bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease
Authors: Yang J J , Tuttle R , Falk R J , Jennette J C 
Published: November 2003

Abstract
The major subtypes of anti-neutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence assay (IFA) are P-ANCA and C-ANCA. In patients with vasculitis, myeloperoxidase (MPO) is the major P-ANCA antigen and proteinase 3 (PR3) is the major C-ANCA antigen. BPI and azurocidin, which are also called 57-kD cationic antimicrobial protein (CAP 57) and 37-kD cationic antimicrobial protein (CAP 37), respectively, have been proposed as less frequent target antigens for C-ANCA and P-ANCA. In patients with renal disease, we determined the frequency of antibodies against BPI and azurocidin. By IFA on alcohol-fixed neutrophils, monoclonal and polyclonal anti-BPI antibodies produced a C-ANCA pattern, whereas rabbit anti-azurocidin antibody produced a P-ANCA pattern. By ELISA, sera from 229 P-ANCA-positive patients, 99 C-ANCA-positive patients and 48 ANCA-negative (by IFA) patients with renal biopsies were tested for reactivity with recombinant human BPI and purified human azurocidin. Of these sera, 17.5% of P-ANCA, 30.3% of C-ANCA and 20.8% of IFA-ANCA-negative sera were positive for anti-BPI; and 8.3% of P-ANCA, 3.0% of C-ANCA and 8.3% of IFA-ANCA-negative sera were positive for anti-azurocidin. There was no statistical difference in frequency of anti-BPI between pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) and other glomerular disease (OGD), and there was a lower frequency of anti-azurocidin in NCGN samples than in OGD samples. By Western blot, anti-BPI-positive sera reacted with a 57-kD BPI band and anti-azurocidin-positive sera with a 29-kD azurocidin band. In conclusion, there is a low frequency of anti-BPI and anti-azurocidin antibodies in ANCA-positive patient sera; however, this does not correlate with NCGN, which is a marker for ANCA-associated small vessel vasculitis, and a similar positivity is found in IFA-ANCA-negative patients with renal disease. Therefore, serologic detection of anti-BPI and anti-azurocidin is not diagnostically specific in patients with renal disease.
Natural killer (NK) lymphocytosis induced by Epstein–Barr virus (EBV) reactivation in monoclonal gammopathy of undertermined significance (MGUS)
Authors: Ishiyama T , Koike M , Watanabe K , Watanabe H , Fukuchi K , Tsuruoka N 
Published: November 2003

Abstract
We investigated the relationship between NK lymphocytosis and EBV infection in MGUS. We found that two out of 10 patients showed an increase of NK cells compared with normal controls. In addition, these two patients had far higher levels of CD5LOW+ NK cells (activated NK cells) than controls. EBV DNA was detected by polymerase chain reaction in peripheral blood mononuclear cells from the two patients, although the other eight patients with MGUS and all 20 normal controls had no detectable EBV DNA. Furtheremore, EBV DNA was detected in sorted CD5LOW+ NK cells. These results suggest that reactivation of EBV might be related to the increase of NK cells, particularly CD5LOW+ NK cells in some patients with MGUS.
Structural polymorphisms of complement receptor 1 (CR1) in systemic lupus erythematosus (SLE) patients and normal controls of three ethnic groups
Authors: Moulds J M , Reveille J D , Arnett F C 
Published: November 2003

Abstract
CR1 exhibits a molecular weight polymorphism and variability in the number of C3b-binding sites. Because this may affect immune complex clearance, we used erythrocytes to investigate the CR1 size polymorphism in SLE patients from three ethnic groups. The CR1-C allele was found more frequently in African–Americans, but the frequency did not differ between controls (10%, n = 63) and SLE patients (9%, n = 79). A 160-kD band similar to CR1-C was noted in a number of patients and was shown to be a proteolytic cleavage fragment. The study shows that the smallest form of CR1, i.e. CR1-C, is not a genetic risk factor for SLE and that the frequencies of the CR1 structural alleles do not differ from race-matched healthy controls.
Elastase, but not proteinase 3 (PR3), induces proteinuria associated with loss of glomerular basement membrane heparan sulphate after in vivo renal perfusion in rats
Authors: Heeringa P , Van Den Born J , Brouwer E , Dolman K M , Klok P A , Huitema M G , Limburg P C , Bakker M A H , Berden J H M , Daha M R , Kallenberg C G M 
Published: November 2003

Abstract
Elastase, but not PR3, induces proteinuria associated with loss of glomerular basement membrane (GBM) heparan sulphate after in vivo renal perfusion in rats. PR3 and elastase are cationic neutral serine proteinases present in the azurophilic granules of polymorphonuclear leucocytes. Release of these proteolytic enzymes along the glomerular capillary wall may induce glomerular injury. Here, we investigated the effects of PR3 and elastase on the induction of proteinuria and glomerular injury after renal perfusion of these enzymes in Brown–Norway rats. Perfusion of active elastase induced a dose-dependent proteinuria 24 h after perfusion, while inactivated elastase did not. Perfusion of comparable amounts of active PR3 did not induce proteinuria. Light and electron microscopy showed no morphological abnormalities in any experimental group. However, immunohistology revealed that proteinuria occurring after perfusion of active elastase was associated with a strong reduction in intraglomerular expression of the heparan sulphate side chain and, to a lesser extent, of the protein core of heparan sulphate proteoglycans (HSPG). In vitro, both elastase and PR3 digested HSPG. However, PR3 bound to a lesser extent to HSPG than elastase. We conclude that elastase, but not PR3, induces proteinuria after in vivo renal perfusion. This differential effect probably relates to different binding to the GBM of those enzymes due to differences in their isoelectric points. Degradation of heparan sulfate proteoglycans, leading to the disappearance of their side chains that contribute to the polyanionic structure of the GBM, appears to be involved in the induction of proteinuria after perfusion of elastase.
Histaminergic regulation of interferon-gamma (IFN-γ) production by human natural killer (NK) cells
Authors: Asea A , Hansson M , Czerkinsky C , Houze T , Hermodsson S , Strannegård Ö , Hellstrand K 
Published: November 2003

Abstract
Monocytes, recovered from human peripheral blood by counter-current centrifugal elutriation, effectively inhibit the production of IFN-γ by CD3−/56+ NK cells in response to IL-2. This study aimed at defining the nature of the inhibitory signal, particularly the importance of monocyte-derived reactive metabolites of oxygen. It was found that monocytes recovered from patients with chronic granulomatous disease (CGD), a condition characterized by deficient NADPH-oxidase activity of phagocytes, did not inhibit IFN-γ production by NK cells. Further, catalase, a scavenger of hydrogen peroxide, completely reversed the inhibitory signal, whereas scavengers of the superoxide anion, hypohalous acids, the hydroxyl radical, or nitric oxide synthesis inhibitors such as L-NMMA were ineffective. Inhibition of IFN-γ production was operating on a pre-translational level, as indicated by the inability of enriched NK cells to accumulate IFN-γ mRNA in the presence of elutriated monocytes. Hydrogen peroxide, at micromolar concentrations, reconstituted the inhibition of IFN-γ production when added to enriched NK cells. Histamine, a biogenic amine which inhibits the generation of reactive oxygen metabolites in monocytes, abrogated the inhibition of IFN-γ production in NK cells; by this mechanism, histamine strongly synergized with IL-2 to induce IFN-γ in mixtures of NK cells and monocytes. The synergizing effect of histamine was specifically mediated by H2-type histamine receptors. We conclude that: (i) the induction of IFN-γ mRNA in NK cells is effectively down-regulated by products of the oxidative metabolism of monocytes; and (ii) histamine effectively enhances IFN-γ production by preventing monocyte-induced oxidative damage to NK cells.
Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver
Authors: Gabay C , Singwe M , Genin B , Meyer O , Mentha G , Le Coultre C , Vischer T , Guerne P-A 
Published: November 2003

Abstract
To investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.
Dendritic cells and tolerance induction
Authors: Steptoe R J , Thomson A W 
Published: November 2003

Abstract
Dendritic cells (DC) are widely accepted as the most potent antigen-presenting cells (APC), and considerable interest has been generated in their potential for the immunological therapy of cancer and infectious disease. Recently, however, a broader understanding of the phenotypic diversity and functional heterogeneity of DC has been acquired. Thus, in addition to having a role in central tolerance, DC are now regarded as potential modulators of peripheral immune responses. Harnessing this potential may offer a new approach to the immunosuppressive therapy of allograft rejection or autoimmunity. Here, the concept of ‘tolerogenic’ DC is placed in the context of rapidly accumulating new evidence of the diverse properties of these important APC.
IL-4 down-regulates the responsiveness of human intraepithelial lymphocytes
Authors: Ebert E C , Roberts A I 
Published: November 2003

Abstract
IL-4 is an important regulator of intestinal inflammation, yet little is known regarding its action on intestinal lymphocytes. Intestinal lymphocytes were isolated from jejunal mucosa of patients undergoing gastric bypass operations for morbid obesity. The impact of IL-4 was measured by its effects on proliferation using 3H-thymidine incorporation, IL-2 production using the CTLL assay, and IL-2 receptor generation using immunofluorescence. The production of IL-4 was measured by ELISA. IL-4 significantly inhibited the proliferation of intraepithelial lymphocytes (IEL) to a variety of stimuli as well as the development of lymphokine-activated killer (LAK) cells. In contrast, it had no effect on the proliferation of CD8+ T cells from peripheral blood. The inhibitory effect of IL-4 on IEL did not occur during activation, since IL-2 production and receptor expression were not altered. Rather, it occurred during cell cycling, since over 50% inhibition resulted whether IL-4 was added at the initiation of an IL-2-stimulated culture or after 24 or 48 h incubation. IL-4 was secreted by activated lamina propria lymphocytes (LPL) but not by IEL. IL-4,produced by activated LPL, may enter the epithelial compartment and down-regulate responsiveness of IEL.
Intrathyroidal cytokine gene expression in Hashimoto's thyroiditis
Authors: Ajjan R A , Watson P F , Mcintosh R S , Weetman A P 
Published: November 2003

Abstract
Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease in which cytokines are likely to have a role in the initiation and perpetuation of the disease. Using the reverse transcription-polymerase chain reaction (RT-PCR) we analysed the cytokine profile in four HT tissue samples. Furthermore, cell fractionation was carried out on two tissue samples and cytokine profile was studied in CD4+ and CD8+ T cells, in addition to the residual cellular infiltrate composed of CD4− and CD8− cells. Our results showed IL-1β, IL-4 and IL-6 mRNA expression in three out of four tissue samples, whereas IL-1α, IL-2, IL-8, IL-10, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) were expressed in all tissue samples studied. Expression of IL-1α and IL-1β was absent in both CD4+ and CD8+ subsets. However, IL-2, IL-4, IL-6, IL-8, IFN-γ and TNF-α mRNA were detected in both CD4+ and CD8+ subsets. IL-10 was expressed in the CD4+ subset in one sample, whereas it was negative in both CD8+ fractions. All the cytokines studied were expressed in the residual infiltrate. These results suggest a mixed Th1 and Th2 response in HT, both of which may have an important role in the pathophysiology of the thyroid destructive process through cell-mediated cytotoxicity, and/or humoral autoimmunity manifested by autoantibody production.
Intracellular cytokine production by human CD4+ and CD8+ T cells from normal and immunodeficient donors using directly conjugated anti-cytokine antibodies and three-colour flow cytometry
Authors: North M E , Ivory K , Funauchi M , Webster A D B , Lane A C , Farrant J 
Published: November 2003

Abstract
Using three-colour flow cytometry, we have measured intracellular IL-2, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) induced in human CD4+ and CD8+ T cells from normal donors and patients with common variable immunodeficiency (CVID). Since a new range of directly FITC-conjugated anti-cytokine antibodies was used, conditions were optimized for the concentration of antibody, for cell permeabilization and fixation, and for the time of exposure to monensin to retain the cytokines within the cell. Kinetics of intracellular cytokine production were measured for up to 20h in culture with phorbol myristate acetate (PMA) and ionomycin, or with phytohaemagglutinin (PHA). Kinetic studies of activation with PMA and ionomycin show that a higher proportion of normal CD4+ cells can make IL-2 than the other two cytokines, and that there are more TNF-α-positive CD4+ cells than cells with IFN-γ. For normal CD8+ cells the highest production of cytokine is of IFN-γ (up to 50% of the cells) especially at longer times (10–20h) of stimulation. For CD8+ cells, IL-2-positive cells exceed those with TNF-α. The other mitogenic stimulus used (PHA) was grossly inferior to PMA and ionomycin in its ability to induce intracellular cytokines. The time of exposure to monensin was also examined. Its continuous presence in the cultures (up to a maximum of 20h) increased the detection of IL-2-positive cells without apparently reducing the percentage of cytokine-positive CD4+ or CD8+ cells. Finally, using optimal conditions, we compared cytokine production in cells from patients with the disease CVID and showed normal cellular levels of ability to produce IL-2 and TNF-α but significantly raised levels of production of IFN-γ in both CD4+ and CD8+ lymphocytes. This suggests that the pathology of this disease may involve an excessive Th1-type response.
Thy-1 molecule associates with protein tyrosine kinase(s) in rat mesangial cells
Authors: Narisawa-Saito M , Yamanashi Y , Morioka T , Oite T , Shimizu F 
Published: November 2003

Abstract
Glycophosphatidylinositol (GPI)-linked Thy-1 molecules, well known cell surface markers of murine T cells, are present on the glomerular mesangial cells of the rat kidney. The administration of anti-Thy-1.1 MoAbs 1-22-3 and OX-7 to rats induces severe and mild complement-dependent mesangial proliferative glomerulonephritis, respectively. In order to determine whether protein-tyrosine kinase (PTK) activity is associated with Thy-1 molecules on rat mesangial cell surface, we performed an immune complex kinase assay, using anti-Thy-1 MoAbs 1-22-3 and OX-7, followed by reimmunoprecipitation with anti-phosphotyrosine, anti-fyn, anti-lck and anti-lyn antibodies. Physical association of PTK, p59fyn and p56/53lyn with Thy-1 molecules was demonstated in cultured rat mesangial cells. The activities of these kinases detected in MoAb 1-22-3 precipitates were higher than those in MoAb OX-7 precipitates. These results suggest that Thy-1 molecule transduces some signals also in rat mesangial cells.
Evidence for a selected humoral immune response encoded by VH4 family genes in the synovial membrane of a patient with rheumatoid arthritis (RA)
Authors: Voswinkel J , Trümper L , Carbon G , Hopf T , Pfreundschuh M , Gause A 
Published: November 2003

Abstract
The analysis of rearranged antibody-encoding genes from B cell foci in rheumatoid synovial tissue has characterized these cells as highly mutated memory B cells with a high proportion of members of the VH4 family. In order to characterize further the VH4 response in one patient, B cell-rich areas from different sections of synovial membrane (SM) were identified by CD20 staining, isolated by microdissection and pooled, in order to analyse highly enriched B cells without selection by in vitro culture procedures. From DNA of about 5 × 103 B cells rearranged VH genes were amplified by polymerase chain reaction (PCR) and cloned. Sequencing of 11 clones containing rearranged VH4 gene products revealed that seven were potentially functional, and all were mutated with 84–96% homology to known germ-line (gl) genes and VH4 gl genes amplified from the patient’s genomic DNA. Analysis of the complementarity determining region (CDR) 3 revealed that two products represented members of one B cell clone which differed by five nucleotide changes. Three of the five mutations encoded amino acid replacements in CDRs indicating antigen-driven expansion of one specific clone. Additional analyses of 25 members of three B cell clones from isolated aggregates showing intraclonal diversity in one of three clones provided further evidence that antigen selection takes place in the SM. Overall, the pattern of mutations and the replacement to silent (R:S) ratios were diverse, with six products indicating antigen selection by their high R:S ratios in CDRs. Although DNA analysis does not allow a characterization of antibody specificities, we can conclude from our analysis of antibody-encoding genes that selection by antigen and expansion of specific clones occur in the SM against the background of polyclonal activation.
Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases
Authors: Vignola A M , Chanez P , Chiappara G , Merendino A , Zinnanti E , Bousquet J , Bellia V , Bonsignore G 
Published: November 2003

Abstract
Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-β and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-β and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-β and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-β and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-β and fibronectin than those from control subjects. The spontaneous release of TGF-β is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-β release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-β in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.
IL-3 derived from CD4− T cells is essential for the in vitro expansion of mast cells from the normal adult mouse spleen
Authors: Harada M , Sumichika H , Hamano S , Ito O , Tamada K , Takenoyama M , Kimura G , Nomoto K 
Published: November 2003

Abstract
A null cell line (SCM1) was established by a culture of spleen cells (SC) from normal adult C57Bl/6 mice with complete medium alone for 10 days and followed by weekly cultures with a 25% WEHI-3 cell culture supernatant. Phenotype analysis showed that the SCM1 cells were negative for CD3, Thy1.2, B220, Mac-1, Gr-1, NK1.1 and MHC class II, but were positive for MHC class I, FcγRII/III, FcεRI, c-kit and the receptor against wheat germ agglutinin. These findings suggested that the SCM1 cells were mast cells. In an in vitro proliferation assay, SCM1 cells proliferated in the presence of either IL-3 or stem cell factor (SCF), but not in the presence of IL-4, whereas IL-4 showed an augmenting effect on their proliferation in the presence of either IL-3 or SCF. In analysing the mechanism by which such mast cells could be expanded from normal adult mouse SC, the addition of anti-IL-3 MoAb, but not anti-SCF MoAb, into the initial culture inhibited the subsequent expansion of either IL-3- or SCF-responding cells. The prior depletion of CD4+ T cells abrogated the capacity of the SC to enhance the expansion of SCF-responding cells, and this inability was restored by the addition of IL-3. Moreover, the culture supernatant of normal adult SC alone contained considerable levels of IL-3. Taken together, our findings suggest that, in an in vitro culture, CD4+ T cell-derived IL-3 therefore enhances the expansion of mast cells from the normal adult mouse spleen.
Site-directed serology of HIV-1 subtype B infection: relation between virus specific antibody levels and disease progression
Authors: Broström C , Sönnerborg A , Kim S , Sällberg M 
Published: November 2003

Abstract
Activated T helper (Th) cell-dependent (TD) antibody responses were determined over an 8–10 year period in 28 patients infected with HIV-1 subtype B. Twelve patients remain asymptomatic with normal CD4+ cell counts for 101–114 months. These individuals were defined as long-term asymptomatic (LTA). Sixteen patients progressed to severe immunodeficiency within 58–120 months. In samples derived close to the diagnosis of HIV-1, CD4+ cell counts were higher among the LTAs (P &lt; 0.01). Antibody production driven by activated Th cells was determined using peptides corresponding to HIV-1 V3US/Eur, gp41, and the hepatitis C virus (HCV) core proteins. The less Th cell-dependent B cell antibody response was represented by measles virus immunity. Close to HIV-1 diagnosis, variable third (V3), gp41, HCV core, and measles antibody titres were at similar levels among the LTAs and the progressors. With time the LTAs displayed unchanged levels of V3 and gp41 antibodies, and slightly decreasing levels of HCV core antibodies (P &lt; 0.05). In contrast, the progressors showed a decrease in all these antibody responses (P &lt; 0.05, for all). In both groups, the levels of measles antibody remained stable. Our data show that no significant change of the antibody responses of LTAs is seen, even after 101–114 months of known HIV-1 infection. Furthermore, the marked decrease of TD antibody production in the progressors suggests that activated Th cells may be excellent targets for HIV-1 infection.