bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases
Authors: MURATORI P , MURATORI L , GUIDI M , MACCARIELLO S , PAPPAS G , FERRARI R , GIONCHETTI P , CAMPIERI M , BIANCHI F B 
Published: May 2003

SUMMARY
Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P &lt; 0·05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease.
Oral administration of type II collagen suppresses pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis
Authors: DING C H , LI Q , XIONG Z Y , ZHOU A W , JONES G , XU S Y 
Published: May 2003

SUMMARYThe objective of this study was to investigate the effect of the oral administration of type II collagen (CII) on pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis (AA). Sprague-Dawley rats were fed with bovine CII either before immunization with Complete Freund's adjuvant (CFA) or after initiation of arthritis. Hind paw secondary swelling was measured and synoviocytes were harvested. Sera from portal vein of oral tolerized rats were collected and in vitro synoviocytes culture or synoviocytes-Peyer's Patches (PP) cells coculture system were developed. Interleukin (IL)-1 activity was measured by a mouse thymocyte activation assayed by MTT dye reduction and tumour necrosis factor (TNF) activity was measured by an L929 cytotoxicity bioassay. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured by biochemical methods. We found that feeding with CII (5, 50 and 500 µg/kg) for 7 days before immunization significantly suppressed hind paw secondary swelling measured at day 16, 20, 24 and 28 (all P &lt; 0·01) and pro-inflammatory mediator (IL-1, TNF, NO and MDA) production by synoviocytes (all P &lt; 0·01) in rats with AA. Feeding with CII (5, 50 and 500 µg/kg) for 7 days after initiation of arthritis had a similar effect. CII (1, 10, 100 µg/ml) had no effect on IL-1 and TNF production by synoviocytes in vitro, but CII 10 µg/ml suppressed IL-1 and TNF production by synoviocytes-PP cells coculture system (P &lt; 0·01), which was antagonized by anti-TGF-β antibody (10 µg/ml) (P &lt; 0·01). Portal serum (1 : 10) from oral tolerized rats suppressed IL-1 and TNF production by synoviocytes (P &lt; 0·01), which was also antagonized by anti-TGF-β antibody (10 µg/ml) (P &lt; 0·01). We conclude that oral administration of CII had prophylactic and therapeutic effects on AA and over-production of IL-1, TNF, NO and MDA by synoviocytes was suppressed. Bystander active suppression may be the main mechanism of oral CII in the suppression of synoviocyte function.
Measurement of soluble Fcγ receptor type IIIa derived from macrophages in plasma: increase in patients with rheumatoid arthritis
Authors: MASUDA M , MORIMOTO T , KOBATAKE S , NISHIMURA N , NAKAMOTO K , DONG X H , KOMIYAMA Y , OGAWA R , TAKAHASHI H 
Published: May 2003

SUMMARY
FcγRIII (CD16) is found in two alternative forms, a transmembrane FcγRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcγRIIIb present on neutrophils. Previously, we measured soluble FcγRIIIa (sFcγRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcγRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcγRIIIb and FcγRIIIa. The level of sFcγRIIIa, as well as the total sFcγRIII (sFcγRIIIa plus sFcγRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcγRIIIaMφ in plasma with a newly developed anti-FcγRIII MoAb, MKGR14 (mIgM), which recognizes FcγRIIIaMφ specifically. From the recovery of purified sFcγRIIIaMφ, the amount of sFcγRIIIaMφ present was about half that of sFcγRIIIaNK, and that of sFcγRIIIa was about 50 times lower than that of sFcγRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcγRIIIaMφ in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcγRIIIaMφ and sFcγRIIIa levels were increased as proportionally as the Lansbury Index. The sFcγRIIIa, but not sFcγRIIIaMφ levels, were increased directly proportional to C-reactive protein. sFcγRIIIaMφ may be a novel marker of disease activity in RA.
Interleukin-12 alone can not enhance the expression of the cutaneous lymphocyte associated antigen (CLA) by superantigen-stimulated T lymphocytes
Authors: SIGMUNDSDÓTTIR H , GUDJÓNSSON J E , VALDIMARSSON H 
Published: May 2003

SUMMARY
It has been reported that bacterial superantigens induce interleukin (IL)-12 dependent expression of the cutaneous lymphocyte associated antigen (CLA) and that this may be relevant to the association between certain skin diseases and infections including psoriasis and streptococcal tonsillitis. We have confirmed that the streptococcal pyrogenic superantigen C (SpeC) increases CLA expression by both CD4+ and CD8+ T cells when PBMCs are incubated in medium enriched with fetal calf serum (FCS). However, such an increase could not be induced in medium enriched with human serum (HS) even when recombinant IL-12 was added to the PBMCs cultures. Strikingly, CD4+ T cells incubated with SpeC in HS showed a marked reduction in CLA expression, which was not due to apoptosis. In contrast, SpeC did induce T cell proliferation and expression of CD25, CD54 and CD103 in the presence of HS indicating that the absence of SpeC induced CLA expression in HS was not due to SpeC inhibitors. Although addition of low amounts of lipopolysaccharide endotoxin (LPS) caused a highly significant increase in CLA expression in the absence of SpeC in cultures enriched with HS, a combination of LPS and SpeC did not increase CLA expression beyond that induced by LPS alone. The superantigen-induced CLA expression in FCS was partially inhibited by anti-IL-12 but not by anti-IL-18 or antibodies to transforming growth factor (TGF)-β. It is concluded that IL-12 alone can not increase CLA expression but requires the help of other factor(s) present in FCS but not in HS. Although LPS can induce CLA expression it does not seem to be the factor that interacts with IL-12 to induce superantigen-mediated CLA expression in cultures enriched with FCS.
Insight into antibody responses induced by plasmid or adenoviral vectors encoding thyroid peroxidase, a major thyroid autoantigen
Authors: GUO J , PICHURIN P , NAGAYAMA Y , RAPOPORT B , MCLACHLAN S M 
Published: May 2003

SUMMARYPlasmid and adenoviral vectors have been used to generate antibodies in mice that resemble human autoantibodies to the thyrotrophin receptor. No such studies, however, have been performed for thyroid peroxidase (TPO), the major autoantigen in human thyroiditis. We constructed plasmid and adenovirus vectors for in vivo expression of TPO. BALB/c mice were immunized directly by intramuscular injection of TPO-plasmid or TPO-adenovirus, as well as by subcutaneous injection of dendritic cells (DC) infected previously with TPO-adenovirus. Intramuscular TPO-adenovirus induced the highest, and TPO-plasmid the lowest, TPO antibody titres. Mice injected with TPO-transfected DC developed intermediate levels. Antibodies generated by all three approaches had similar affinities (Kd ∼10−9m) and recognized TPO expressed on the cell-surface. Their epitopes were analysed in competition assays using monoclonal human autoantibodies that define the TPO immunodominant region (IDR) recognized by patients with thyroid autoimmune disease. Surprisingly, high titre antibodies generated using adenovirus interacted with diverse TPO epitopes largely outside the IDR, whereas low titre antibodies induced by DNA-plasmid recognized restricted epitopes in the IDR. This inverse relationship between antibody titre and restriction to the IDR is likely to be due to epitope spreading following strong antigenic stimulation provided by the adenovirus vector. However, TPO antibody epitope spreading does not occur in Hashimoto's thyroiditis, despite high autoantibody levels. Consequently, these data support the concept that in human thyroid autoimmunity, factors besides titre must play a role in shaping an autoantibody epitopic profile.
The production of tumour necrosis factor-alpha is decreased in peripheral blood mononuclear cells from multidrug-resistant tuberculosis patients following stimulation with the 30-kDa antigen of Mycobacterium tuberculosis
Authors: LEE J-S , SONG C-H , LIM J-H , KIM H-J , PARK J-K , PAIK T-H , KIM C-H , KONG S-J , SHON M-H , JUNG S-S , JO E-K 
Published: May 2003

SUMMARY
The clearance of intracellular bacteria requires the appropriate induction of proinflammatory cytokines and chemokines to recruit macrophages and T cells to the site of infection. In this study, we investigated the production of tumour necrosis factor (TNF)-α, interleukin (IL)-8 and interferon (IFN)-γ by the peripheral blood mononuclear cells (PBMC) of patients with multidrug-resistant tuberculosis (MDR-TB) in response to in vitro stimulation with the 30-kDa antigen of Mycobacterium tuberculosis. The results were compared with those from cases of newly diagnosed TB (N-TB) and TB with treatment failure (TF-TB), and healthy tuberculin reactors (HTR). The most significantly depressed TNF-α levels were found in MDR-TB patients. IFN-γ production was depressed significantly in all groups of TB patients compared with the HTR group. TNF-α secretion in response to the 30-kDa antigen was unchanged by coculturing with recombinant human interferon (rhIFN)-γ, and was increased dramatically following IL-10 neutralization with an anti-human IL-10 antibody. The IL-8 levels were depressed significantly in MDR-TB patients compared with N-TB patients, but were similar to the IL-8 levels in TF-TB patients. Furthermore, rhTNF-α directly increased IL-8 secretion, and neutralizing antibody to TNF-α inhibited IL-8 production by the PBMC of MDR-TB patients that were stimulated with the 30-kDa antigen. Taken together, these data suggest that the PBMC of MDR-TB patients typically show TNF-α depression in response to the 30-kDa antigen, and this effect is modulated by IL-10. In addition, we highlight the role of TNF-α in IL-8 secretion in MDR-TB patients.
Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis
Authors: FRIESE M A , MANUELIAN T , JUNNIKKALA S , HELLWAGE J , MERI S , PETER H H , GORDON D L , EIBEL H , ZIPFEL P F 
Published: May 2003

SUMMARYRheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-γ and dexamethasone, whilst the pro-inflammatory cytokine TNF-α had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.
Difference in antigenic determinant profiles between human and rat myeloperoxidase
Authors: PATRY Y C , NACHMAN P H , AUDRAIN M A P , FALK R J , MEFLAH K , ESNAULT V L M 
Published: May 2003

SUMMARY
We tested whether rat and human MPO have similar antigenic determinants using 36 human MPO-ANCA positive sera, one mouse anti-rat MPO and four mouse anti-human MPO monoclonal reagents. Purified rat and human MPO were used in ELISA, with or without crossinhibition by preincubation with human MPO or irrelevant antigen in the liquid phase. Only one human MPO ANCA positive serum exhibited significant binding in rat MPO ELISA. This binding was poorly inhibited by preincubation with human MPO in the liquid phase, but was conserved after adsorption of non specific anti-rat activity in a chromatography column. Three mouse anti-human MPO IgG monoclonal antibodies did not recognize rat MPO. Only one mouse anti-human MPO IgA monoclonal antibody bound to rat MPO. This binding was poorly inhibited by preincubation with human MPO (35% at 2 µg/ml). Conversely, the mouse anti-rat MPO monoclonal did not bind human MPO. We have concluded that: (1) Most human MPO-ANCA recognize antigenic determinants on human MPO which are absent on rat MPO. Therefore, human auto-antibodies bind to epitopes which recently appeared after species evolution; (2) Inversely, the mouse anti-rat MPO monoclonal do not bind human MPO. Therefore, rat MPO epitopes have been altered during species evolution; (3) Mice injected with human MPO preferentially develop antibodies against xeno-epitopes which are not present in rodents. Therefore, human MPO may not be the best antigen to raise ANCA in animal models and (4) A comparison of the amino acid sequences of rat and human MPO may help elucidate the major antigenic epitopes.
Specific lytic activity against mycobacterial antigens is inversely correlated with the severity of tuberculosis
Authors: DE LA BARRERA S S , FINIASZ M , FRIAS A , ALEMÁN M , BARRIONUEVO P , FINK S , FRANCO M C , ABBATE E , SASIAIN M DEL C 
Published: May 2003

SUMMARY
The ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis (Mtb)-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3+γδ TCR+ T (γδ T) cells bearing CD56 and/or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8+ CTL and class-II restricted CD4+ CTL were generated in PPD+N and to a lesser extent in PPD–N. Mtb-stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4–CD8–γδ T cells, while lytic activity of CD4+ and CD8+CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb-induced CD4+ CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb-induced CD8+ CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb-induced γδ CTL from patients and PPD–N employed the latter mechanism cells from PPD+N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.
Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology inHelicobacter pylori-infected mice
Authors: RAGHAVAN S , FREDRIKSSON M , SVENNERHOLM A-M , HOLMGREN J , SURI-PAYER E 
Published: May 2003

SUMMARYHelicobacter pylori induces symptomatic chronic gastritis in a subpopulation of infected individuals. The mechanism(s) determining the development and severity of pathology leading to symptoms are not fully understood. In a mouse model of H. pylori infection we analysed the influence of immunoregulatory CD4+CD25+ T cells on H. pylori colonization and gastritis. Athymic C57BL/6 nu/nu mice were reconstituted with (a) lymph node (LN) cells (b) LN cells depleted of CD25+ T cells (CD25– LN) or (c) not reconstituted at all. Mice were then infected orally with 3 × 108H. pylori SS1 bacteria. At 2 and 6 weeks after the inoculation there was a significant (P &lt; 0·001) reduction in H. pylori colonization in athymic mice transferred with CD25– LN cells compared to mice transferred with LN cells. Colonization was still reduced at 12 weeks after inoculation. Mice transferred with CD25– LN cells showed an earlier onset and increased severity of gastritis as compared to mice receiving LN cells. Splenic cells isolated from mice receiving CD25– LN cells produced the highest level of IFN-γ on stimulation with H. pylori antigens in vitro, had a higher H. pylori-specific DTH response and increased infiltration of CD4+ T cells and macrophages in the gastric mucosa. Athymic mice not transferred with T cells had persistent high H. pylori colonization and displayed a normal gastric epithelium without inflammatory cells. In conclusion, CD4+CD25+ cells reduce immunopathology in H. pylori infection, possibly by reducing the activation of IFN-γ producing CD4+ T cells, even at the expense of a higher H. pylori load in the gastric mucosa.
Raised serum levels of interleukin-18 is associated with disease progression and may contribute to virological treatment failure in HIV-1-infected patients
Authors: STYLIANOU E , BJERKELI V , YNDESTAD A , HEGGELUND L , WÆHRE T , DAMÅS J K , AUKRUST P , FRØLAND S S 
Published: May 2003

SUMMARY
To gain further insight into the possible role of interleukin (IL)-18 in HIV-1 infection we examined serum levels of IL-18 in various clinical and immunological stages of HIV-1 infection during cross-sectional (n = 41) and longitudinal testing (n = 20) and during HAART (n = 21, 24 months follow-up). Our main findings were that HIV-1-infected patients had significantly raised IL-18 levels comparing healthy controls, particularly in those with advanced disease, that while HAART induced a marked decline in IL-18, virological treatment failure was associated with persistently raised IL-18 levels during such therapy and that our in vitro experiments showed an IL-18-mediated up-regulation of the HIV-1 coreceptor CXCR4 and the pro-apoptotic mediator TRAIL in PBMC from HIV-1-infected patients receiving HAART. HIV-1 infection appears to be characterized by persistently raised IL-18 levels and during HAART, such a pattern was associated with virological treatment failure, possibly contributing to immunodeficiency and HIV-1 replication in these patients.
Beta-2-glycoprotein I expression on monocytes is increased in anti-phospholipid antibody syndrome and correlates with tissue factor expression
Authors: CONTI F , SORICE M , CIRCELLA A , ALESSANDRI C , PITTONI V , CARONTI B , CALDERARO C , GRIGGI T , MISASI R , VALESINI G 
Published: May 2003

SUMMARY
It is well known that monocytes may play an active role in thrombogenesis, since they may express on their surface tissue factor, the major initiator of the clotting cascade. The results of this investigation demonstrate beta-2-glycoprotein I (β2-GPI) mRNA expression by human peripheral blood monocytes, indicating that these cells synthesize β2-GPI. In addition, we show β2-GPI expression on cell surface of these cells by flow cytometric analysis, and the presence of this protein in cell lysate by Western blot. Interestingly, β2-GPI expression on monocytes is significantly increased in patients with anti-phospholipid syndrome (APS) or systemic lupus erythematosus (SLE) as against healthy blood donors and correlates with tissue factor expression on monocytes. These findings support the view that monocytes are able to synthesize β2-GPI and suggest that patients with APS may have increased β2-GPI exposure on cell surface, which leads to persistently high monocyte tissue factor expression and consequently to a prothrombotic diathesis.
Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle‐aged men compared with those in young men
Authors: Diver Michael J. , Imtiaz Komal E. , Ahmad Aftab M. , Vora Jiten P. , Fraser William D. 
Published: June 2003

Summarybackground Conflicting views are reported on the association between advancing age and gradually diminishing concentrations of serum total testosterone in men. The putative loss of diurnal rhythm in serum total testosterone in older men is reported to be in part due to low concentrations in the morning when compared to concentrations found in young men. We have measured total, free and bioavailable testosterone along with SHBG in samples taken every 30 min throughout a 24‐h period in 10 young and eight middle‐aged men.results Both young and middle‐aged men displayed a significant diurnal rhythm in all variables, with a minimum fall of 43% in total testosterone from peak to nadir in all subjects. Subjecting the data to a time series analysis by least squares estimation revealed no significant difference in mesor (P = 0·306), amplitude (P = 0·061) or acrophase (P = 0·972) for total testosterone between the two groups. Comparing bioavailable testosterone in the two groups revealed no significant difference in mesor (P = 0·175) or acrophase (P = 0·978) but a significant difference (P = 0·031) in amplitude. Both groups display a significant circadian rhythm (middle‐aged group P < 0·001; young group P = 0·014). Free testosterone revealed a highly significant rhythm in both the young group (P < 0·001) and the middle‐aged group (P = 0·002), with no significant difference between the groups in mesor (P = 0·094) or acrophase (P = 0·698). Although analysis of the SHBG data revealed a significant rhythm in the young group (P = 0·003) and the older group (P < 0·001), the acrophase occurred in the mid afternoon in both groups (15·12 h in the young and 15·40 h in the middle‐aged). The older men had a significantly greater amplitude (P = 0·044) but again no significant difference was seen in mesor (P = 0·083) or acrophase (P = 0·477) between the two groups. Acrophases for total, bioavailable and free testosterone occurred between 07·00 h and 07·30 h; for SHBG the acrophase occurred at 15·12 h in the young group and 15·40 h in the middle‐aged group.conclusions The study suggests that the diurnal rhythm in these indices of androgen status is maintained in fit, healthy men into the 7th decade of life.