bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced IL-10 secretion by CD4+ T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR)
Authors: Moss R B , Bocian R C , Hsu Y-P , Dong Y-J , Kemna M , Wei T , Gardner P 
Published: November 2003

Abstract
Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. However, chronic respiratory inflammation and infection remain unexplained phenomena in disease pathogenesis. Non-transformed, antigen-responsive CD4+ T cells cloned from healthy controls and CF patients homozygous or heterozygous for the δF508 mutation transcribed CFTR mRNA and expressed immunoreactive cytoplasmic CFTR protein. T cell clones (TCC) from controls and CF patients displayed equivalent Ca2+-mediated Cl− current; however, TCC from patients with CF but not controls displayed defective cAMP-mediated Cl− current. Although CF-derived TCC preserved mitogen and antigen proliferative responses and specificity to tetanus toxoid epitopes, they selectively secreted ≈ 45% less IL-10 compared with control TCC after activation with concanavalin A (Con A) (624 ± 101 versus 1564 ± 401 pg/ml per 106 cells, respectively; P = 0.04) or anti-CD3/phorbol ester (5148 ± 1634 versus 11 788 ± 2390 pg/ml; P = 0.05). This difference was independent of atopy. Secretion of interferon-gamma, IL-2, and IL-4 was comparable in CF and control TCC after both forms of activation, while IL-5 was reduced in CF TCC following anti-CD3/phorbol myristate acetate (PMA) but not after Con A. We conclude that expression of mutant CFTR in human TCC is accompanied by ion channel dysfunction characteristic of the CF phenotype, and is accompanied by a reduction in IL-10 secretion after polyclonal activation. It is possible that disruption of IL-10-mediated anti-inflammatory homeostasis may contribute to early onset sustained inflammation in CF airways.
Diabetic sera react with the glutamic acid decarboxylase molecule in a dimeric-oligomeric form
Authors: Rowley M J , Chen Q Y , Teoh K L , Zimmet P Z , Tuomi T , Knowles W J , Mackay I R 
Published: November 2003

Abstract
Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). This was initially identified as a 64–65 kD molecule according to migration in gels after immunoprecipitation from pancreatic islets. We studied the antigenicity of two different radiolabelled preparations of GAD, derived either by affinity purification from porcine brain and known to contain GAD 65 and GAD 67, or by expression from a cDNA for human GAD 65 by rabbit reticulocyte lysate (RRL). Radiolabelled immunoprecipitated pellets from the reaction of potent antisera to GAD from patients with IDDM were examined by autoradiography after SDS–PAGE under reducing or non-reducing conditions. Also, preparations of porcine brain GAD were ‘depleted’ of GAD by exposure to antisera, and then similarly re-examined. Autoradiography of radiolabelled GAD either affinity purified from porcine brain, or expressed by RRL, showed that the immunoprecipitated protein migrated under non-reducing conditions according to a Mr of ∼110–130 kD, corresponding to dimeric forms of monomeric GAD of ∼55–65 kD. Depletion by immunoprecipitation of this minor higher Mr component from preparations of GAD left, in the supernatant, an abundance of GAD of Mr 64–65 kD corresponding to monomer that was completely non-reactive with potent IDDM sera. We conclude that IDDM sera react with the GAD molecule in a dimeric (or oligomeric) form. Our findings have general connotations for self-tolerance and autoimmunity.
Primary localized amyloidosis of the eyelid: two cases of immunoglobulin light chain-derived proteins, subtype λV respectively λVI
Authors: Olsen K E , Sandgren O , Sletten K , Westermark P 
Published: November 2003

Abstract
Primary localized amyloidosis has been described in many different organs in the body. Studies by immunohistochemical techniques have suggested an immunoglobulin light chain origin of the amyloid material. Only in a limited number of cases has the amyloid protein been characterized by amino acid sequence analysis as subtypes of immunoglobulin light chain or heavy chain. In this report, two cases of primary localized amyloidosis of the eyelid are presented. The amyloid substance has been extracted and a major fibril protein subjected to amino acid sequence analysis. Both amyloid proteins were part of the variable region of immunoglobulin light chains, subtype λV and subtype λVI, respectively. While λVI has been shown to be a common subtype in systemic immunoglobulin light chain-amyloidosis, it has never been demonstrated in localized amyloid. Very few λV immunoglobulin light chains have been characterized and the subgroup has never been found in amyloid before.
IL-1β production by human polymorphonuclear leucocytes stimulated by anti-neutrophil cytoplasmic autoantibodies: relevance to systemic vasculitis
Authors: Brooks C J , King W J , Radford D J , Adu D , McGrath M , Savage C O S 
Published: November 2003

Abstract
Neutrophils accumulate in the acute blood vessel lesions of patients with autoimmune systemic vasculitis. They have been shown previously to produce the cytokine IL-1β in response to stimulation with TNF. This study demonstrates that neutrophils can be stimulated by anti-neutrophil cytoplasmic antibodies (ANCA), which are present in patients with systemic vasculitis, to express mRNA and protein for IL-1β. Both human ANCA and MoAbs to a variety of autoantigens recognized by ANCA, including proteinase 3, myeloperoxidase, bactericidal/permeability increasing protein and elastase, are effective. This response can be inhibited by actinomycin and cycloheximide, suggesting a requirement for de novo protein synthesis. IL-1β production can be inhibited by pooled human intravenous immunoglobulins but not by FK506 or cyclosporin A. These data suggest that ANCA in patients with active vasculitis may stimulate neutrophils to produce cytokines. It is hypothesized that cytokine production from neutrophils that accumulate in significant numbers in vasculitic lesions contribute to and augment the local inflammatory response by the activation of vascular endothelial cells and infiltrating leucocytes.
Structural peculiarities of a truncated VκIII immunoglobulin light chain in myeloma with light chain deposition disease
Authors: Decourt C , Cogné M , Rocca A 
Published: November 2003

Abstract
We report on the primary sequence of the monoclonal immunoglobulin light chain (LC) REV involved in myeloma-associated light chain deposition disease (LCDD). This sequence was deduced from that of the corresponding complementary (c)DNA in bone marrow plasma cells. Products of three independent amplifications by polymerase chain reaction (PCR) were sequenced and found to be identical. The κ mRNA encoding this N-glycosylated LC showed an overall normal structure consisting of a VκIII segment rearranged to JκII. Direct N-terminal amino acid sequencing of the circulating monoclonal IgA2,κ showed identity with the bone marrow-derived sequence. The κ-chain presented several unusual features affecting both the leader sequence and the variable (V) region. Four unique amino acid substitutions were found at positions -8, -3, -2 and -1 in the leader sequence and probably resulted in an unusual cleavage by signal peptidase, thus making the LC truncated by one residue and accounting for its unique hydrophobic N-terminus: Ile-Ile-Leu. Additional peculiarities were observed in the V region, including a Thr74 → Asn substitution creating a N-glycosylation site, and Thr53 → Ile, which was only reported once among human κIII chains, in another LCDD case, and may be of special significance at a position usually harbouring a polar amino acid.
Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis
Authors: Kaneko H , Saito K , Hashimoto H , Yagita H , Okumura K , Azuma M 
Published: November 2003

Abstract
CD28 on T cells provides a potent costimulatory signal for T cell activation. Down-regulation of CD28 on peripheral T cells has been reported in certain clinical conditions, but full studies on the mechanism and biological significance have not been performed. Our extensive phenotype analysis of peripheral blood lymphocytes (PBL) from SLE patients revealed that the absolute number of CD28+ T cells of both CD4 and CD8 phenotypes was selectively decreased, while that of CD28− T cells was maintained. CD28+ T cells from SLE patients exhibited mostly normal proliferative responses to both CD28-dependent and -independent stimulations. In contrast, CD28− T cells were hyporesponsive to anti-CD3 stimulation in both SLE and normal controls. These results implied that the selective decrease of CD28+ T cells in SLE does not result from a hyporesponsiveness of CD28+ T cells. To investigate the reason for the selective loss of CD28+ T cells, we determined the appearance of apoptotic cells in culture with or without anti-CD3 stimulation. Apoptotic cells defined by merocyanine (MC)540 were gradually increased from 12 h to 24 h. Anti-CD3-induced apoptosis of CD28+ T cells was significantly accelerated in SLE, whereas apoptosis of CD28− T cells was hardly detected in both SLE and normal controls. Comparative analysis between CD28+ and CD28− T cells on CD95 (Fas) and Bcl-2 expression, which are related to activation-induced cell death (AICD), did not show a major difference, although CTLA4, which has been demonstrated to transmit an apoptosis-inducing signal, was expressed only on CD28+ T cells. Our results suggest that CD28-mediated costimulation influences T cell susceptibility to AICD and may be involved in T cell lymphopenia in SLE.
Isolation of antigens recognized by coeliac disease autoantibodies and their use in enzyme immunoassay of endomysium and reticulin antibody-positive human sera
Authors: Börner H , Osman A A , Meergans TH , Weiske T , Mothes TH 
Published: November 2003

Abstract
Components were isolated from rat liver, sheep lung, rhesus and orang-utan intestine. In enzyme immunoassay, these components detected 57%, 72%, 84% and 88% of human sera containing endomysium and reticulin antibodies (EmA and ARA). At most, 7% of EmA/ARA-negative sera reacted with the antigens. The spectrum of EmA/ARA-positive sera reactive with the various components was different but overlapping. When the antigens of sheep lung and orang-utan intestine were used as a cocktail, 98% of EmA/ARA-positive sera (45/46), but only 2% of control sera (1/46) were detected. The isolated antigens from sheep lung and monkey intestines were able to absorb EmA and ARA from human sera and thus should be suspected to contain the epitopes recognized by EmA and ARA, whereas the rat liver component did not bind. Therefore, the spectrum of autoantibodies in coeliac disease might comprise more than that covered by the terms EmA and ARA. The N-terminal amino acid sequence of some of the antigens was homologous with casein, gliadin, fibrinogen, and collagen.
Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy
Authors: Kahaly G , Pitz S , Müller-Forell W , Hommel G 
Published: November 2003

Abstract
Glucocorticoids are usually given for management of Graves' ophthalmopathy (GO), but they may cause side effects. By comparison, intravenous administration of immunoglobulins resulted in clinical improvement and decreased antibody titres in a large number of autoimmune diseases. Therefore, a randomized trial was done, in which 19 patients with active GO were treated with a 20-week course of oral prednisolone (P, starting dose 100 mg/day), and 21 received 1 g immunoglobulin/kg body weight for 2 consecutive days every 3 weeks. The immunoglobulin course was repeated six times. Before and at the end (20 weeks) of immunomodulating therapy, ophthalmological investigation and quantitative magnetic resonance (MR) imaging were performed. A successful outcome was observed in 12 (63%) P-and in 13 (62%) immunoglobulin-treated patients. Overall, there were no marked differences in degree of improvement between the two groups. Responders to treatment in both groups showed improvements in proptosis (median from 24.5 to 21.5 mm; P &lt; 0.005), visual acuity (from 0.6 to 0.85; P &lt; 0.001), intraocular pressure (from 25 to 20 mmHg; P &lt; 0.0001), lid aperture (from 14 to 12 mm; P &lt; 0.01) and a decrease in eye muscle area (inferior, from 44 to 33 mm2; medial, from 43 to 34 mm2; both P &lt; 0.0005). Among the immunoglobulin-treated patients, there was a marked decrease of thyroid antibody titres. Side effects were more frequent and severe during P than during immunoglobulin therapy. Thus, with respect to the above mentioned objective parameters, P and immunoglobulin appeared to be equally effective in treatment of active GO.
Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity
Authors: Kiely P D W , O'Brien D , Oliveira D B G 
Published: November 2003

Abstract
Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti-and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann–Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-γ), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.
Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients
Authors: Baskin B , Pettersson E , Rekola S , Smith C I E , Islam K B 
Published: November 2003

Abstract
IgA nephropathy (IgAN), the most common form of glomerulonephritis, is characterized by normal to elevated levels of serum IgA. In order to understand the molecular mechanism(s) involved in the production of IgA in IgAN, peripheral blood mononuclear cells (PBMC) from these patients were analysed in this study. IL-10, transforming growth factor-beta 1 (TGF-β1) and CD40 have previously been shown to be involved in IgA production. We show here that CD40L expression was increased three-fold in these patients. However, expression of TGF-β1 in serum levels was comparable to controls. In vitro stimulation of PBMC with a polyclonal activator resulted in a three-fold increase in synthesis of both IgA subclasses, with a preference for IgA1 RNA. Insitu hybridization studies also showed a three-fold increase in the numbers of IgA1- and IgA2-producing cells, but the subclass distribution was similar to the controls. Furthermore, using the nested primer polymerase chain reaction (PCR) for amplifying switch (Sμ/Sα) breakpoints we could demonstrate that in unstimulated PBMC the switch frequency did not differ from that of control donors. Sequence analysis of the amplified switch breakpoints and the Iα regulatory region from patients showed no structural abnormality. Although we have previously demonstrated a correlation to in vivo germ-line RNA expression and class switching, no Iα transcripts were detected in unstimulated PBMC from these patients. However, stimulation of PBMC with TGF-β1 resulted in Iα production. Taken together, results from in vivo and in vitro studies suggest that increased cytokine production and hyperresponsiveness to polyclonal stimulation may play an important role in the increased synthesis of IgA. The preference for IgA1 is due to increased production of IgA1 per cell, and the absence of Iα RNA indicates that additional defect(s) in immune regulation may play an important role in the pathogenesis of IgAN.
Erythema nodosum leprosum is associated with up-regulation of polyclonal IgG1 antibody synthesis
Authors: Kifayet A , Shahid F , Lucas S , Hussain R 
Published: November 2003

Abstract
Erythema nodosum leprosum (ENL) is a serious complication of lepromatous (L) disease in leprosy. We have previously shown that of the four IgG subclasses, IgG1 and IgG3 Mycobacterium leprae-specific antibodies are significantly lower in leprosy patients during ENL reaction compared with untreated L patients. To see if this decrease results from a down-regulation of antibody synthesis during ENL, the frequency of antibody-secreting B cells (ABSC) in the blood compartment was determined by ELISPOT and related to serum immunoglobulin concentrations (μg/ABSC). Control groups consisted of 16 patients with stable L disease and 32 healthy endemic controls (EC). Paired samples were analysed during acute ENLS (n = 13) and after the reaction had subsided to identify changes associated with ENL. Polyclonal (PC) IgG1 was elevated in L patients compared with EC (325 μg versus 180 μg). Interestingly, patients during acute ENL showed concentrations higher than L patients (419 μg), which decreased after the reaction had subsided (260 μg), indicating the transient nature of the antibody response. IgG2 antibodies showed the reverse trend and were lower during ENL and increased after the reaction had subsided. The mean concentrations for PC IgG3 and IgG4 antibodies were similar during ENL and after the reaction had subsided. Thus, decrease in M. leprae-specific IgG1 and IgG3 antibodies is not related to down-regulation of B cell responses. Identification of factors which regulate PC IgG1 antibody synthesis may provide additional insights into determinants of ENL reactions.
Expression of leucocyte chemoattractants by interstitial renal fibroblasts: up-regulation by drugs associated with interstitial fibrosis
Authors: González-Cuadrado S , Bustos C , Ruiz-Ortega M , Ortiz A , Guijarro C , Plaza J J , Egido J 
Published: November 2003

Abstract
Interstitial inflammation is a strong predictor of long-term renal damage. The potential role of renal interstitial fibroblasts in recruitment of inflammatory leucocytes into the interstitium is unclear. We have thus studied the mRNA expression of several leucocyte chemotactic factors by rat renal interstitial fibroblasts and its modulation by cytokines. In addition, the effects of two unrelated drugs associated with the development of interstitial fibrosis, namely puromycin aminonucleoside (PAN) and cyclosporin A (CsA), were also studied. Rat renal interstitial fibroblasts showed constitutive mRNA expression for the chemokines monocyte chemoattractant protein 1 (MCP-1) and interferon-inducible protein 10 (IP-10). In addition, these cells also exhibited constitutive mRNA expression for cyclophilin B, an immunophilin recently found to have leucocyte chemoattractant properties. The inflammatory cytokine tumour necrosis factor-alpha up-regulated IP-10 and MCP-1 mRNA expression (10- and four-fold, respectively), but had no effect on cyclophilin B mRNA levels. IP-10 and MCP-1 produced about a four-fold increase in MCP-1 and cyclophilin B mRNA expression, but did not affect IP-10 mRNA. PAN caused an augmentation in IP-10, MCP-1 and cyclophilin B mRNA levels (12-, 9.5, and two-fold, respectively), while CsA increased only cyclophilin B mRNA in a dose-dependent manner. In conclusion, rat renal interstitial fibroblasts express mRNA for chemotactic factors and this expression is up-regulated by inflammatory cytokines, PAN and CsA. The present findings suggest that renal interstitial fibroblasts may play an active role in the recruitment of inflammatory leucocytes into the interstitium.
RANTES in onchocerciasis: changes with ivermectin treatment
Authors: Cooper P J , Guderian R H , Prakash D , Remick D G , Espinel I , Nutman T B , Taylor D W , Griffin G E 
Published: November 2003

Abstract
Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-α) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-α were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P &lt; 0.001) and lymphoedema (P &lt; 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.
Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines—regulation by oxygen tension and extracellular matrix
Authors: Derevianko A , D'Amico R , Simms H 
Published: November 2003

Abstract
The kinetics of IL-8, tumour necrosis factor-alpha (TNF-α) and IL-1β release by PMN adhered to fibronectin, laminin or plastic for 24h in response to continuousstimulation with lipopolysaccharide (LPS; 50ng/ml), n-formyl-Met-Leu-Phe (fMLP; 100mm), or phorbol myristate acetate (PMA; 10ng/ml), was investigated under altered oxygen tension conditions. Cell supernatants were sampled for cytokine content every 6h and measured by ELISA. IL-8 was the most abundant cytokine, produced in a range of up to 5.4ng/ml; TNF-α and IL-1β were produced in a range of up to 1ng/ml. During normoxia, LPS was the most potent stimulus, inducing the release of each cytokine, while fMLP showed a less pronounced effect on IL-8 and IL-1β production and markedly inhibited TNF-α production. PMA markedly suppressed IL-8 and IL-1β release and failed to induce any release of TNF-α. Hypoxia had an overall inhibitory effect on cytokine release except for PMA-induced IL-1β release, and hypoxia/reoxygenation had a significant up-regulating effect except for a further inhibition of fMLP-induced release of TNF-α. Integrin–matrix protein ligation differentiated both spontaneous and externally induced cytokine release and its sensitivity to alteration in oxygen tension. Thus the process of PMN elaboration of inflammatory cytokines is controlled on multiple levels of signal transduction, differentiated by integrin–extracellular matrix interactions, and is sensitive to alterations in microenvironmental oxygen tension.