bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis
Authors: Shijubo N , Imai K , Shigehara K , Hinoda Y , Abe S 
Published: November 2003

Abstract
sICAM-1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM-1 concentrations reflect disease activity in these diseases. We measured circulating sICAM-1 concentrations and serum angiotensin-converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM-1 concentrations (62.8±33.5U/ml) and SACE activity (23.7±7.4U/l) compared with controls (circulating sICAM-1 50.9±12.1U/ml, and SACE 13.5±3.8U/l). Successive measurements showed that circulating sICAM-1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM-1 values (102.2±35.3U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) (46.4±12.6U/ml). However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM-1 (&gt;75U/ml, mean of controls+2s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM-1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis.
Different expression of IL-2 receptor α-chain on a lamina propria T cell population and goblet cells in rats orally tolerized or sensitized to ovalbumin (OA) after colonization with an OA-producing Escherichia coli
Authors: Dahlman-Höglund A , Ahlstedt S , Hanson L Å , Dahlgren U , Telemo E 
Published: November 2003

Abstract
The aim of this study was to compare the local gut immune response in sensitized and orally tolerized experimental animals. The development of IgE/IgG antibodies and the DTH to OA was studied in rats made orally tolerant to OA and compared with sensitized control rats after colonization with an Escherichia coli genetically engineered to produce OA. At 3 weeks of age, pups were weaned onto a standard diet without OA or an OA-containing diet for 4 weeks and then switched to a standard diet without OA. Both groups of rats were parenterally immunized with a mixture of OA and human serum albumin (HSA) in Freund's complete adjuvant when they were 8 weeks old. After DTH measurement 2 weeks later, all rats were colonized with an E. coli producing OA for 5 days. The local immune response in the small intestine was assessed, using immunohistochemistry, as the expression of MHC class II molecules and IL-2 receptor (IL-2R) α-chain. The OA-tolerant rats showed the classical signs of oral tolerance, with a reduced IgE and IgG antibody and DTH response to OA before colonization. The difference between the two groups in the anti-OA antibody response became even more pronounced after colonization with the E. coli that produce OA. Rats orally tolerant to OA maintained a normal villus architecture after colonization, with a normal expression of MHC class II molecules similar to non-treated adult rats, but with a significantly higher (P=0.004) expression of IL-2R α-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The tolerant rats showed a very weak staining with the anti-IL-2R α-chain-specific antibody on a few goblet cells in only one out of seven rats. In the sensitized control rats, a marked local immune response was seen with an intense staining with a monoclonal anti-IL-2R α-chain-specific antibody on goblet cells in five out of seven rats (P=0.019) and also an increased expression of MHC class II molecules in the epithelial cells and cells in the lamina propria of all rats. Rats orally tolerant to OA maintained a normal villus architecture after colonization, but with a significantly higher (P=0.004) expression of IL-2R α-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The novel finding that goblet cells express IL-2R α-chain and the striking difference in expression of the receptor and the numbers of goblet cells between tolerant and sensitized rats may suggest a direct T cell regulation of the goblet cells. A possibility that oral tolerance might be maintained by the activated T cells expressing IL-2R α-chain in the lamina propria of the villus core is also discussed.
Raised anti-endothelial cell autoantibodies (AECA), but not anti-neutrophil cytoplasmic autoantibodies (ANCA), in recurrent oral ulceration: modulation of AECA binding by tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)
Authors: Healy C M , Carvalho D , Pearson J D , Thornhill M H 
Published: November 2003

Abstract
Recurrent oral ulceration (ROU) is a common oral mucosal condition of unknown etiology. However, there is evidence to suggest that vasculitis may play a role. Here we investigate the presence in ROU of two autoantibodies associated with vasculitis, AECA and ANCA. AECA target as yet unidentified antigens on the endothelial cell surface and have been identified in patients with vasculitic disorders and inflammatory conditions with a vasculitic component. ANCA target specific neutrophil-associated proteins and are detected in specific vasculitic and chronic inflammatory disorders. AECA and ANCA levels were studied in 20 ROU patients and 20 controls. IgG AECA to the endothelial cell line ECV 304 were detected in 19 ROU patients and four controls. Levels were significantly raised in ROU both to ECV 304 (P &lt; 0.000 05) and to human umbilical vein endothelial cells (HUVEC) (P &lt; 0.005). Although levels were highest during episodes of ulceration, they were also raised between episodes. Stimulation of endothelial cells with TNF-α significantly increased AECA binding of both ROU (P &lt; 0.005) and control samples (P &lt; 0.0001), while IFN-γ decreased binding (ROU P &lt; 0.0001; controls P &lt; 0.05). In contrast, ANCA were detected in only one patient and none of the controls. The presence of raised levels of AECA lends support to the hypothesis that a vasculitic process may underlie ROU. Moreover, these findings suggest that endothelial cell expression of AECA target antigens is increased by TNF-α and decreased by IFN-γ stimulation.
Gold and d-penicillamine induce vasculitis and up-regulate mRNA for IL-4 in the Brown Norway rat: support for a role for Th2 cell activity
Authors: QASIM F J , THIRU S , GILLESPIE K 
Published: November 2003

SUMMARY
d-penicillamine (DP) and gold salts which are used as immune-modulating agents in the treatment of rheumatoid arthritis are known to be capable of causing autoimmune manifestations. Most autoimmune diseases in man are dominated by Th1-type responses, and one might presume that effective immunotherapy counteracts Th1 activity, perhaps by causing a shift to a Th2 response. The mechanism of action of gold and DP is not clear, but some clues may be obtained from their effects in animal models. DP, gold salts and mercuric chloride (HgCl2) are known to induce Th2-dominated autoimmune syndromes in genetically susceptible rodent strains, and we have demonstrated recently that HgCl2 up-regulates messenger RNA (mRNA) for IL-4 in the Brown Norway (BN) rat. In the BN rat HgCl2 treatment is also associated with the development of vasculitis, and anti-myeloperoxidase (MPO) antibodies are found in the serum. The present study examined and confirmed the hypothesis that, since gold and DP induce an autoimmune syndrome similar to HgCl2 in the BN rat, they may also induce vasculitis and an up-regulation in mRNA for IL-4. Tissue injury was assessed macroscopically and histologically on day 5 and day 15 after the start of injections with gold, DP or HgCl2, serum titres of IgE and presence of anti-MPO antibodies were determined using ELISA, and a semi-quantitative assay using reverse transcription-polymerase chain reaction was used to assay the level of mRNA for IL-4 in spleen and caecum. The relative degree of tissue injury reflected the potency of induction of IgE by the three agents (HgCl2 being most potent and DP least potent). The lesions were identical histologically, supporting the premise that the vasculitis is a manifestation of the autoimmune syndrome rather than non-specific HgCl2 toxicity. Both gold and DP induced less up-regulation of mRNA for IL-4 than HgCl2. HgCl2 (but not gold or DP) induced anti-MPO antibodies. It would be interesting to examine patients treated with gold and DP to see if there is evidence of a Th2-type response in those developing autoimmune complications, and whether or not the bias to a Th2 enviroment contributes to efficacy of treatment of the underlying disease.
Examination of the mechanism by which heparin antagonizes activation of a model endothelium by interferon-gamma (IFN-γ)
Authors: DOUGLAS M S , RIX D A , DARK J H , TALBOT D , KIRBY J A 
Published: November 2003

SUMMARY
IFN-γ increases the potential immunogenicity of vascular endothelial cells by up-regulation of intercellular adhesion molecule-1 (ICAM-1) and class I MHC antigen expression and by induction of class II MHC antigens and certain chemokines. In this study the mechanism by which the glycosaminoglycan (GAG) heparin antagonizes the activation of a model endothelium by IFN-γ was investigated. Radioligand binding assays demonstrated that total binding of 125I-IFN-γ to the EAhy.926 endothelial hybridoma cell line was reduced in the presence of heparin or heparan sulphate (HS); the structurally dissimilar GAG chondroitin sulphate had no effect. Treatment of the cells with chlorate, a metabolic inhibitor of GAG sulphation, was found to reduce both the subsequent binding of IFN-γ and its ability to induce expression of class II MHC antigens. Treatment with heparinase II dramatically reduced the binding of IFN-γ, while chondroitin ABC lyase had no effect. A cationic peptide from the C-terminal region of IFN-γ was also found to reduce binding of intact IFN-γ to the cells. These results appear to demonstrate that IFN-γ is sequestered at the surface of endothelial cells by electrostatic interaction between specific basic amino acid residues and sulphated domains on HS, the most abundant endothelial GAG. This interaction is competitively inhibited by heparin, which is structurally related to HS. These observations are consistent with the model that IFN-γ is bound by membrane-associated HS before engagement with the high-affinity receptor and signal transduction. Inhibition of the interaction between proinflammatory cytokines and membrane-associated GAG molecules may provide a mechanism for inducing clinically useful immunosuppression.
Syncytial cell formation in vivo by type C retroviral particles in the systemic lupus erythematosus (SLE) lung
Authors: TAMURA N , SEKIGAWA I , HASHIMOTO H , YAMAMOTO N , KIRA S 
Published: November 2003

SUMMARY
Significant numbers of syncytial cells were observed in the bronchoalveolar lavage fluid (BALF) of a 42-year-old patient who had SLE with interstitial pneumonia. Electron microscopic study of the BALF cells and positive reverse transcriptase activity in the supernatant of the cultured cells revealed unknown retroviral particles in the BALF cells. No antibodies to known human retroviruses or proviral sequences were detected. Type C retroviral particles and positive reverse transcriptase activity were also observed in co-cultured U937 cells. To evaluate the pathogenic role of unknown type C retroviral particles, screening for antibodies to this retroviral particle was performed by immunofluorescence in 26 patients with idiopathic pulmonary fibrosis, 17 patients with SLE, 22 patients with lung cancer, and 58 healthy volunteers. Serum antibody to this putative type C retrovirus was detected in 24% of SLE patients, 27% of idiopathic pulmonary fibrosis patients, none of the lung cancer patients and 2% of healthy volunteers. Although no direct evidence of this virus as the pathogen for SLE could be demonstrated, a possible role in the development of SLE and interstitial pneumonia might be suggested.
Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity
Authors: HOMBACH A , TILLMANN T , JENSEN M , HEUSER C , SIRCAR R , DIEHL V , KRUIS W , POHL C 
Published: November 2003

SUMMARY
Specific activation of resting lymphocytes for tumour targeting can be achieved by bispecific monoclonal antibodies (bi-MoAbs) with specificity for tumour antigens and T cell-activating antigens in combination with a costimulatory anti-CD28 antibody. In this study we focus on the immunomodulatory function of an anti-CD3/CA19-9 bi-MoAb in combination with a costimulatory anti-CD28 antibody which may result not only in antigen-specific, T cell-mediated tumour cell lysis but also in recruitment of other cellular effector functions. In combination with costimulatory anti-CD28 antibodies, resting peripheral lymphocytes could be activated specifically to secrete high amounts of Th1 cytokines (IL-2, interferon-gamma (IFN-γ)) characterizing a cellular immune response. In contrast, no IL-4 and only low amounts of IL-10 could be detected. Furthermore, bi-MoAb-mediated CA19-9-specific activation of T cells was accompanied by recruitment of MHC- and CA19-9-independent cytotoxicity, as was determined by lysis of different CA19-9−cell lines. This MHC-independent cytotxicity was mediated at least in part by activated natural killer (NK) cells, as depletion of CD16+ NK cells resulted in substantial decrease of cytotoxicity against CA19-9− targets. Our results indicate that specific activation of resting T cells with CD3-associated bi-MoAbs in combination with an anti-CD28 antibody leads to a Th1 differentiation pathway and is accompanied by recruitment of MHC-independent lymphokine-activated killer (LAK) cell cytotoxicity which can possibly be directed against a heterogeneous tumour.
Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behçet's disease (BD) in Japan
Authors: KANEKO S , SUZUKI N , YAMASHITA N , NAGAFUCHI H , NAKAJIMA T , WAKISAKA S , YAMAMOTO S , SAKANE T 
Published: November 2003

SUMMARY
BD is prevalent in the area of the Silk Route. It has been shown that hsp are involved in the T cell activation in patients with BD in the UK, where this disease has developed sporadically. We have thus examined whether the T cell response to the hsp-derived peptides may be induced in patients with BD in Japan, an east pole of the Silk Route. As with patients in the UK, the human 60-kD hsp peptide 336–351 also yielded vigorous proliferation of T cells in Japanese patients with BD, but neither in normal subjects nor in patients with rheumatoid arthritis (RA); there was significant association between proliferation by this peptide and the presence of ocular lesion, but not any other symptoms of BD. To clarify whether the peptide stimulates T cells as a polyclonal activator, a specific antigen or a superantigen-like substance, we analysed T cell receptor (TCR) usage of responding T cells by means of MoAbs specific for TCR Vβ subfamily and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP)-based technique. We found that T cells with certain TCR Vβ subfamilies (including Vβ5.2–3, 8, 13.6, 18, 21.3) were increased in circulation and responded to the hsp peptide in an antigen-specific fashion. In addition, TCR Vβ gene-amplified products of freshly isolated T cells of patients with BD formed several bands in the PCR-SSCP analysis; some of them became prominent after stimulation with the peptide. This suggests that T cells in patients with this disease have already been expanded oligoclonally in vivo, which may be a result of stimulation by triggering antigens, including the hsp peptide. In addition, hsp peptide stimulation induced proinflammatory cytokine mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour necrosis factor-alpha (TNF-α) and TNF-β in eight out of eight patients studied. Taken together, the results suggest that hsp antigen may play a role in the pathogenesis of BD, not only in the area of the Silk Route, but also outside the Silk Route area.
Somatic hypermutation of immunoglobulin genes in human neonates
Authors: RIDINGS J , NICHOLSON I C , GOLDSWORTHY W , HASLAM R , ROBERTON D M , ZOLA H 
Published: November 2003

SUMMARY
The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high-affinity variants, is operative in the neonate. Re-arranged VH6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal VH6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.
Localization of rat CD1 transcripts and protein in rat tissues—an analysis of rat CD1 expression by in situ hybridization and immunohistochemistry
Authors: KASAI K , MATSUURA A , KIKUCHI K , HASHIMOTO Y , ICHIMIYA S 
Published: November 2003

SUMMARY
CD1 molecules are cell surface glycoproteins non-covalently associated with β2-microglobulin. Recently, functional features of the CD1 family such as a target ligand and an antigen-presenting structure for T cells have been reported. In the current study, tissue distribution of rat CD1 was analysed by in situ hybridization (ISH) in conjunction with immunohistochemistry to clarify the precise localization of both transcripts and proteins. CD1 transcripts were detected by ISH in a variety of organs: spleen, thymus, liver, lung, heart, kidney, small intestine and skin. In most organs, CD1 immunoreactivity paralleled the amount of CD1 mRNA expression and was localized in the same regions as its gene transcripts. However, there was a clear difference between the level of rat CD1 transcription and protein expression in the small intestine. CD1 mRNA was detected in the enterocytes of crypts of Lieberkuhn, but not in those of the intestinal villi, while immunoreactivity of CD1 protein was observed in the cells of the intestinal villi but not in those of crypts of Lieberkuhn. This suggests that CD1 gene transcription occurs in the enterocytes of intestinal crypts, and that as the cells of intestinal crypts migrate from the crypts to the intestinal villi, CD1 proteins are synthesized and accumulated in the intestinal villi. Such CD1 expression in the enterocytes appears to be consistent with migration-associated differentiation, and suggests that rat CD1 may take part in mucosal immunity as a first line of defence. In addition, clear cell membrane CD1 immunoreactivity on lymphoid cells raises the possibility that intercellular interaction via rat CD1 and T cell receptors may be involved in both lymphoid cell differentiation and immunoregulation.
Up-regulation of macrophage colony-stimulating factor (M-CSF) and migration inhibitory factor (MIF) expression and monocyte recruitment during lipid-induced glomerular injury in the exogenous hypercholesterolaemic (ExHC) rat
Authors: MIYAZAKI K , ISBEL N M , LAN H Y , HATTORI M , ITO K , BACHER M , BUCALA R , ATKINS R C , NIKOLIC-PATERSON D J 
Published: November 2003

SUMMARY
Although macrophages play an important role in lipid-induced glomerular injury, we know little of the mechanisms by which hyperlipidaemia induces monocyte recruitment. This study investigated the role of M-CSF and macrophage MIF in monocyte recruitment during the development of lipid-induced glomerular injury in the susceptible ExHC rat strain. Groups of five ExHC rats were fed a high cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil, and killed after 3 days, 1, 2 or 6 weeks. Control animals were killed on day 0 or after 6 weeks on a normal diet. Animals were hypercholesterolaemic 3 days after the induction of the HCD, but showed no change in plasma triglycerides over the 6-week period. Glomerular macrophage accumulation was first evident at 1–2 weeks and increased up to week 6, when macrophage-derived foam cells were seen in almost all glomeruli, and segmental lesions and mild proteinuria were also evident. Combined in situ hybridization and immunohistochemistry staining demonstrated that, coincident with the induction of hypercholesterolaemia on day 3, there was marked up-regulation of M-CSF and MIF mRNA expression by intrinsic glomerular cells (mostly mesangial cells and podocytes) which preceded monocyte recruitment. There was a highly significant correlation between the number of M-CSF and MIF-positive cells and glomerular macrophage accumulation over the 6-week period. Although some glomerular macrophages and foam cells exhibited M-CSF and MIF expression, the major source of these molecules was intrinsic glomerular cells. No local macrophage proliferation was observed during the development of glomerular lesions. In conclusion, hypercholesterolaemia caused marked up-regulation of M-CSF and MIF expression by intrinsic glomerular cells, which correlated with monocyte recruitment and the development of lipid-induced glomerular injury. This is the first study to implicate local synthesis of MIF in the pathogenesis of lipid-induced lesions.
Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens: dissociation between different immune functions
Authors: SHIRKEY B L , SLAVIN S , VISTICA B P , PODGOR M J , GERY I 
Published: November 2003

SUMMARY
Linomide (LS-2616, quinoline-3-carboxamide) has been reported to exert a diverse range of effects on the immune system. On one hand, this drug was found to stimulate the immune system and to enhance activities such as DTH or allograft rejection. On the other hand, linomide was shown to inhibit the induction of experimental autoimmune encephalomyelitis and myasthenia gravis, as well as the development of diabetes in non-obese diabetic (NOD) mice. Here we report the effects of linomide in animals immunized with uveitogenic retinal antigens. Treatment with linomide completely inhibited the development of experimental autoimmune uveoretinitis (EAU) in mice immunized with interphotoreceptor retinoid-binding protein and markedly suppressed EAU in rats immunized with S-antigen (S-Ag). In addition, linomide-treated rats exhibited reduced antibody production and lymphocyte proliferative response to S-Ag. In contrast to these suppressive activities, linomide treatment did not affect the development of adoptively transferred EAU in rats and moderately enhanced the DTH reactions to S-Ag in immunized rats in which EAU and other immune responses to this antigen were suppressed.