bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFα*2 marks high risk of severe disease duringPlasmodium falciparummalaria and other infections in Sri Lankans
Authors: WATTAVIDANAGE J , CARTER R , PERERA K L R L , MUNASINGHA A , BANDARA S , MCGUINNESS D , WICKRAMASINGHE A R , ALLES H K , MENDIS K N , PREMAWANSA S 
Published: March 2003

SUMMARYWe have investigated the association between alleles of the genes for tumour necrosis factor-alpha (TNF-α) and TNF-β and severity of disease during malarial (Plasmodium falciparum) and other infections in the Sri Lankan population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicated infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-α and TNF-β allelic types were identified using the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes and restriction enzyme digestion. The odds in favour of carrying the TNFα*2 allele, mainly of the heterozygous genotype (TNFα*1,*2), were two to three times greater among individuals with severe disease, of either malarial or other infectious origin, relative to healthy controls or to those with uncomplicated malarial infections. No significant risk was associated with either of the alleles of TNF-β.
Conformationally altered β2-glycoprotein I is the antigen for anti-cardiolipin autoantibodies
Authors: CHAMLEY L W , DUNCALF A M , KONARKOWSKA B , MITCHELL M D , JOHNSON P M 
Published: March 2003

SUMMARYAnti-cardiolipin autoantibodies (aCL) induce thrombosis and recurrent fetal death. These antibodies require a ‘cofactor’, identified as β2-glycoprotein I (β2-GPI), to bind phospholipids. We show here that aCL can bind β2-GPI in the absence of phospholipid. Binding of aCL to β2-GPI is dependent upon the β2-GPI being immobilized on an appropriate surface including cardiolipin, irradiated polystyrene and nitrocellulose membrane. This effect cannot be explained by increased antigen density of β2-GPI immobilized on these surfaces. Rather, conformational changes that occur following the interaction of β2-GPI with phospholipid render this protein antigenic to aCL. Liquid-phase β2-GPI was not antigenic for aCL. Thus, aCL cannot bind circulating β2-GPI. These findings may explain why patients with aCL can remain healthy for many years but then undergo episodes of thrombosis or fetal loss without changes in their circulating aCL profile, as the triggering event for these pathologies can be predicted to be one that renders β2-GPI antigenic for aCL.
Cytokine flow cytometry differentiates the clinical status of multiple sclerosis (MS) patients
Authors: INOGÉS S , MERINO J , BANDRÉS E , DE CASTRO P , SUBIRÁ M L , SÁNCHEZ-IBARROLA A 
Published: March 2003

SUMMARYIn this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-γ) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P &lt; 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-γ was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-β of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients.
Increased bcl-2 expression in lymphocytes and its association with hepatocellular damage in patients with autoimmune hepatitis
Authors: YACHIDA M , KUROKOHCHI K , ARIMA K , NISHIOKA M 
Published: March 2003

SUMMARYThe proto-oncogene product bcl-2 is known to inhibit apoptotic cell death, and its dysregulation might play a critical role in the development of autoimmune disease. To elucidate the role of bcl-2 in autoimmune hepatitis (AIH), its expression in peripheral blood mononuclear cells (PBMC) and in liver-infiltrating lymphocytes (LIL) was investigated. Increased bcl-2 expression in PBMC was found in AIH patients compared with that in chronic hepatitis C (CHC) patients and in healthy controls. The level of bcl-2 expression significantly correlated with serum ALT level. Further analysis showed that CD4+ T cells are enriched in bcl-2-expressing PBMC. To characterize the Th1/Th2 profile of bcl-2-expressing CD4+ T cells, intracellular interferon-gamma (IFN-γ) and IL-4 were analysed. The results revealed that most of the bcl-2-expressing cells were found to be IFN-γ-secreting Th1 cells. In three patients for whom their clinical courses could be followed, bcl-2 expression was decreased after the initiation of immunosuppressive therapy with corticosteroids. However, the level of IFN-γ+ cells was not altered. Immunohistochemical analysis also showed that large amounts of bcl-2+ cells were observed in periportal area in the liver. In conclusion, bcl-2-expressing cells were shown to be increased in peripheral blood and liver in AIH and the bcl-2 product was expressed mainly in CD4+ Th1-type cells, suggesting that these cells might promote the cellular immune response and contribute to the development of hepatitis and hepatocellular damage in AIH.
Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment
Authors: TAMURA J , KUBOTA K , MURAKAMI H , SAWAMURA M , MATSUSHIMA T , TAMURA T , SAITOH T , KURABAYSHI H , NARUSE T 
Published: March 2003

SUMMARYIt has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3−CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity.
Effects of glycyrrhizin, an active component of licorice roots, onCandida albicansinfection in thermally injured mice
Authors: UTSUNOMIYA T , KOBAYASHI M , HERNDON D N , POLLARD R B , SUZUKI F 
Published: March 2003

SUMMARYDue to the generation of burn-associated CD8+ CD11b+ TCR γ/δ+ type 2 T cells (burn-associated type 2 T cells), the susceptibility of thermally injured mice to infection with C. albicans has been shown to be increased by up to 50-fold when compared with normal mice. Glycyrrhizin (GR), an active component of licorice roots, reduced the susceptibility of thermally injured mice to C. albicans infection to levels observed in normal mice. Thermally injured mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C. albicans infection. The following demonstrated that susceptibility to fungal infection was similar in thermally injured mice and normal mice inoculated with T6S cells (a clone of burn-associated type 2 T cells). This susceptibility of T6S mice (normal mice inoculated with T6S cells) was reversible by (i) administration of GR, (ii) inoculation of CD4+ T cells from GR-treated mice, and (iii) injection of a mixture of MoAbs targeted against type 2 cytokines (IL-4 and IL-10). After stimulation with anti-CD3 MoAb, splenic T cells from thermally injured and T6S mice, treated with GR or inoculated with CD4+ T cells from GR-treated mice, did not have type 2 cytokines in culture supernatants. They were present in splenic T cell cultures from thermally injured and T6S mice that were treated with saline or inoculated with naive T cells. These results suggest that GR, by inducing CD4+ T cells which suppress type 2 cytokines produced by burn-associated type 2 T cells, improves the resistance of thermally injured mice to C. albicans. An anti-type 2 T cell action of the CD4+ T cells derived from GR-treated mice was previously described.
Nitrotyrosine formation after activation of murine macrophages with mycobacteria and mycobacterial lipoarabinomannan
Authors: VENKATAPRASAD N , RIVEROS-MORENO V , SOSNOWSKA D , MORENO C 
Published: March 2003

SUMMARYMurine peritoneal macrophages, elicited with thioglycollate, were stimulated in vitro with lipopolysaccharide (LPS). The production of nitrite, superoxide anion (SOA), and the accumulation of nitrotyrosine in the cells increased after treatment, and all were inhibitable by the NO synthase inhibitor NG-monomethyl-l-arginine monoacetate (l-NMMA). This effect suggests a direct correlation between the accumulation of those metabolites and NO synthase activity. Lipoarabinomannan (LAM) purified from Mycobacterium tuberculosis was added to peritoneal macrophages in the presence of interferon-gamma (IFN-γ); the cells produced nitrite and SOA, both inhibitable by l-NMMA. There was, as well, accumulation of nitrotyrosine in the macrophage proteins. Strikingly, the amount of nitrotyrosine measured after LAM plus IFN-γ, or LAM plus the low molecular weight adjuvant glutamylmuramyl dipeptide (GMDP), increased significantly in the presence of l-NMMA. These results suggest that murine macrophages, upon LAM stimulation, might generate reactive nitrogen metabolites by a route other than NO synthase. Nitrotyrosine accumulation after infection of macrophages in vitro, with either live bacille Calmette–Guérin (BCG) or live M. tuberculosis, in the presence or absence of IFN-γ, showed no correlation with nitrite production, suggesting a low superoxide production.
Anti-tissue transglutaminase, anti-endomysium and anti-R1-reticulin autoantibodies—the antibody trinity of coeliac disease
Authors: LOCK R J , GILMOUR J E M , UNSWORTH D J 
Published: March 2003

SUMMARY
Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase.
Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection
Authors: JOBE O , ARIYOSHI K , MARCHANT A , SABALLY S , CORRAH T , BERRY N , JAFFAR S , WHITTLE H 
Published: March 2003

AbstractProviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21.1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22.1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0.02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-γ) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.
In vivomodulation of cytokine synthesis by intravenous immunoglobulin
Authors: SEWELL W A C , NORTH M E , CAMBRONERO R , WEBSTER A D B , FARRANT J 
Published: March 2003

AbstractWe examined the effects of intravenous immunoglobulin (IVIG) on cytokine regulation in vivo using samples taken before and after replacement-dose (200–400 mg/kg) IVIG in a group of patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). The intracellular cytokine content of CD4+ and CD8+ lymphocytes, and their CD28+/− subsets, were measured following in vitro activation with phorbol myristate acetate (PMA) and ionomycin. The cytokines IL-2, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), and the early activation marker CD69, were assessed by four-colour flow cytometry of whole blood cultures taken before and after IVIG infusion. There was a significant increase in IL-2 expression in CD4+ (and CD4+28−) cells and an increase in TNF-α expression in CD8+28− cells following IVIG in CVID, but not in XLA patients. IFN-γ and CD69 expression were not affected by IVIG infusion. This increase in TNF-α and IL-2, combined with unchanged IFN-γ expression, is evidence against the putative ‘anti-inflammatory’ role of IVIG, and may explain the failure of resolution of granulomata in CVID patients treated with IVIG alone.
Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1α may be involved in the development of pulmonary fibrosis
Authors: HASEGAWA M , SATO S , TAKEHARA K 
Published: March 2003

SUMMARYTo determine the role of chemokines in the pathogenesis of systemic sclerosis (SSc), we examined serum levels, spontaneous production by peripheral blood mononuclear cells (PBMC), and histological distribution in the affected skin, of MCP-1, MIP-1α and MIP-1β in SSc patients. Serum levels of these chemokines were examined by ELISA in 58 patients with SSc and 20 normal controls. The levels of these chemokines in culture supernatants from PBMC were also measured by ELISA. Serum levels and spontaneous production levels by PBMC of MCP-1, MIP-1α, and MIP-1β were significantly elevated in patients with SSc compared with normal controls. Elevated serum levels of MCP-1 and MIP-1α significantly correlated with the presence of pulmonary fibrosis. MCP-1 expression in the skin of SSc was immunohistochemically examined using anti-MCP-1 MoAb. MCP-1 was strongly expressed in the epidermis, inflammatory mononuclear cells, and vascular endothelial cells in the sclerotic skin of SSc patients, but not expressed in any control skin. Furthermore, the MCP-1 expression in inflammatory mononuclear cells and endothelial cells significantly correlated with earlier onset of SSc. Thus, MCP-1, MIP-1α and MIP-1β may be involved in the disease process, possibly by augmenting leucocyte migration into the affected tissues in SSc. Furthermore, MCP-1 and MIP-1α may play an important role in the development of pulmonary fibrosis in SSc.
Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression
Authors: KRAUSE I , BLANK M , LEVI Y , KOIKE T , BARAK V , SHOENFELD Y 
Published: March 2003

SUMMARYMice with experimental anti-phospholipid syndrome (APS), induced by active immunization with a human anti-cardiolipin MoAb (H-3), were treated with mouse anti-idiotypic MoAb (anti-H3, named S2.9) and with an irrelevant anti-idiotype. The immunized mice produced high titres of mouse anti-cardiolipin antibodies along with clinical manifestations of experimental APS: prolonged activated partial thromboplastin time (aPTT), thrombocytopenia and high rate of fetal loss. Treatment with the specific anti-Id (S2.9) as a whole molecule or F(ab)2 fraction, resulted in a decrease in serum levels of the anti-cardiolipin antibodies, rise in platelet count, shortened aPTT and reduced rate of fetal loss. The anti-Id effect was associated with a rise in the number of IL-2 and interferon-gamma (IFN-γ)-secreting cells (Th1) and reduction in IL-4- and IL-6-secreting cells (Th2). The beneficial effect of the anti-Id treatment in mice with experimental APS induced by active immunization with an idiotype further supports the idiotypic aetiology of experimental APS and points to the role of Th1 cytokines in suppression of its manifestations.
Immunogenetic risk factors for anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis
Authors: Gencik M , Borgmann S , Zahn R , Albert E , Sitter T , Epplen J T , Fricke H 
Published: March 2003

SUMMARYWegener's granulomatosis (WG) and microscopic polyangiitis are systemic autoimmune diseases characterized by the presence of ANCA in the sera of patients. Little is known about the aetiologic factors and genetic predisposition as well as the pathogenesis of these disease entities. A slightly decreased representation of HLA-DRB1*13 and HLA-DQB1*0603 individuals was observed in our cohort of ANCA-associated systemic vasculitis (AASV) patients compared with controls. In addition, HLA-DRB1*04 individuals were over-represented in a subgroup of patients with WG in end-stage renal disease as a result of renal vasculitis. In order to identify other genes relevant for these diseases, we investigated highly polymorphic markers in the vicinity of several immunorelevant genes, i.e. tumour necrosis factor (TNF)α, IL-2, IL-5 receptor α (IL-5RA), in a group of 102 patients with AASV and compared the representation with controls. Furthermore, functional polymorphisms were directly analysed in the promotor region of TNFα as well as in the coding region of the FcγIIRA genes. Polymorphisms of the TNFα promotor (TNF-308) as well as in the FcγIIRA gene were excluded as risk factors for the disease in our cohort. No major phenotype distribution differences were observed between patients and controls for the IL-2 and IL-5RA microsatellites. Most importantly, several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)-ANCA+ AASV. Thus, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASV patients.
Natural killer cells in cross-regulation of IL-12 by IL-10 inLeishmaniaantigen-stimulated blood donor cells
Authors: Akuffo H , Alexis A , Eidsmo L , Saed A , Nylén S , Maasho K 
Published: March 2003

SUMMARYWe have previously shown that natural killer (NK) cells play a role in protection against leishmaniasis. Furthermore, we have shown that NK cells in mononuclear cells derived from unexposed donors are induced to proliferate in vitro in response to leishmanial antigens. Since interleukin (IL)-12, a strong inducer of NK cells, acts on the early events in NK cells and T-cells, and is considered as an adjuvant for use in a potential antileishmaniasis antigen, we wished to investigate how this cytokine influences the in vitro Leishmania induced proliferative and cytokine response in healthy donors. We demonstrate that in an innate response to Leishmania antigen involving NK cells, a critical level of IL-12 is required to induce interferon (IFN)-γ secretion below which, IL-10 is released in amounts which apparently inhibit IFN-γ secretion and cellular proliferation. However, at higher IL-12 levels, there is simultaneous secretion of IFN-γ and IL-10 as well as proliferation of cells. In a similar vein, exogenous IL-10 in turn inhibited IFN-γ secretion as well as proliferation when used at low/medium concentrations, but at high concentrations this effect was abolished and replaced by the simultaneous detection of IFN-γ, IL-10 and proliferation. The contribution of NK cells in cross regulation of these two very important immuneregulatory cytokines and the effect of exogenous IL-12 in a Leishmania driven response are discussed.
Clinical and immunological evaluation of patients with mild IgG1 deficiency
Authors: Van Kessel D A , Horikx P E , Van Houte A J , De Graaff C S , Van Velzen-Blad H , Rijkers G T 
Published: March 2003

SUMMARY
Serum IgG subclass concentrations were determined in patients visiting, the pulmonology out-patient clinic with chronic respiratory tract problems. A total of 24 patients with a serum IgG1 concentration &lt; 4.9 g/l (i.e. below the reference range) and normal values for IgG2, IgM and IgA were included. Patients with a selective IgG1 deficiency were vaccinated with a 23-valent pneumococcal polysaccharide vaccine. There were nine patients with a poor antibody response to pneumococcal capsular polysaccharide antigens. Responsiveness to protein antigens was intact in all patients. Patients with pneumonia showed a significantly lower anti-polysaccharide response in the IgG2 subclass than patients without pneumonia. Patients with recurrent sinusitis showed a significantly lower response in the IgA isotype after vaccination with pneumococcal polysaccharide vaccine compared with non-sinusitis patients. It can be concluded that patients with recurrent sinopulmonary infections and a mild IgG1 subclass deficiency have an impaired IgG1 anti-polysaccharide response, which can extend to decreased IgG2 and IgA anti-polysaccharide responses.