bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developments in the therapeutic use of erythropoiesis stimulating agents
Authors: Jelkmann Wolfgang 
Published: July 2010

SummaryRecombinant human erythropoietin (rHuEPO) has become the standard therapy for treatment of the anaemia of chronic kidney disease (CKD) during the past two decades. In addition, rHuEPO can be indicated for the treatment of cancer patients on chemotherapy and surgical patients to avoid allogeneic red blood cell transfusion. This review first describes recent attempts in developing rHuEPO congeners (mutated and pegylated rHuEPOs) and mimetics with prolonged half‐lives and improved application requirements. Secondly, the pathophysiological background of the regulatory guideline, that blood haemoglobin levels in anaemic CKD or cancer patients on chemotherapy should not be raised above the target value of 120 g/l, is discussed. Finally, potential novel indications are considered for the use of rHuEPO and its analogues as pleiotropic cytoprotectant agents for cardio‐, nephro‐, hepato‐ and neuroprotection.
Current status of globin gene therapy for the treatment of β‐thalassaemia
Authors: Lisowski Leszek , Sadelain Michel 
Published: July 2010

Summaryβ‐Thalassaemia major is a congenital anaemia for which there is presently no curative therapy other than allogeneic haematopoietic stem cell transplantation. This therapeutic option, however, is not available to most subjects for whom there is no available human leucocyte antigen‐matched bone marrow donor. The transfer of a regulated globin gene in autologous haematopoietic stem cells is therefore a direly needed alternative treatment. This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid‐specific, differentiation‐ and stage‐restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, it has been demonstrated that an optimized combination of proximal and distal transcriptional control elements permits lineage‐specific and elevated β‐globin expression in vivo, resulting in the correction of anaemia and secondary organ damage in β‐thalassaemic mice. Several groups have extended these findings to various models of β‐thalassaemia and sickle cell disease. Different globin vectors, however, do not express β‐globin at the same level, and accordingly require the delivery of markedly different vector copy numbers to correct anaemia. Insulators are under investigation to assess whether they might enhance globin gene expression or vector safety. Altogether, recent advances in globin vector design bode well for upcoming clinical trials to assess the therapeutic value of globin gene transfer.
Serological and histological characterization of the new mutant strain of lpr mice, CBA/KUms-lprcg/lprcg
Authors: KIMURA M , MOHRI H , SHIMADA K , WAKABAYASHI T , KANAI Y , MATSUZAWA A 
Published: July 2010

SUMMARYCBA/KIJms-lprcg/lprcg mice with a novel mutation producing systemic lymphoproliferation wereinvestigated for their serological and histological characteristics. The mutant mice showed elevatedlevels of serum immunoglobulin, C1q-binding immune complexes and antibodies to nuclear antigenssuch as dsDNA and ssDNA and poly(ADP-ribose). In contrast, histopathological lesions, e.g.glomerulonephritis, vasculitis or interstitial pneumonitis, were not revealed by histological andimmunofluorescent examinations, except for lymphocytic infiltration in various organs. These resultssuggest that this mutant mouse strain may provide a new animal model For autoimmunity. However, further investigations are required to clarify whether this strain is unique as compared with otherwell-known lupus-prone strains of mice with respect to serological and histological abnormalities andbecome to be a new model of systemic autoimmune disease.
Cytokine regulation of intercellular adhesion molecule-1 (ICAM-1) expression on human glioblastoma cells
Authors: KUPPNER M C , MEIR E VAN , HAMOU M F , TRIBOLET N DE 
Published: July 2010

SUMMARYIntercellular adhesion molecule-l (ICAM-1) has recently been identified as one of the ligands for lymphocyte function-associated antigen-1 (LFA-1). Immunohistochemical staining of frozen tissue sections using the ICAM-1 antibody RR1/1 demonstrated significant levels of ICAM-1 expression on human glioblastoma cells and on intratumoural vascular endothelial cells. ICAM-1 was weakly expressed or absent from low grade gliomas and absent from normal and fetal brain. ICAM-1 expression was similar to that of MHC class II, HLA-DR antigens. Glioblastoma cell lines constitutively expressed ICAM-1 to a minimal or moderate extent. Surface antigen expression of ICAM-1 and ICAM-1-specific mRNA could be significantly increased by incubating glioblastoma cells with interleukin-1β (IL-lβ), tumour necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). IL-2, IL-4, IL-6 and transforming growth factor β2 (TGF-β2) had no significant effect on surface antigen expression. Significant enhancement of ICAM-1 expression was obtained using TNF-α and IL-β at 1 -10 U/ml and at 500 U/ml of IFN-γ. Induction of ICAM-1 specific mRNA was observed 4 h after cytokine treatment and decreased by 24 h. Surface antigen expression of ICAM-1 increased for up to 48 h after treatment.
Kupffer cell numbers during human development
Authors: COPE E M W , DILLY S A 
Published: July 2010

SUMMARY
Immunohistological assessment of Kupffer cells was made using the antibody MAC387 and an antibody to lysozyme. Autopsy liver samples from 13 fetuses aged from 17 weeks gestation to term, and from 10 neonates and children aged 1 day to 18 months, were studied. For comparison, 10 normal adult autopsy liver specimens were included. The number of positively staining cells per unit area was counted for periportal sinusoids (zone 1) and centrilobular sinusoids (zone 3). No difference was found between zone 1 and zone 3 macrophage numbers with either antibody at any stage of development. Hepatic sinusoidal macrophage numbers were low during early gestation but increased during intra-uterine life to reach approximately normal adult values in the neonatal period. The numbers of cells staining with MAC387 or lysozyme were similar in each case except for hepatic sinusoidal macrophages in fetuses of less than 30 weeks gestation. Here anti-lysozyme stained significantly fewer cells, suggesting that lysozyme production may be low in immature fetuses. No difference was found between infants of similar maturity who had died immediately or had lived for more than 48 h and hence been exposed to gut antigens.
Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia
Authors: LASSALLE P , GOSSBT F , GRUART V , PRIN L , CAPRON M , LAGRUE G , KUSNIERZ J P , TONNEL A B , CAPRON A 
Published: July 2010

SUMMARY
We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema. a chemotactic activity towards eosinophils was detected in the serum (30 ± 6 and 42 ± 12 eosinophils per high-power field; P &lt; 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti-endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P &lt; 0.01) or to patients with HES (P &lt; 0.01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions.
Activation of lymphocytes after platelet allotransfusion possessing only class I MHC product
Authors: PÓCSIK É , MIHALIK R , GYÓDI É , RÉTI M , PÁLÓCZI K , PETRÁNYI G G , BENCZÚR M 
Published: July 2010

SUMMARYAfter platelet allotransfusion, we found a characteristic increase in the expression of interleukin-2 receptor, dipeptydilpeptidase IV (CD26), activation-inducer molecule (AIM, CD69) and transferrin receptors (CD71) on day 3 indicating that important functional molecules expressed on the activation of lymphocytes by allogeneic platelets. At the same time, no consistent increase of other activation molecules such as Ki-1 (CD30), intercellular adhesion molecule (ICAM-1, CD54) and Ki-24 (CDw70) antigen expression was detected, probably as a result of the selective activation of some lymphocyte subsets. In order to obtain further evidence for the in vivo activation triggered by allogeneic platelets, a subsequent step of T cell activation towards differentiation was investigated with monoclonal antibodies to leucocyte common antigens. A sharp expression of the UCHL1, coupled with a decrease of the CD45R molecule was detected on day 7 or 14, suggesting a T cell priming.
Flow cytometric and functional analysis of mononuclear cells infiltrating the liver in experimental autoimmune hepatitis
Authors: KOHDA H , SEKIYA C , KANAI M , YOSHIDA Y , UEDE T , KIKUCHI K , NAMIKI M 
Published: July 2010

SummaryExperimental autoimmune hepatitis was produced by immunizing Wistar rats with syngeneic liver proteins. Mononuclear cells infiltrating the liver tissue were identified by immunohistochemical techniques using monoclonal antibodies specific for subpopulations of rat lymphocytes. The strong infiltration of CD8+ cytotoxic T lymphocytes (CTL) were found in the portal areas. Subpopulations of mononuclear cells infiltrating the liver, spleen cells and peripheral blood lymphocytes were identified by flow cytometry. Flow cytometric analysis revealed the presence of CD5- and CD8+ lymphocytes in the liver tissues. Mononuclear cells infiltrating the liver were isolated from Wistar rats having autoimmune hepatitis to determine whether those exhibit cytotoxicity against syngeneic hepatocytes; they exhibited cytotoxicity against isolated syngeneic hepatocytes, but failed to lyse K562 cells, syngeneic concanavalin A-activated splenocytes and allogeneic hepatocytes. Depietion of CD8+ T cells significantly reduced the cytotoxic ability of mononuclear cells infiltrating into the liver against syngeneic hepatocytes. These findings support the idea that liver cell injury in experimental autoimmune hepatitis may at least in part be mediated by CTL.
Increased serum neopterin in patients with HIV-1 infection is correlated with reducedin vitrointerleukin-2 production
Authors: FUCHS D , SHEARER G M , BOSWELL R N , CLERICI M , REIBNEGGER G , WERNER E R , ZAJAC R A , WACHTER H 
Published: July 2010

SUMMARYRecently we have observed that the CD4+ T cell response of peripheral blood mononuclear cells (PBMC) to soluble antigens is the first to be lost in the course of HIV-1 infection followed by the loss of response to HLA alloantigens. In this study we compared serum neopterin concentrations of individuals with early stages of HIV-1 infection (stages WR1 and WR2, Walter Reed staging system) with in vitro interleukin-2 (IL-2) production of PBMC in response to stimulation with soluble antigens (influenza A virus and tetanus toxoid) and alloantigens. Neopterin concentrations were significantly higher in HIV-l-seropositive individuals who showed deficient IL-2 production in response to recall antigens only or to all of the stimuli tested in vitro, compared with HIV-l seropositive individuals who exhibited no CD4+ T cell defects. No difference in serum neopterin concentrations was observed between the group that was functionally deficient to soluble antigens only versus those who were unresponsive to both types of stimuli. It appears that the selective loss of the MHC self-restricted CD4+ T cell function is associated with an increase in serum neopterin levels. Neopterin concentrations are an estimate of the activation status of macrophages. We conclude that defective in vitro production of lymphokines by T lymphocytes is associated with activated macrophages in vivo.
Serum sickness and acute renal failure after streptokinase therapy for myocardial infarction
Authors: DAVIES K A , MATHIESON P , WINEARLS C G , REES A J , WALPORT M J 
Published: July 2010

SUMMARY
A patient developed serum sickness and acute renal failure following therapy with streptokinase for myocardial ischaemia. There was a previous history of a cellulitic infection of the leg. and antibodies to streptokinase were measurable in a serum sample taken from the patient before therapy. A cryoglobulin was detected at the lime of presentation with serum sickness. This contained polyclonal IgG (with anti-streptokinase activity), streptokinase, and C3. Circulating immune complexes were demonstrated by C1q-binding assay. Deposition of C3 was observed in skin and renal biopsies, and bound to erythrocytes. Renal histology, however, showed acute tubular necrosis, with no vasculitis or inflammatory cell infiltrate. This case provides an unusual example of the characterization of an immune complex comprising a specific antibody and an exogenous antigen, and has clinical implications for the use of streptokinase.
Suppression of HLA class II expression on thyrocytes by interferon-alpha 1
Authors: GUERIN V , TODD I , HAMMOND L J , BOTTAZZO G F 
Published: July 2010

SUMMARYInappropriate expression of HLA class II molecules by human thyroid epithelial cells (thyrocytes) is commonly associated with autoimmune thyroid disease. HLA class 11 expression can be modulated in thyrocytes in vitro by a variety of substances: in particular, it is readily induced by interferon-gamma (IFN-γ). Here we show that recombinant IFN-α1 (rIFN-α1) does not induce HLA class II expression by thyrocytes. but rather it suppresses the induction of such expression by rIFN-γ. Similar effects were observed with IFN-α derived from a lymphoblastoid cell line. The effect of rIFN-α1 on thyrocytes differs from its effect on human monocytes, reported by others, in which it was found to enhance the expression of HLA class II. Thus, rIFN-α1 appears to have a differential effect on HLA class II expression, depending on the cell type involved.
IgA Polyspecific autoantibodies in IgA nephropathy
Authors: MATSIOTA P , DOSQUET P , LOUZIR H , DRUET E , DRUET P , AVRAMEAS S 
Published: July 2010

SUMMARY
The specificity of circulating and kidney-bound IgA during IgA nephropathy is suit a matter of discussion. In the present study, high levels of IgA antibodies directed against a panel of self and non-out of the seven kidney biopsies studied. After immunoedsorption of pooled selected serum samples on TNP and getin-coated columns, polyspecific IgA antibodies were elated. This supports the hypothesis that IgA-bearing B cells clones most probably producing polyspecific antibodies are a major feature of human IgA nephropathy. These findings also suggest that it may be hazardous to draw conclusions from the findings of apparent monospecific IgA antibodies in this condition.
Functional characterization of SV40-transformed adherent synovial cells from rheumatoid arthritis
Authors: GOTO M , OKAMOTO M , SASANO M , NISHIZAWA K , AOTSUKA S , YAMAGUCHI N , OBINATA M , IKEDA K 
Published: July 2010

SUMMARYA total of 14 transformed cell clones were obtained by micro-injecting origin-defective SV40 DNA into three types of cloned adherent synovial cells (ASC) (dendritic cells (DCs), macrophage-Iike cells (MCs), and fibroblast-like cells (FCs)) from two rheumatoid arthritis patients (five DC clones (SV40-DCs), five MC clones (SV40-MCs) and four FC clones (SV40-FCs)). All the transformed cell nuclei expressed SV40-specific T antigen. The cells which formed a colony had a few times shorter doubling time than the original cells. IL-1α, IL-lβ and prostaglandin E2 were detected in the culture supernatant from the unstimulated transformed cells like untransformed cells. The SV40-DCs showed the most potent accessory cell function in oxidative mitogenesis assay among the three types of SV40-ASCs. Granulocyte macrophage colony stimulatory factor (GM-CSF) was detected only in the culture supernatant from the SV40-MCs without stimulation. Extensive phenotypic analysis revealed relatively cell-specific markers. SV40-DCs were HLA-DP+ and glial fibrillary acidic protein positive. SV40-MCs stained positive for 5′-nucleotidase and nonspecific esterase. These transformed ASCs retained much of the original cellular physiology of rheumatoid arthritis (RA) ASCs and may be a useful tool for characterizing the role of ASCs in the pathogenesis of RA.
FcγRII restriction fragment length polymorphism (RFLP): analysis in systemic lupus erythematosus and scleroderma and evidence of an alpha gene duplication
Authors: JAZWINSKA E C , OLIVE C , HOGARTH P M , GATENBY P A , SERJEANTSON S W 
Published: July 2010

SUMMARYThe characteristic finding of high levels of circulating immune complexes in patients with the autoimmune connective tissue diseases systemic lupus erythemalosus (SLE) or scleroderma has raised the possibility that these patients may have a primary defect in immune complex clearance. The Fc receptor for IgG (FcγR) plays a central role in the phagocytosis of antibody complexes. We have analysed FcγR (type II) RFLPs identified in TaqI-and MspI-restrictcdgenomic DNAand found that their distribution in SLE and selerodenna did not differ significantly from controls. Hybridization with specific regions of the FcγRII cDNA clone indicate that part of the FcγRIIα locus is duplicated in some individuals. A further FcγRII gene has recently been identified (FcγRIIα). This gene shows &gt; 95% homology with FcγRIIα and may thus be the candidate gene for the apparant α duplication seen in some individuals. It is possible that an individual may possess one. two, three or four TaqI FcγRIIα/α′alleles. correlating with incidence and numerical heterogeneity in FcγRIIα and α′. The physiological effects of this numerical heterogeneity remain to be investigated.
Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis
Authors: ROSSI F , JAYNE D R W , LOCKWOOD C M , KAZATCHKINE M D 
Published: July 2010

SUMMARYAnti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab′)2 fragments from IVIg and affinity chromatography of ANCA IgG on Scpharose-bound F(ab′)2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with β and/or α idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis. which were found to contain high litres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.
Induction of suppressor cells byMycobacterium paratuberculosisantigen in inflammatory bowel disease
Authors: EBERT E C , BHATT B D , LIU S , DAS K M 
Published: July 2010

SUMMARYWe studied the M. paratuberculosis-induced proliferation and suppressor cell generation by peripheral blood lymphocytes from patients with inflammatory bowel disease. Peripheral blood lymphocytes were separated from 33 patients with Crohn's disease, 18 with ulcerative colitis, nine with other intestinal diseases, and five with autoimmune disorders. Proliferation of peripheral blood lymphocytes from normal individuals in response to 10 μg/ml of M. paratuberculosis antigen was reduced by depletion of CD4+ T cells. The ability of M. paratuberculosis antigen to suppress concanavalin A-induced proliferation (expressed as a percentage suppression) was reduced by depletion of CD8+ T cells. This suppression was the same whether peripheral blood lymphocytes were from normal individuals, patients with intestinal diseases other than inflammatory bowel disease, or patients with autoimmune disorders (47 ± 14%, 44 ± 24%, and 30 ± 26%, respectively). In contrast, the suppression induced by M. paratuberculosis for patients with Crohn's disease and ulcerative colitis (66 ± 22% and 67 ± 22%) was much greater than that for normal individuals (P &lt; 0.001). In particular, lymphocytes from patients with active Crohn's disease demonstrated little proliferation in response to this antigen but marked suppressor activity (79 ± 13%). How the immunomodulatory effects of this antigen relate to the pathogenesis of the inflammatory bowel diseases remains to be determined.
Plasma membrane association of primary biliary cirrhosis mitochondrial marker antigen M2
Authors: SUNDIN U , SUNDQVIST K G 
Published: July 2010

SUMMARYAntibody reactivity against the ‘mitochondrial M 2 antigen’ was determined in sera from 10 patients with primary biliary cirrhosis (PBC). using Western blotting after SDS-PAGE separation of rat liver mitochondria (RLM) and plasma membrane proteins. The molecular weights of the major M2 antigens in rat liver mitochondria were 67 and 50 kD Two of the 10 PBC patients did not react to any of these major antigens, eight reacted to the 67-kD and four of those also to the 50-kD antigen. The 67- and 50-kD antigens were present in both plasma membrane and RLM and had affinity to concanavalin A. Antibody reactivity against the 67-kD antigen could be detected in both IgG and IgA as well as in the IgM class. The reactive IgG subclasses to both types of antigen preparations were mainly of the GI and G3 isotypes. This reactivity was always stronger with antigens from the plasma membrane preparations. Sera from two patients with high antibody litres against mitochondria also reacted with IgG2 against the 50-kD antigen from plasma membrane, but not to the corresponding antigen in mitochondria. Reactivity of antibodies in PBC sera to the periphery of viable hepatocytes and radioactive surface labelling of the 50-kD component are both consistent with a plasma membrane localization of M2. Serum from healthy controls and several patients with different diseases did not contain antibodies reactive against any of the antigens described. We suggest that antigens, partly identical to the mitochondrial M2, are located in the plasma membrane compartment. The PBC pathogenetical consequences of these findings arc discussed.