bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine-induced lupus
Authors: NÄSSBERGER L , SJÖHOLM A G , JONSSON H , STURFELT G , ÅKESSON A 
Published: July 2010

SUMMARY
Anti-neutrophil cytoplasm antibody (ANCA) has been shown to be no marker of systemic lupus erythematosus (SLE) including lupus nephritis or of progressive systemic sclerosis (PSS). Antibodies against myeloperoxidase (anti-MPO) and elastase, two granulocyte lysosomal enzymes, were found in patients with SLE but not in those with PSS, except for one patient who had anti-MPO. Anti-MPO was present in 21% of patients with SLE, and at low concentrations in about 80% of these cases. Anti-elastase was found in four patients with SLE. In another group of six patients with a SLE-like syndrome induced by anti-hypertensive treatment with the anti-hypertensive hydralazine, anti-MPO antibodies occurred in all six, and anti-elastase antibodies in five. Monitored during a 2-year follow-up period, anti-MPO antibodies were found to persist, whereas anti-elastase antibodies were rapidly eliminated, after withdrawal of the drug.
Participation of eosinophils in the toxic oil syndrome
Authors: TEN R M , KEPHART G M , POSADA M , ABAITUA I , SOLDEVILLA L , KILBOURNE E M , DUNNETTE S L , GLEICH G J 
Published: July 2010

SUMMARYThe participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS.
Immunologic abnormality in NZB/W Fl mice. Thymus-independent expansion of B cells responding to interleukin-6
Authors: MIHARA M , FUKUI H , KOISHIHARA Y , SAITO M , OHSUGI Y 
Published: July 2010

SummaryWe have previously reported that B cell abnormality in NZB/W Fl mice developed independently of thymus. Here we examined further whether B cells from NZB/W F1 mice respond to interleukin-6 (IL-6), a factor for terminal differentiation of B cells. When freshly isolated splenic B cells were incubated for 5 days in the presence of human IL-6, an increased production of both IgM and IgG, including anti-DNA antibody, was evident in NZB/W Fl mice; there was no increase in BALB/c mice. A magnitude of augmentation in IgG but not IgM production by IL-6 became more apparent in older NZB/W F1 mice. The increased immunoglobulin production seen with IL-6 was neutralized by treatment with rabbit anti-recombinant human IL-6 antibody. As B cells from athymic NZB/W Fl nude mice also responded to IL-6, it was suggested that B cells in NZB/W Fl mice differentiated into the IL-6-responding state in a thymus-independent manner. This B cell abnormality may be associated with the pathogenesis of autoimmune disease in NZB/W Fl mice.
HL-60 cells induced to differentiate towards neutrophils subsequently die via apoptosis
Authors: MARTIN S J , BRADLEY J G , COTTER T G 
Published: July 2010

SUMMARYThe human promyelocytic HL-60 cell line can be induced to differentiate to neutrophil-like cells in response to a variety of chemical stimuli. We have found that retinoic acid-treatment of HL-60 cells over a period of 6–8 days resulted in a progressive increase in the proportion of cells with mature neutrophil morphologies and was closely followed by an increase in the proportion of cells exhibiting the morphological characteristics of apoptosis, the non-pathological mode of cell death. Using Percoll step-density gradients we have demonstrated a marked increase in the buoyant density of these cells and have used this density difference to obtain enriched fractions of cells for more detailed study. Degradation of the nuclear DNA of these cells into integer multiples of about 200 base pairs, indicative of endogenous endonuclease activation a major characteristic of programmed cell death, was also demonstrated. From these observations we conclude that the mode of cell death in cultures of terminally differentiated HL-60 cells is that of apoptosis. These results parallel those of a recent report which has shown apoptosis to be the mode of cell death of ageing peripheral blood neutrophils. Because of this, we believe that our observations further validate the use of the HL-60 cell line as a model system for the study of human granulopoiesis in vitro and further, that this model system may be useful for gaining insight into the underlying mechanisms involved in apoptosis.
Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation
Authors: PIDDLESDEN S , LASSMANN H , LAFFAFIAN I , MORGAN B P , LININGTON C 
Published: July 2010

SUMMARYThe effects of decomplementation by cobra venom factor (CVF) on the pathogenesis of inflammation and demyelination in experimental allergic encephalomyelitis (EAE) and acute antibody-mediated demyelinating EAE (ADEAE) have been quantified histologically and immunocytochcmically. In rats immunized with 50 μg of myelin basic protein in Freund's complete adjuvant containing 100μg heat-killed Mycobacterium tuberculosis H37Ra, clinical signs of EAE were completely suppressed by two injections of CVF given 9 and 12 days post-immunization. Suppression of clinical disease was associated with a dramatic reduction in peri-vascular inflammation in the CNS. although immunohistochemical staining identified small numbers of infiltrating T cells and macrophages. In contrast, CVF treatment had no significant effect on the clinical severity of ADEAE and although C9 deposition within the CNS was virtually abolished, there was no statistically significant decrease in the extent of demyelination or inflammation. These observations indicate that in the absence of complement components C3 and C5 an antibody-dependent cell-mediated cytotoxic response plays an important role in the pathogenesis of antibody-mediated demyelination. The major role of the complement cascade in EAE appears to be the generation of pro-inflammatory factors that enhance the inflammatory response within the CNS in animals facing a mild encephalitogenic challenge.
Cytokine-independent progression of immunoglobulin productionin vitroby B lymphocytes from patients with systemic lupus erythematosus
Authors: PELTON B K , SPECKMAIER M , HYLTON W , FARRANT J , DENMAN A M 
Published: July 2010

SUMMARYB lymphocytes from patients with systemic lupus erythematosus (SLE) secreted high levels of immunoglobulin spontaneously when cultured in vitro. Addition of the cytokines interleukin-2, interleukin-4 and interleukin-6 either alone or in combination failed to augment spontaneous immunoglobulin synthesis. Percoll-separated low-density SLE B lymphocytes matured into immunoglobulin-secreting cells also independent of exogenous interleukins. During maturation these cells became enlarged and less dense, and began to express CD23. This was in contrast to normal B cells, which did not secrete immunoglobulin spontaneously but synthesized IgM after interleukin stimulation. These results indicate that in vitro immunoglobulin synthesis by SLE B cells is already initiated in these cells and progresses independently of further stimulatory manoeuvres.
Cyclosporin A in the prevention and treatment of experimental autoimmune glomerulonephritis in the brown Norway rat
Authors: REYNOLDS J , CASHMAN S J , EVANS D J , PUSEY C D 
Published: July 2010

SUMMARY
Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of collagenase-solubilized homologous glomerular basement membrane (GBM) in Freund’scomplete adjuvant. This model of anti-GBM disease is characterized by the development. over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with oral cyclosporin A (CsA) at different doses, starting at the time of immunization and during the course of the disease. Prctreatmcnt with CsA 5 mg/kg daily produced a moderate reduction in circulating anti-GBM antibody levels, reduced deposition of antibody on the GBM and decreased albuminuria. Doses of 10 and 20 mg/kg CsA produced a marked reduction in circulating antibody, absence of delectable deposited antibody and virtual absence of albuminuria. Renal function remained normal in CsA-treated and control animals. When CsA treatment was introduced at 2 or 4 weeks after immunization, there were significant effects on the subsequent autoimmune response and albuminuria at 10 and 20 mg/kg daily. These studies demonstrate that CsA in conventional doses has a therapeutic effect in this model of anti-GBM disease, and suggest a role for T lymphocytes in the palhogcncsis of EAG.
Clinical efficacy of intravenous immunoglobulin in patients with severe inflammatory chest disease and IgG3 subclass deficiency
Authors: BERNATOWSKA-MATUSZKIEWICZ E , PAC M , SKOPCYNSKA H , PUM M , EIBL M M 
Published: July 2010

SUMMARY
To investigate the efficacy of i.v. IgG treatment in pediatric patients with inflammatory lung disease, a prospective, controlled clinical trial was carried out over a 2-year study period. Patients were enrolled on the basis of severe clinical symptomatology. After 1 year of conventional treatment, the patients received 400 mg/kg per month of an i.v. IgG product containing only trace amounts of IgG3 in addition to their regular treatment throughout the second year. Significant clinical improvement, as documented by duration of hospital stay (first year 27.8 days, second year 4.9 days), use of antibiotics (132.8 versus 30.9 days) and use of steroids (21.4 versus 0.7 days) could be observed. Data obtained on a subgroup of patients with lgG3 deficiency were analysed separately. These results indicate that patients with severe chest disease who have lgG3 deficiency will also benefit from i.v. IgG treatment. The mode of action cannot be attributed to replacement of the respective isotypes, but is probably due to the effect of i.v. IgG in preventing repeated viral infections.
Human double-negative (CD4-CD8-) T cells bearing αβ T cell receptor possess both helper and cytotoxic activities
Authors: MATSUMOTO M , YASUKAWA M , INATSUKI A , KOBAYASHI Y 
Published: July 2010

SUMMARYExpression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunological functions of T cells. However, a minor T cell subset, which lacks both CD4 and CD8 molecules but bears the usual form of T cell receptor (TCR) αβ (CD4-CD8-TCRαβ+ T cells), has recently been found not only in mice but also in humans, and its role in immune response is now of considerable interest. In order to clarify the characteristics of this newly defined T cell subpopulation, we established five IL-2-dependent CD4-CD8-TCRαβ+ T cell clones from the peripheral blood of a healthy individual, and examined their various biological functions. It was found that all clones not only helped B cells in immunoglobulin production, but also exerted major histocompatibility complex-unrestricted cytotoxicity. Although their CD3/TCR complexes were functionally competent, the cytotoxicity seemed to be mediated via unknown molecules other than the CD3/TCR complex, as evidenced by the failure of CD3 MoAb to inhibit the cytotoxic activity. Our present findings showed that CD4-CD8-TCRαβ+ T cells possess potential bifunction, i.e. helper and cytotoxic activities. Their roles in the pathogenesis of immunodeficiency are discussed.
Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases
Authors: KAVERI S-V , DIETRICH G , HUREZ V , KAZATCHKINE M D 
Published: July 2010

SUMMARYIntravenous immunoglobulin (IVIg) therapy is increasingly used in autoimmune diseases. Although its efficacy has only been established in a few specific antibody-mediated autoimmune conditions, accumulating evidence on the regulatory role of circulating immunoglobulins in the selection of peripheral B cell repertoires makes it an attractive potential therapeutic option to clinical immunologists. This overview briefly discusses the current use of IVIg in human autoimmune diseases with a particular emphasis on the possible mechanisms by which IVIg could suppress pathological autoimmune responses.
Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis
Authors: LÖHR H , MANNS M , KYRIATSOULIS A , LOHSE A W , TRAUTWEIN C , BÜSCHENFELDE K-H MEYER ZUM , FLEISCHER B 
Published: July 2010

SUMMARYAutoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P4S0dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+CD8- T cells. Five CD4+CD8- T cell clones proliferated specifically in the presence of recombinant human LKM-1 antigen (rLKM). This reaction was restricted to autologous antigen-presenting cells and to HLA class II molecules. In order to see whether rLKM was also recognized by peripheral blood T lymphocytes (PBL) we tested the proliferative response of PBL from several individuals. PBL from three of the four patients with LKM-1 antibody-positive AI-CAH proliferated to rLKM, whereas no response was seen with PBL from patients with LKM-1 antibody-negative chronic liver diseases and from healthy blood donors. These data demonstrate that the LKM-1 antigen is recognized by liver-infiltrating T cells in LKM-1 antibody-positive AI-CAH. For further functional characterization, liver-derived T cell clones were tested for their cytotoxic activity. In the presence of phytohacmagglutinin 24 out of 26 CD4-CD8+ but also 20 out of 63 CD4+CD8- T cell clones lysed autologous as well as allogenic EBV-transformed B cell lines or K562 cells. Five CD4-CD8+ T cell clones lysed autologous but not allogenic B cell lines spontaneously in a HLA class I-restricted manner. Although the antigen specificity of these clones is still unknown the data show the presence of autoreactive T cells at the site of inflammation that could contribute in the pathogenesis of AI-CAH.
Antibodies to acetylcholine receptors in myasthenia gravis.In vitrosynthesis by peripheral blood lymphocytes before and after thymectomy
Authors: KUKS J B M , LIMBURG P C , OOSTERHUIS H J G H , THE T H 
Published: July 2010

SUMMARYPokeweed antiogen (PWM)-d riven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was stucture. in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence: of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and I year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.
Phagocytosis ofGiardia lambliatrophozoites by cytokine-activated macrophages
Authors: BELOSEVIC M , DANIELS C W 
Published: July 2010

SUMMARYPhagocytosis of Giardia lamblia trophozoites by cytokine-activaled and non-activated bone marrow-derived macrophages was examined in vitro. Macrophages treated with recombinant interferon-gamma (IFN-γ) and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages. Maximal uptake of parasites occurred after 4 h and 6 h of incubation where 81.4% and 79.1% of macrophages were positive for trophozoites. Other cytokines tested, IL-2, IL-3, IL-4, IL-5, GM-CSF, CSF-I and tumour necrosis factor-alpha (TNF-α) either alone or in combination with LPS, failed to activate macrophages to phagocytose G. lamblia. The induction of this activated macrophage anti-microbial function was achieved pharmacologically using phorbol myristate acetate (PMA) and ionophore A23187. The giardicidal activity of macrophages activated with IFN-γ and LPS or that induced by PMA and A23187 was inhibited by H-7, indicating the role for protein kinase C in the intracellular events following activation.
Biochemical and functional characterization of the leucocyte tyrosine phosphatase CD4S (CD4SRO, 180 kD) from human neutrophils.In vivoupregulation of CD45RO plasma membrane expression on patients undergoing haemodialysis
Authors: PULIDO R , ALVAREZ V , MOLLINEDO F , SÁNCHEZ-MADRID F 
Published: July 2010

SUMMARYThe biochemical and functional characterization, and the regulation of plasma membrane expression of the leucocyte tyrosine phosphatase CD45, have been investigated in neutrophils from healthy donors and patients undergoing haemodialysis. CD45 proteins of 180 kD and 130–150 kD were precipitated from neutrophils from both healthy subjects and haemodialysed patients. Prolonged storing, as well as trypsin treatment of samples containing the 180-kD CD45 protein, generated the 130–150-kD polypeptides. The 130–150-kD CD45 polypeptides carried extracellular CD45 epitopes, including the sialic acid-related UCHLI epitope (CD45RO). Furthermore, these trypsin-generated CD45 polypeptides did not possess phosphatase activity, which could be detected on the 180-kD protein. A remarkable quantitative increase of cell surface expression of the neutrophil CD45 components was detected both after in vitro neutrophil activation and after dialysis treatment with neutropenic membranes. The CD45 biochemical pattern did not qualitatively change upon either in vitro or in vivo dialysis-induced neutrophil activation. The upregulated expression of CD45 on neutrophils from dialysed patients correlated with the neutropenic effect induced by the different dialyser membranes. Maximal upregulation of CD45 expression was observed after 15 min of dialysis with neutropenic membranes, and normal expression levels were restored after I h. By contrast, increase of CD45 plasma membrane expression induced in vitro by treatment of normal neutrophils with the degranulatory agents fMLP or Ca2+ ionophore was maintained. These results demonstrate that neutrophil cell surface expression of the 180-kD CD45 protein is upregulated during the in vivo haemodialysis process, and suggest that a proteolytic activity could regulate the enzymatic activity of CD45 by degranulation of its cytoplasmic phosphatase domains.
Antibodies against sulphatide in sera from patients with autoimmune rheumatic diseases
Authors: AOTSUKA S , OKAWA-TAKATSUJI M , UWATOKO S , YOKOHARI R , IKEDA Y , TODA G 
Published: July 2010

SUMMARY
We tested sera of patients with various autoimmune rheumatic diseases for the presence of antibodies against sulphatide (an acidic glycosphingolipid), identified as a target antigen for antibodies against the liver cell membrane. Thirty-five percent (7/20) of patients with lupus in the active stage possessed anti-sulphatide antibodies, whereas 10% (2/20) of those in the inactive stage and 20% (4/20) of those in the stationary stage possessed such antibodies. Moreover, 10%. (3/29) of patients with other autoimmune rheumatic diseases also possessed anti-sulphatide antibodies. The level of anti-sulphatide antibodies was significantly correlated with the levels of anti-double-stranded (ds) DNA antibodies (r = 0.634, P &lt;0.001) and dextran sulphate-binding IgG (r = 0.407, P &lt; 0.001). The serum levels of antibodies against sulphatide were correlated with a history of seizures or psychosis in patients with autoimmune rheumatic diseases. Gels coupled with polyanionic dextran sulphate, monoanionic sulphanilic acid and DNA were shown effectively to adsorb anti-sulphatide antibodies in the sera of patients with active systemic lupus erythematosus (SLE) and autoimmune chronic active hepatitis (AI-CAH). These results suggest that the observed reactivity with sulphatide is due to the presence of antibodies capable of reacting with various anionic molecules in the sera of patients with autoimmune rheumatic diseases as well as those with AI-CAH.
Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease
Authors: BECKER H , LANGROCK A , FEDERLIN K 
Published: July 2010

SUMMARYCD4+ (helper/inducer) T lymphocyte subsets were studied in the peripheral blood from patients with mixed connective tissue disease (MCTD) by double-labelling immunofluorescence. The proportion of CD4+CD45RA+ cells was higher (P &lt; 0·01) when compared with controls, whereas CD4+CD29+ cells were markedly diminished (P &lt; 0·001). CD4+CD29+ cells were lower than in patients with progressive systemic sclerosis who were studied in parallel. Upon stimulation with phytohaemagglutinin, CD4+ cells from MCTD patients showed a strong reactivity to acquire the CD29+ phenotype. Expression of high levels of CD29 and other adhesion molecules might lead to facilitated localization of CD4+ cells to inflamed tissue. It is suggested that an increased responsiveness of CD4+ cells to activation signals in vivo and accumulation of CD4+CD29+ cells at tissue sites could result in depletion of this cell subset in the peripheral blood of patients with MCTD.
IL-2 production by intestinal lamina propria cells in normal inflamed and cancer-bearing colons
Authors: PULLMAN W E , DOE W F 
Published: July 2010

SUMMARYBiologically significant levels of IL-2 activity were produced by isolated lamina propria mononuclcar cells (LPMC) from normal intestine (n= 12). cancer-bearing colons (n= 35) and inflammatory bowel disease (IBD) affected tissue (n= 12). The levels of IL-2 produced were similar for all three sources of LPMC (normal 252 ± 48 U/ml, I BD-affected mucosa 197 ± 42 U/ml and colon cancer 285 ± 43 U/ml). These levels were significantly greater than those produced by peripheral blood mononuclcar cells (20·5 U/ml, P &lt; 0·01) on a per cell basis. In mucosa from cancer-bearing colons the amount of IL-2 produced by LPMC was unaffected by the invasiveness of the colon cancer. LPMC IL-2 production was markedly suppressed by drugs used in IBD therapy. 5-Aminosalicylic acid (5-ASA) reduced activity in a dose-dependent fashion. At a dose equivalent to the faecal therapeutic level of 0·5 mg/ml activity, IL-2 production by LPMC was suppressed to 3·4% of controls. Similarly, exposure of LPMC to cyclosporin A (CyA) and hydrocortisone (HC) at therapeutic levels reduced I L-2 activity to less than 1% of controls. The major producers of IL-2 activity were shown to be CD3+ T lymphocytes and those bearing the activation markers IL-2R and TFR. Suppression of mucosal IL-2 production represents an important therapeutic mechanism ofdrugs used in the management of IBD including HC, 5-ASA and CyA. These results suggest that mucosal T cells produce appreciable levels of IL-2 activity that may be important in maintaining immune homeostasis in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucosal lesions of IBD.