bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer (NK) T cells are significantly decreased in the peripheral blood of patients with rheumatoid arthritis (RA)
Authors: Yanagihara Y , Shiozawa K , Takai M , Kyogoku M , Shiozawa S 
Published: March 2003

SUMMARYThe number of NK T cells was measured in relation to the Th1/Th2 imbalance observed in RA. Peripheral blood samples of patients with RA (n = 60) and healthy controls (n = 36) were stained with anti-NK receptor 1A (anti-NKR-P1A), anti-CD56, and anti-CD3 MoAbs, and examined by three-colour flow cytometry. NK T (NKR-P1A+CD3+) cells in the peripheral blood were decreased in RA compared with the controls: 25 ± 20/μl versus 143 ± 53/μl (P &lt; 0.0001). CD56+CD3+ cells were also decreased in RA: 60 ± 46/μl versus 116 ± 54/μl (P &lt; 0.0001). The decrease was significant when adjusted to the number of total lymphocytes (P &lt; 0.0001) or NK (CD56+CD3−) cells (P &lt; 0.0001), and showed no correlation with age, sex, disease duration, disease activity, functional class, x-ray stage, drug treatment, joint score, grip strength, C-reactive protein, rheumatoid factor or erythrocyte sedimentation rate of the patients. The results show that the levels of NK T cells are depressed in the peripheral blood of patients with RA, suggesting that the measurement of NK T cells in peripheral blood may have clinical importance for a Th1-type autoimmune disease like RA.
A switch towards Th2 during serological rebound in children with congenital toxoplasmosis
Authors: Kahi S , Cozon G J N , Pinon J M , Greenland T , Wallon M , Al Kurdi M , Ferrandiz J , Peyron F 
Published: March 2003

SUMMARYSerological rebounds occur frequently in patients with congenital toxoplasmosis, but remain poorly understood. A link between Th1 and Th2 cytokines and the pathophysiology of infectious diseases has been reported. Production of interferon-gamma (IFN-γ) and IL-4 in supernatants of whole blood after in vitro specific Toxoplasma gondii stimulation and serum-specific IgE levels were studied in 31 congenitally infected children. IFN-γ was produced at higher levels by lymphocytes from children with stable congenital toxoplasmosis (n = 18) than from children showing serological rebound (n = 13) (P &lt; 0.04). Conversely, supernatants from children with serological rebound showed higher levels of IL-4 than those from children with stable congenital toxoplasmosis (P &lt; 0.03). The polarized Th2 response was confirmed by a greater (IL-4:IFN-γ) × 100 ratio (P &lt; 0.0001) and production of T. gondii-specific IgE in six out of 13 children showing serological rebound. These results suggest a role of Th2 cytokines in destabilization of congenital toxoplasmosis and perhaps in local reactivation of the parasite.
Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes
Authors: Klein R , Zanger U M , Berg T , Hopf U , Berg P A 
Published: March 2003

SUMMARY
Anti-liver-kidney microsome antibodies (anti-LKM) occur in autoimmune hepatitis (AIH) type II and in a subset of patients with hepatitis C. Anti-LKM1 in AIH are directed against cytochrome P4502D6 (CYP2D6), but conflicting data exist concerning the specificity of anti-LKM in hepatitis C. The aim of this study was to evaluate binding specificities of anti-LKM antibodies in both diseases using novel test antigens as well as their inhibitory capacity on CYP2D6 enzyme activity. Sera from 22 patients with AIH type II and 17 patients with hepatitis C being anti-LKM-positive in the immunofluorescence test were investigated for binding to native recombinant CYP2D6 and liver microsomes by ELISA and immunoblotting, and to synthetic peptides covering the region 254–339 (254–273, 257–269, 270–294, 291–310, 307–324, 321–339, 373–389) as well as the novel peptide 196–218 by ELISA. Furthermore, all sera were tested for inhibition of CYP2D6-dependent bufuralol 1′-hydroxylase activity. Twenty of the 22 AIH type II sera (91%) and nine of the 17 hepatitis C sera (53%) were positive for CYP2D6 by ELISA and/or immunoblotting. The previously described major peptide epitope comprising CYP2D6 amino acids 257–269 was recognized by 16 of the 22 AIH sera but by only one hepatitis C serum. A further epitope, 196–218, could be defined for the first time as another immunodominant epitope for AIH because it was recognized by 15 of the 22 AIH (68%) but only three of the 17 hepatitis C sera (18%). With the exception of the peptide 254–273, the other peptides showed no significant reactivity. Analysing the inhibitory properties of anti-LKM antibodies it emerged that 95% of AIH sera and 88% of hepatitis C sera inhibited enzyme function. These data indicate that anti-LKM antibodies in AIH and hepatitis C react with CYP2D6, as shown by their inhibitory activity, and that besides the known epitope 257–269 a further immunodominant epitope exists on CYP2D6 which is recognized by sera from patients with AIH II but hardly by sera from patients with hepatitis C.
Comparative analysis of epitope recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different autoimmune disorders
Authors: Powers A C , Bavik K , Tremble J , Daw K , Scherbaum W A , Banga J P 
Published: March 2003

SUMMARYAutoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221–359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453–569). Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. Amino acids 270–359 (IDDM-E1) are targeted by one APS2 IgG antibody and MICA-4, while two other APS2 IgG antibodies, MICA-2 and MICA-3, target amino acids 443–585 (IDDM-E2). Using GAD65/67 chimera that span the IDDM-E2 region, we found that MICA-2 binds amino acids 514–528 of GAD65, but two APS2 IgG antibodies require this region and amino acids 529–570. In contrast, the binding of MICA-3 requires two discontinuous amino acid segments of GAD65 (452–513 and 528–569), but not amino acids 514–528. These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM.
Properdin deficiency in a large Swiss family: identification of a stop codon in the properdin gene, and association of meningococcal disease with lack of the IgG2 allotype marker G2m(n)
Authors: Späth P J , Sjöholm A G , Fredrikson G , Misiano G , Scherz R , Schaad U B , Uhring-Lambert B , Hauptmann G , Westberg J , Uhlén M , Wadelius C , Truedsson L 
Published: March 2003

SUMMARYProperdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was &lt; 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin-deficient males in the family had survived meningitis caused by Neisseria meningitidis serogroup B without sequel. Two point mutations were identified when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase chain reaction (PCR) products. The critical mutation was found at base 2061 in exon 4, where the change of cytosine to thymine had generated the stop codon TGA. The other mutation was positioned at base 827 in intron 3. The stop codon in exon 4 was also demonstrated by standard dideoxy sequencing in three additional family members. The question was asked if genetic factors such as partial C4 deficiency and IgG allotypes could have influenced susceptibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-deficient males with meningitis differed from the other properdin-deficient persons in that they lacked the G2m(n) allotype, a marker known to be associated with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by independent factors influencing the immune response.
Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-γ)
Authors: Ochiai K , Tanabe E , Ishihara C , Kagami M , Sugiyama T , Sueishi M , Koya N , Tomioka H 
Published: March 2003

SUMMARYThe purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN-γ receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti-CD16 magnetic bead-negative selection. IFN-γ significantly up-regulated survival and CD69 expression in 24–48 h cultured eosinophils. Further, IFN-γ induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG-490 inhibited the tyrosine phosphorylation of JAK2, IFN-γ-induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN-γ induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN-γ–IFN-γR interaction.
Circulating antibodies against α-enolase in patients with primary membranous nephropathy (MN)
Authors: Wakui H , Imai H , Komatsuda A , Miura A B 
Published: March 2003

SUMMARY
MN is characterized by the glomerular deposition of IgG4 immune complexes. This suggests that nephritogenic immune responses in MN are of the Th2 T helper cell type; however, the pathogenesis of MN is still unknown. In this study we examined sera from patients with primary MN for antibodies to renal proteins. A 47-kD protein in both human and porcine renal extracts was found by immunoblotting to react specifically with serum IgG from some patients. This protein was purified from porcine kidney and identified as α-enolase on the basis of its partial amino acid sequences. Sera from 87 patients with primary MN, 24 patients with secondary MN (15 rheumatoid arthritis patients, nine systemic lupus erythematosus patients), and 16 healthy subjects were examined by ELISA using purified α-enolase. In 60 (69%) patients with primary MN and 14 (58%) patients with secondary MN, the measured optical density values, and hence serum anti-α-enolase antibody levels, were greater than the mean + 2 s.d. of healthy subjects. Immunoblot analysis showed that IgG1 or IgG3 was the predominant subclass (Th1 T helper cell type subclass) of antibodies against α-enolase in patients with primary and secondary MN. Since circulating antibodies against α-enolase have recently been reported in patients with various autoimmune disorders, our results suggest that a number of patients with presumed primary MN may also have abnormalities in Th1 T helper cell-mediated immune responses.
Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients withStaphylococcus aureusbacteraemia with or without endocarditis
Authors: Söderquist B , Sundqvist K-G , Vikerfors T 
Published: March 2003

SUMMARYThe aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-α) concentrations were significantly correlated (P &lt; 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.
Serum thrombomodulin—a reliable marker of disease activity in systemic lupus erythematosus (SLE): advantage over established serological parameters to indicate disease activity
Authors: Boehme M W J , Raeth U , Galle P R , Stremmel W , Scherbaum W A 
Published: March 2003

SUMMARYTo date no specific serological parameter is available to assess disease activity in SLE. Soluble serum thrombomodulin is a new marker of endothelial cell injury and vasculitis. The objective of this study was to compare in vivo soluble thrombomodulin as marker of disease activity in SLE with established and recent serological parameters. One hundred and twenty-four sera of 30 patients with proven SLE with different disease activities were tested for serum levels of thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), IL-2R, IL-6, IL-10, dsDNA by ELISA and dsDNA additionally by radioimmunoassay (RIA). C-reactive protein (CRP), complement component C3, IgG, creatinine, anti-nuclear antibodies (ANA) and intermediate filament antibodies were measured by standard laboratory tests. The clinical disease activity was evaluated by the Systemic Lupus Activity Measure (SLAM). Correlations of the different serological SLE disease activity parameters with the SLAM scores revealed the highest significance for serum thrombomodulin (correlation coefficient 0.82). This was further confirmed by the intra-individual analysis of follow-up sera. In addition, a moderate correlation could be found for IL-6, IL-10, ICAM-1, CRP and erythrocyte sedimentation rate (ESR). In summary, soluble thrombomodulin is the most important serological parameter of disease activity in SLE currently available, as shown by the in vivo studies. Soluble thrombomodulin might be a valuable serological parameter for therapeutical considerations.
Virulent or avirulent (dhfr-ts−)Leishmania majorelicit predominantly a type-1 cytokine response by human cellsin vitro
Authors: Brodskyn C , Beverley S M , Titus R G 
Published: March 2003

SUMMARYIn this study we have compared the immune response of normal human cells cultured in vitro to two virulent strains of Leishmania major (CC1 and LV39), and to an avirulent vaccine strain (dhfr-ts−) made by targeted deletion of the essential gene DHFR-TS. We utilized an in vitro system in which naive T cells from normal human donors were primed with autologous Leishmania-infected macrophages. All three parasites infected macrophages and transformed into amastigotes within the cells. However, whereas LV39 and CC1 replicated in macrophages, dhfr-ts− did not. When peripheral blood lymphocytes (PBL) were stimulated with autologous macrophages infected with any of the three parasites, the lymphocytes produced a type-1-biased cytokine response. Finally, addition of IL-12 during the first stimulation period increased the production of interferon-gamma but decreased IL-5 secretion. On the other hand, anti-IL-12 resulted in the opposite effect.
Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes againstTrichosporon asahii
Authors: Sasaki E , Tashiro T , Kuroki M , Seki M , Miyazaki Y , Maesaki S , Tomono K , Kadota J-I , Kohno S 
Published: March 2003

SUMMARYTrichosporon asahii is an emerging opportunistic pathogen in immunocompromised patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral blood monocytes and murine peritoneal macrophages against T. asahii isolates, and the effects of M-CSF on the anti-fungal activity of mononuclear phagocytes. We also established a neutropenic mouse model of disseminated trichosporonosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity of mononuclear cells, and infected mice treated with human M-CSF at 10 × 106 U/kg showed a significant improvement in survival rate, with fewer fungal colony counts in the lung compared with control mice. Mice treated with human M-CSF showed higher concentrations of tumour necrosis factor-alpha (TNF-α) in the lung and plasma compared with control mice. The survival rate was significantly reduced in mice treated with anti-mouse TNF-α. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-α, and suggest that the administration of M-CSF to patients with disseminated trichosporonosis may be a useful adjunct to conventional anti-microbial therapy and prophylaxis.
Identification of distinct lymphocyte subsets responding to subcellular fractions ofMycobacterium bovisbacille Calmette–Guérin (BCG)
Authors: Batoni G , Esin S , Pardini M , Bottai D , Senesi S , Wigzell H , Campa M 
Published: March 2003

SUMMARYIn order to investigate the ability of Mycobacterium bovis BCG vaccination to induce immune responses toward different classes of mycobacterial antigens and the cell populations involved in such responses, proliferation of distinct human lymphocyte subsets from BCG-vaccinated donors in response to different subcellular fractions of BCG was analysed and compared with that of not sensitized subjects. Proliferation of different cell subsets was evaluated by flow cytometric determination of bromodeoxyuridine incorporated into DNA of dividing cells and simultaneous identification of cell surface markers. Although a certain degree of variability was observed among different donors, after 6 days of in vitro stimulation BCG-vaccinated subjects displayed, as a mean, a stronger blastogenic response to all the classes of antigens compared with non-sensitized ones. PPD, culture filtrates and membrane antigens induced a predominant proliferation of CD4+ T cells. In contrast, preparations enriched in cytosolic antigens elicited strong proliferation of γδ+ T cells which, as a mean, represented 55% of the proliferating cells. Although to a lesser extent, proliferation of γδ+ T cells was also elicited by preparations enriched in membrane and cell wall antigens. In response to the latter preparation proliferation of CD4+ T cells and CD16+/CD3− (natural killer (NK)) cells was observed, as well. In particular, cell wall antigens were found to induce significantly higher levels of proliferation of NK cells compared with all the other classes of antigens.
Immune response of tonsillar lymphocytes toHaemophilus parainfluenzaein patients with IgA nephropathy
Authors: Suzuki S , Fujieda S , Sunaga H , Sugimoto H , Yamamoto C , Kimura H , Abo T , Gejyo F 
Published: March 2003

SUMMARYThe pathogenesis of IgA nephropathy (IgAN) is unclear. We have previously shown glomerular deposition of Haemophilus parainfluenzae (HPI) antigens and the presence of IgA antibody against HPI antigens in patients with IgAN. We examined the immune response to HPI antigens in tonsillar lymphocytes from patients with IgAN. Lymphocytes isolated from the palatine tonsils of 13 IgAN patients and 16 patients with chronic tonsillitis but without renal disease were used as controls. We examined lymphocyte proliferation and production of IgA antibody against HPI antigens by measuring thymidine uptake and IgA antibody in culture supernatants after lymphocyte incubation with HPI antigens. Patients with IgAN showed a significantly higher stimulation index to HPI antigens (thymidine incorporation in tonsillar lymphocytes with HPI/thymidine incorporation in unstimulated tonsillar lymphocytes) than controls (P &lt; 0.002). Lymphocytes from patients with IgAN also showed a significantly higher level of IgA antibody and IgA1 antibody against HPI antigens in culture supernatants than lymphocytes from controls (P = 0.0002 and P = 0.004, respectively). Our results suggest that HPI antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that an immune response to HPI antigens may play a role in the pathogenesis of this disease in some cases.
Trypanosoma cruzi-induced immunosuppression: B cells undergo spontaneous apoptosis and lipopolysaccharide (LPS) arrests their proliferation during acute infection
Authors: Zuñiga E , Motran C , Montes C L , Diaz F L , Bocco J L , Gruppi A 
Published: March 2003

SUMMARYAcute infection with Trypanosoma cruzi is characterized by multiple manifestations of immunosuppression of both cellular and humoral responses. B cells isolated at the acute stage of infection have shown marked impairment in their response to polyclonal activators in vitro. The present work aims at studying the B cell compartment in the context of acute T. cruzi infection to provide evidence for B cell activation, spontaneous apoptosis and arrest of the cell cycle upon mitogenic stimulation as a mechanism underlying B cell hyporesponse. We found that B cells from acutely infected mice, which fail to respond to the mitogen LPS, showed spontaneous proliferation and production of IgM, indicating a high level of B cell activation. Furthermore, these activated B cells also exhibited an increase in Fas expression and apoptosis in cultures without an exogenous stimulus. On the other hand, B cells from early acute and chronic infected mice did not present activation or apoptosis, and were able to respond properly to the mitogen. Upon in vitro stimulation with LPS, B cells from hyporesponder mice failed to progress through the cell cycle (G0/G1 arrest), nor did they increase the levels of apoptosis. These results indicate that B cell apoptosis and cell cycle arrest could be the mechanisms that control intense B cell expansion, but at the same time could be delaying the emergence of a specific immune response against the parasite.
Cultured human monocytes secrete fibronectin in response to activation by proinflammatory cytokines
Authors: Kitamura N , Nishinarita S , Takizawa T , Tomita Y , Horie T 
Published: March 2003

SUMMARYWe studied the effects of the cytokines IL-1α, IL-6, tumour necrosis factor-alpha (TNF-α), IL-4, IL-10, IL-13 and transforming growth factor-beta (TGF-β) on fibronectin (FN) production by cultured-human monocytes. IL-1α, IL-6 and TNF-α all increased FN production, an indicator of monocyte activation. These cytokines increased FN production in a dose-dependent fashion, with a 4-h treatment being sufficient to measure FN production by radioimmunoassay. Conversely, IL-4, IL-10 and IL-13 strongly inhibited cytokine-induced FN production, while TGF-β only partially inhibited FN production. The combination of suboptimal doses of cytokines (IL-1α+ IL-6, IL-1α+ TNF-α, IL-6 + TNF-α), which could not singly induce substantial amounts of FN, were able to induce FN production by cultured monocytes. Northern blot analysis with a cDNA specific for FN confirmed the expression of FN mRNA in cultured monocytes stimulated with a single cytokine or a combination of cytokines. Our data demonstrate that monocytes may not always require high concentrations of cytokines for activation in vitro, and that the synergistic or additive action of low levels of cytokines on monocyte activation may be sufficient to promote immune or inflammatory reactions. Our data also suggest that certain T cell cytokines may regulate monocyte activation.