bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ivermectin-induced immunopotentiation in onchocerciasis: recognition of selected antigens following a single dose of ivermectin
Authors: Akuffo H , Maasho K , Lavebratt C , Engström K , Britton S 
Published: November 2003

SUMMARY
Onchocerciasis is associated with blindness and gross skin changes, believed to be a consequence of the immune response to antigens released from the offspring of the female worm of Onchocerca volvulus, the microfilariae (mf). An effective microfilaricidal drug is now available which quickly reduces the mf burden without affecting the adult worm. There exist foci in onchocerciasis endemic areas where some of the patients have many mf in their skin but relatively few clinical symptoms. This state of hyposensitivity is believed to be due to immunosuppression. The aim of this study was to address the question of the basis of, and the effect of ivermectin treatment on this immunosuppression. Female adult worms of O. volvulus were used as whole or fractionated antigens to stimulate peripheral blood mononuclear cells. Microfilariae are found in the reproduction tract of the female worms, and thus an antigen preparation of the female adult O. volvulus contains both exclusive adult antigens as well as antigens from microfilariae. Cells were obtained from onchocerciasis patients, individuals of similar socio-economic status living in the same Ghanaian village, but who showed no parasitological or clinical evidence of onchocerciasis (exposed endemic controls), healthy Ghanaians living in areas where transmission of onchocerciasis does not seem to occur (non-exposed endemic controls) and unexposed healthy Swedish donors. As a group, cells from onchocerciasis patients proliferated to a lesser degree than cells from the exposed endemic control and the non-exposed endemic control groups to the whole worm antigen, whereas the phytohaemagglutinin (PHA) response was strongest in the patients. Proliferative responses of above 1000 ct/min to fractions of the worm extract were only evident in the cells from a few individuals in each of the various groups. However, 28 days following ivermectin treatment, cells from all onchocerciasis patients were able to mount significantly enhanced proliferation to a fraction of approximately 96 kD (fraction 3), while only four of nine of this group showed an increased response to the whole worm antigen. The proportional increase in the response to the whole organism in these individuals was of a much lower magnitude than the increased response to fraction 3. The O. volvulus antigen-specific immunosuppression observed in these onchocerciasis patients appears to be due to suppressive antigens which have the capacity to mask the potential response to selected antigens of O. volvulus, and ivermectin treatment possibly modulates the immune response, allowing for stepwise recognition of such antigens. Since ivermectin treatment kills only the microfilariae and not the adult worm, the putative suppressive antigens would be expected to be from the microfilariae.
Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis
Authors: Roche P W , Winter N , Triccas J A , Feng C G , Britton W J 
Published: November 2003

SUMMARY
Proteins secreted across the cell wall of mycobacteria are important antigens recognized early in the host response to mycobacterial infection. MPT64 is a 23-kD secreted protein restricted to members of the Mycobacterium tuberculosis complex which elicits T cell responses and cutaneous DTH reactions in Myco. tuberculosis-infected animals. Patients with tuberculosis and their tuberculin-positive contacts respond to the protein, but recipients of bacille Calmette–Guérin (BCG) vaccine strains lacking the mpt64 gene do not. In the present study, we describe the development of a unique recombinant mycobacterial vector which secretes the encoded Myco. tuberculosis protein MPT64 at high levels into the culture filtrate, from which the protein is isolated by a single-step affinity chromatographic step. The purified protein was recognized by both polyclonal and monoclonal anti-MPT64 antibodies. The T cell reactivity of the protein was confirmed by its ability to stimulate human anti-rMPB64 T cell lines. The Myco. smegmatis recombinant MPT64 protein was superior to the Escherichia coli rMPB64 protein, which has identical amino acid sequence, in eliciting cutaneous DTH reactions in guinea pigs sensitized with Myco. tuberculosis. Animals sensitized with BCG strains lacking the mpb64 gene failed to respond to MPT64. Similarly, interferon-gamma (IFN-γ) responses in tuberculosis patients and their contacts were higher to the Myco. smegmatis form of the protein. The potential of this form of the Myco. tuberculosis MPT64 protein as a skin test reagent for tuberculosis is discussed.
Differential expression of Fc receptors for IgG by monocytes and granulocytes from neonates and adults
Authors: Maeda M , van Schie R C A A , Yüksel B , Greenough A , Fanger M W , Guyre P M , Lydyard P M 
Published: November 2003

SUMMARY
The immature neonatal immune system is thought to result in increased risk of infection. Receptors for the Fc moiety of IgG (FcγR) are important in antibody-mediated clearance of microbes by granulocytes and monocytes/macrophages. As an approach to understanding their role in neonatal life, we have compared the constitutive expression of the three Fc receptors—FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16)—by neonatal and adult blood monocytes and granulocytes using quantitative immunofluorescence by flow cytometry. Our results confirm that there is a small subpopulation of FcγRII-positive monocytes in adult blood, and furthermore show that this is absent or at a low percentage in cord blood samples. However, the main population of cord blood monocytes expresses low, but significantly higher levels of FcγRIII than adult monocytes. No differences were seen in the quantitative expression of FcγRI and FcγRII. Neonatal granulocytes expressed significantly higher levels of both FcγRI and FcγRII but significantly lower levels of FcγRIII. The data are discussed in terms of the possible role of cytokines and susceptibility to infection.
Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics
Authors: Cook R T , Waldschmidt T J , Cook B L , Labrecque D R , Mclatchie K 
Published: November 2003

SUMMARY
Chronic alcoholics are frequently immunodeficient, have polyclonal hypergammaglobulinaemia, and often have autoantibodies. Recent work in other diseases has shown that functional distinctions of possible relevance to autoimmunity and immunodeficiency can be found among the B cell subsets defined by differential expression of the surface markers CD5 and CD45RA. Therefore, we have evaluated the CD5,CD45RA B cell subsets of both chronic alcoholics without evidence of active liver disease (AWLD), and alcoholics admitted for acute alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry in 20 patients and 29 controls revealed a sharp decrease in the percentage of alcoholics’ B cells which were CD5+, 37.6% versus 16.3%, P&lt;0.00001; absolute CD5+ B cell numbers were similarly reduced (58.9 cells/μl versus 20.9; P=0.0012). In addition to the loss of CD5+ B cells, there was a reduction in the percentage of B cells which are CD5−CD45RAhi, leaving many patients with a B cell profile which was predominantly CD19+CD5−CD45RAlo. This subset appears phenotypically similar to the IgM-producing CD5−CD45RAlo subset described by others, and may be enriched for autoantibody-producing cells. One outlier patient was an ALD with 61% of B cells which were CD5+, which also is a profile consistent with increased autoantibody production.
Presence of covalent bonds between immune deposits and other macromolecules in murine renal glomeruli
Authors: Mannik M 
Published: November 2003

SUMMARY
Microscopic studies have suggested that immune deposits persist for a long time in subepithelial areas of renal glomeruli in human diseases and in experimental models. This study showed quantitatively that in an experimental murine model radiolabelled antibodies in subepithelial immune deposits remained constant for 9 months at about 3 μg/mouse. The extraction of these antibodies was incomplete with 1% SDS at 8 months after immune deposit formation. Furthermore, in the extracted material some antibodies were covalently bound to other molecules. This study demonstrates that covalent bond formation contributes to the persistence of immune deposits in renal glomeruli.
T cell responses to myeloperoxidase (MPO) and proteinase 3 (PR3) in patients with systemic vasculitis
Authors: Griffith M E , Coulthart A , Pusey C D 
Published: November 2003

SUMMARY
T cell-mediated immune responses are likely to be important in the pathogenesis of systemic vasculitis. However, identifying the T cells involved has proved difficult, and there are conflicting reports regarding T cell proliferation in response to different autoantigens. Perinuclear (P) and cytoplasmic (C) anti-neutrophil cytoplasmic antibodies (ANCA) are closely associated with systemic vasculitis, and are generally specific for MPO or PR3, respectively. We studied the proliferative responses to MPO and PR3 of peripheral blood mononuclear cells from patients with P-ANCA or C-ANCA specific for these antigens by ELISA. These responses were compared with those of normal controls, and of disease controls with P- or C-ANCA not specific for MPO or PR3. The patient group as a whole showed significant T cell proliferation in response to the autoantigens compared with controls (P=0.005). Cells from nine of 13 P-ANCA-positive, anti-MPO-positive patients proliferated in response to MPO, compared with five of 16 controls (P=0.04). Cells from five of eight C-ANCA-positive, anti-PR3-positive patients proliferated in response to PR3, compared with two of 11 controls (P=0.05). These experiments demonstrate that patients with P-ANCA or C-ANCA possess T cells which respond to MPO or PR3, respectively. As in other autoimmune diseases, responses to both antigens were also seen in a proportion of healthy controls. Further analysis of these responses will be important in understanding the pathogenesis of systemic vasculitis and in designing specific immunotherapy.
Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits
Authors: Rygg M 
Published: November 2003

SUMMARY
Serum amyloid A (SAA) is an acute-phase plasma protein which increases 100- to 1000-fold in response to inflammatory stimuli. In this study pregnant rabbits were subjected to laparotomy and their fetuses were injected with lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and scanning densitometry. In vitro derived RNA was used as standard for quantitative mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed by biological assays. Fetal rabbits responded to cytokine stimulation by increased hepatic SAA mRNA expression, both during late gestation and in the early neonatal period. However, differences in dose–responses, kinetics and mRNA concentrations were seen dependent on gestational age. IL-1 and tumour necrosis factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits corresponded with high levels in fetal, but not in maternal, serum. High levels of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult serum 1 day after a normal delivery. The study details the complexity of the cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.
Retinoic acid modulates the in vivo and in vitro growth of IL-6 autocrine human myeloma cell lines via induction of apoptosis
Authors: Levy Y , Labaume S , Colombel M , Brouet J C 
Published: November 2003

SUMMARY
We previously showed that IL-6 is an autocrine growth factor for two human myeloma cell lines, RPMI 8226 and U266. We investigated here the in vitro and in vivo effects of all-trans retinoic acid (RA) on the growth and survival of these two cell lines. RA induced a dramatic dose- and time-dependent inhibition of the proliferation of both cell lines. This inhibition was correlated with a down-modulation of the cell surface expression of the IL-6 binding chain (gp80) and the transducing chain (gp130) of the IL-6 receptor (IL-6R). Long-term culture experiments showed that down-modulation of gp80 expression was complete at days 15 and 30 in the presence of 10–5 and 10–7 mol/l of RA, respectively. Gp130 expression was greatly decreased, albeit still detectable, in similar culture conditions. RA-mediated interruption of the IL-6 autocrine loop was associated with a decrease of bcl-2 oncoprotein expression and apoptosis of the myeloma cells which was RA concentration- and time-dependent. The in vivo relevance of the effects of RA was studied on tumours which developed in nude mice inoculated with a subclone of RPMI 8226. Whereas tumours grew in all control mice, 40% of tumours regressed within 20 days in RA-treated mice. Cells from regressing tumours featured characteristics of apoptosis and exhibited low gp80 and gp 130 expression. Our study indicate that long-term RA treatment interferes in vivo and in vitro with IL-6 autocrine growth of myeloma cell lines, leading to apoptosis.
Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1
Authors: Rajagopalan-Levasseur P , Lecointe D , Bertrand G , Fay M , Gougerot-Pocidalo M-A 
Published: November 2003

SUMMARY
l-arginine-dependent reactive nitrogen intermediates have been identified as macrophage cytotoxic effector molecules against intracellular pathogens. To determine its role, ex vivo production of NO by peritoneal macrophages of C3H/HeN mice and Dunkin–Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pneumophila serogroup 1 strain was compared with bacterial clearance from the lungs. While the virulent strain was cleared from mice lungs, the guinea pigs died within 96 h. In vivo infection with both strains resulted in the production of NO by mouse peritoneal macrophages ex vivo. In contrast, guinea pig macrophages did not produce detectable NO. In addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent strain, irrespective of stimulation with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-γ). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by host macrophages.
Tumour necrosis factor-alpha (TNF-α) gene polymorphism and expression in pre-eclampsia
Authors: Chen G , Wilson R , Wang S H , Zheng H Z , Walker J J , McKillop J H 
Published: November 2003

SUMMARY
Pre-eclampsia is an endothelial disorder and TNF-α has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-α mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-α expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-α gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-α expression. Our results show that TNF-α mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-α may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-α in mediating endothelial disturbances, and suggest a key role for TNF-α in the development of pre-eclampsia.
Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients
Authors: García-Cózar F J , Molina I J , Cuadrado M J , Marubayashi M , PeÑa J , Santamaría M 
Published: November 2003

SUMMARY
Defective T cell functions, including IL-2 production and proliferation, have been shown in SLE patients. After T cell stimulation (first signal), a costimulatory signal (second signal) is required to achieve complete T cell activation. Main costimulatory signals are provided to T cells by B7 antigens (CD80 and CD86, expressed on antigen-presenting cells (APC)) upon interaction with its receptor, the CD28 molecule expressed on T cells. The aim of this study was to investigate the role of CD28/B7 interactions in the impaired T cell responses of SLE patients. We show that stimulation of T cells with phytohaemagglutinin (PHA) in the presence, but not in the absence, of anti-CD28 MoAb or B7+ cells results in tyrosine phosphorylation of specific substrates, transcription of mRNA and production of IL-2 that is indistinguishable in SLE patients and healthy controls. Moreover, proliferation of costimulated T cells from SLE and controls was specifically abrogated by blocking the CD28/B7 interactions by means of addition to the culture of the CTLA4-Ig fusion protein. However, in most patients activated APC failed to up-regulate B7 molecules, giving rise to ineffective costimulatory signalling to T cells. These results indicate that the CD28/B7 costimulatory pathway is defective in SLE patients.
Anti-neutrophil cytoplasmic antibodies (ANCA) directed against bactericidal/permeability increasing protein (BPI): a new seromarker for inflammatory bowel disease and associated disorders
Authors: Stoffel M P , Csernok E , Herzberg C , Johnston T , Carroll S F , Gross W L 
Published: November 2003

SUMMARY
It was our purpose to determine the immunodiagnostic value of ANCA directed against BPI in diseases known to be associated with ANCA, such as ANCA-associated vasculitides, inflammatory bowel disease (IBD) and the associated condition primary sclerosing cholangitis. The immunoreactivity of recombinant BPI (rBPI) was established in order to develop an ELISA specific for rBPI. By means of this assay, BPI-ANCA were assessed in sera of 178 patients with IBD or the associated disorder primary sclerosing cholangitis, 112 patients with ANCA-associated vasculitides, and in sera of 182 disease and 140 healthy controls. BPI-ANCA were found to be closely associated with IBD and primary sclerosing cholangitis (34% and 44% of ANCA-positive sera, respectively). By contrast, BPI-ANCA positivity was low (&lt;10%) in the double-negative sera of patients with ANCA-associated vasculitides and in disease and healthy controls. BPI-ANCA appear to constitute an important marker for IBD and primary sclerosing cholangitis, but not for the ANCA-associated vasculitides.
Prevention of adjuvant arthritis in Lewis rats by neonatal bacille Calmette–Guérin (BCG) infection
Authors: Esaguy N , Águas A P 
Published: November 2003

SUMMARY
Tolerization of pathogenic antigens is one of the experimental strategies that has been proposed to prevent autoimmune disease. We have investigated here whether neonatal intraperitoneal infection of Lewis rats with Mycobacterium bovis-BCG has any effect on the expression of adjuvant arthritis (AA), an autoimmune disease that is produced by immunization of the rats with dead mycobacteria in mineral oil (i.e. Freund’s complete adjuvant (FCA)). We found that neonatal infection with 108 viable BCG bacilli rendered all Lewis rats resistant to the expression of AA after FCA immunization. This BCG-induced protection from reactive arthritis was not seen in Lewis rats infected with smaller inocula (106 BCG bacilli) or if the infection was performed after the neonatal period (e.g. at 3 weeks of age). Neonatal administration of 65-kD mycobacterial heat shock protein (hsp65, a key antigen in the etiopathogenesis of AA) failed to protect Lewis rats from AA; injection of lactoferrin (an autoantigen that may be involved in the physiopathology of autoimmune arthritis) to newborn Lewis rats decreased the severity of AA observed after FCA immunization of the animals. Western blotting revealed that Lewis rats that had acquired resistance to AA also showed changes in their repertoire of antibody specificities; among these alterations was decreased anti-hsp65 reactivity. We conclude that neonatal infection with BCG, but not hsp65 injection, renders Lewis rats resistant to AA and that the phenomenon is associated with change in the repertoire of specificities of circulating antibodies.
Longitudinal study of the frequency of cytotoxic T cell precursors in kidney allograft recipients
Authors: Mestre M , Massip E , Bas J , Alsina J , Romeu A , Castelao A M , Buendia E , Grinyó J M 
Published: November 2003

SUMMARY
Clonal deletion or inactivation of donor-specific alloreactive cells are important mechanisms that are believed to account for acquired immune tolerance in allograft recipients. Serial assessment of precursor cytotoxic T lymphocyte frequencies (CTLpf) by limiting dilution analysis (LDA) provides information at the clonal level on changes in the alloimmune response of graft recipients. We performed a longitudinal study of 15 cadaveric kidney recipients before and every 3 months throughout the first year after transplantation (Tx). Pre-Tx values of donor CTLpf showed high interindividual variability without a predictive value for the clinical outcome. All patients with well functioning kidneys had decreased CTLpf at 3 months post-Tx in comparison with pre-Tx values. This decrease was donor-specific in four patients and was permanent in two cases throughout the study. Most patients presented decreased anti-donor CTLpf values from 6 to 9 months, whereas a partial recovery of donor CTLpf was observed in three patients. Reversible acute rejection was diagnosed in three patients, and it was associated with a marked increase in anti-donor CTLpf, returning to pre-Tx values by 9 months post-Tx. In addition, one patient with chronic rejection displayed a transient increase in CTLpf 6 months after Tx. The results of this sequential study indicate the establishment of a state of either hyporesponsiveness or functional clonal inactivation, transient or permanent, which could facilitate allograft acceptance.