bluuebunny/crossref_metadata_2025_split huggingface dataset:
New monoclonal anti-human Fc gamma receptor II antibodies induce platelet aggregation
Authors: NOMURA S , YAMAGUCHI K , KIDO H , KAWAKATSU T , IWATA K , FUKUROI T , SUZUKI M , YANABU M , SOGA T , NAGATA H , KOKAWA T , YASUNAGA K 
Published: July 2010

SUMMARYWe developed two new monoclonal antibodies, designaled NNKY3-2 and NNKY4-7, that recognized a 40-kD platelet protein. They appeared to be monoclonal anti-Fc gamma receptor II (FC-/RII) antibodies from the results of flow cytometric binding inhibition studies using another monoclonal anti-FcγRII antibody (2E1). The addition of NNKY3-2 or NNKY4-7 to platetet-rich plasma (PRP) led to a typical aggregation pattern preceded by a lag phase, but their addition to washed platelets did not induce aggregation. The aggregation of PRP by these antibodies was inhibited by prostaglandin E1 (PGE1) or staurosporine (protein kinase C inhibitor), whereas it was only slightly affected by a monoclonal anti-GPIIb/IIIa antibody or Arg-Gly-Asp-Ser, Furthermore, these antibodies induced the aggregation of washed platelets plus normal serum, but not that of washed platelets plus heat-treatcd serum (destruction of complement activity). These results suggest that NNKY3-2 or NNKY4-7-induced aggregation involves an unusual pathway independent of fibrinogen, and that the important factor is the participation of complement. NNKY3-2 and NNKY4-7 may be useful to study the relationship between autoantibodies, the Fc receptor, and complement in idiopathic thrombocytopenic purpura.
FcγRIIα: sequencing of the ligand binding domain in systemic lupus erythematosus patients
Authors: JAZWINSKA E C , BANYER J L , GATENBY P A , SERJEANTSON S W 
Published: July 2010

SUMMARYThe receptor for the Fc portion of IgG (FcγR) is involved in the slow clearance of immune complexes. To perform this role it must be cross-linked by IgG bound in its extracellular domains. It has been suggested that defective FcγR-mediated clearance of immune complexes may play a role in the pathogenesis of autoimmune connective tissue disorders. We have sequenced DNA encoding the second extracellular domain of FcγRIIα in six patients with SLE, to investigate whether point mutations may be responsible for encoding a defect in the IgG binding capacity of the receptor. We were able to identify the point mutation which discriminates high and low responder genotypes but found no other change from the published DNA sequence for this region.
Acquired resistance to type II collagen-induced arthritis in rhesus monkeys is reflected by a T cell low-responsiveness to the antigen
Authors: BAKKER N P M , VAN ERCK M G M , HART L A T , JONKER M 
Published: July 2010

SUMMARYTen out of 14 rhesus monkeys developed arthritis after a single immunization with bovine type II collagen (B-CII). In contrast to primary resistant monkeys, arthritic animals showed a B-CII specific T cell proliferation during the induction phase of the disease. All surviving animals showed a full remission of the disease. Two monkeys acquired resistance to collagen-induced arthritis (CIA) after one period of disease, but in three animals a booster immunization with B-CII induced a slight flare-up. It is demonstrated that B-CII immunized rhesus monkeys have the capacity to restore resistance to CIA. The development of resistance to CIA is reflected by a decreased T cell responsiveness to B-CII, It is shown that the lack of IL-2 plays a role in B-CII-induced T cell low-responsiveness. A potential role of CD8+ T cells in the down regulation of the T cell response to B-CII is discussed.
The effect of FK506 and cyclosporin A on antigen-induced arthritis
Authors: BLACKHAM A , GRIFFITHS R J 
Published: July 2010

SUMMARYFK506 and cyclosporin A inhibited the development of antigen-induced arthritis in the rat and rabbit. FK506 was five times more potent than cyclosporin A in the rat and approximately 20 times more potent in the rabbit. FK506 was effective in both species if administered either from the day of intra-articular administration or antigen or when the arthritis was established. In the rabbit, arthritis returned when administration of FK506 was stopped. FK506 (10 mg/ kg day) caused renal damage which was not observed at a dose of 2.5 mg/kg/day. Both of these doses were equally effective at inhibiting the arthritis. The conclusion from these studies is that FK506 is a more effective antiarthritic agent than cyclosporin A and that a pronounced therapeutic effect can be achieved at non-toxic doses of the drug.
Cell-bound IgE and increased expression of Faɛ-receptors on dendritic cells in cutaneous infiltrates of mycosis fungoides
Authors: PREESMAN A H , VAN DE WINKEL J G J , MAGNUSSON C G M , TOONSTRA J , VAN DER PUTTE S C J , VAN VLOTEN W A 
Published: July 2010

SUMMARYSkin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections wilh IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CDI4+) or Langerhans cells (CDl+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgGl, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of igE demonstrated that IgE interacled with Fcɛ-receptors through isotype-specific structures on the Fcɛ-fragment. Four anti-CD23 monoclonal antibodies, however, were unuble to stain vacant Fcɛ-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-γ, induce Fcɛ-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel wilh elevated serum IgE levels.
Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders
Authors: REYNOLDS S P , EDWARDS J H , JONES K P , DAVIES B H 
Published: July 2010

SUMMARYTwenty-one symptomatic subjects with pigeon breeders’ lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge.
Changes in serum immunoglobulin patterns in adults with common variable immunodeficiency
Authors: SELIGMANN M , AUCOUTURIER P , DANON F , PREUD'HOMME J L 
Published: July 2010

SUMMARY
Striking variations of serum immunoglobulin class and IgG subclass levels were observed in five patients with common variable immunodeficiency. They occurred mainly in untreated patients or, in those patients who received substitutive therapy, could not be merely due to replacement. They result in major changes in the immunoglobulin deficiency patterns, such as a shift from profound hypoimmunoglobulinaemia to IgA/IgG2/lgG4 deficiency or to isolated IgG2 deficiency. These findings have practical implications for the diagnosis and management of patients with primary humoral immunodeficiency.
Altered production of tumour necrosis factors alpha and beta and interferon gamma by HIV-infected individuals
Authors: VYAKARNAM A , MATEAR P , MEAGER A , KELLY G , STANLEY B , WELLER I , BEVERLEY P 
Published: July 2010

SUMMARYIn vitro studies shows that recombinant tumour necrosis factor (TNF) α and β, and interferon-gamma (IFN-γ) can enhance HIV replication, and peripheral blood mononuclear cells (PBMC) infected with HIV in vitro secrete high levels of the same cytokines. As T cells secrete all three mediators, the capacity of T cell activation signals to trigger cytokine production in PBMC from HIV-infected individuals was investigated as such patients may be immunocompromised. We demonstrate that asymptomatic seropositives in CDC group II/III as well as patients who have progressed to CDC group IV of the disease proliferate efficiently to anti-CD3 antibody, recombinant interleukin-2 (rIL-2), phytohaemagglutinin (PHA), PHA plus phorbol 12, 13 dibutyrate (PMA) but secrete significantly (P&gt;0.05) higher amounts of TNF-α, TNF-β and IFN-γ compared with controls in response to the same stimulants. We also show a difference between group II/III and group IV patients with the latter secreting more TNF-α and IFN-γ. The kinetics of TNF-α and -β and IFN-γ production was stimulus dependent with overall levels varying in time for each stimulus. Furthermore, the kinetics of the response to all three stimulants were altered in seropositives; CDC group II/III and group IV patients secreted higher levels of cytokines over several time points compared to controls. The altered production of these mediators by HIV-infected patients may contribute to disease progression and to the pathogenesis of AIDS.
Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE)
Authors: VAN DER ZEE J M , SIEGERT C E H , DE VREEDE T A , DAHA M R , BREEDVELD F C 
Published: July 2010

SUMMARY
IgG anti-endothelial antibodies (AEA), as measured by EL1SA or immunoblotting technique could be delected in serum samples or 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA litres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endolhelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE.
Localization of 20-kD homologous restriction factor (HRF20) in diseased human glomeruli. An immunofluorescence study
Authors: TAMAI H , MATSUO S , FUKATSU A , NISHIKAWA K , SAKAMOTO N , YOSHIOKA K , OKADA N , OKADA H 
Published: July 2010

SUMMARYThe 20-kD homologous restriction factor (HRF20), which is identical to CD59, is a membrane-associated protein which inhibits the reaction of C9 to form membrane attack complex (MAC) of homologous complements. In various human glomerular diseases deposition of complement components is frequently seen and MAC is reported to associate with immune deposits. Using a specific monoclonal antibody, 1F5, against HRF20, we attempted to study the localization of HRF20 in human glomerulonephritides and to compare the localization of HRF20 with those of immune deposits and MAC. The frozen sections of kidney specimens were fixed in acetone at room temperature before staining. In normal kidneys and kidney specimens from the patients with minimal change nephrotic syndrome, membranous nephropathy. and IgA nephropathy. HRF20 was strongly localized in the peritubular capillaries and along Bowman’s capsules. A weaker but well-defined staining was obtained in the mesangial area and faint staining was seen along the glomerular capillary walls. In contrast, glomerular capillary walls were rather strongly stained in the cases with diffuse lupus nephritis which had subendothelial dense deposits. These data suggest that HRF20 (CD59) is present in the human glomeruli and its expression is enhanced under certain conditions such as lupus nephritis.
Variable gene usage of T cell receptor γ- and δ-chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis
Authors: OLIVE C , GATENBY P A , SERJEANTSON S W 
Published: July 2010

SUMMARYThe synovial tissue and fluid of patients with rheumatoid arthritis (RA) contain activated T cells that probably have a central role in the disease process which leads to joint destruction. A subset of T cells, γδ T cells detected at the site of inflammation, may be important in the pathogenesis of the disease. This study investigated variable (V) gene usage of γδ T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR γ-and γ-chain transcripts. Most patients showed no restriction in Vγ gene usage since synovial mononuclear cells (SMC) expressed TcR γ-chain transcripts which used the same set of Vγ genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC Vδ-chain repertoire biased towards Vδ1, but Vδ2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR δ-chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR δ-chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of Vδ4. Vδ4 mRNA transcripts were expressed in PBMC of only two of seven RA patients in contrast with eight of the nine controls (P=0.03). These findings are compatible with reports that γδ T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to VγL9/Vδ2-bearing T cells, if a superantigen is involved in the pathogenesis of RA.
Flare-up of experimental arthritis in mice with murine recombinant IL-1
Authors: DE VAN LOO A A J , ARNTZ O J , VAN DEN BERG W B 
Published: July 2010

SUMMARYIntra-articular injections of murine recombinant IL-1 (mrIL-1) during the chronic phase of antigen-induced arthritis (AIA) induced a flare-up of the smouldering inflammation. The exacerbation was characterized by acute and transient joint swelling and this coincided with the extravascular accumulation of neutrophils. IL-1 injected into arthritic joints of neutropenic mice demonstrated that joint swelling was independent of the neutrophil influx into the joint. Both phenomena were absent when IL-1 was injected into a naive joint. The IL-1-induced flare-up was not T cell mediated as in the antigen-induced flare-up, and suggestive evidence is presented that IL-1 sensitivity depended on the resident macrophage population. This explained why the hypersensitivity is not restricted to the immunologically mediated arthritis but reflects a more general hypersensitivily of previously injured joints, e.g. zymosan-induced arthritis and IL-l-affected joints. In addition, IL-1 could also potentiate the antigen-specific flare-up of chronic AIA and prolongs the duration of the exacerbation. Our data indicate that joints bearing a chronic infiltrate are at risk from exacerbations in two ways: a T cell mediated rechallenge with antigen, and a non-specific reactivation by systemic and local IL-1 generation.
Soluble IL-2 receptor and tumour necrosis factor-α in plasma of haemophilia patients infected with HIV
Authors: NORONHA I L , DANIEL V , SCHIMPF K , OPELZ G 
Published: July 2010

SUMMARYWe measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-a (TNF-a) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seroncgative patients (mean 570 ± 27 U/ml versus 361 ± 17 U/ml in the control group, P &lt; 0.0001), in 78% of 68 HIV-seropositive patients (928·49 U/ml, P&lt;0.0001), and in 95% of 19 AIDS/ARC patients (1578 ± 199 U/ml. P&lt;0.0001 compared with controls and with HIV-seronegative patients; P&lt;0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P&lt;0.0001), and CD4/CD8 ratios (P&lt;0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P&lt;0.001). We found a significant association of sIL-2R and plasma neopterin (P&lt;0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight percent of HIV-seronegative patients. 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-a. We conclude that sIL-2R and TNF-a plasma levels arc elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.
Epstein-Barr virus and HIV play no direct role in persistent generalized lymphadenopathy syndrome
Authors: BOYLE M J , SCULLEY T B , COOPER D A , TURNER J J , PENNY R , SEWELL W A 
Published: July 2010

SUMMARYPersistent generalized lymphadenopathy (PGL) and polyclonal B cell activation are features of infection with HIV. Epstein-Barr virus (EBV) and HIV are known to activate B cells in vitro, but whether they are important B cell activators in patients infected with HIV is less clear. In this study, lymph node tissue was obtained from 10 patients with PGL and assessed for evidence of EBV and HIV gene sequences. DNA was extracted and specific viral gene sequences identified using the polymerase chain reaction (PCR). EBV sequences were difficult to detect in the PGL tissue, with a signal intensity similar to that of other benign and malignant lymphoid conditions not associated with EBV. HIV sequences were also rare in the PGL tissue, consistent with HIV infection of the small number of peripheral blood cells and nodal T cells likely to be present in such a sample. These findings suggest that the polyclonal B cell activation typical of HIV is not driven by direct EBV or HIV infection of B cells.
Elevations in cytosolic free Ca2+ are not required to trigger apoptosis in human leukaemia cells
Authors: LENNON S V , KILFEATHER S A , HALLETT M B , CAMPBELL A K , COTTER T G 
Published: July 2010

SUMMARYPrevious studies have indicated that Ca2+ is a trigger for apoptosis (programmed cell death) in thymocytes and related cell lines. Recently we have shown that levels of apoptosis in leukaemic cells are diminished in Ca2+-deficient conditions, indicating that Ca2+ may be important in the mechanism of apoptosis in these cells. In the present study we investigated the possibility that Ca2+ serves as a trigger for apoptosis in the human leukaemic cell line, HL-60. Using fura-2 to measure cytosolic free Ca2+ concentrations, [Ca2+]i, in cell suspensions, and by using ratio imaging of fura-2 in single cells, we did not observe an early significant increase in [Ca2+]i, in HL-60 cells undergoing apoptosis. The latter stages of apoptosis were, however, accompanied by increasing [Ca2+]i, these increases were apparently a result of, rather than a cause of, apoptosis. Furthermore, apoptosis could be induced in HL-60 cells under conditions of vastly reduced [Ca2+]i achieved by loading these cells with fura-2 in the presence of EGTA. These results indicate that elevation of [Ca2+]i is not a prerequisite for apoptosis in HL-60 cells and that apoptosis can occur in these cells in the presence of low[Ca2+]i.
Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of AIDS in HIV-1-infected haemophiliac patients
Authors: WEBSTER A , PHILLIPS A N , LEE C A , JANOSSY G , KERNOFF P B , GRIFFITHS P D 
Published: July 2010

SUMMARYAfter a maximum of 11 years (median 8·3 years) from the time of HIV seroconversion. 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV scroncgatives. The age-adjusted relative risk for AIDS among CMV scropositives was 2·4 (P= 003). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (−0·087 ± 109/l per annum versus-0·082 ± 109/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the lime of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-l-ncgative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0·94 ± 10+/l and 0·97 ± 109/l. respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0·07 ± 109/l) than in the seronegative group (0·04 ± 109/l). but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.