bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of proliferative responses and cytokine mRNA profiles induced by Vespula venom in patients with severe reactions to wasp stings
Authors: BONAY M , ECHCHAKIR H , LECOSSIER D , LAINÉ P , HERMAN D , HANCE A J , SOLER P , TAZI A 
Published: November 2003

SUMMARY
The reasons why severe allergic reactions to bee and wasp stings develop in only a small portion of exposed individuals are incompletely understood, but differences in T cell responses to venom antigens comparing allergic and non-allergic individuals are likely to be important. To identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula venom-allergic patients and non-allergic individuals were compared. Mononuclear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 ± 8387 ct/min, n = 19), and the extent of proliferation was greater for patients with a history of multiple prior stings and those with high levels of venom-specific IgE. Although mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 ± 711 ct/min, n = 8), production of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-γ) in response to Vespula venom by cells from non-allergic subjects was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that these individuals had been previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients released a more restricted profile of cytokines following stimulation with venom. Only IFN-γ mRNA expression was detected in all individuals evaluated, whereas IL-2 mRNA was not detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells from these individuals, because polyclonal stimulation with phorbol myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the two groups. These studies demonstrate clear differences in the T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.
Effector molecules of the host defence mechanism against Mycobacterium avium complex: the evidence showing that reactive oxygen intermediates, reactive nitrogen intermediates, and free fatty acids each alone are not decisive in expression of macrophage antimicrobial activity against the parasites
Authors: TOMIOKA H , SATO K , SANO C , AKAKI T , SHIMIZU T , KAJITANI H , SAITO H 
Published: November 2003

SUMMARY
In this study, we evaluated the roles of reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and free fatty acids (FFA) as effectors of the macrophage-mediated host defence mechanism against Mycobacterium avium complex (MAC). First, M. avium (three strains) and M. intracellulare (two strains) were treated with the H2O2-Fe2+-mediated halogenation system, acidified NaNO2-derived RNI, or FFA (linolenic acid) in sodium acetate buffer pH 5.5, and then counted for the number of residual colony-forming units (CFU) of organisms. Although these effectors exerted strong bactericidal activity against the MAC, the susceptibility of test organisms markedly varied from strain to strain. There was no significant relationship between the degree of resistance of a given MAC strain to these effectors and its virulence in mice, indicating that ROI, RNI, and FFA each alone are not decisive as the effector components of the host defence mechanism against the MAC. Second, the increase in ROI-producing ability in murine peritoneal macrophages due to tumour necrosis factor-alpha (TNF-α) treatment was not accompanied by parallel potentiation of anti-MAC activity of the same macrophage population. This excludes the possibility that ROI play a central role in macrophage-mediated killing and inhibition of MAC organisms. Third, anti-MAC activity of BAM3 macrophage cell line was not significantly attenuated by NG-monomethyl-l-arginine (NO synthase-inhibitor causing reduction of RNI production) or by quinacrine (phospholipase A2-inhibitor causing reduction of FFA release), indicating that RNI and FFA each alone do not play crucial roles in the expression of macrophage antimicrobial activity against the MAC. The present findings suggest important roles of collaborating actions of various antimicrobial effectors and/or the participation of other kinds of effectors in macrophage-mediated killing and inhibition of MAC organisms.
Autoantibody reactive with the human general transcription factor TFIIF in sera from patients with autoimmune disorders
Authors: CAI Y , KITAJIMA S , ETOH F , KINOSHITA S , OKUBO K , HAMASAKI N 
Published: November 2003

SUMMARY
Transcription factor (TF) IIF, a heteromeric protein composed of two subunits, RAP30 and RAP74, is required for both specific initiation and elongation of mRNA synthesis by RNA polymerase II. We have identified high titre of specific autoantibodies against the RAP74 subunit of TFIIF in sera from patients with systemic lupus erythematosus (SLE) as well as those with rheumatoid arthritis (RA), periarteritis nodosa (PN), Sjögren's syndrome (SS), dermatomyositis (DM), and mixed connective tissue disease (MCTD) by Western blot or immunoprecipitation. The epitopes recognized by autoantibodies were shown to be preferentially clustered at the central charged region. Anti-RAP74 autoantibody was shown to suppress the activity of TFIIF-stimulated elongation of mRNA synthesis by RNA polymerase II. It is concluded that some patients with autoimmune disorders develop specific autoantibodies against the RAP74 subunit of TFIIF.
Anti-Ro fine specificity defined by multiple antigenic peptides identifies components of tertiary epitopes
Authors: SCOFIELD R H , ZHANG F-C , KURIEN B T , HARLEY J B 
Published: November 2003

SUMMARY
Anti-Ro (or SSA) is a clinically important autoantibody that is found in 25–40% of patients with systemic lupus erythematosus as well as an even greater proportion of patients with Sjögren's syndrome or subacute cutaneous lupus. We have studied the binding of anti-Ro sera to multiple antigenic peptides constructed from the sequence of the 60-kD Ro molecule. The results demonstrate that sera bind these peptides in solid-phase assay. Surprisingly, some of these peptides also form a precipitin line in double immunodiffusion with anti-Ro sera. Formation of lines of identity in double immunodiffusion as well as absorption studies indicate that peptides distant in the primary amino acid sequence and without shared sequence are bound by the same antibody. In addition, data from surface plasmon resonance demonstrate that peptides identified in this manner have protein–protein interactions. Thus, these techniques may identify the components of conformational epitopes.
Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-α) receptors in type C chronic liver disease
Authors: KAKUMU S , OKUMURA A , ISHIKAWA T , YANO M , ENOMOTO A , NISHIMURA H , YOSHIOKA K , YOSHIKAI Y 
Published: November 2003

SUMMARY
We previously reported that the number of TNF-α-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-αRI (p55) and -αRII (p75), and IL-10, all of which act as TNF-α buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-αR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-αRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-αRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.
CD8+ CD28− T cells in vertically HIV-infected children
Authors: BRUGNONI D , AIRO’ P , TIMPANO S , MALACARNE F , UGAZIO A G , CATTANEO R , DUSE M 
Published: November 2003

SUMMARY
To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28− cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P &lt; 0.001). In fact, in HIV-infected children, this percentage was elevated from the first year of life, while in healthy seroreverted children, the proportion of CD28− cells among CD8+ cells rose progressively with age (r = 0.49; P = 0.008). In HIV+ children, the CD8+ CD28−, but not CD8+ CD28+ cell proportion was significantly correlated with immunological markers of disease progression, such as CD4+ cell loss (r = −0.65; P &lt; 0.001) and the level of in vitro spontaneous lymphocyte apoptosis (r = 0.53; P = 0.03).
Effects of rapamycin on apoptosis of rheumatoid synovial cells
Authors: MIGITA K , EGUCHI K , ICHINOSE Y , KAWABE Y , TSUKADA T , AOYAGI T , NAGATAKI S 
Published: November 2003

SUMMARY
In the present study, we investigated the effects of an immunosuppressant, rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down-regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent manner. In contrast, Fas antigen expression was not influenced by rapamycin treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results suggest that rapamycin augments the sensitivity of rheumatoid synovial fibroblasts to apoptosis by down-regulating bcl-2 expression. This pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium may represent a new therapeutic approach for rheumatoid arthritis.
Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin
Authors: BLANK M , CINES D B , AREPALLY G , ELDOR A , AFEK A , SHOENFELD Y 
Published: November 2003

SUMMARY
Heparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder that occurs in ≈1% of patients treated with heparin. Affected patients commonly develop antibodies that recognize PF4/heparin complexes that may form on the surface of activated platelets and on the endothelium. However, it has not been established that anti-PF4/heparin antibodies are responsible for the clinical manifestations of HIT. To address this issue, we employed a recently developed model of active immunity to study the effect of IgG anti-PF4/heparin antibody in vivo. In previous studies we have shown that it is possible to induce autoimmune diseases such as systemic lupus erythematosus (SLE), anti-phospholipid syndrome (APS) or vasculitis in naive mice by active immunization with anti-DNA, anti-cardiolipin and anti-neutrophil cytoplasmic antibodies, respectively. Immunized animals develop anti-idiotypic antibodies (Ab2) and, after 2–4 months, anti-anti-idiotypic antibodies (Ab3). Ab3s generated in this manner often simulate the binding activity of Ab1 and their expression correlates with the development of specific clinical manifestations typical of the respective human disease. Based on this experience, naive BALB/c mice were immunized with IgG anti-PF4/heparin antibodies isolated from two patients with HIT. The actively immunized mice developed mouse anti-PF4/heparin antibody (Ab3). Administration of unfractionated heparin, but not low molecular weight heparin (LMWH), to the actively immunized animals induced thrombocytopenia by day 4 of drug exposure. There was no evidence of thrombosis. The results of this study support the importance of anti-PF4/heparin antibodies in the pathogenesis of HIT. Further, this model may help to elucidate the factors responsible for thrombosis as well as providing means to assess new treatment options for patients with this disorder.
Induction of proinflammatory cytokine and antioxidant enzyme gene expression following brief myocardial ischaemia
Authors: CHANDRASEKAR B , COLSTON J T , FREEMAN G L 
Published: November 2003

SUMMARY
The purpose of this study was to determine if proinflammatory cytokines are up-regulated during reperfusion following sublethal ischaemia, and whether concurrent up-regulation of antioxidant enzymes occurs. Open-chest rats were subjected to 15 min of ischaemia followed by 1 or 3 h reperfusion (R). Myocardium from the ischaemic zone showed a significantly higher (P &lt; 0·01) generation of thiobarbituric acid-reactive substances at 1 h and 3 h R. Northern blots showed a weak signal in controls for IL-6 mRNA (0·13 ± 0·01); this was elevated to 0·68 ± 0·12 at 1 h and 0·69 ± 0·10 at 3 h R. Neither IL-1β nor tumour necrosis factor-alpha (TNF-α) were detectable in controls. IL-1β rose to 0·78 ± 0·07 at 1 h and 0·51 ± 0·08 at 3 h R, and TNF-α rose to 0·69 ± 0·10 at 1 h and 0·38 ± 0·15 at 3 h R. Western blotting showed no signals in the control, but readily detectable signals at 1 h R; these remained high (IL-6) or decreased (IL-1β and TNF-α) at 3 h R. mRNA analysis for antioxidant enzymes revealed a weak signal in controls for catalase (CAT; 0·16 ± 0·08), glutathione peroxidase (GSH-Px; 0·15 ± 0·06) and superoxide dismutase (SOD; 0·21 ± 0·05). After 1 h R, levels increased significantly for CAT (0·46 ± 0·10; P &lt; 0·025) and GSH-Px (0·51 ± 0·13; P &lt; 0·01), but remained similar to controls for SOD (0·26 ± 0·15). At 3 h R the mRNA levels were significantly elevated for the three enzymes (CAT 0·48 ± 0·13; GSH-Px 0·47 ± 0·10; SOD 0·54 ± 0·08). We conclude that mRNA for proinflammatory cytokines is expressed early in reperfusion, and that the proteins are present in heart tissue. Also, reperfusion is associated with rapid expression of genes for antioxidant enzymes, which may enhance reactive oxygen intermediate (ROI) scavenging.
Colchicine derivatives inhibit neopterin production in human peripheral blood mononuclear cells (PBMC)
Authors: ALTINDAG Z Z , WERNER-FELMAYER G , SAHIN G , WACHTER H , FUCHS D 
Published: November 2003

SUMMARY
Colchicine is a microtubule disrupting agent, mostly used as treatment in various kinds of inflammatory diseases such as acute familial Mediterranean fever and Behcet's disease, as well as gout. In patients with familial Mediterranean fever treatment with colchicine induces a decline of urinary neopterin concentrations which indicates a decrease of cell-mediated immune activation. In this study, we investigated a potential effect of colchicine on the T cell/macrophage system in vitro. The human myelomonocytic cell line THP-1 and PBMC were treated with colchicine or the colchicine derivative, colcemide, in the presence or absence of 250 U/ml interferon-gamma (IFN-γ) or 10 μg/ml lipopolysaccharide (LPS) for 48 h or 96 h. Colchicine and colcemide increased neopterin/protein production in unstimulated THP-1 cells, but no such effect was apparent in cells stimulated with IFN-γ. By contrast, when PBMC were treated with colchicine or colcemide a significant reduction in neopterin formation was evident in cells without and with prestimulation by IFN-γ or LPS. In parallel, reduced production of IFN-γ was observed in PBMC. These data suggest that colchicine and colcemide are able to inhibit T cell activation within the cellular immune response.
Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1
Authors: BAUER L , BOHLE B , JAHN-SCHMID B , WIEDERMANN U , DASER A , RENZ H , KRAFT D , EBNER C 
Published: November 2003

SUMMARY
Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mice was identified by the use of overlapping peptides. This peptide (BV139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.
Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells
Authors: AROSA F A , OLIVEIRA L , PORTO G , DA SILVA B M , KRUIJER W , VELTMAN J , DE SOUSA M 
Published: November 2003

SUMMARY
The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.
Calorie restriction decreases platelet-derived growth factor (PDGF)-A and thrombin receptor mRNA expression in autoimmune murine lupus nephritis
Authors: TROYER D A , CHANDRASEKAR B , BARNES J L , FERNANDES G 
Published: November 2003

SUMMARY
Calorie restriction (CR) and supplementation with fish oil (FO) are known to increase the life span and diminish histological evidence of glomerulonephritis in lupus prone (NZB×NZW)Fl (B/W) mice. Cellular proliferation is an important pathological element in the development of lupus nephritis, and we have examined the expression of thrombin receptor (TR) and the mitogenic agents PDGF-A and -B. Weanling B/W mice were fed either ad libitum or a calorie restricted (CR; 40% less calories than ad libitum) diet supplemented with either 5% (w/w) corn oil (CO) or FO. CR animals consumed 2·7–3·0 g of wet food per day versus 4·5–5·0 g for the ad libitum animals. Renal RNA was extracted from young (3·5–4·0 months of age) and old (8–10 months of age) mice. Densitometric analysis (reference gene GAPDH) of blots from Northern (PDGF-A and -B) and ribonuclease protection assays (TR) produced the following data: (i) in young mice no signal was detected for PDGF-A, -B and TR in all four groups, while the signals were readily detectable in old mice; (ii) in old mice low and similar levels of PDGF-B were detected, and neither CR nor the source of lipid altered its expression; (iii) CR significantly inhibited PDGF-A and TR expression in both CO (ad libitum versus CR; PDGF-A, 3·25-fold, P&lt;0·025; TR, 3·7-fold, P&lt;0·01) and FO (ad libitum versus CR; PDGF-A, 4·56-fold, P&lt;0·01; TR, 3·6-fold, P&lt;0·025) groups; (iv) although FO (versus CO) produced a trend towards decreased expression, results were not statistically significant. We conclude that suppression of renal disease in lupus-prone mice by CR is accompanied by decreased expression of PDGF-A and the thrombin receptor.
Enrichment of antibodies against phospholipids in circulating immune complexes (CIC) in the anti-phospholipid syndrome (APLS)
Authors: ÅRFORS L , LEFVERT A K 
Published: November 2003

SUMMARY
The aim of this study was to analyse and characterize immunoglobulins in CIC and serum from patients with anti-cardiolipin antibodies. CIC from five patients were isolated by gradient centrifugation and gel filtration. The distribution between serum and CIC of immunoglobulin reactivity against different phospholipids was determined. Serum and CIC contained antibodies against cardiolipin and other negatively charged phospholipids. The relative concentration of these antibodies was higher in the immune complexes than in corresponding sera, and the avidity of antibodies in immune complex form was higher. The presence of high concentrations of antibodies to negatively charged phospholipids in CIC from patients with anti-cardiolipin antibodies could be of pathogenic significance in APLS by conferring characteristics to the complexes of importance for binding to membrane components. This could have special implications with regard to platelet and complement activation, thrombocytopenia and thrombophilia.