bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone deacetylase inhibitor, PXD101, potentiates bortezomib‐induced anti‐multiple myeloma effect by induction of oxidative stress and DNA damage
Authors: Feng Rentian , Oton Ana , Mapara Markus Y. , Anderson Gülsüm , Belani Chandra , Lentzsch Suzanne 
Published: July 2010

SummaryClinical trials have shown the high anti‐myeloma activity of the proteasome inhibitor bortezomib. The present study examined the activity of bortezomib combined with PXD101, a histone deacetylase inhibitor, against multiple myeloma (MM) and osteoclastogenesis. Treatment of myeloma cell lines with combinations of bortezomib and PXD101 led to synergistic inhibition of proliferation and induction of cell death. The combination significantly decreased the viability of primary human CD138+ myeloma cells but not of bone marrow mononuclear cells. Further studies showed a dose‐dependent activation of caspases‐3, ‐8 and ‐9 and nuclear fragmentation in myeloma cells. Bortezomib/PXD101 treatment markedly triggered reactive oxygen species (ROS) generation that was accompanied by p53, H2A.X and p38–mitogen‐activated protein kinase phosphorylation. ROS generation could be blocked by the free radical scavenger N‐acetyl‐l‐cysteine. The combination of bortezomib and PXD101 also resulted in synergistic inhibition of osteoclast formation. In conclusion, bortezomib and PXD101 have different molecular targets. The combination induces cell death in myeloma cells via ROS‐mediated DNA damage and also inhibits osteoclastogenesis. Therefore, this study provides the rationale for the clinical evaluation of bortezomib combined with PXD101 in patients with MM.
Platelet glycoprotein VI‐related clinical defects
Authors: Arthur Jane F. , Dunkley Scott , Andrews Robert K. 
Published: July 2010

SummaryHuman patients with defects associated with the platelet collagen receptor, glycoprotein (GP)VI, are rare and usually described as having a mild bleeding disorder. However, here we review clinical profiles of patients with familial or acquired GPVI defects, revealing the bleeding defect is often severe and associated with immune dysfunction. GPVI is a member of the immunoreceptor family, and co‐expressed on platelets with Fc receptor γ‐chain (FcRγ). Ligand binding to GPVI leads to activation of platelet integrins, in particular αIIbβ3 that mediates platelet aggregation; and activation of endogenous platelet metalloproteinases resulting in ectodomain shedding and release of a soluble GPVI fragment. Increasing evidence supports the functional importance of GPVI/FcRγ in thrombus formation at arterial shear rates, and expression levels of platelet GPVI may be a marker of thrombotic risk. Over the past 20 years, patients have been reported with GPVI‐related defects involving: (i) an acquired deficiency, resulting from (a) anti‐GPVI autoantibodies or (b) other causes; or (ii) a congenital deficiency, where (c) GPVI is not expressed or (d) is expressed in a dysfunctional form with defective signalling to αIIbβ3. Clinical consequences of GPVI‐related defects may be uniquely informative about the role of platelet GPVI in health and disease.
Polyamine oxidase activity in rheumatoid arthritis synovial fluid
Authors: FERRANTE A , STORER R J , CLELAND L J 
Published: July 2010

SUMMARYOxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity
Macrophage heterogeneity in human fetal tissue. Fetal macrophages
Authors: OLIVER A M 
Published: July 2010

SUMMARYThe immunophenotype of the macrophage population in human fetal tissue was studied, using a panel of monoclonal antibodies against cells of the macrophage/monocyte lineage. Using a double-labelling technique two main populations were observed in tissue from 14 weeks of estimated gcstational age (EGA): EBM11 + DR + and EBM11 DR− cells of which a small proportion were also RFD7+. Most macrophages were negative with 3.9, an antibody specific for the adhesion molecule P150.95 and LP9 which is specific for a lysosomal enzyme. The exception to this was a small population of positive cells in the thymus. Small numbers of 3.9+ cells were also infrequently observed in tissue at and above 17 weeks of EGA. while occasional RFD9+ cells were only observed in most tissues, before this time. The higher percentage of macrophages were DR+ DQ−DP−. with a few DQ+ cells appearing at 15 weeks of EGA. In the thymus. DQ+ cells outnumbered DP+ cells especially in the medulla. These results indicate the heterogeneous and immature nature of the fetal macrophage population and point to the importance of age, tissue-specific factors and probable immune mediators in macrophage differentiation.
Decreased serum levels of IgE and IgE-binding factors in individuals infected with HTLV-I
Authors: MATSUMOTO T , MIIKE T , MIZOGUCHI K , YAMAGUCHI K , TAKATSUKI K , HOSODA M , KAWABE T , YODOI J 
Published: July 2010

SUMMARYThe cell surface expression of low-affinity Fc epsilon receptor (FceRII), which is identical to CD23, and the serum levels of IgE binding factors (IgE BFs), a soluble form of FceRII, and IgE were investigated in HTLV-I-infected individuals, and the results were compared with those for HTLV-I-negative controls. The occurrence of FcεRII+ mononuclear cells did not differ among the blood samples from the HTLV-I-infected groups; however, the levels of serum IgE BFs were significantly decreased (P&lt;0.001) in patients with adult T cell leukaemia (ATL), compared with HTLV-I-negative controls. The serum IgE levels were also significantly decreased in these groups, including cases of ATL (P&lt;0.001) and HTLV-I-associated myelopathy (P&lt;0.05), and HTLV-I carriers (p&lt;0.05), as compared with HTLV-I-negative controls. Since cases of strongyloidiasis or filariasis are frequently found among HTLV-I-infected individuals in Japan, these results may explain in part their defective defence mechanisms for parasites. The possible involvement of IgE BFs in the development of immune deficiency state in HTLV-I infection is also discussed.
In vitroproduction of tumour necrosis factor and prostaglandin E2 by peripheral blood mononuclear cells from tuberculosis patients
Authors: CADRANEL J , PHILIPPE C , PEREZ J , MILLERON B , AKOUN G , ARDAILLOU R , BAUD L 
Published: July 2010

SUMMARYWe investigated the production of tumour necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) from tuberculosis patients and healthy controls. PBMC from tuberculosis patients generated constitutively more TNF-α than did control PBMC. This production was significantly higher for patients with high-grade fever and cachexia. The increase of TNF-α production by PBMC from tuberculosis patients was associated with a comparatively weaker elevation of PGE2 synthesis which did not parallel fever or weight loss. In vitro treatment of control PBMC with the tuberculin purified protein derivative (PPD) promoted an increased TNF-α production which was similar to that of untreated PBMC from tuberculosis patients. Thus, the increased TNF-α production in tuberculosis could be explained by the in vivo exposure of PBMC to mycobacterial antigens. In contrast, the concentration of PGE; was weaker in the medium of untreated PBMC from tuberculosis patients than in the medium of PPD-treated control PBMC, suggesting that PGE, synthesis by PBMC was limited in tuberculosis by unidentified factors.
Natural killer cell activity, interferon-gamma and antibodies to herpes viruses in patients with Behçet's disease
Authors: HAMZAOUI K , AYED K , SLIM A , HAMZA M , TOURAINE J 
Published: July 2010

SUMMARYInterferon-gamma (IFN-γ) titres in 20 patients with active Behçet's disease were examined and compared with those of 20 normal donors. Sera from Behçet's disease patients revealed an IFN-γ increase but no correlation between IFN level and natural killer (NK) activity. The analysis of lymphocyte subsets by monoclonal antibodies registered an increase of CD8+ T subpopulation and cells co-expressing CD8+ -Leu 7a+ markers. Moreover, a high number of cells expressing CD25+ and HLA-DR+ phenotype has been noted in patients with active Behçet's disease. Serological analysis showed a high level of IgG antibodies to HSV-1. The increase of IFN-γ litre, the high number of activated T cells and the increasing level of IgG antibodies to HSV-1 are important manifestations during the active stage of Behçet's disease. These findings are discussed in relation to the immunopathogenesis of Behçet's disease.
Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture
Authors: MCLACHLAN S M , TAVERNE J , ATHERTON M C , COOKE A , MIDDLETON S , PEGG C A S , CLARK F , SMITH B REES 
Published: July 2010

SUMMARYIn autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-α(TNF-α), interferon-gamma (IFN-γ), interleukin-1 (IL-1 α and β) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-α nor IL-2 affected thyroid cell survival, IFN-γ was usually inhibitory and IL-lα slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-γ, IL-2 and TNF-α inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-γ may inhibit thyroid cell proliferation and TNF-α, IFN-γ and IL-2 may down-regulate thyroid autoantibody synthesis.
Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus
Authors: NIKAIDO T , SHIMADA K , SHIBATA M , HATA M , SAKAMOTO M , TAKASAKI Y , SATO C , TAKAHASHI T , NISHIDA Y 
Published: July 2010

SUMMARYPatients with systemic lupus erythematosus (SLE) produce autoantibodies against a variety of nuclear antigens including Ki antigen. Although anti-Ki autoantibodies were found in a significant number of SLE patients, the nature of Ki antigen is poorly characterized. By using anti-Ki serum as a probe we have cloned a bovine cDNA directing the synthesis in Escherichia coli of a polypeptide immunologically indistinguishable from the authentic Ki antigen. A homologous human cDNA was also cloned and its nucleotide sequence predicted the entire primary structure of a novel nuclear protein with a molecular weight of 29 508 and with highly hydrophilic and weakly acidic character. The gene is highly conserved not only in the coding region but also in the 3′-untranslated region. The bacterially produced Ki antigen would be valuable for diagnosis of SLE.
Lymphoid and non-lymphoid cells in the adenoid of children with otitis media with effusion: a comparative study
Authors: VAN NIEUWKERK E B J , DE WOLF C J M , KAMPERDIJK E W A , VAN DER BAAN S 
Published: July 2010

SUMMARYWe characterized on immuno- and enzymecytochemical level the lymphoid and non-lymphoid cells in the adenoid of children with upper respiratory tract infections (URI) and otitis media with effusion (OME) and compared these with the adenoid of children with URI without OME and with the adenoid of ‘healthy’ children and adults. Besides macrophages and dendritic cells we also showed the presence of MHC class II positive, ciliated, epithelial cells. These non-lymphoid cells were present in all adenoids. However, their number was less than 1% of all cells. We found no difference in lymphocyte subsets from children with URI+OME compared with those from children with URI alone. These two groups showed a significant decrease of CD8-positive (suppressor/cytotoxic) cells and a slight increase in CD22-positive B cells in comparison to ‘healthy’ children. No difference was found in percentages of CD4-positive (helper/inducer) cells. The localization of the lymphoid subsets in adenoids of children with URI and/or OME did not differ from those of ‘healthy’ children and adults.
C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus
Authors: WILD G , WATKINS J , WARD A MILFORD , HUGHES P , HUME A , ROWELL N R 
Published: July 2010

SUMMARY
The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, Clq binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.
Selective concentration of IgD class-specific antibodies in human milk
Authors: LITWIN S D , ZEHR B D , INSEL R A 
Published: July 2010

SUMMARY
The participation of human IgD class antibody in local immune responses of breast tissue was studied by analysing the sera-to-milk ratios of total IgD, IgM, IgA, IgG isotypes and albumin found in matched samples, and by analysing the sera-to-milk (S/M) ratios of IgD, IgM, IgA, IgG antibodies against Haemophilus influenzae capsular polysaccharide (PRP), phosphorylcholine, tetanus and in some cases diphtheria antigens. The study group consisted of eight women immunized during pregnancy with PRP, and control, unimmunized women. Albumin, and total IgG showed high S/M ratios. IgA had a low S/M ratio as expected, consistent with reports that IgA is locally concentrated. Total IgD and IgM isotype ratio values were intermediate between IgG and IgA suggesting they were selectively concentrated in breast fluids due to local production or transport mechanisms, or both. Ratios for specific antibodies of IgA and IgM isotypes and for total IgA and IgM isotype showed parallel data. Among the IgD antibodies, those specific for PRP and phosphorylcholine suggested a higher degree of selective concentration as compared with tetanus antigen. In the group of unimmunized women, although selective concentration of total IgD was observed, specific antibody studies were inconclusive due to the low milk IgD antibody levels encountered. The results indicate that IgD (and also IgM) may participate in local immune responses of human breast tissues and fluids; possibly influenced by the nature of the antigen, the state of immunization and the hormonal environment (pregnancy).
Identification of protein components reactive with anti-PM/Scl autoantibodies
Authors: GELPI C , ALGUERÓ A , MARTINEZ M ANGELES , VIDAL S , JUAREZ C , RODRIGUEZ-SANCHEZ J L 
Published: July 2010

SUMMARYThe PM/Scl antigen from mammalian cells has been characterized as a nucleolar and nucleoplasmic molecular complex containing at least 16 polypeptides ranging in molecular weight from 110 to 20 kD. Of these polypeptides. we have found those of68, 39 and 20 kD to be in a phosphorilated form. Whereas the entire complex was precipitated by all the anti-PM/Scl sera tested, in immunoblots the antibodies specifically recognized determinants on the 110-kD protein. This protein was immunoprecipitated more preferentially from nuclcoli extracts than from total cell extracts. Moreover, this protein disappeared from the immunoprecipitates when treated with DNAse. Likewise, the immunoblol reaction of the specific antibodies with the 110-kD protein was abolished by treatment of the extracts with DNAse and trypsin, and was resistant when extracts were treated with RNAsc. Affinity-purified antibodies from this protein selectively stained the nucleoli and the nucleoplasm of the mammalian cells. Moreover, when the cultured cells used in immunofluorescence were treated with DNAse, the affinity purified antibodies from the 110-kD protein gave negative fluorescence. However, when whole anti-PM/Scl sera were used, a nucleolar and nucleoplasmic staining was found. We conclude that the 110-kD protein has at least one of the autoimmunogenic epilopes of the PM/Sel antigen, recognized by all anti-PM/Scl sera tested. Other epitopes differing in their DNAse sensitivity may also be present in the PM/Scl antigen.
Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis
Authors: VINCENT C , SERRE G , BASILE J-P , LESTRA H C , GIRBAL E , SEBBAG M , SOLEILHAVOUP J-P 
Published: July 2010

SUMMARYSerum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgGl was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgGl,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and II (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgGI (alone) and lgG(I +4), which together represented 18 sera (58%). The large predominance of IgGI AKA and the quasiabsence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis.
Effects of neutral pepsin on the deposition of dietary antigens in glomeruli from IgA nephropathy
Authors: SATO M , KOJIMA H , KINO K , KOSHIKAWA S 
Published: July 2010

SUMMARY
Recently we reported on the participation of dietary antigens in the pathogenesis of IgA nephropathy. Particularly, the glomerular deposition of dietary antigens (casein, soybean protein, rice protein) was observed in some cases with IgA nephropathy. It is known that human urinary pepsin (HUP) prepared from the urine of a healthy adult acts as an immune complexase at neutral pH. In this study, the effects of incubation with HUP on the glomerular deposition of dietary antigens was investigated by an immunofluorescence technique in 48 patients with IgA nephropathy. four patients with Henoch Schonlein purpura nephritis and 69 with other glomerulonephritides. In 33 cases (68·8%) soybean protein and in 12 (25·0%) casein was found in biopsies of patients with IgA nephropathy. After a 3-day incubation with HUP there was no change in the deposition of IgA in 12 cases, a decrease in 22 and complete elimination in 14 cases. The deposits of soybean protein increased in 12 cases, did not change in 20, decreased or was abolished in five and was positively converted in 11. Exceptionally, in five patients treated with HUP, the deposition of soybean protein appeared concomitantly with the disappearance of IgA deposits. Such a concomitance did not occur either in other glomerulonephritides or in studies of other dietary antigens. Thus it appears that soybean protein may be deposited in the glomerular mesangium as an antigen in some patients with IgA nephropathy.
Frequencies of interleukin-5 mRNA-producing cells in healthy individuals and in immunoglobulin-deficient patients, measured byin situhybridization
Authors: SMITH C I E , MÖLLER G , SEVERINSON E , HAMMARSTRÖM L 
Published: July 2010

SUMMARYInterleukin-5 (IL-5) has previously been demonstrated to enhance immunoglobulin synthesis, especially IgA. Thus, it could be hypothesized that a defect production of IL-5 may cause immunoglobulin deficiency. We have analysed the frequency of IL-5 mRNA-producing cells in healthy adults and in patients with common variable immunodeficiency or selective IgA deficiency. Unstimulated lymphocytes were rarely found to synthesize IL-5 as measured by in situ hybridization. However, pokeweed mitogen and several other activating ligands induced the synthesis of IL-5 mRNA in peripheral blood and spleen lymphocyte cultures. After pokeweed mitogen activation, the number of IL-5 mRNA-producing cells most often peaked on day 3 with a maximal frequency of around 1–2% of mononuclear cells. In a kinetic study we were unable to detect any peak frequency differences between healthy controls (mean 0.44%) and 20 patients (mean 0.58%), Thus, although IL-5 has been reported to be an important regulator of IgA synthesis, a defect production does not seem to be the underlying mechanism in human immunoglobulin deficiency.
Effects of interleukin-2 and interleukin-2-activated cells onin vitromyelopoiesis
Authors: CLERIGUE M , PISA P , TSAI L , HANSON M 
Published: July 2010

SUMMARYLymphokine-activated killer (LAK) cells from human peripheral blood mononuclear cells cultured with recombinant interleukin-2 (IL-2) have been used clinically in adoptive immunotherapy for cancer patients. To study the influence of LAK cells and IL-2 on haematopoiesis, an in vitro assay system for colony formation of granulocyte-macrophage progenitor cells (GM-CFC) was used. LAK cells from cultures of either human peripheral blood (PB) or human bone marrow (BM) mononuclear cells were both inhibitory to allogeneic BM-derived GM-CFC. Inhibitory activity could be transferred with supernatants from co-cultures of LAK cells and BM targets, but also from the IL-2 activated PB- or BM-derived cells alone. The inhibitory activity from the initially non-cytotoxic/non-inhibitory BM population was rapidly induced by IL-2 activation, and preceded the generation of cytotoxic LAK cells in the culture. These experiments show that inhibition of haematopoietic progenitor cells by IL-2 is not dependent on generation of cytotoxic LAK cells, but rather the result of IL-2-induced cytokine production. We conclude that the synergistic action of interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) may contribute to inhibition, but that also other cytokines are responsible for the observed inhibition of BM-derived GM-CFC.