents, environmental and genetic factors might be responsible for the observed difference among the various reports. The IgG2 level in our Chinese population seemed to be higher than that in Caucasians, which might account for the very low incidence of invasive Haemophilus influenzae type b disease among the Chinese. Our IgG l level also plateaued later and at a higher level than that in other studies.
Molecular analysis of C3 allotypes in patients with nephritic factor
Authors: FINN J E , MATHIESON P W 
Published: July 2010

SUMMARYThe autoantibody nephritic factor (NeF) leads to complement consumption in vivo and is associated with type II mesangiocapillary glomeruloncphritis(MCGN II) and partial lipodystrophy (PLD). The third component of complement (C3) exists in two common allotypic forms. C3S and C3F, distinguished at the protein level by electrophoresis. An increased frequency of the rarer C3F allele has been reported in several autoimmune conditions, including one small series of patients with NeF. However, patients with NeF have low levels of circulating C3 so that allotyping at the protein level is difficult. The molecular basis of the S/F polymorphism has recently been established: a single base change at the DNA level encodes a single amino acid substitution at the protein level. A second polymorphism, closely linked to the first, is defined by the MoAb HAV4–1, and is also due to a single base change. These polymorphisms can therefore be analysed at the DNA level. We have used the amplification refractory mutation system (ARMS), a modification of the polymerase chain reaction (PCR), to analyse these two C3 polymorphisms at the DNA level in 26 patients with NeF. The allele frequencies of C3S and C3F were 0·673 and 0·327 (predicted values 0·79 and 0·2, x2= 4·813, P &lt; 0·05), giving a relative risk of 2·1 for the development of NeF conferred by the presence of a C3F allele. The HAV 4–1 allele frequencies were (-) 0·71 and (+)0·29. i.e. not significantly different than predicted from the linked C3S/F allele frequencies. This is the largest series of patients with NeF yet published, and our data confirm an association between C3F and NeF. Possible mechanisms for this link are discussed.
Serum markers of T cell activation in relapses of Wegener's granulomatosis
Authors: STEGEMAN C A , TERVAERT J W COHEN , HUITEMA M G , KALLENBERG C G M 
Published: July 2010

SUMMARYLevels of soluble IL-2 receptor (sIL-2R). soluble CD4 (sCD4) and CDS (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373–2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486–3404 U/ml) at the moment of relapse for the whole group (P= 0·10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686–1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469–3404 U/ml) at the moment of relapse (P &lt; 0·01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P&lt;0·05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least I month. The level of slL-2R at the moment of relapse correlated with the level of C-rcactive protein (P= 0·488, P&lt;0·05) and with the disease activity score (r= 0·824, P&lt;0·002). There were no significant changes in levels of sCD4 or sCD8. although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis arc accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.
Gender-related influences on the development of chronic graft-versus-host disease-induced experimental lupus nephritis
Authors: TREURNIET R A , BERGIJK E C , BAELDE J J , DE HEER E , HOEDEMAEKER J , BRUIJN J A 
Published: July 2010

SUMMARYAutoimmune diseases are far more common in women than in men. In the incidence of systemic lupus erythematosus (SLE), the female-to-male ratio is as high as 10:1. This suggests that sex hormones may play a fundamental role in determining the susceptibility to these diseases. In order to investigate the sex-related differences in the inducibility of chronic graft-versus-host disease-related experimental lupus nephritis, lymphocytes from female DBA/2 donor mice were administered to either male or female (C57BL10 × DBA/2)F1 recipients. An additional group of male recipients received lymphocytes from male DBA/2 donors. After four cell transfers, female recipients developed a significantly higher albuminuria than both male groups. Serum concentrations of autoantibodies against glomerular basement membrane (GBM). collagen IV, and laminin were significantly higher in females 2–4 weeks after induction. Levels of circulating autoantibodies against renal tubular epithelial antigens (RTE) and nuclear antigens were not different between the sexes. In transfer studies, the necessity of the presence of anti-GBM and anti-RTE autoantibodies for the development of glomerulonephritis was confirmed. These findings indicate that: (i) in this model of lupus nephritis, susceptibility to glomerulonephritis is strongly influenced by sex-related genes; and (ii) among the variety of autoantibodies occurring in this model of SLE, both anti-GBM and anti-RTE autoantibodies play a key role in the pathogenesis of glomerulonephritis.