bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of apoptosis-specific autoantibodies directed against granzyme B-induced cleavage fragments of the SS-B (La) autoantigen in sera from patients with primary Sjögren's syndrome
Authors: Huang M , Ida H , Kamachi M , Iwanaga N , Izumi Y , Tanaka F , Aratake K , Arima K , Tamai M , Hida A , Nakamura H , Origuchi T , Kawakami A , Ogawa N , Sugai S , Utz P J , Eguchi K 
Published: September 2005

SummaryThe objective of this study was to detect autoantibodies against granzyme B cleavage products in sera from patients with primary Sjögren's syndrome (SS). Cell lysates derived from human salivary gland (HSG) cell lines were incubated with granzyme B. The susceptibility to the generation of cleavage fragments of SS autoantigens was assayed by immunoblotting using sera from 57 primary SS patients, 17 primary SS patients with malignant lymphoma (ML), 28 systemic lupus erythematosus (SLE) patients, and 20 healthy controls. A 27 kD protein was recognized by serum autoantibodies in 8 (14·0%) of 57 primary SS patients, 5 (29·4%) of 17 SS patients with ML, 2 (7·1%) of 28 SLE patients, but not in 20 normal subjects. This protein was recognized by anti-SSB (La) monoclonal antibodies. Granzyme B-treated recombinant La protein was also shown to migrate as a discrete 27 kD protein by SDS PAGE. Blocking studies demonstrated the existence of an apoptosis-specific B cell epitope present in sera from 2 of 8 primary SS patients and in 2 of 5 primary SS patients with ML which recognized the 27 kD protein. Granzyme B-induced La fragments are generated during cytotoxicity in vitro. This is the first report describing autoantibodies in sera from primary SS patients that specifically recognize fragments of the La protein that are produced by the granzyme B protease.
Expression of immunoglobulin E-dependent histamine-releasing factor in idiopathic nephrotic syndrome of childhood
Authors: Toyabe S , Kaneko U , Hara M , Uchiyama M 
Published: September 2005

SummaryConcanavarin-A (conA)-stimulated peripheral blood mononuclear cells (PBMNC) from patients with idiopathic nephrotic syndrome (INS) produce putative factors that increase vascular permeability. These factors are expressed in the nephrotic phase but are reduced in the convalescent phase. To identify the genes that are expressed only in the nephrotic phase, we performed cDNA subtraction using conA-stimulated PBMNC from three patients with INS. We isolated several gene transcripts in all three subtracted cDNA libraries. Among these genes, IgE-dependent histamine-releasing factor (HRF) was overexpressed in the nephrotic phase not only at the mRNA level but also at the protein level in another 10 patients with INS. Moreover, we found increased secretion of HRF from conA-stimulated PBMNC in the nephrotic phase. The results suggest that HRF is involved in the pathogenesis of idiopathic nephrotic syndrome.
Cross-recognition between histones and La/SSB may account for anti-DNA reactivity in SLE patients
Authors: Touloupi E , Routsias J G , Tzioufas A G 
Published: September 2005

SummaryAntibodies to La/SSB are detected in sera of patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE). The vast majority of anti-La/SSB positive sera contain antibodies directed towards a linear B-cell epitope of La/SSB spanning the sequence 349–364aa (pep349–364). The aim of this study was to evaluate the fluctuation of antibody levels to major B-cell epitopes of La/SSB over time and investigate for their possible crossreactions. Sequential sera from 15 SLE and 15 pSS patients, followed from 3 to 10 years were obtained. All patients with SLE were positive for anti-Ro/SSA, anti-La/SSB and anti-dsDNA antibodies and patients with pSS were positive for anti-Ro/SSA and anti-La/SSB antibodies. Sera from 30 patients with SLE without anti-La/SSB antibodies and 30 healthy individuals served as disease and negative control respectivelly. All sera tested for the presence of anti-pep349–364 antibodies, using a specific ELISA. Specific anti-pep349–364 IgG was purified from sera of SLE patients and evaluated for cross reactivity against dsDNA and histones. In all SLE sera the levels of anti-pep349–364 antibodies varied in time and fluctuated in parallel with anti dsDNA antibodies. Anti-pep349–364 IgG purified from 7 SLE patients. Five out of 7 were found to react with calf thymus DNA in ELISA. All purified (7/7) anti-pep349–364 IgG preparations reacted with histone H1 and failed to produce a positive immunofluorescence pattern in Crithidia luciliae anti-dsDNA assay which lacks histones. Competative inhibition experiments demonstrated that histone H1 could inhibit completely the binding of anti-pep349–364 IgG to pep349–364 while pep349–364 inhibited by 70% the binding of anti-pep349–364 IgG to histone H1. These findings indicate that a subgroup of SLE patients possess cross-reacting anti-histone H1 antibodies and anti-pep349–364 antibodies, which can be faulty considered as anti-dsDNA reactivity in regular ELISA techniques.
Reduced iC3b-mediated phagocytotic capacity of pulmonary neutrophils in cystic fibrosis
Authors: Morris M R , Doull I J M , Dewitt S , Hallett M B 
Published: September 2005

SummaryCystic fibrosis (CF) is characterized by a neutrophil-dominated chronic inflammation of the airways with persistent infections. In order to investigate whether neutrophils contribute to an inadequacy in the pulmonary defence mechanism, the phagocytic activity of pulmonary and peripheral blood neutrophils from CF and non-CF respiratory patients were compared. Neutrophils were isolated from both the blood and bronchoalveolar lavage fluid of 21 patients with CF (12 male, 9 female; mean age 7·5 years, range 0·25–16·4 years) and 17 non-CF subjects (9 male, 8 female; mean age 5·4 years, range 0·2–13·1 years). The ex vivo phagocytic rate of normal pulmonary neutrophils to internalize zymosan particles opsonized with iC3b was faster than that of circulating neutrophils (P &lt; 0·05), but the maximum capacity (9 particles/cell) was similar. In contrast, pulmonary neutrophils from patients with CF had a lower phagocytic capacity than circulating neutrophils either from the same patients or from normal subjects. This deficiency could not be attributed to (i) the cell surface density of CR3 (CD18/CD11b) receptors, which were not significantly different between the other groups (ii) the signalling ability of the CR3 receptors, using cytosolic free Ca2+ signalling as the receptor activity read-out or (iii) a decrease in cellular ATP concentration. As CFTR was not detectable on neutrophils from any source by either histochemistry or Western blotting, it was concluded that the reduced phagocytic capacity was not the direct result of a CFTR mutation, but was attributed to a failure of neutrophil phagocytic priming during translocation into the CF lung.
The disease progression in the keratin 14 IL-4-transgenic mouse model of atopic dermatitis parallels the up-regulation of B cell activation molecules, proliferation and surface and serum IgE
Authors: Chen L , Lin S-X , Overbergh L , Mathieu C , Chan L S 
Published: September 2005

SummaryWe have previously characterized the keratin 14 interleukin-4-transgenic (IL-4-Tg) mouse model of atopic dermatitis as a chronic pruritic inflammatory skin disease typified by skin infiltration of inflammatory cells and early up-regulation of Th2 cytokines and late surge of Th1 cytokines. In the present study, we examined the involvement of B cells. Systematic examinations of the following immunological parameters on B cells were carried out in non-Tg control mice and in IL-4-Tg mice at before disease onset and early and late disease stages so that we could determine the immunological sequence of events leading to the disease development: surface expressions of IA/IE, activation and costimulatory molecules, proliferation under LPS or IgM stimulation, quantification of cell surface and serum IgE, IgG1, and IgG2a. Our results showed that as the disease progresses from before onset to early disease and to late disease, there is a parallel increase in surface markers of B cell activation (IA/IE, CD44, CD69, CD80 and CD86), in B cell proliferation, and in cell surface and serum IgE. Significant increases of Th2-driven serum IgG1 and IgE in early disease was followed by significant increase of Th1-driven IgG2a in late disease. Importantly the significant increases of activation molecule (IA/IE), proliferation (to LPS), and surface IgE on B cells of the IL-4-Tg mice precedes the up-regulation of serum IgE and disease onset. These data suggest that activated B cells may play a role in atopic dermatitis disease development by up-regulating serum IgE concentration, which serves as a marker of disease onset.
Enhancement of NF-κB activity by resveratrol in cytokine-exposed mesangial cells
Authors: Uchida Y , Yamazaki H , Watanabe S , Hayakawa K , Meng Y , Hiramatsu N , Kasai A , Yamauchi K , Yao J , Kitamura M 
Published: September 2005

SummaryResveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-κB (NF-κB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-κB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-κB-dependent gene, intercellular adhesion molecule-1. The NF-κB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-κB activity. The enhanced activation of NF-κB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-κB inhibitor, IκBβ, but not IκBα. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-κB, was not involved in the regulation of NF-κB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-κB under certain circumstances.
Prevalence of the −295 T-to-C promoter polymorphism of the interleukin (IL)-16 gene in periodontitis
Authors: Folwaczny M , Glas J , Török H-P , Tonenchi L , Paschos E , Malachova O , Bauer B , Folwaczny C 
Published: September 2005

SummaryInterleukin (IL)-16 is involved in the regulation of the expression of several proinflammatory cytokines, i.e. tumour necrosis factor (TNF)α and interleukin (IL)-1β. The present study aimed to determine the prevalence of the −295 promoter polymorphism of the interleukin (IL)-16 gene in periodontal disease. A total of 123 patients with periodontal disease and 122 healthy controls were genotyped for the −295 IL-16 promoter polymorphism. Genotyping has been performed by PCR and restriction fragment length polymorphism (RFLP) analysis. The frequencies of alleles and genotypes as well of haplotypes within both study groups were compared using the Pearson χ2 test at a level  of  significance  of  5% (P &lt; 0·05).  The  distribution  of  genotypes  for  the −295 IL-16 gene polymorphism showed no significant difference between periodontitis patients and healthy control subjects (P = 0·886). Also stratification analysis according to the disease severity revealed no significant difference regarding the genotype distribution among both study groups. Herein the IL-16 −295 gene polymorphism was not associated with chronic periodontitis.
Reactivity of T cells from women with antibodies to the human platelet antigen (HPA)-1a to peptides encompassing the HPA-1 polymorphism
Authors: Jackson D J , Murphy M F , Soothill P W , Lucas G F , Elson C J , Kumpel B M 
Published: September 2005

SummaryThe human platelet antigen-1a (HPA-1a) is the most common alloantigenic target in fetal and neonatal alloimmune thrombocytopenia (NAIT). Treatment currently depends on the outcome in previous pregnancies. HPA-1 specific T cell responses were determined in 14 HPA-1a alloimmunized women during or after pregnancies affected by NAIT. Peripheral blood mononuclear cells were incubated with peptides encompassing the Leu33Pro polymorphism (residues 20–39 and 24–45 in both Leu33 (HPA-1a) and Pro33 (HPA-1b) forms) or control recall antigens in the presence of autologous sera and T cell proliferation was measured by 3H-thymidine incorporation. Control antenatal and postpartum sera suppressed T cell proliferation and use of such sera was avoided. Most patients (86%) responded to the HPA-1a peptides with 64% also having weaker T cell proliferation to the HPA-1b peptides; 14% had no activity towards any peptide despite responding to control antigens. Administration of IVIG during pregnancy appeared to reduce T cell reactivity to HPA-1 peptides. Postnatal anti-HPA-1a T cell responses from women who had a severe history of NAIT (an intracranial haemorrhage in a previous fetus) were greater than those from women with a mild history. This assay may have the potential to predict disease severity if performed prior to or early in pregnancy.
Identification of Pseudomonas aeruginosa-induced genes in human mast cells using suppression subtractive hybridization: up-regulation of IL-8 and CCL4 production
Authors: Sun Genlou , Liu Fang , Lin Tong-Jun 
Published: September 2005

Summary
Mast cells have recently been found to be a major player in the host defence against bacterial infection through secretion of potent mediators. Identification of bacteria-induced mast cell mediators and intracellular signalling molecules involved during bacterial infection remains a major area of investigation. Recently we found an active interaction between mast cells and Pseudomonas aeruginosa bacteria. To further characterize specific genes in mast cells modulated by P. aeruginosa, we used a new approach for the study of mast cell–bacteria interaction; the suppression subtractive hybridization (SSH). SSH approach does not require a prerequisite knowledge of target genes and does not rely on the availability of the assay reagents for the specific genes. Using SSH, 94 clones were randomly selected from the subtracted cDNA library for differential screening leading to the identification of 14 P. aeruginosa–up-regulated transcripts. Sequence analysis revealed that expression of IL-1, IL-8 and CCL4 was increased by human mast cells after P. aeruginosa infection. Increased production of IL-1, IL-8 and CCL4 was confirmed at the protein levels. In addition, sequence analysis of the clones also suggests that ribosomal protein S3 and cytochrome b as well as additional 4 uncharacterized genes may potentially be involved in P. aeruginosa pathogenesis. Thus, SSH is an effective approach by identifying potential molecular targets for the study of mechanisms involved in P. aeruginosa and mast cell interaction.
Effects of pH and predation by Chaoborus larvae on the plankton of a shallow and acidic forest lake
Authors: IRFANULLAH HASEEB MD. , MOSS BRIAN 
Published: September 2005

Summary1. Eutrophic acid lakes are not common. Delamere Lake in Cheshire, U.K. is shallow and acid (mean pH 4.5) with a very high phytoplankton crop (mean 290 μg chlorophyll a L−1), dominated by Dictyosphaerium pulchellum. Rotifers were dominant in the pelagic waters but small cladocerans (Alona guttata, Chydorus sphaericus and Scapholeberis mucronata) were occasional in the littoral waters. Chaoborus flavicans larvae were the top predators in this fishless lake. Two mesocosm experiments were carried out in which pH and Chaoborus populations were manipulated.2. Progressively higher concentrations of D. pulchellum were maintained in the elevated pH treatments (pH 6 and 8; P < 0.001) with increased amounts of a Chlamydomonas species at the end of the experiment. Highest species richness was seen at ambient pH. Thus the low pH of Delamere Lake alone did not control the structure of the phytoplankton community. Keratella quadrata showed significantly higher abundance at pH 6 than in other pH treatments (P < 0.001). Species richness of rotifers was unaffected by pH.3. Most Cladocera were C. sphaericus. Although never seen in the open lake, Daphnia pulex appeared in all the pH treatments. Low pH did not control small Cladocera abundance in Delamere Lake, but probably hampered reproduction in Daphnia. Negative correlations between chlorophyll a concentrations and Daphnia in the mesocosms (r2 = 0.215, P < 0.05), however, indicated the potential of large‐bodied daphniids in controlling phytoplankton.4. Neither different combinations of Chaoborus instars (none, instars 1 and 2 and instars 3–5) nor different densities of instars 3–5 (0.15, 0.5 and 1.0 L−1) had a negative impact on Cladocera. Daphnia pulex remained unaffected in the experiment, perhaps because of its large size, and C. sphaericus because of its high reproductive rate compensating predatory losses.5. Very low pH in Delamere Lake might suppress Daphnia by hampering its reproduction. Consequently, Daphnia may be vulnerable to invertebrate predation even at low predator density in the lake.
Morphological adaptations of emergent plants to water flow: a case study with Typha angustifolia, Zizania latifolia and Phragmites australis
Authors: ASAEDA TAKASHI , FUJINO TAKESHI , MANATUNGE JAGATH 
Published: September 2005

Summary1. Water velocity plays an important role in shaping plant community structure in flowing waters although few authors have yet attempted to explain the adaptation of plants to flow.2. We aimed to test two hypotheses, that: (i) some emergent macrophytes reconfigure their shoot distribution in fast currents and form clumps, and (ii) the shape and morphology of such clumps minimises drag caused by the current. The study focuses on three emergent macrophytes that co‐occur along a gradient of water velocity.3. The species showed a clear zonation in response to water depth and current velocity. Phragmites australis occupied shallower and more slowly flowing water than Typha angustifolia and Zizania latifolia, which had similar preferences.4. Both T. angustifolia and Z. latifolia shoots were more clumped at high velocity, whereas they were more randomly distributed at low flow or in stagnant water. Because of the low shoot density, water flowed more easily through T. angustifolia clumps, whereas Z. latifolia clumps had a high shoot density and large amounts of trapped litter, causing stagnant water in the centre of the clump. The clumps of Z. latifolia with a high density of shoots were longer and narrower than T. angustifolia clumps. Phragmites australis was less tolerant of flow than the other two species and large amounts of litter trapped in the clumps impaired flow.5. The shoot distribution of both T. angustifolia and Z. latifolia is reconfigured at high flow and this minimises drag on the clumps.
A novel mechanism of immune regulation: interferon‐γ regulates retention of CD4+ T cells during delayed type hypersensitivity
Authors: Seabrook Tim J. , Borron Paul J. , Dudler Lisbeth , Hay John B. , Young Alan J. 
Published: September 2005

SummaryThe local immune response is characterized by an increase in the rate of entry of lymphocytes from the blood into regional lymph nodes and changes in the output of cells in lymph. While significant data are available regarding the role of inflammation‐induced vascular adhesion processes in regulating lymphocyte entry into inflamed tissues and lymph nodes, relatively little is known about the molecular processes governing lymphocyte exit into efferent lymph. We have defined a novel role for lymphatic endothelial cells in the regulation of lymphocyte exit during a delayed type hypersensitivity (DTH) response to mycobacterial purified protein derivative (PPD). Soluble, pro‐adhesive factors were identified in efferent lymph concomitant with reduced lymphocyte output in lymph, which significantly increased lymphocyte binding to lymphatic endothelial cells. While all lymphocyte subsets were retained, CD4+ T cells appeared less susceptible than others. Among a panel of cytokines in inflammatory lymph plasma, interferon (IFN)‐γ alone appeared responsible for this retention. In vitro adhesion assays using physiological levels of IFN‐γ confirmed the interaction between recirculating lymphocytes and lymphatic endothelium. These data demonstrate a new level of immune regulation, whereby the exit of recirculating lymphocytes from lymph nodes is selectively and sequentially regulated by cytokines in a manner equally as complex as lymphocyte recruitment.
Cholesterol depletion inhibits src family kinase‐dependent calcium mobilization and apoptosis induced by rituximab crosslinking
Authors: Unruh Tammy L. , Li Haidong , Mutch Cathlin M. , Shariat Neda , Grigoriou Lana , Sanyal Ratna , Brown Christopher B. , Deans Julie P. 
Published: September 2005

SummaryThe monoclonal antibody (mAb) rituximab produces objective clinical responses in patients with B‐cell non‐Hodgkin's lymphoma and antibody‐based autoimmune diseases. Mechanisms mediating B‐cell depletion by rituximab are not completely understood and may include direct effects of signalling via the target antigen CD20. Like most but not all CD20 mAbs, rituximab induces a sharp change in the solubility of the CD20 protein in the non‐ionic detergent Triton‐X‐100, reflecting a dramatic increase in the innate affinity of CD20 for membrane raft signalling domains. Apoptosis induced by rituximab hypercrosslinking has been shown to require src family kinases (SFK), which are enriched in rafts. In this report we provide experimental evidence that SFK‐dependent apoptotic signals induced by rituximab are raft dependent. Cholesterol depletion prevented the association of hypercrosslinked CD20 with detergent‐insoluble rafts, and attenuated both calcium mobilization and apoptosis induced with rituximab. CD20 cocapped with the raft‐associated transmembrane adaptor LAB/NTAL after hypercrosslinking with CD20 mAbs, regardless of their ability to induce a change in the affinity of CD20 for rafts. Taken together, the data demonstrate that CD20 hypercrosslinking via rituximab activates SFKs and downstream signalling events by clustering membrane rafts in which antibody‐bound CD20 is localized in a high‐affinity configuration.
Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues
Authors: Kinashi Tatsuo , Katagiri Koko 
Published: September 2005

SummaryRap1 has emerged as an important regulator of adhesion in multicellular organisms. In the immune system, Rap1 functions as an inside‐out signalling molecule for leucocyte integrins following stimulation with chemokines or antigens. Regulator of adhesion and cell polarization enriched in lymphoid tissues (RAPL) is a novel Rap1 effector molecule that mediates Rap1 signalling to integrins. The Rap1–RAPL complex regulates the spatial distribution of the integrin lymphocyte function‐associated antigen‐1 as well as cell polarization. The linking of inside‐out signalling with polarization synergistically promotes highly efficient lymphocyte trafficking. Targeted deletion of RAPL in mice has demonstrated multiple indispensable roles for this protein in lymphocyte and dendritic cell trafficking critical for immunosurveillance.