bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis
Authors: Hommes D W , Meenan J , Dijkhuizen S , Ten Kate F J W , Tytgat G N J , Van Deventer S J H 
Published: November 2003

Abstract
Inflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 μg/kg. rhG-CSF caused a time- and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B4 (LTB4) and thromboxane B2 (TXB2) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB4: both P&lt;0.01; TXB2: both P&lt;0.01. Prostaglandin E2 (PGE2) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.
Relevance of lymphoproliferative disorders and of anti-C1 inhibitor autoantibodies in acquired angio-oedema
Authors: Cicardi M , Beretta A , Colombo M , Gioffré D , Cugno M , Agostoni A 
Published: November 2003

Abstract
We looked for autoantibodies to C1 inhibitor (C1-INH) and evaluated the relationship of their presence to the associated lymphoproliferative diseases and to the cleaved form of C1-INH in 13 patients with acquired C1-INH deficiency (acquired angio-oedema (AAE)). At the time of manifestation of angio-oedema symptoms or within a few years the following diseases were diagnosed: liver angioma (n = 1), M-components (n = 7, one of whom also had echinococcal liver cysts), breast cancer (n= 1), chronic lymphocytic leukaemia (CLL; n= 1); three patients had no associated disease. Anti-C1-INH autoantibodies, measured both as immunoglobulin binding to C1-INH immobilized onto microtitre plates (ELISA) and as plasma inhibitory activity of C1-INH function, were found in 12 patients. Binding of C1-INH to paraproteins, transferred to Immobilon after agarose gel electrophoresis, was detectable in five of seven M-components associated with AAE. Immunoblotting analysis of SDS–PAGE-separated plasma demonstrated that C1-INH circulated in the cleaved 96-kD form in the 12 patients with autoantibodies, but not in the one without. In conclusion, the large majority of our patients have autoantibodies to C1-INH. Circulating autoantibodies are necessary for the generation of cleaved C1-INH. The paraproteins associated with AAE are frequently autoantibodies to C1-INH and thus account for its consumption.
Antibodies to membranes of endothelial cells and fibroblasts in scleroderma
Authors: Hill M B , Phipps J L , Cartwright R J , Milford Ward A , Greaves M , Hughes P 
Published: November 2003

Abstract
Anti-endothelial and other cell membrane-reactive antibodies in scleroderma were characterized by immunoblotting sera with membrane and cytosol preparations of human umbilical vein endothelial cells (HUVEC), dermal fibroblasts and a T cell lymphoma HUT78. Antibodies reactive with HUVEC membranes were found in 17 of 20 patients with scleroderma (33 bands) in contrast to only two of 20 controls (two bands; P&lt;0.01) and three of 11 patients with myocardial infarction (four bands). Eleven of the 20 patients possessed antibodies that were specific for HUVEC membrane and did not cross-react with other cell lines. Analysis of patient subgroups showed that HUVEC membrane antibodies were present in nine of 11 patients with systemic sclerosis and in all nine with the CREST syndrome, and were HUVEC-specific in five and six of these cases, respectively. Although considerable heterogeneity was seen, antibodies to an 18–19-kD membrane epitope were found in 11 of the 20 patients but in none of the controls (P&lt;0.01). This antibody which reacted particularly with HUVEC (n=9) and HUT78 membranes (n=9) was associated with CREST syndrome rather than systemic sclerosis (9/9 versus 1/11; P&lt;0.01), and after elution was shown to possess anticentromere activity. In addition, antibodies reactive with both fibroblast (n=11; 18 bands) and HUT78 membranes (n=18; 42 bands) were detected and were specific for either fibroblast or HUT78 membranes in nine and 14 patients, respectively. There was no significant difference in the incidence of these fibroblasts and HUT78 membrane antibodies in the two patient subgroups. These findings support the concept that membrane-reactive antibodies, including anticentromeric antibodies, may play a central role in the pathogenesis of scleroderma, through their ability to react with endothelial cells.
Contribution of tumour necrosis factor-alpha (TNF-α) in host defence mechanism against Cryptococcus neoformans
Authors: Kawakami K , Qifeng X , Tohyama M , Qureshi M H , Saito A 
Published: November 2003

Abstract
We investigated the role of TNF-α in the host defence mechanism against infection with a virulent strain of Cryptococcus neoformans. Administration of exogenous recombinant human TNF-α significantly prolonged the survival time of mice infected by intratracheal instillation of the organism. Surprisingly, neutralizing MoAb to murine TNF-α did not shorten their survival time, a finding inconsistent with previous results. To investigate the cause of this inconsistency, we examined the production of TNF-α in the lungs of infected mice. During the course of cryptococcosis, there was little or no generation of TNF-α mRNA in the lung. This might be partly due to a direct inhibitory action of the fungal microorganism on TNF-α production by macrophages. In vitro production of TNF-α by murine interferon-gamma (IFN-γ)- and lipopolysaccharide (LPS)-stimulated macrophages was strongly inhibited by co-culturing with the whole yeast cells. In contrast, administration of recombinant murine IL-12 markedly induced TNF-α production and the neutralizing anti-TNF-α MoAb strongly blocked IL-12-induced protection of mice against cryptococcal infection. These results indicate that endogenously synthesized TNF-α has the potential to contribute to the elimination of C. neoformans and partly mediates the protective effect of IL-12.
Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA)
Authors: MARINOVA-MUTAFCHIEVA L , WILLIAMS R O , MASON L J , MAURI C , FELDMANN M , MAINI R N 
Published: November 2003

SUMMARY
This report contains a description of the cellular localization and kinetics of proinflammatory cytokine expression in murine CIA, a model for rheumatoid arthritis. Tissue cryostat sections of undecalcified paws from type II collagen-immunized DBA/1 mice, taken 1–10 days after the onset of clinical arthritis, were examined for the presence of tumour necrosis factor-alpha (TNF-α), IL-1β and IL-6 using an indirect immunoperoxidase technique. In parallel, interferon-gamma (IFN-γ) production by lymph node cells, stimulated in vitro with type II collagen, was assessed as a marker of T cell activity. The main areas of TNF-α, IL-1β and IL-6 expression were in the synovial lining layer and in tissue contiguous with cartilage and bone (the marginal zone), in particular at sites of pannus formation and joint erosion. There was a progressive increase in the number of TNF-α-, IL-1β- and IL-6-positive cells from day 1 to day 10 of arthritis, during which time IFN-γ production by CD4+ T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF-α was consistently detected at day 1 of arthritis, whereas IL-1β-positive cells were not found until day 3, suggesting that the expression of TNF-α precedes that of IL-1β.
Adhesion molecule expression in vivo on extraocular muscles (EOM) in thyroid-associated ophthalmopathy (TAO)
Authors: PAPPA A , CALDER V , FELLS P , LIGHTMAN S 
Published: November 2003

SUMMARY
TAO is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles (EOM) and/or the orbital fat/connective tissue with associated deposition of glycosaminoglycans (GAG) in the interstitial spaces. In this study, the presence and distribution of the vascular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), endothelial-leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the leucocyte integrins CD11a/CD18, CD11b/CD18, CD11c/CD18 were investigated. Nineteen EOM biopsies were collected from 17 patients with early (n = 6) and late (n = 13) TAO as well as from 12 non-TAO control patients. Consecutive cryostat sections of these biopsies were immunostained with MoAbs to the above-mentioned molecules and haematoxylin and eosin. Primary antibody binding was visualized using an avidin-biotin system. In early untreated TAO specimens, the interstitial and perimysial connective tissue surrounding EOM fibres and numerous mononuclear cells stained strongly for ICAM-1. In contrast, the vascular endothelial cells (ulex lectin-positive) stained strongly for ELAM-1 (E-selectin), VCAM-1 as well as ICAM-1. In late disease, the same distribution of immunoreactivity for ICAM-1, ELAM-1 and VCAM-1 was observed, but with significantly lower staining. The leucocyte integrins (CD11a, CD11b, CD11c) were again expressed at significantly higher levels in early TAO specimens compared with late TAO specimens and were minimal or absent in the EOM biopsies harvested from control patients. In conclusion, increased expression of adhesion molecules studied correlated with early active disease and was reduced in later stages.
Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones
Authors: LAGIER B , LEBEL B , BOUSQUET J , PÈNE J 
Published: November 2003

SUMMARY
Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio &gt;1), Th0 (ratio  0.1 and 1) or Th1 (ratio &lt;0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P&lt;0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P&lt;0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.
Normal CD5+ B lymphocytes are poor stimulators in the autologous mixed lymphocyte reaction (AMLR)
Authors: FERNANDEZ L A , CHENG R , SADEK I , NEVILL T J , MACSWEEN J M 
Published: November 2003

SUMMARY
The AMLR is decreased in chronic lymphocytic leukaemia (CLL), which is characterized by a monoclonal expansion of CD5+ B lymphocytes. Since B cells are used to stimulate the AMLR, we investigated the capacity of normal CD5+ B cells to function as stimulators in the AMLR. We isolated B cells from the peripheral blood of normal individuals and fractionated them into subpopulations enriched for CD5+ and CD5− cells, which were used as stimulators in the AMLR. We found that the CD5− B cells were excellent stimulators, whereas stimulation of AMLR by B cells enriched for CD5+ cells resulted in significantly reduced proliferative responses (P&lt;0.005). This suggests that the reduced AMLR in CLL is due to the predominance of CD5+ B lymphocytes in the stimulating cell population.
Difficulties in the ascertainment of C9 deficiency: lessons to be drawn from a compound heterozygote C9-deficient subject
Authors: HOBART M J , FERNIE B A , WÜRZNER R , OLDROYD R G , HARRISON R A , JOYSEY V , LACHMANN P J 
Published: November 2003

SUMMARY
A group of patients with long-surviving mismatched kidney allografts were investigated for complement function using haemolytic assays in agarose gels. One patient was found to have no alternative pathway activity but a low normal classical pathway. Surprisingly, investigation revealed that the patient's complement was normal for all components except C9, which was functionally absent. The patient was shown to be heterozygous for DNA markers in the C6, C7 and C9 region of chromosome 5 and therefore appears to be a compound heterozygote for two uncharacterized C9 deficiency genes. Serological analysis by ELISA revealed that he has trace concentrations of a non-functional C9 molecule. Western blot analysis was not sufficiently sensitive to permit detection of this molecule. We hypothesize that the patient is heterozygous for a complete deficiency of C9 and for a gene directing hyposynthesis of a defective C9. We also suggest that C9 deficiency may be more common among Caucasians than has been reported.
Regulatory role of exogenous IL-10 in the development of immune response versus Cryptococcus neoformans
Authors: MONARI C , RETINI C , PALAZZETTI B , BISTONI F , VECCHIRELLI A 
Published: November 2003

SUMMARY
The most important event involved in host defence against Cryptococcus neoformans is the development of an adequate cell-mediated immune response. IL-10, abundantly produced during AIDS progression, could be a negative factor that affects the T cell response through its own immunosuppressive action on antigen-presenting cells. To determine whether this cytokine affects the course of immune response against C. neoformans, we added exogenous IL-10 to cultured Cryptococcus-laden monocytes plus T lymphocytes. The data from this study confirmed the down-regulatory effect of exogenous IL-10 on monocytes and expanded the known inhibitory role to include an increase of the deleterious effect due to capsular material of C. neoformans on (i) lymphoproliferation, (ii) down-regulation of MHC class II molecules, (iii) inhibition of IL-2 mRNA expression and protein secretion by T lymphocytes. These results indicate that the presence of IL-10 in AIDS patients, due to the progression of disease, could represent a pivotal problem contributing to augment the pathogenic effect of C. neoformans.
Genetic differences in immune reactivity to mercuric chloride (HgCl2): immunosuppression of H-2d mice is mediated by interferon-gamma (IFN-γ)
Authors: DOTH M , FRICKE M , NICOLETTI F , GAROTTA G , VAN VELTHUYSEN M-L , BRUIJN J A , GLEICHMANN E 
Published: November 2003

SUMMARY
Upon treatment with HgCl2, H–2s mice, such as B10.S, develop an activation of B lymphocytes that depends, at least partially, on activation of T helper type 2 (Th2) cells and results in increased serum levels of IgG1 and IgE, appearance of IgG autoantibodies, and development of immune glomerulonephritis and vasculitis. Results of previous studies and of experiments presented here indicate that the B cell activation and systemic autoimmune disease fail to develop in MHC-congenic B10.D2 (H-2d) and B10.BR (H–2k) mice treated with HgCl2, although B10.D2 T cells showed signs of activation by and specificity for HgCl2 comparable to those seen in strain B10.S. Here, we report that following HgCl2 injections the antibody response to sheep erythrocytes is normal in B10.S, but suppressed in B10.D2 mice. This suppression was prevented by MoAb to mouse IFN-γ. Conversely, treatment of B10.D2 mice with murine recombinant IFN-γ (rIFN-γ) was able to reproduce the immunosuppression seen after HgCl2 treatment. In B10.S mice, it took administration of both rIFN-γ and HgCl2 to suppress the anti-sheep erythrocyte response. Although rIFN-γ diminished the increase in IgE serum levels of HgCl2-treated B10.S mice, it failed to prevent their autoantibody production and immune glomerulonephritis. These findings further strengthen the concept that B10.S mice react to HgCl2 by preferential activation of their Th2 cells producing IL-4, whereas B10.D2 mice react to HgCl2 by preferential activation of their Th1 cells, which produce IFN-γ and thus suppress antibody responses.
Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD)
Authors: BOUMA G , OUDKERK POOL M , CRUSIUS J B A , TH SCHREUDER G M , HELLEMANS H P R , MEIJER B U G A , KOSTENSE P J , GIPHART M J , MEUWISSEN S G M , PEÑA A S 
Published: November 2003

SUMMARY
Family and epidemiological studies support a genetic susceptibility to UC and CD. Conflicting reports regarding associations between UC and HLA-DR2 and between CD and various HLA alleles have been published. The aim of this study was to determine whether molecularly defined HLA-DR genes are associated with these diseases in a Dutch group of patients. Fifty-nine unrelated Dutch UC patients and 89 CD patients were typed using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB1*15 allele was increased in UC patients compared with controls (42% versus 26% in controls; P = 0.006; odds ratio (OR) = 2.1), and was predominantly found in female patients (53% versus 24%; P = 0.001; OR = 3.5). The DRB1*15 allele was increased in UC patients having a positive family history (P = 0.01; OR = 5.8). Among the 16 patients who showed an increase in extent of disease during follow up, 10 were DRB1*15+ (P = 0.002; OR = 4.8). The frequency of the DRB1*13 allele was decreased in patients with UC (15% versus 28% in controls; P = 0.04; OR = 0.5). In CD, no association was observed between disease or particular clinical subgroups and any allele tested. The present study provides additional evidence for the genetic association between UC and HLA-DRB1*15, and supports recent findings that the susceptibility gene(s) for CD is not located in the HLA class II region.
Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE)
Authors: WU Z-Q , DRAYTON D , PISETSKY D S 
Published: November 2003

SUMMARY
To elucidate the mechanisms of anti-DNA production, we assessed the binding of sera of normal human subjects (NHS) and patients with SLE to a panel of bacterial and mammalian DNA. Using single-stranded DNA as antigens in an ELISA, NHS showed significant binding to some but not all bacterial DNA, while lacking reactivity to calf thymus DNA. Among bacterial DNA, the highest levels of binding were observed with DNA from Micrococcus lysodeikticus and Staphylococcus aureus. In contrast, SLE sera showed high levels of binding to all DNA tested. To evaluate further immunochemical properties of the anti-DNA antibodies, the subclass distribution of these responses was evaluated by subclass-specific reagents. While NHS showed a predominance of IgG2 antibodies to bacterial DNA, SLE sera had a predominance of IgG1 antibodies to these antigens. Together, these results provide further evidence for the antigenicity of bacterial DNA and suggest that NHS and SLE anti-DNA differ in the patterns of epitope recognition as well as mechanisms of induction.
Molecular aberrations in the MHC class I-restricted pathway for antigen presentation in methylcholanthrene sarcomas from nude mice: discrepancies between MHC mRNA and surface protein
Authors: ENGEL A-M , SVANE I M , MADSEN M W , PEDERSEN M , WERDELIN O 
Published: November 2003

SUMMARY
In a previous study, we demonstrated that eight sarcomas induced by chemical carcinogenesis in nude mice were rejected by syngeneic immunocompetent recipients at a much higher rate than eight sarcomas induced with the same method in syngeneic immmunocompetent mice. In the present study, we investigated these 16 sarcomas for structural and quantitative aberrations in components of the MHC class I-restricted antigen-processing and -presentation pathway. Considerable discrepancies between mRNA levels and cell surface protein expression of MHC class I (Kd, Dd and Ld) molecules were observed almost exclusively in the tumours derived from nude mice. Several of the nude mouse-derived tumours also displayed incongruent levels of heavy chain mRNA and β2-microglobulin mRNA. These findings are taken as indications of abnormal regulation of gene transcription in nude mouse tumours, and if this abnormal regulation extends to the entire genome, it may explain the pronounced immunogenicity of these tumours. Proteasome composition, heat shock protein expression, TAP-molecule inducibility and intercellular adhesion molecule-1 expression were investigated in the same tumours. We found no indications of structural defects or quantitative differences in these molecules between the two groups of tumours.