bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expression of IL-2, IL-4 and interferon-gamma (IFN-γ) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B
Authors: Fukuda R , Ishimura N , Nguyen TX , Chowdhury A , Ishihara S , Kohge N , Akagi S , Watanabe M , Fukumoto S 
Published: July 2010

SUMMARYTo investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-γ and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n= 9), decreasing (n= 8), and stable phase (n= 6). Both IL-2 and IFN-γ mRNA were preferentially expressed in increasing phase than in decreasing phase (P &lt; 0.01, P &lt; 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P &lt; 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.
Expression of a unique protein on colon cancer cells that reacts with a novel monoclonal antibody and ulcerative colitis serum
Authors: HASSAN T , KANISAWA Y , MEYERS S , DASGUPTA A , DAS K M 
Published: July 2010

SUMMARYWe earlier developed a MoAb, 7E12H12 (IgM isotype), against a protein present in normal colonic epithelial cells. To examine if 7E12H12-reactive protein is expressed in colon cancer cells and is recognized by ulcerative colitis (UC)-associated autoantibody, we investigated several colon cancer cell lines. 7E12H12 reactivity against the cells was examined by indirect immunofluorescence assay and whole cell ELISA against six colon cancer cell lines HT-29, LoVo, COLO 205, DLD-1, LS 180 and SW 1116. A competitive ELISA was developed using 7E12H12 MoAb and patients' serum to examine the cross-reactive antibodies in the serum. Among the six colon cancer cell lines only LS 180, DLD-l and SW 1116 reacted with 7E12H12 MoAb, while others did not. The mean (s.e.m.) inhibition of the binding or 7E12H12 MoAb to LS 180 cells by UC serum (n= 51) was 42±2±1%, whereas in normal subjects (n= 17) it was 14±2±6%, in Crohn's disease (n= 19) it was 15±3±2±5%, in infectious diarrhoea (n= 10) it was 11%±3%, and in systemic lupus erythematosus (n= 10) it was 2%±0±6%. The inhibition by the UC group was significantly (P&lt;0±001 - &lt;0±000l) higher than any of the non-UC groups, and this inhibition was mainly by IgG1 antibody. The protein in the specific colon cancer cells recognized by the 7E12H12 MoAb cross-reacts with UC-IgG1 antibody and may provide an in vitro system to examine the autoimmune mechanisms in UC.
Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy
Authors: ALLEN A C , HARPER S J , FEEHALLY J 
Published: July 2010

SUMMARYThe mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown, Mesangial IgA is of the IgA I subclass, and since no consistent antigenic target for the IgA I has been described, we have investigated the glycosylation of the molecule, as a potential non-immunological abnormality which may contribute to its deposition. IgA 1 is rich in carbohydrate, carrying N-linked moieties in common with IgG, but also O-linked sugars, which are rare in serum proteins, and not expressed by IgG or lgA2, Lectin binding assays were designed to examine the expression of terminal galactose on the N-linked carbohydrate chains of purified serum IgG and IgAI, and the O-linked sugars of IgAI and C1 inhibitor (one of the very few other serum proteins with O-linked glycosylation). No evidence was found for abnormalities of N-linked glycosylation of either isotype in IgA nephropathy compared with matched controls. However, in IgA nephropathy, reduced terminal galactosylation of the hinge region O-linked moieties was demonstrated; this was not seen in C1 inhibitor, which showed normal or increased galactosylation of the O-linked sugars. This abnormality of IgA1 has considerable implications for the pathogenesis of IgA nephropathy, since the O-linked sugars lie in an important functional location within the IgA1 molecule, close to the ligand of Fc receptors. Changes in the carbohydrates in this site may therefore affect interactions with receptors and extracellular proteins, leading to anomalous handling of the IgA1 protein in this condition, including failure of normal clearance mechanisms, and mesangial deposition.
Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus
Authors: SILVERMAN E D , BUYON J , LAXER R M , HAMILTON R , BINI P , CHU J-L , ELKON K B 
Published: July 2010

SUMMARYThis study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery of a child with NLE (21 with congenital heart disease block (CHB) and 20 with dermatologic NLE) and 19 sera from anti-Ro and/or anti-La antibody-positive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La and anti-r-Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-r-La antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (0.67 ± 0.43 versus 0.14 ± 0.30; P &lt; 0.0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0.51 ± 0.45 versus 0.83 ± 0.37 respectively; P= 0±0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0.77 ± 0.35) compared with non-NLE mothers (0.29 ± 0.39; P&lt;0.0001). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0.82 ± 0.37 versus 0.71 ± 074; P= 0.32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (5.1 ± 0.54 versus 2.3 ± 0.54 respectively; P &lt; 0.0001). More importantly, when we examined the individual polypeptides. we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30%versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference In the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE. Antibodies directed against the DD polypeptide derived from the recombinant La protein were seen only in the sera of mothers of children with NLE.
γδ T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies
Authors: O'HANLON T P , MESSERSMITH W A , DALAKAS M C , PLOTZ P H , MILLER F W 
Published: July 2010

SUMMARYAutoreactive αβ T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). γδ T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of γδ T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate γδ T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). γδ TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. γδ TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the Vγ3 and Vδ1 transcripts, whose expression was prominent among γδ positive patients. DNA sequence analysis of Vγ3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the Vγ3-N-Jγ junctional domain. No amino acid sequence similarities were evident within the Vδ-N-Dδ-N-Jδ region of Vδ1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike αβ T cells, γδ T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of γδ TCR gene expression detected among these patients implies that γδ T cell infiltration, when it occurs, is a secondary event perhaps resulting from non-specific inflammatory processes.
Age-related changes in surface antigens on peripheral lymphocytes of healthy children
Authors: OSUGI Y , HARA J , KURAHASHI H , SAKATA N , INOUE M , YUMURA-YAGI K , KAWA-HA K , OKADA S , TAWA A 
Published: July 2010

SUMMARYThe age-related changes in proportion of various subsets within lymphocytes were investigated in cord blood and peripheral blood from healthy children and adults. The percentages of T and B cells did not show age-related changes, whereas natural killer (NK) cells increased significantly with age. Within lymphocytes or the CD3+ T cell population the proportion of CD45RAbright+ lymphocytes decreased and that of CD45RO+ cells increased, while that of CD45RAdim+ cells showed no age-related change. Within lymphocytes, the percentage of CD45RAbright+ CD4+ cells decreased, together with a decline of that of CD4+ cells. The proportions of CD45RAbright+ CD8+ cells and S6F1bright+ CD8+ cells increased with age, and the age-dependent increase of the proportion of CD8+ cells seems to be mainly attributable to the increases in these subsets. The CD45RAdim+ CD4+ and CD45RAdim+ CD8+ cells co-expressing CD45RO at a low level nevertheless showed no age-related changes. In γδ T cells, both δTCS1+ and δTCS1- T cells increased with age, but the δTCS1-γδ T cells increased more than the δCS1+ subset. Among lymphocytes, the percentages of CD20+, CD21+ and CD22+ cells remained similar, with no age-related changes, but the proportion of CD5+ cells within lymphocytes or B cells decreased. The proportions of CD16+ NK cells among lymphocytes increased with age, and this change was attributable to the increase of CD56+ cells.
Effect of HIV vertical transmission on the ontogeny of T cell antigens involved in the regulation of humoral immune response
Authors: Brugnoni D , Soresina A , Airo' P , Ugazio A G , Notarangelo L D , Cattaneo R , Duse M 
Published: July 2010

SUMMARYHIV infection causes progressive impairment of humoral immunity, including defective specific antibody production. To evaluate whether vertical HIV infection interferes with the expression on CD4+ lymphocytes of developmentally regulated molecules, that play a crucial role in the generation of immunological memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV-infected children and 36 seroreverted children born to HIV+ mothers were studied. The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls (P &lt; 0·004). This correlated with the depletion of CD4+ lymphocytes (r= 0·75; P &lt; 0·001). CD40L expression rose progressively with age (r= 0·36: P= 0·03) in seroreverted children, but not in HIV-infected children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression and thus to effective T–B cell cooperation), this process is largely defective in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO isoform was increased among HIV-infected infants during the first years of life. However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC) progressively increased with age in controls (r= 0·69; P= 0·03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiological process of antigen priming, contributing to poor immunological memory to T cell-dependent antigens.
In vitrostimulation of peripheral blood mononuclear cells (PBMC) from HIV- and HIV+ chancroid patients byHaemophilus ducreyiantigens
Authors: Van Laer L , Vingerhoets J , Vanham G , Kestens L , Bwayo J , Otido J , Piot P , Roggen E 
Published: July 2010

SUMMARYThe cellular immune responses to fractionated Haemophilus ducreyi antigens, coated on latex beads, were assessed in patients with chancroid and in controls, using an in vitro lymphocyte proliferation assay. Several tractions of H. ducreyi antigen revealed stimulating activity. However, only the molecular size ranges 91–78 kD, 59–29 kD, and 25–21 kD induced proliferation that may be specifically related to H. ducreyi infection. Lymphocytes from four HIV- patients, successfully treated for chancroid, were not stimulated by H. ducreyi antigen. In general, lymphocytes from HIV+ chancroid patients were less responsive to H. ducreyi antigen compared with those from HIV- chancroid patients. However, two HIV-infected patients showed exceptionally strong responses to high molecular weight fractions. To our knowledge this is the first report demonstrating that H. ducreyi contains specific T cell-stimulating antigens. Based on this work, further identification and purification of the T cell antigens is feasible.
γδ T cells in rhesus monkeys and their response to simian immunodeficiency virus (SIV) infection
Authors: Gan Y H , Pauza C D , Malkovsky M 
Published: July 2010

SUMMARYRecent reports of the increase in peripheral blood γδ T cells in HIV+ patients prompted us to examine the γδ T cell system in rhesus monkeys (Macaca mulatta) and the responses of these cells to SIV infection. Our results reveal differences in the γδ T cell subset composition and their expression of CD8 in the peripheral blood of monkeys and humans. The outgrowth of T cells in response to Daudi cells is similar to that in humans, but the exposure to IL-2 stimulates preferentially the simian Vγ1 subset rather than the Vγ9/Vγ2 subset as found in humans. Upon SIV infection of the monkeys, we observed a transient increase of the percentage of total γδ T cell and the Vγ9 subset. γδ T cells from infected animals also express more activation markers such as CD69, CD44 and the memory marker CD45RO. However, they respond to a lesser degree to Daudi or IL-2 stimulation in the outgrowth experiments compared with uninfected animals, although the subset composition of total γδ T cells is similar in infected and uninfected animals. The results clearly indicate that γδ T cells in rhesus monkeys are influenced by SIV infection. The detailed analysis of the γδ T cell response to SIV infection can serve as a model for understanding human γδ T cell responses to HIV infections.
Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease
Authors: RiganÒ R , Profumo E , Ioppolo S , Notargiacomo S , Ortona E , Teggi A , Siracusano A 
Published: July 2010

SUMMARYThe relation of interferon-gamma (IFN-γ), IL-4, IL-10 production and specific IgE, total IgG, IgG subclass expression to the effectiveness of pharmacological treatment in human hydatid disease (Echinococcus granulosus infection) was evaluated in 27 hydatid patients divided into four clinical groups according to their response to albendazole/mebendazole therapy (full, partial, low and non-responders). After parasite antigen stimulation, peripheral blood mononuclear cells (PBMC) from full responders produced significantly more IFN-γ (P= 0·038), significantly less IL-4 (P= 0·001) and less IL-10 than PBMC from non-responders. PBMC from partial and low responders produced intermediate cytokine concentrations. ELISA determining immunoglobulin production showed that sera from all non-responders had IgE and IgG4 antibodies, both regulated by IL-4. In contrast to IgG4, IgE decreased rapidly in full responders. Full responders also showed the highest percentage of IgG3 reactions. Qualitative analysis of total IgG responses in hydatid patients’ sera determined by immunoblotting showed that binding profiles to hydatid cyst fluid antigen differed in the four groups of treated patients. Non-responders had the highest percentage of reactions to all subunits of antigens 5 and B, and full responders had the highest percentage of reactions to antigen 5 alone. The high IFN-γ production associated with a lack of IL-4 and low IL-10 production in the full responders, and vice versa the high IL-4 and IL-10 production associated with lack of or low IFN-γ production in the non-responders implies Th1 cell activation in protective immunity and Th2 cell activation in susceptibility to hydatid disease. IgE may be a useful marker of therapeutic success in hydatid patients with pretreatment specific IgE antibodies. IgG subclass responses and differential immunoglobulin subclass binding pattern to hydatid antigens may also be useful in the immunosurveillance of hydatid disease.
Interferon-gamma (IFN-γ) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes
Authors: Coers W , Vos J T W M , Van Der Meide P H , Van Der Horst M L C , Huitema S , Weening J J 
Published: July 2010

SUMMARYThe subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury-induced membranous nephropathy consist of autoantibodies directed to laminin P1 and of complement. The animals develop massive proteinuria within 10–14 days which is associated with obliteration of foot processes of glomerular visceral epithelial cells (GVEC), or podocytes. Previous studies indicate that these autoantibodies are probably not the sole mediator of proteinuria and GVEC damage. In this study we investigated whether circulating or macrophage-derived cytokines can contribute to the GVEC changes as detected in vivo. In vivo at the height of the proteinuria. increased intraglomerular IFN-γ immunoreactivity was found. In diseased rats a five-fold increase in intraglomerular macrophages was found, but we could not detect intraglomerular IFN-α, IFN-β, IL-1β or tumour necrosis factor-alpha (TNF-α) by using immunohistology. Subsequently, we exposed cultured GVEC to these cytokines to investigate their cytotoxic effects on several physiological and structural parameters. IFN-γ and IL-4 were the only cytokines that exerted toxic effects, resulting in a rapidly decreased transepithelial resistance of confluent monolayers. which was closely associated with altered immunoreactivity of the light junction protein ZO-I. IL-4 also affected vimentin and laminin immunoreactivity. IFN-γ and IL-4 only interfered with monolayer integrity when added to the basolateral side of the GVEC, indicating specific (receptor-mediated) effects. Only IL-4 decreased the viability of the cells, and treated monolayers demonstrated an increased passage of the 44-kD protein horseradish peroxidase. From our experiments we concluded that IFN-γ subtly affected monolayer integrity at the level of the tight junctions, and that IL-4 additionally induced cell death. We hypothesize that the toxic effects of the cytokines IFN-γ and IL-4 as seen with cultured podocytes are necessary together with the autoantibodies. for the ultimate induction of proteinuria in mercury nephropathy in the DZB rat.
CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C
Authors: Pham B N , Martinot-Peignoux M , Mosnier J F , Njapoum C , Marcellin P , Bougy F , Degott C , Erlinger S , Cohen J H M , Degos F 
Published: July 2010

SUMMARYThe pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 × 106 Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and 4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+ ratio of liver-derived lymphocytes was significantly higher (P &lt; 0·01) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of γ/δ T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+CD8+ ratio, the percentage of γ/δ T lymphocytes or CD2+CD57+ cells according to genotype, the differences were not significant. These results suggest that the CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C, and that T lymphocytes may be involved in the pathogenesis of liver lesions in chronic hepatitis C.
Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's phenomenon
Authors: Riente L , Marchini B , Dolcher M P , Puccetti A , Bombardieri S , Migliorini P 
Published: July 2010

SUMMARY
The frequency and specificity of antibodies to native and denatured collagens were evaluated in systemic sclerosis (SSc) and in primary Raynaud's phenomenon (PRP) by direct and competitive ELISA. Antibodies reactive with denatured collagen type I (CI) were found in 43% of the SSc sera, and anti-CIV and anti-CV in 31%. In PRP, anti-CI, anti-CIV and anti-CV antibodies were detected in 8% of patient sera. Anti-CI, anti-CIV and anti-CV antibodies reacted with determinants expressed on the native as well as on the denatured molecule. Anti-CI and anti-CIV were cross-reactive; a reactivity with CII and a lower one with CV were detected. Anti-CV antibodies also reacted with CI and CII and, in a smaller proportion of cases, with CIV. Anti-collagen antibodies, affinity-purified from blotted collagen IV and V and cyanogen bromide (CBr)-digested CI, displayed the cross-reactivities shown by inhibition studies on sera. Moreover, antibodies eluted from a CBr fragment of CI reacted with the other CBr fragments as well. These data show that one-third of SSc sera contain antibodies that react with epitopes expressed on native as well as on heat-denatured CI, CII, CIV and CV, and therefore have the potential to bind collagens in vivo.