bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased prevalence of antibodies to enteropathogenicYersinia enterocoliticavirulence proteins in relatives of patients with autoimmune thyroid disease
Authors: STRIEDER T G A , WENZEL B E , PRUMMEL M F , TIJSSEN J G P , WIERSINGA W M 
Published: December 2004

SUMMARYInfections have been implicated in the pathogenesis of a number of autoimmune diseases, and Yersinia enterocolitica (YE) might play a role in the development of autoimmune thyroid disease (AITD). Clinical evidence in support of this hypothesis has been inconclusive. We reasoned that looking earlier in the natural course of AITD might enhance chances of finding evidence for YE infection. Consequently, we determined seroreactivity against YE in subjects at risk of developing AITD, i.e. in 803 female relatives of AITD patients in self-proclaimed good health. As a comparison group we used 100 healthy women who participated in a program for reference values. IgG and IgA antibodies to virulence-associated outer membrane proteins (YOPs) of YE were measured by a specific assay. Serum thyroid peroxidase antibodies (TPO-Ab) as indicators of AITD were considered to be positive at levels of&gt; 100 kU/l. The prevalence of YOP IgG-Ab was higher in AITD relatives than in controls (40·1% vs. 24%, P = 0·002), and the same was true for YOP IgA-Ab (22% vs. 13%, P &lt; 0·05). Of the 803 AITD relatives, 44 had an increased or decreased plasma TSH, and 759 were euthyroid as evident from a normal TSH; the prevalence of YOP-Ab did not differ between these three subgroups. TPO-Ab were present in 10% of controls and in 27% of the AITD relatives (P &lt; 0·001). The prevalence of TPO-Ab in the euthyroid AITD relatives was not different between YOP IgG-Ab positive and negative subjects (23·3% vs. 24·7%, NS), nor between YOP IgA-Ab positive and negative subjects (21·2% vs. 24·9%, NS). In conclusion, healthy female relatives of AITD patients have an increased prevalence of YOP antibodies, which, however, is not related to the higher prevalence of TPO antibodies in these subjects. The findings suggest a higher rate of persistent YE infection in AITD relatives. Susceptibility genes for AITD may also confer a risk for YE infection.
Mycophenolic acid inhibits activation of inducible nitric oxide synthase in rodent fibroblasts
Authors: MILJKOVIC Dj , CVETKOVIC I , STOSIC-GRUJICIC S , TRAJKOVIC V 
Published: December 2004

SUMMARYMycophenolate mofetil (MMF) is an immunosuppressive drug that acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH). MMF has recently been shown to inhibit the enzymatic activity of inducible NO synthase (iNOS) and subsequent production of the cytotoxic free radical nitric oxide (NO) in endothelial cells. We here investigated the effect of bioactive MMF compound mycophenolic acid (MPA) on iNOS-mediated NO synthesis in fibroblasts, which are important source of NO in rheumatoid arthritis and during rejection of solid organ transplants. MPA exerted dose-dependent inhibition of NO synthesis, measured as nitrite accumulation, in IFN-γ + LPS-stimulated L929 mouse fibroblast cell line and rat primary fibroblasts. The effect of MPA was not mediated through interference with IMPDH-dependent synthesis of iNOS co-factor BH4 and subsequent suppression of iNOS enzymatic activity, as direct BH4 precursor sepiapterin failed to block the action of the drug. MPA suppressed the IFN-γ + LPS-induced expression of fibroblast iNOS protein, as well as mRNA for iNOS and its transcription factor IRF-1, as assessed by cell-based ELISA and semiquantitative RT-PCR, respectively. MPA suppression of fibroblast NO release, iNOS, and IRF-1 activation, was efficiently prevented by exogenous guanosine, indicating that the drug acted through reduction of IMPDH-dependent synthesis of guanosine nucleotides. These results suggest that MPA inhibits NO production in fibroblasts by blocking guanosine nucleotide-dependent expression of iNOS gene, through mechanisms that might involve the interference with the induction of iNOS transcription factor IRF-1.
Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection
Authors: TITANJI K , NILSSON A , MÖRCH C , SAMUELSSON A , SÖNNERBORG A , GRUTZMEIER S , ZAZZI M , DE MILITO A 
Published: December 2004

SUMMARYNerve growth factor (NGF) regulates B cell activation and differentiation and is an autocrine survival factor for memory B lymphocytes. We have reported recently that the number of memory B cells is reduced during HIV-1 infection. In this study we evaluated whether alteration in the NGF supply was involved in memory B cell loss in HIV-1-infected subjects. High rate of cell death in vitro was observed in memory B cells from HIV-1-infected individuals compared to uninfected donors (26·2 ± 2·5%versus 7·9 ± 1·4%, P &lt; 0·001). The increased expression of Fas on memory B cells from infected subjects did not enhance the susceptibility of the cells to Fas-mediated apoptosis in vitro. The frequency of NGF detection in plasma from HIV-1-infected subjects was significantly lower than in healthy donors (33·6%versus 63·6%, P &lt; 0·001). Also, the median plasma NGF in HIV-1-infected individuals was significantly lower than in uninfected controls (5 versus 14 pg/ml, respectively, P &lt; 0·01). Interestingly, the plasma NGF level was correlated directly 1to the percentage of memory B cells (P &lt; 0·05). HIV-1-infected subjects with a low number of peripheral memory B cells had a reduced incidence of plasmatic NGF (7·4%) compared to patients with a normal level of memory B cells (37%, P &lt; 0·01). Moreover, the addition of recombinant NGF (1 µg/ml) to cultures of purified B cells reduced cell death of memory B cells from HIV-1-infected subjects from 24·04 ± 3·0% to 17·4 ± 1·3% (P &lt; 0·01). HIV-1-infected individuals also carried higher levels of natural anti-NGF autoantibodies compared to uninfected subjects. In conclusion, we found that memory B cells from HIV-1-infected individuals are primed for cell death. Our study suggests an association between low frequency of plasma NGF detection and the increased cell death of memory B lymphocytes observed during HIV-1 infection. Low levels of NGF in plasma may be due to reduced supply or to NGF binding to natural anti-NGF autoantibodies.
A marked difference in pathogenesis and immune response induced by differentMycobacterium tuberculosisgenotypes
Authors: LÓPEZ B , AGUILAR D , OROZCO H , BURGER M , ESPITIA C , RITACCO V , BARRERA L , KREMER K , HERNANDEZ-PANDO R , HUYGEN K , VAN SOOLINGEN D 
Published: December 2004

SUMMARYIn the last decade, an unprecedented genetic diversity has been disclosed among Mycobacterium tuberculosis strains found worldwide. However, well-conserved genotypes seem to prevail in areas with high incidence of tuberculosis. As this may be related to selective advantages, such as advanced mechanisms to circumvent [M. bovis Bacille Calmette–Guerin (BCG)-induced] host defence mechanisms, we investigated the influence of strain diversity on the course of experimental disease. Twelve M. tuberculosis strains, representing four major genotype families found worldwide today, and the laboratory strain H37Rv were each used to infect BALB/c mice by direct intratracheal injection. Compared with H37Rv, infections with Beijng strains were characterized by extensive pneumonia, early but ephemeral tumour necrosis factor-alpha (TNF-α) and inducible isoform of nitric oxide synthetase (iNOS) expression, and significantly higher earlier mortality. Conversely, Canetti strains induced limited pneumonia, sustained TNF-α and iNOS expression in lungs, and almost 100% survival. Strains of the Somali and the Haarlem genotype families displayed less homogeneous, intermediate rates of survival. Previous BCG vaccination protected less effectively against infection with Beijing strains than against the H37Rv strain. In conclusion, genetically different M. tuberculosis strains evoked markedly different immunopathological events. Bacteria with the Beijing genotype, highly prevalent in Asia and the former USSR, elicited a non-protective immune response in mice and were the most virulent. Future immunological research, particularly on candidate vaccines, should include a broad spectrum of M. tuberculosis genotypes rather than a few laboratory strains.
Increased susceptibility to airway responses in CD40-deficient mice
Authors: TAKAHASHI H , EBIHARA S , KANDA A , KAMANAKA M , SATO T , HABU S , KIKUTANI H , SASAKI H 
Published: December 2004

SUMMARYThe interaction between CD40 and its ligand (CD154) is crucial for IL-12 production and effective humoral immunity such as IgE production. Although the interaction seems to play a crucial role in asthmatic inflammation, previous studies investigating the role of the CD40 and CD154 interaction in experimental animal models of asthma are complicated due to multistep reactions in developing asthma. Here, in order to investigate the role of CD40 in the effector phase in the development of airway responses, we used CD40-deficient mice backcrossed with mice transgenic for an ovalbumin (OVA)-specific TCR (TCRtg). Using intranasal OVA administration followed by aerosol inhalation of OVA, greater airway hyperreactivity and eosinophilia in bronchoalveolar lavage fluid (BALF) were observed in CD40-deficient mice backcrossed with TCRtg mice (CD40–/–/ TCRtg mice), compared with control littermates (CD40+/+/ TCRtg mice). CD4+ helper T cell subset analysis of lung draining lymph nodes revealed that the Th1 component was significantly decreased in CD40–/–/ TCRtg mice. Airway hyperreactivity and airway eosinophilia significantly correlated with the predomination of Th2 cells. Cytokine measurements in BALF also showed decreased IL-12 and the predominance of Th2 cells in CD40–/–/ TCRtg mice. These results suggest that CD40 may play a protective role in developing asthma in the phase after establishing specific memory T cells through the regulation of the balance between Th1 and Th2 cells presumably via induction of IL-12.
Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis
Authors: HO C Y , WONG C K , LI E K , TAM L S , LAM C W K 
Published: December 2004

SUMMARYTo study the immunosuppressive and anti-inflammatory effects of combined leflunomide and methotrexate (MTX) therapy on chemokine expression in patients with rheumatoid arthritis (RA), nine patients were enrolled for the combination therapy for 24 weeks. These patients have been on treatment with MTX 15 mg/week for not less than 3 months before entry to the study. A loading dose of l00 mg/day of leflunomide was given for 3 days, followed by 10 mg/day for the rest of the study period. Plasma concentrations of monocyte chemotactic protein-1 (MCP-1), thymus- and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) were assayed before and after combination treatment by ELISA. Gene expression of inflammatory cytokines and chemokines of peripheral blood mononuclear cells was analysed by cDNA expression array. Plasma MCP-1, TARC and MDC concentrations were significantly lower in patients after combination treatment [median (interquartile range) before versus after treatment: MCP-1 of 118·0 (64·0–515·2) versus 3·2 (0·0–22·8) pg/ml, P &lt; 0·01; TARC of 126·1 (27·2–197·4) versus 0·0 (0·0–52·5) pg/ml, P &lt; 0·05; MDC of 503·3 (446·2–600·9) versus 366·8 (337·4–393·4) pg/ml, P &lt; 0·05]. Positive correlations among reductions in plasma chemokines and clinical outcome measures were also found. Expression of chemokine genes including MDC and TARC was suppressed after combination treatment [% suppression of 38·7 (54·3–13·0) and 53·7 (55·9–28·4), respectively]. Combination therapy with leflunomide and MTX exhibits anti-inflammatory activity in the suppression of chemokine expression and subsequent recruitment of inflammatory cells into the inflammatory sites in RA.
Treatment of acute kidney allograft rejection with a non-mitogenic CD3 antibody
Authors: MEIJER R T , SURACHNO S , YONG S L , BEMELMAN F J , FLORQUIN S , TEN BERGE I J M , SCHELLEKENS P T A 
Published: December 2004

SUMMARYT3/4.A is a non-mitogenic murine IgA mAb to human CD3 that was selected for clinical studies to provide an alternative for the mitogenic, T cell-activating, therapeutic mAb OKT3. Previously, we reported that T3/4.A is better tolerated in humans than the IgG2a-CD3 mAb T3/4.2a. Here we report the results of a phase II clinical trial to assess the immunosuppressive potential of T3/4.A. Eighteen first kidney transplant recipients with a first rejection episode were included. Baseline immunosuppression consisted of cyclosporin and prednisolone. Rejection treatment consisted of 5 mg mAb per day during 10 days. Fourteen patients responded, of whom four experienced a second rejection within 2 weeks, one experienced chronic rejection after 2·5 years, whereas the others remained rejection-free after treatment (median duration of follow-up 42 months). Four patients did not respond and eventually lost their graft. These results are similar to treatment results with OKT3, as reported in the literature. Following the first dose of T3/4.A, side effects were limited, and reduced compared to OKT3-treated controls. On the second day, 15 patients developed transient vomiting and/or diarrhoea, which coincided with elevated serum levels of proinflammatory cytokines. Minimal or even no side effects occurred during the remaining days, which is in sharp contrast to that seen generally during OKT3 treatment. Both T cell numbers and TCR expression were reduced during the therapy. We conclude that T3/4.A is a good alternative for OKT3 to treat rejection episodes in renal transplant recipients.
Increased numbers of CD38 molecules on bright CD8+ T lymphocytes in infectious mononucleosis caused by Epstein–Barr virus infection
Authors: ŽIDOVEC LEPEJ S , VINCE A , ÐAKOVIĆ RODE O , REMENAR A , JEREN T 
Published: December 2004

SUMMARYThe aim of this study was to quantify the expression of CD38 on CD8+ T lymphocytes of patients with infectious mononucleosis (IM) caused by Epstein–Barr virus (EBV) and cytomegalovirus (CMV). CD38 quantification technique chosen for this study was based on the enumeration of CD38 antibody binding sites in comparison to the quantification standards rather than determining relative fluorescence, which is difficult to standardize. The study enrolled 19 patients with typical clinical and laboratory parameters compatible with EBV-induced IM as well as 10 patients with atypical clinical presentation of this disease. Furthermore, CD38 expression was analysed in a group of 13 patients with IM caused by CMV infection. CD38 quantification was performed within 6 days of the presentation of symptoms. All three groups of IM patients showed a statistically significant increase in the number of anti-CD38 antibody binding sites (which correspond to the number of CD38 molecules) on bright CD8+ T lymphocytes compared to healthy controls. The numbers of CD38 molecules expressed on CD8+ T lymphocytes did not differ significantly between IM patients with typical and atypical clinical presentation of the disease. Patients with CMV-induced IM had significantly lower numbers of CD38 molecules expressed on CD8+ T lymphocytes. Therefore, we conclude that CD38 quantification could be helpful in differential diagnostics of IM cases with atypical clinical presentation.
Hypogalactosylation of serum IgG in patients with coeliac disease
Authors: CREMATA J A , SORELL L , MONTESINO R , GARCÍA R , MATA M , CABRERA G , GALVAN J A , GARCÍA G , VALDÉS R , GARROTE J A 
Published: December 2004

SUMMARYCoeliac disease (CD) is described as an autoimmune enteropathy associated with the presence of IgG and IgA antigliadin and antitransglutaminase autoantibodies. While of diagnostic significance, the role of these autoantibodies in the immunopathogenesis of CD is elucidated. An inappropriate T cell immune response to gluten is also involved in the pathogenesis of CD, as evidenced by autoantibody switching. The N-glycans released from serum IgG of CD patients and three groups of healthy controls, of differing age ranges, were analysed by NH2-high performance liquid chromatography (HPLC). The fucosylated biantennary N- glycans were the most abundant neutral oligosaccharides; in particular, the agalacto form (G0F) showed a mean value of 42% (s.d. ± 7·4), 30% (s.d. ± 5·9), 26% (s.d. ± 4·2) and 35% (s.d. ± 6·8) for CD patients, healthy children, healthy adults under 40 and healthy adults over 40 years old, respectively. The ratio of asialo agalacto fucosylated biantenna to asialo monogalacto fucosylated biantenna (G0F)/(G1F) for CD patients showed a significant increase compared to healthy children (P &lt; 0·0002), healthy adults under 40 (P &lt; 0·0002) and healthy adults over 40 years old (P &lt; 0·01). Hypogalactosylation was more pronounced for CD patients than for the patients with other autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis.
Critical roles of CD30/CD30L interactions in murine autoimmune diabetes
Authors: CHAKRABARTY S , NAGATA M , YASUDA H , WEN L , NAKAYAMA M , CHOWDHURY S A , YAMADA K , JIN Z , KOTANI R , MORIYAMA H , SHIMOZATO O , YAGITA H , YOKONO K 
Published: December 2004

SUMMARYCD30/CD30L is a member of tumour necrosis factor (TNF) receptor/TNF superfamily and has been implicated in immune-regulation. A genetic study has also suggested a possible implication of CD30 in spontaneous autoimmune diabetes in NOD mice. In this study, we investigated the involvement of CD30/CD30L in the development of diabetes in NOD mice. Flow cytometric analysis showed that CD30 and CD30L were highly expressed on CD4+ or CD8+ T cells in the spleen and pancreatic lymph node of younger NOD mice. In addition, islet-specific CD4+ or CD8+ T cell lines expressed CD30 and CD30L. Administration of a neutralizing anti-CD30L monoclonal antibody (mAb) from 2 to 10 week of age completely suppressed the development of spontaneous diabetes in NOD mice. In addition, the treatment with anti-CD30L mAb also inhibited the development of diabetes induced by adoptive transfer of spleen cells from diabetic NOD mice or islet-specific CD4+ or CD8+ T cell lines into NOD-SCID mice. Furthermore, anti-CD30L mAb inhibited T cell proliferation in response to islet antigens. These results suggested that CD30/CD30L interaction plays important roles in both induction and effector phases of autoimmune diabetes in NOD mice.
Predictive markers for development of strongyloidiasis in patients infected with both Strongyloides stercoralis and HTLV-1
Authors: SATOH M , KIYUNA S , SHIROMA Y , TOMA H , KOKAZE A , SATO Y 
Published: December 2004

SUMMARY
Severe strongyloidiasis has often been reported to occur in some patients infected with both Strongyloides stercoralis (S. stercoralis) and human T-cell leukaemia virus type 1 (HTLV-1); however, there are few useful predictive markers for the risk of development of strongyloidiasis in these patients. To search for such predictive markers, we examined peripheral blood and stool samples of individuals infected with both S. stercoralis and HTLV-1 in Okinawa, Japan, an area in which both of these are endemic. The HTLV-1 proviral load and antibody titre were examined in relation to the S. stercoralis load as measured by the direct faecal smear method in patients infected with both S. stercoralis and HTLV-1. The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) antibody titre was also measured in these patients in order to examine the relationship between host immunity and HTLV-1 proviral load or antibody titre. The direct faecal smear-positive group showed both a higher HTLV-1 proviral load and HTLV-1 antibody titre than the -negative group (P &lt; 0·05). In contrast, inverse correlations of these parameters with the EBNA antibody titre were observed, especially for proviral load (ρ = −0·387, P &lt;  0·05). These results suggest that HTLV-1 proviral load and antibody titre influence the S. stercoralis load via disturbance of the host immunity, and that proviral load would be an especially useful predictive marker of the risk of development of strongyloidiasis in patients infected with both S. stercoralis and HTLV-1.
CD8β/CD28 expression defines functionally distinct populations of peripheral blood T lymphocytes
Authors: WERWITZKE S , TIEDE A , DRESCHER B E , SCHMIDT R E , WITTE T 
Published: December 2004

SUMMARYPeripheral blood CD8+ T lymphocytes generally express the CD8 coreceptor as an αβ heterodimer. On these cells, the CD8β chain is present either at high (CD8βhigh) or low density (CD8βlow). CD8βhigh cells are CD28+, whereas CD8βlow cells are CD28+ or CD28–. Therefore, three subpopulations of CD8+ T cells can be described: (i) CD8βhighCD28+ (ii) CD8βlowCD28+, and (iii) CD8βlowCD28– cells. Phenotypic and functional characterization of these CD8+ T cell subsets revealed significant differences. CD8βhighCD28+ cells predominantly express CD45RA. In contrast, CD8βlowCD28+ cells frequently express CD45R0 and the activating NK receptor CD161. CD8βlowCD28– cells frequently revert to the CD45RA phenotype. In addition, these cells express CD16, CD56, CD94, and the killer-inhibitory receptors NKB1 and CD158a. Intracellular IL-2 was frequently detected in CD8βhighCD28+ cells and CD8βlowCD28+ cells, but not CD8βlowCD28– cells. CD8βlowCD28+ cells and CD8βlowCD28– cells frequently stained positive for IFN-γ. In addition, these cells contain intracellular perforin and granzyme A. Expression of Fas (CD95) as well as susceptibility to apoptosis is markedly increased in CD8βlowCD28+ and CD8βlowCD28– cells as compared to CD8βhighCD28+ cells. In vitro activation of peripheral blood lymphocytes triggered expansion of CD8βhighCD28+ cells as well as a development into CD8βlowCD28+ and CD8βlowCD28– cells. Similarly, activation of CD8βhighCD28+ cord blood cells resulted in the appearance of CD8βlowCD28+ and CD8βlowCD28– cells. These data suggest that CD8βhighCD28+ cells can differentiate into CD8βlowCD28+ and CD8βlowCD28– cells upon TCR stimulation. Therefore, the CD8β/CD28 subsets in peripheral blood may reflect distinct stages of post-thymic CD8+T cell development.
Mannan-binding lectin in children with Escherichia coli O157:H7 haemmorrhagic colitis and haemolytic uraemic syndrome
Authors: PROULX F , WAGNER E , TOLEDANO B , DECALUWE H , SEIDMAN E G , RIVARD G-E 
Published: December 2004

SUMMARY
Mannan-binding lectin (MBL) triggers complement activation upon binding to microbial surfaces. MBL deficiency has been associated with increased susceptibility to severe bacterial infections. We hypothesized that MBL deficiency may predispose children to Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections and the associated haemolytic uraemic syndrome (HUS). We compared circulating levels of MBL among children with uncomplicated O157:H7 haemorrhagic colitis (HC), patients with O157:H7 HUS, normal and diseases control groups. Circulating MBL concentrations on admission were as follows: 3·22 ± 2·43 µg/ml among normal controls (n = 23); 2·90 ± 2·44 µg/ml in patients with rotavirus enteritis (n = 10); 2·78 ± 1·65 µg/ml in children with HC due to non-STEC bacterial pathogen (n = 15); 2·67 ± 2·44 µg/ml in patients with uncomplicated O157:H7 HC (n = 27); 2·80 ± 2·97 µg/ml in children with O157:H7 HUS (n = 15); 6·70 ± 4·49 µg/ml in patients with chronic renal failure unrelated to O157:H7 infection (n = 6). Higher MBL levels were found in patients with chronic renal failure compared to O157:H7 HC (P &lt; 0·047). However, MBL concentrations &lt;0·5 µg/ml, which have been associated with MBL deficiency in relation to increased susceptibility to infections, were noted at comparable rates between the different groups (P = NS). Our data does not support that MBL deficiency may predispose to O157:H7 infections nor than the development of diarrhoea associated HUS.