bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of interferon-gamma in lymphocytic thyroiditis: its functional and pathological effect on human thyrocytes in culture
Authors: KUNG A W C , MA L , LAU K S 
Published: July 2010

SUMMARY
lnlerferon-gamma (IFN-γ) has been recognized to possess diverse non-immunological effects on epithelial cells such as cellular growth and differentiation. We have previously demonstrated that IFN-y suppressed thyroid-stimulating hormone (TSH(-stimulated thyroglohulin (TG) synthesis in human thyrocytes through inhibition of TG gene transcription. To define the pathological mechanism involved in the action of IF'N-y, we studied the ultrastructural changes of human thyrocytes cultured in monolayer. Stimulation of the thyrocytes with TSH 10 mU/ml for 2 days resulted in marked increase in TG release into the medium. This was accompanied by elongation of microvilli. increase in follicles and acinar formation, increase in secretory granules and prominence of Golgi apparatus and rough-surfaced cndoplasmic rcticulum. Addition of IFN-y (300 L ml) resulted in marked degeneration with shrinkage of the cell membrane, vacuolation of cytoplasm, swollen mitochondria and presence of lysosomal granules. C'o-culluring the thyrocytes with the IFN-y and TSH resulted in suppression of the morphological responsiveness to TSH. There was also suppression of TSH-induced TG secretion. However, at 500 U'ml IFN-y did not cause lysis of the thyrocytes as estimated by the cellular DN A content. Furthermore, binuclcatcd cells were frequently encountered in those wells that were treated with IFN-y for cither 2 or 5 days. The findings suggest that IFN-γ resulted in de-differentiation and degeneration of the thyrocytcs. which subsequently regained the growth potential and showed attempts at regeneration. This may explain why most patients with lymphocytic thyroiditis recover from the acute injury and do not suffer from permanent hypothyroidism.
Lymphocyte subsets and β2-microglobulin expression in chronic hepatitis C/non-A, non-B. Effects of interferon-alpha treatment
Authors: WEJSTÅL R , NORKRANS G , WEILAND O , SCHVARCZ R , FUCHS D , WACHTER H , FRYDEN A , GLAUMANN H 
Published: July 2010

SUMMARY
Thirty-three patients with chronic hepatitis C/non-A. non-B were included in a randomized controlled study of interferon-alpha 2b (IFN-α2b) treatment, 3 × 106 U three times weekly for 36 weeks. Using an immunoperoxidase technique, frozen liver biopsy specimens were examined with MoAbs for the presence of T helper cells (CD4), T suppressor/cytotoxic cells (CD8), total T cells (CD2) and B cells (CD22) before and after treatment, β2-microglohulin (β2-MG) expression on hepatocytes was semiquantified using a scoring system on sections from paraffin-embedded biopsy specimens. Serum levels of β2-MG were analysed with a radioimmunoassay technique. Intralobular T helper and T suppressor/cytotoxic cells declined significantly in the treated patients but not in the controls. The portal CD4/CD8 ratio did not change. Before treatment, serum β2-MG levels and hepatocyte β2-MG expression were significantly higher in patients with chronic active hepatitis compared to patients with chronic persistent hepatitis. Serum β2-MG levels increased significantly in responders during IFN treatment, with a maximum after 12 weeks. However, in the liver, the hepatocyte β2-MG expression was significantly decreased after treatment. Thus. IFN-α treatment does not seem to induce an increased HLA class I antigen hepatocyte expression in chronic non-A, non-B hepatitis, which favours the hypothesis that its anti-viral effects are more important in modulating the disease activity.
Antibodies to hepatitis C virus in essential mixed cryoglobulinaemia
Authors: DAMMACCO F , SANSONNO D 
Published: July 2010

SUMMARY
Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepatitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti-HCV antibodies were detected in 13 patients (50%) by ELISA and confirmed in 11 of them (42.3%) by 4-RIBA, the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed, 7/11 (63.6%) anti-HCV+ patients showed histological and clinical pictures of CALD, compared with 1/15 (6.6%) anti-HCV− patients (P&lt;0.01). With the exception of the patient who was found to be HBsAg+, no liver tissue expressed hepatitis B virus-related antigens in the hepatocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease.
High antibody levels to the mycobacterial fibronectin-binding antigen of 30–31 kD in tuberculosis and lepromatous leprosy
Authors: ESPITIA C , SCIUTTO E , BOTTASSO O , GONZÁLEZ-AMARO R , HERNÁNDEZ-PANDO R , MANCILLA R 
Published: July 2010

SUMMARYImmunoblot assays showed that mycobacterial fibronectin-binding antigens are important targets of the humoral immune response in tuberculosis and leprosy. Using culture filtrate antigens of Mycobacterium tuberculosis, strong reactivity with the fibronectin-binding of 30–31 kD (Fn 30–31) was demonstrated in 55.9% of tuberculosis sera and in 56.5% of lepromatous leprosy sera. Sera from patients with tuberculoid leprosy and control sera gave very weak binding. Reactivity of tuberculosis and lepromatous leprosy sera with the fibronectin-binding antigen of 58–60 kD (Fn 58–60) was less conspicuous. The ability to react with fibronectin of the antigens of 58–60 and 30–31 kD was demonstrated by parallel labelling with a fibronectin-biotin conjugate. Fn 30–31 was purified to homogeneity by a two-step procedure and used for ELISA. Positive titres were found in 63% out of 65 tuberculosis sera and in 60.5% out of 43 lepromatous leprosy sera. Antibody titres in lepromatous leprosy sera were higher than in tuberculosis sera. Our observations indicate indirectly that M. leprae possess a highly immunogenic molecule homologous to M. tuberculosis Fn 30–31, which elicits a high antibody response in lepromatous leprosy but not in tuberculoid leprosy. In this investigation, direct evidence for the presence of this antigen in M. leprae was obtained by immunochemistry of lepromatous leprosy lesions with a monospecific antibody raised against M. tuberculosis Fn 30–31.
Detection of antibodies to human nerve antigens in sera from leprosy patients by ELISA
Authors: PARK J Y , CHO S N , YOUN J K , KIM D I , CELLONA R V , FAJARDO T T , WALSH G P , KIM J D 
Published: July 2010

SUMMARY
Anti-neural antibodies have been implicated to play a role in the pathogenesis of nerve damage in leprosy patients. To find the relationship between anti-neural antibodies and clinical findings, we attempted to detect antibodies against neurofilament-enriched proteins by ELISA in sera from leprosy patients. Of 289 sera from leprosy patients, 74(25.6%) had significant anti-neural antibodies: in contrast, 1 (5.0%) of 20 tuberculosis patients and 11 (7.1%) of 154 controls were seroreactive to nerve antigen. When clinical types were considered, a significant level of anti-neural IgG antibodies was detectable in 53 (30·1%) of 176 sera from lepromatous patients compared with 21(18.6%) of 113 sera from tuberculoid patients, indicating that lepromatous patients were more likely to be seropositive to nerve antigens in ELISA. Some of the ELISA-reactive sera showed antibody reactivity with 38-kD, 40-kD and 43-kD nerve antigens in Western blotting analysis. There was no apparent correlation between seroreactivity to nerve antigens and bacterial load in leprosy patients. Although there was no statistical significance, anti-neural antibodies were detectable more often among the patients on chemotherapy than the untreated and among the patients with erythema nodosum leprosum than without. The results, therefore, suggest that anti-neural antibodies arc elicited during the course of leprosy and may be associated with the extensiveness of nerve involvement in the patients.
An association between homozygous C3 deficiency and low levels of anti-pneumococcal capsular polysaccharide antibodies
Authors: HAZLEWOOD M A , KUMARARATNE D S , WEBSTER A D B , GOODALL M , BIRD P , DAHA M 
Published: July 2010

SUMMARYInherited deficiencies of complement components are associated with an increased risk of infection by encapsulated, high grade bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis. Hence, the levels of antibodies to bacterial capsular polysaccharide antigens were measured using ELISA in 65 patients with inherited deficiencies covering the classical, alternative and terminal components of the complement cascade. Three of the four C3-deficient individuals studied were found to be almost totally deficient in specific anti-pneumococcal capsular polysaccharide (PCP) antibodies. These individuals had a history of recurrent pneumococcal sepsis. While single individuals with Clr, C2 and ClInh deficiency were found to have low anti-PCP antibody levels, no other group of complement deficiency had significantly reduced anti-PCP antibody levels compared with 100 controls. Antibody levels to the other two polysaccharides were not significantly lower in the patient groups. These findings suggest that C3 may be able to provide a stimulatory signal to promote the production of anti-PCP antibodies.
Evidence for the presence of activated CD4 T cells with naive phenotype in the peripheral blood of patients with rheumatoid arthritis
Authors: MAURER D , FELZMANN T , HOLTER W , PETERA P , SMOLEN J , KNAPP W 
Published: July 2010

SUMMARYWe have investigated whether T cell activation in rheumatoid arthritis (RA) preferentially engages distinct T cell subpopulations in the peripheral blood (PB) and in the synovial fluid. We found that CD25 expression was enhanced among PB CD4 T cells of RA patients as compared with CD4 cells of patients with reactive arthritis, degenerative joint disease or of healthy controls. Within the CD4 T lymphocyte subset we found that the CD45RO− (naive) cells selectively in RA displayed higher levels of CD25 protein and of interferon-gamma mRNA expression when compared with the respective subset of all other investigated groups. These results show that in the PB of RA, but not in the PB of the other arthropathies or healthy controls, CD45RO− CD4 T lymphocytes exist which display well-defined signs of activation.
Regulation of IL-2 production by mononuclear cells from rheumatoid arthritis synovial fluids
Authors: FLESCHER E , BOWLIN T L , TALAL N 
Published: July 2010

SUMMARYProducts of polyamine oxidation down-regulate IL-2 production by peripheral blood T cells. We show here that the production of IL-2 by rheumatoid arthritis synovial fluid mononuclear cells is inversely correlated with the concentrations of polyamines in these cells. In addition, the inhibition of polyamine biosynthesis or oxidation in cultures of these cells enhances their ability to produce IL-2. Our findings suggest that polyamine oxidation plays an important role in the suppression of T cell function characteristic of rheumatoid arthritis synovial fluids.
Effect of 12,13-phorbol dibutyrate and ionomycin on defective B cells in common variable immunodeficiency
Authors: FRANZ A , BRYANT A , WEBSTER A D B , FARRANT J 
Published: July 2010

SUMMARY
Secretion or IgM and IgG in vitro by B cells from patients with common variable immunodeficiency (CVI) has been used to classify the disease into three groups. On stimulation with anti-IgM and IL-2, group A patients' cells fail to secrete IgM or IgG, group B patients' cells secrete no IgG and significantly lower levels of IgM than normal cells, and group C patients' cells produce normal levels of both isotypes, Direct activation of protein kinase C using 12, 13-phorbol dibutyrate and ionomycin followed by IL-2 or IL-4 has been reported to induce immunoglobulin secretion by normal human B cells. We therefore attempted to induce B cells from group A and group B CVI patients to secrete IgM and IgG after direct activation of protein kinase C together with IL-2 or IL-4. The data show that the failure of secretion of immunoglobulin by B cells from CVI patients could not be reversed using this approach. This finding suggests that the activation channel involving protein kinase C in B cells from CVI patients is not involved in the defect in cell differentiation.
IL-2 infusion abrogates humoral immune responses in humans
Authors: GOTTLIEB D J , PRENTICE H G , HESLOP H E , BELLO C , BRENNER M K 
Published: July 2010

SUMMARYAlthough IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin: memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression.
Up-regulation of tumour necrosis factor-alpha receptors on monocytes by desferrioxamine
Authors: PHILIPPE C , FOUQUERAY B , PEREZ J , BAUD L 
Published: July 2010

SUMMARYThe effect of endogenously generated reactive oxygen metabolites on the interaction of human blood monocytes with tumour necrosis factor-alpha (TNF-α) was investigated. Pre-exposure of unactivated human blood monocytes to dimethylthiourea, a scavenger of hydroxyl radical (OH˙) or to desferrioxamine (DFX), an iron chelator preventing the synthesis of OH˙, enhanced the specific binding of 125I-TNF-α to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX-induced up-regulation of 125I-TNF-α binding depended on the concentration of the drug (1–5 mm) and on the duration of the treatment (1–18 h). It was not due to a reduction of receptor occupancy by endogenously generated TNF-α. Scatchard analysis of binding data revealed that DFX caused an approximately two-fold increase in the number of type II TNF-α receptors, with no change in their affinity. This up-regulation, that did not require synthesis of new proteins, was associated with a decrease in the internalization rate of TNF-α receptors, the half-life of which was doubled. Conversely, these findings suggest that OH˙ generation by monocytes may have a physiological role in reducing the activity of membrane-associated TNF-α receptors.
Status of immune-based therapies in HIV infection and AIDS
Authors: FAHEY J L , SCHOOLEY R 
Published: July 2010

SUMMARYAs our understanding of HIV disease pathogenesis progresses, approaches to immune-based therapy are evolving. Initial therapies aiming to alter immune function in patients with HIV infection have had mixed results. Clinical benefit in the trials so far has not been dramatic, although the studies are still at an early stage, and the correct protocols for the various agents or combinations of agents have yet to be established. As might be expected, where apparent benefit has occurred, it has been more obvious in those patients whose immune system was still intact.
Inhibitory activity of HIV envelope gp120 dominates over its antigenicity for human T cells
Authors: MANCA F , WALKER L , NEWELL A , CELADA F , HABESHAW J A , DALGLEISH A G 
Published: July 2010

SUMMARYHIV-1 envelope glycoprotein (gp120), as a CD4-binding reactant, has been shown to inhibit in its native form human T cell responses to several antigens. Here we show that gp 120 in soluble form also inhibits activation of a specific human T cell line that responds to gp120-pulsed autologous antigen-presenting cells. In addition the inhibitory property of gp120 for antigen-driven T cell proliferation depends upon its ability to bind CD4 and is lost when CD4-binding capacity is abolished by denaturation, or blocked by complexing with soluble CD4 or with polyclonal antibodies. In contrast, antigenicity of denatured or complexed gp120 for specific human T cells is preserved. Similar effects are also observed with another CD4-binding reactant (i.e. anti-Leu 3a MoAb), which stimulates and/ or inhibits human T cells specific for mouse immunoglobulins depending on native or denatured conformation.
Impaired phagocytosis ofStaphylococcus aureusby granulocytes and monocytes of AIDS patients
Authors: POS O , STEVENHAGEN A , MEENHORST P L , KROON F P , VAN FURTH R 
Published: July 2010

SUMMARYIn the present study the microbicidal activities of granulocytes and monocytes from AIDS patients (CDC group IV) were assessed and compared with those of healthy controls. The phagocytosis and intracellular killing of Staphylococcus aureus by patient and control cells were measured using a method in which the rate of intracellular killing can be assessed independently of the rate of phagocytosis. Both granulocytes and monocytes of AIDS patients showed a decreased phagocytosis of S. aureus in comparison to phagocytes of healthy individuals. The rates of intracellular killing of S. aureus by granulocytes and monocytes did not differ significantly between these patients with late-stage HIV infection and controls.
Anti-mitochondrial antibody IgG subclass distribution and affinity in primary biliary cirrhosis
Authors: ZHANG L , WEETMAN A P , JAYNE D R W , TURNER I , YEAMAN S J , BASSENDINE M F , OLIVEIRA D B G 
Published: July 2010

SUMMARY
We have studied the total IgG subclass and anti-mitochondrial antibody (AMA) specific IgG subclass distribution in primary biliary cirrhosis (PBC) sera. In order to solve the problems caused by the differing affinities of subclass specific monoclonals and the competitive inhibition of antibodies in a whole serum assay, six sera were separated into subclass-specific fractions by affinity-depletion chromatography. AMA subclass distribution of 20 further sera from patients with PBC was assessed using conventional methods and the results were calibrated against one of the fractionated sera. Light chain distribution and AMA functional affinity were also assessed for the fractionated subclasses. Total amounts of IgG3 were significantly increased compared with normal controls. AMA were found in all IgG subclasses and not restricted predominantly to IgG3 as previously described. The functional affinity of IgG3 AMA is generally lower as compared with that of other subclasses. No light chain restriction was found.
Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells
Authors: CHAN T M , FRAMPTON G , STAINES N A , HOBBY P , PERRY G J , CAMERON J S 
Published: July 2010

SUMMARYThe mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that Mo Ab 410 bound to H U VEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones.
Analysis of autoantibody production in SCID-systemic lupus erythematosus (SLE) chimeras
Authors: ASHANY D , HINES J , GHARAVI A , MOURADIAN J , ELKON K B 
Published: July 2010

SUMMARYMice with SCID disease have previously been successfully engrafted with human peripheral blood mononuclear cells (PBMC) obtained from normal individuals and from patients with various diseases. To determine whether SCID mice engrafted with SLE PBMC produced autoantibodies with specificities similar to those in the SLE donor, and to investigate which variables influence autoantibody production in the SCID recipients, we injected PBMC from 16 SLE patients into SCID mice and tested the recipients for autoantibodies to DNA and to five recombinant autoantigens. Ten out of 16 (68%) lupus and six out of nine (67%) normal grafts were successful as determined by the presence of human IgG ± 5 μg/ml of SCID serum post-transfer. Autoantibodies to La/SSB, Ro/SSA, and RNP were detected in five out of 10 SCID-SLE recipients by ELISA and immunoblotting up to 22 weeks post-engraft men I. The detection of autoantibodies in SCID-SLE mice was more closely related to autoantibody levels in donor sera than to total IgG concentrations in the SCID recipients. Autoantibody activity/mg IgG was similar in the donor and recipient sera. Histological evaluation of eight SCID-SLE mice killed 4–22 weeks post-transfer revealed population of the SCID thymus and spleen with mononuclear cells, but no evidence of lupus nephritis or dermatitis. These findings indicate that SCID mice can be engrafted with PBMC from patients with lupus and that specific autoantibodies are produced up to 5 months post-transfer. Failure to develop glomerulonephritis may be explained by low or absent anti-DNA antibodies or by changes in the cellular composition of the PBMC grafts.