bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual mechanism in induction of human neutrophil cytotoxicity: activation of protein kinase C and elevation in intracellular calcium
Authors: GAVIOLI R , SPISANI S , GIULIANI A L , TRANIELLO S 
Published: July 2010

SUMMARYHuman neutrophils can damage the non-immunized K562 cell line when stimulated by phorbol myristate acetate (PMA). The combination of the activation of protein kinase C by phorbol and the increase of free intracellular calcium by ionophore potentiates the lytic reaction. The OKT9-immunized target cells are not able to induce by themselves the lytic response in neutrophils, but by combining the two signals, the antigenic stimulus and PMA, a high level of cytolytic response is attained. The addition of EGTA does not affect neutrophil cytotoxicity against antibody-coated targets, while it markedly reduced the lytic reaction against non-immunized targets; in contrast, the addition of EGTA together with the ionophore ionomycin completely suppresses the lysis of immunized and non-immunized targets. The treatment of neutrophils with the protein kinase C inhibitor H-7 causes a dose-related inhibition of the lytic functions that is greater on unsensitized K562. Thus the interaction of Fc receptors with immunized targets is required for reaching the maximal cytolysis. The enhanced lytic activity that occurs in the presence of immunized targets is mediated by calcium flux, as detected by using the monoclonal antibody AB8.28 which binds to FcIII receptors (FcRIII), thus supporting that both signals are involved.
M5, a phosphoinositol-linked human myelomonocytic activation-associated antigen
Authors: GADD S J , MAJDIC O , KASINRERK W , STOCKINGER H , MAURER D , EHER R , KNAPP W 
Published: July 2010

SUMMARYWhen investigating the previously described monoclonal antibody (MoAb) VIM-5, raised against THP1 cells and binding to human monocytes and granulocytes, we found that the antigen detected by this antibody, designated M5, becomes very strongly expressed on monocytes after overnight culture with phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) but not with recombinant human interferon-gamma (rhIFN-γ). Granulocytes stimulated with formyl-methionyl-leucyl-phenylalinine (FMLP) become negative for binding VIM-5. Immature granulocytes from bone marrow do not express M5, thus its expression on granulocytes is differentiation linked. The antigen bound by VIM-S is sensitive to hydrolysis by phosphoinositol-specific phospholipase C (PI-PLC). The immunoprecipitated MS antigen on monocytes is a broad band, with a peak of 50 kD (unreduced) and two bands of S3 kD and 44 kD (reduced). We have therefore detected an antigen that is up-regulated on stimulated monocytes but, conversely, down-regulated on FMLP-stimulated granulocytes.
Failure of ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort
Authors: DALGLEISH A , SINCLAIR A , STEEL M , BEATSON D , LUDLAM C , HABESHAW J 
Published: July 2010

SUMMARYAntibody-dependent cell-mediated cytotoxicity (ADCC) has been described in a number of virus infections and occurs in HIV infection. In spite of numerous studies on the ability of HIV-positive sera to mediate ADCC, it remains unclear whether ADCC has any functional significance. Here we examine serial serum samples from a cohort of haemophilia patients who became infected from a common source in 1984, and show that there is no significant difference in ADCC values between those who remained asymptomatic and those who progressed to disease. This study does not compare effector cell function and clinical status and does not exclude activity against different target cell lineages in vivo.
Fine specificities of anti-nuclear antibodies in murine models of graft-versus-host disease
Authors: VAN DAM A P , MEILOF J F , VAN DEN BRINK H G , SMEENK R J T 
Published: July 2010

SUMMARYTwo models of murine graft-versus-host disease (GVHD) were studied with respect to autoantibody production and development of systemic lupus erythematosus (SLE) like disease. One model was induced by injection of (B10.A(4R) × B10.A(2R))F1 mice with parental (B10.A(4R)) spleen and lymph node cells (groups I GVHD), the other by injection of (DBA/2 × C57/B16)F1 mice with DBA/2 cells (group II GVHD). Group I GVHD mice remained in a seemingly healthy condition and did not show any proteinuria, in spite of high titres of anti-nuclear antibodies including antibodies to dsDNA, anti-Sm and anti-ribosomal P protein antibodies. Measured levels of these autoantibodies as well as their isotypes were comparable with those found in MRL/lpr and NZB/W mice. Group II GVHD mice developed SLE-like disease signs, including severe proteinuria. At 4 months after induction of the GVHD, almost 50% of these mice had died. At the time nephritis was present, group II mice also produced anti-dsDNA and anti-nuclear antibodies of other (unknown) specificities, but no anti-Sm or anti-P. Furthermore, the incidence of these antibodies was lower than observed in group I GVHD, MRL/lpr or NZB/W mice. It is concluded that (high avidity) anti-dsDNA as well as anti-Sm and anti-P may be present in the circulation without giving rise to the development of nephritis.
Recombinant 70-kD protein used for determination of autoantigenic epitopes recognized by anti-RNP sera
Authors: NYMAN U , LUNDBERG I , HEDFORS E , PETTERSSON I 
Published: July 2010

SUMMARYA panel of high- and low-titre anti-RNP-positive patient sera was tested for reactivity with human snRNP proteins. The U1 snRNP-specific 70-kD peptide was found to be the most prominent RNP antigen recognized by high-titre anti-RNP sera, mainly found in patients with mixed connective tissue disease (MCTD). The reactivity with the 70-kD protein was further analysed with recombinant fusion proteins containing different segments of the protein. One major and two minor antigenic regions were found. Most patient sera, both with high- and low-titre anti-RNP antibodies, only recognized the major region. The most aminoterminal region, showing partial sequence homology with a mouse retroviral p30 gag protein, contained an epitope that was recognized by one serum only.
Autoantibodies to epithelial cells in patients on long-term therapy with leucocyte-derived interferon-alpha (IFN-α)
Authors: KARLSSON-PARRA A , BURMAN P , HAGBERG H , ÖBERG K , ALM G , KLARESKOG L , KARLSSON F A 
Published: July 2010

SUMMARYDuring routine screening for anti-nuclear antibodies, using rat liver tissue as substrate, a reactivity against bile duct epithelium was observed in sera from carcinoid tumour patients given human leucocyte-derived IFN-a (HuLe IFN-a). In a retrospective study, initiated by this observation, the development of serum antibodies to bile duct epithelium was observed in nine out of 12 patients with carcinoid tumours and in three out of 14 patients with hairy-cell leukaemia during their treatment with HuLe IFN-α. However, no bile duct reactivity was observed in sera from carcinoid or hairy-cell leukaemia in patients given recombinant IFN-α. When analysing the reactivity of positive sera against a panel of rat and human tissues, a uniform reactivity was observed against simple epithelial cells lining the gastrointestinal tract, pancreatic secretory ducts, fallopian tube, kidney tubuli. mesothelium and also against carcinoid tumour cells. The mechanisms promoting autoreactivity against this simple epithelial cell auloantigen is so far unknown. The cytoplasmic as well as the restricted staining pattern of simple epithelial cells may indicate autoreactivity against certain cytoskelelal intermediate filaments, such as cytokeratin19, 18 and8, known to be exclusively present in simple epithelial cells and tumours derived from them.
Subpopulations of CD4+ cells in lpr/lpr mice: differences in expression of T cell receptor/CD3 complex and proliferative responses
Authors: ASANO T , YOSHIKAI Y , MATSUMOTO K , MATUZAKI G , NOMOTO K 
Published: July 2010

SUMMARYCD4+ cells from autoimmune-prone C57BL/6 lpr/lpr mice contain two subpopulations, B220 CD4+ and B220+ CD4+ cells. Highly purified B220 CD4+ cells from C57BL/6 +/+ and lpr/lpr mice were examined by comparing functional characteristics and expression of cell surface antigens and T cell receptor (TcR)/CD3 complex. Both Ipr B220+CD4+ and B220+CD4− CD8 cells, most of which were PgP-1 positive, expressed TcR/CD3 complex on the cell surface at lower level as compared with B220 CD4+ cells of age-matched normal mice. In addition, the B220 CD4+ cells were heterogeneous on the basis of surface expression of PgP-1 and CD3 antigens. Normal levels of TcR Cx-, Cβ- and Vβ8-specific mRN A were found in the B220 CD4+cells and B220+ CD4+ cells as compared with normal B220− CD4+ cells, while Vβ8-specific mRN A was preferentially expressed only by B220+ CD4CD8 cells. Either B220+ CD4+ cells and B220+CD4− CD8− cells Tailed to respond to anti-CD3 monoclonal antibody (MoAb) as assessed by proliferative responses and production of interleukin-2 (IL-2). However, appreciable levels of reactivity to anti-CD3 MoAb were detected in the B220 CD4+ cells, although the responsiveness of this subset to such stimuli were reduced, compared with those of normal control. These results indicate that the B220− CD4+ cells in Ipr mice are phenotypically and functionally distinct from normal B220 CD4+ cells.
Sequential serological responses to Aspergillus fumigatus in patients with cystic fibrosis. Use of antigen ‘stretching’ to delineate IgG and IgE activity
Authors: EDWARDS J H , ALFAHAM M , FIFIELD R , PHILPOT C , CLEMENT M J , GOODCHILD M C 
Published: July 2010

SUMMARY
Immunogens from Aspergillus fumigatus were fractionated on the basis of molecular weight. Nine fractions ranging from 900 to 10 kD were used in ELISA and in a radioallergosorbent test (RAST) with sera from cases of allergic bronchopulmonary aspergillosis (ABPA) and from cystic fibrosis (CF) patients with ABPA or other Aspergillus involvement and compared with control subjects. The profile of IgG reactivity to the nine fractions did not vary substantially for all Aspergillus-involved groups producing peaks at &gt; 900 kD and 170 kD whereas the profile for control subjects had a peak at &gt; 900 kD only. The IgE profile for CF patients with ABPA did not differ from the profile of the RAST-positive CF patients without ABPA and provided only one peak of activity at 24 kD. Recovery from an episode of ABPA in CF patients was accompanied by a fall in both IgG and IgE antibody levels to all nine fractions, whereas increases in IgG and IgE to all fractions were seen during an episode of ABPA. Although there was an exaggerated IgG increase to antigens in the 43–170 kD range during ABPA, a meaningful increase was also observed to unfractionated A. fumigatus antigen preparations. With IgE in one detailed study the 24-kD fraction provided a better indication of Aspergillus involvement than the unfractionated A. fumigatus antigens. Sequential studies of IgG and IgE levels were not able to predict an episode of ABPA but were useful in conjunction with clinical assessment in following the course of the illness.
Passive transfer of immunity toMycobacterium aviumin susceptible and resistant strains of mice
Authors: STOKES R W , COLLINS F M 
Published: July 2010

SUMMARYNaturally susceptible mice (C57BL/6) infected with M. avium (strain Weybridge) developed a population of splenic T cells which, on transfer to syngeneic recipient mice, conferred significant protection against a subsequent challenge inoculum of M. avium. Similar T cells from naturally resistant mice (A/J) did not protect syngeneic recipient mice. Growth of M. avium in donor mice only occurred in the C57BL/6 strain. Replication of M. avium in donor mice was necessary for the development of protective T cells. High numbers of killed mycobacterium did not induce immune T cells. In addition. A/J mice inoculated with increasing numbers of viable M. avium (which still did not replicate) failed to develop protective T lymphocytes. Further studies indicated that no protective T cells were present in the M. avium-infected A/J mouse, although evidence for non-specific immunity in these mice was obtained. In addition, BCG (which grows progressively in A/J mice) stimulated a population of splenic T cells which protected recipient mice from subsequent infection with M. tuberculosis.
Early accumulation of suppressor cell precursors in the spleen ofMycobacterium lepraemurium-infected mice and analysis of theirin vitro-induced maturation
Authors: LEMIEUX S , GOSSELIN D , LUSIGNAN Y , TURCOTTE R 
Published: July 2010

SUMMARYSpleen cells harvested from mice infected intraperitoneally with M. lepraemurium 11–17 weeks prior to harvest acquired the capacity to inhibit concanavalin A (Con A) induced proliferation of normal spleen cells when precultured for up to 24 h in mitogen-free medium. The in vitro induced suppressor activity correlated with the length of the preculture period, the time post-infection and the infecting dose. These findings were interpreted as an indication that suppressor cell precursors accumulated in the spleen of infected mice during the early phase of the disease. The interaction of infection-dependent adherent suppressor cell precursors and infection-independent, non-adherent regulatory cells is necessary for the suppressor activity to develop. Both the cells which transmit the inductive signal and the precursor cells which mature into active suppressor cells are radiosensitive, whereas suppressor activity itself is a function of radioresistant adherent cells. Preculture of cells for a short period, before they were cocultured with Con A-stimulated normal spleen cells, allowed the detection of suppressor cells before they were deleterious to the infected host and also turned out to be a relevant in vitro model for characterization of suppressor cell development during M. lepraemurium infection.
Quantitative measurement of SC5b-9 and C5b-9(m) in infarcted areas of human myocardium
Authors: HUGO F , HAMDOCH T , MATHEY D , SCHÄFER H , BHAKDI S 
Published: July 2010

SUMMARYPrevious immunohistochemical work has indicated that terminal C5b-9 complement complexes are selectively deposited in infarcted areas of human myocardium. In the present study, we sought to quantify C5b-9 levels in myocardial tissue, and to differentiate between the membrane-bound C5b-9 (m) and the cytolytically inactive SC5b-9 complex. Paired tissue specimens from infarcted and non-infarcted myocardium were obtained from 36 autopsies. The homogenized and washed tissues were extracted with n-octyl-β-D-glucopyranoside (octylglucoside) detergent, and the concentrations of C5b-9 in the extracts were determined by ELISA. Membrane-derived C5b-9 (m) and SC5b-9 were differentiated from each other on the basis of their characteristic sedimentation behaviour in sucrose density gradients. It was found that infarcted myocardial tissue contained on average an approximately three-fold higher concentration of C5b-9, compared with non-infarcted tissue. This increase was due in part to an increase in levels of C5b-9 (m). The results corroborate previous immunohistochemical data and show that complement activation occurs to completion with the generation of potentially cytotoxic C5b-9 complexes in infarcted myocardial tissues.
Selective IgG subclass deficiency: quantification and clinical relevance
Authors: JEFFERIS R , KUMARARATNE D S 
Published: July 2010

SUMMARYEach of the four human IgG subclasses exhibits a unique profile of effector functions relevant to the clearance and elimination of infecting microorganisms. The quantitative response within each IgG subclass varies with the nature of the antigen, its route of entry and, presumably, the form in which it is presented to the immune system. This results in antibody responses to certain antigens being predominantly or exclusively of a single IgG subclass. An inability to produce antibody of the optimally protective isotype can result in a selective immunodeficiency state. This is particularly apparent for responses to certain bacterial carbohydrate antigens that are normally of IgG2 isotype. A failure to produce the appropriate specific antibody response may result in recurrent upper and/or lower respiratory tract infection. Careful patient investigation can identify such deficiencies and suggest appropriate clinical management. In this review we outline the biology and clinical relevance of the IgG subclasses and summarize current rational treatment approaches.
Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice
Authors: REDDY S , BIBBY N , ELLIOTT R B 
Published: July 2010

SUMMARYWe have previously shown the presence of circulating islet cell cytoplasmic antibodies (ICA) and insulin autoantibodies (IAA) in the NOD mouse before onset of insulin-dependent diabetes mellitus (IDDM). Here we have determined the levels of the two autoantibodies in 28 female NOD mice longitudinally from approximately day 40 to day 250, to examine their ontogeny, association and predictive value for diabetes. All animals (11 diabetic, 17 non-diabetic) showed varying levels of ICA at some stage, while IAA activity was found in 21 out of 28 mice. Expression of both the markers was seen in more than half of the animals by day 60, with higher levels and rates occurring subsequently in both diabetic and non-diabetic groups. The expression of ICA did not always correlate with that of IAA. There was no apparent difference in the ontogeny of ICA and IAA between the two groups. During the study period the number of animals with ICA was similar in the two groups, while the number of those with IAA was higher in the diabetic animals. In this group declining and rising levels of ICA were seen just before clinical diabetes with frequent peaks of IAA. In the same animals, eight out of 11 mice showed co-expression of high levels of both markers either intermittently or persistently prior to onset, whereas only one non-diabetic animal showed this. We conclude that the ontogeny and serum level of ICA or IAA alone could not be used to predict the clinical onset of diabetes in these animals. However, co-expression of high levels of both markers prior to onset may suggest a strong predisposition to clinical diabetes. This may have relevance to attempts to predict the onset of IDDM in humans who have one or both of these immunological markers.
Therapeutic effect of 15-deoxyspergualin on the progression of lupus nephritis in MRL mice. I. Immunopathological analyses
Authors: ITO S , UENO M , ARAKAWA M , SAITO T , AOYAGI T , FUJIWARA M 
Published: July 2010

SUMMARYThe effect of 15-deoxyspergualin (DSP), a newly developed immunosuppressive agent, on the development of spontaneously occurring lupus glomerulonephritis in MRL-lpr mice was examined. Administration of the drug was initiated at the age of 13 or 17 weeks, when polyclonal B cell activation and lupus nephropathy were apparent or became prominent. Treatment with DSP for up to 19 weeks of age at a dose of 2 mg/kg twice a day or 5 mg/kg daily strongly suppressed the increment of IgG-producing cell numbers in the spleen and serum levels of immune complexes and anti-DNA antibodies. Glomerular histoiogical score estimated by light microscopy and IgG and C3 deposition in renal glomeruli were improved, compared with untreated control mice. Thus, DSP was shown to suppress the progression of polyclonal B cell activation and lupus nephropathy in MRL/lpr mice. These results suggest that DSP may be used as a therapeutic agent for systemic lupus erythematosus.
Vβ5 andVβ8 memory T cells in adults and infancy: co-ordinated increase in response to early antigen stimulus
Authors: HAYWARD A R , CLARKE J , COSYNS M 
Published: July 2010

SUMMARYBlood mononuclear cells (MNC) expressing the T cell receptor Vβ gene families were identified with the monoclonal antibodies IC1 (Vβ5) or Mx6 (Vβ8). These cells were typed for expression of the T200 common leucocyte antigen with the CD4SRA antibody defining the 220-kD variant (which characterizes naive cells) and theUCHL1 antibody which defines the 180-kD variant (characterizing memory cells). Of adult MNC, 3±0.44% stained for Vβ5 and 4.12±0.26% stained for Vβ8; similar results were obtained in a group of infants aged less than 3 months, who were exposed to antigen stimulus in the form of infection and/or blood transfusion. While the total percentages of Vβ5 and Vβ8 cells in the blood of adults were not correlated, the proportions of these cells expressing CD4SRO was positively correlated. A similar trend which did not reach statistical significance was present in a group of infants. A minority of the infants studied showed transient deviations from the mean established for adults. The results suggest that naive and memory T cell populations have similar frequencies of Vβ5 and Vβ8 expressing cells, and that age does not affect the frequency of usage of either of these Vβ families.
Monoclonal antibody BA-1 to the human B lymphocyte marker CD24 recognizes a sialic acid (N-acetylneuraminic acid) dependent epitope in multi-valent display on peptide
Authors: MEHMET H , LARKIN M , TANG P W , LEBJEN T W , FEIZI T 
Published: July 2010

SUMMARYEvidence is presented that monoclonal antibody BA-1, directed against a marker (CD24) of human lymphocytes of B cell lineage, recognizes a sialic aeul-dependent cpitopc. This conclusion is based on a scries of experiments exploiting the reaction of this antibody with bovine and ovine submaxillary mucins. Expression of the cpitopc was enhanced following alkaline saponification of bovine submaxillary mucin, which converts 0-acctylatcd ncuraminic acid residues to N-acelylncuraminic acid. The epitope was destroyed following ncuraminidase or mild acid treatment of the mucins, and its expression was diminished following neuraminidasc treatment of B lymphobtastoid cells. Glycopcptidcs obtained by digestion of the bovine mucin with papain, trypsin or pronasc were lacking in antigenicity. However, anligcnic activity could be regenerated after conjugation of pronase glycopepiides to poly-L-lysinc. These results indicate that multivalenl display of sialo-oligosacchar-ide on peptide rather than a protease-susceptible polypcplide domain is required for BA-1 antibody binding.
Adhesion of polymorphonuclear cells to human endothelial cells. Adhesion-molecule-dependent, and Fc receptor-mediated adhesion-molecule-independent mechanisms
Authors: LEEUWENBERG J F M , JEUNHOMME G M A A , BUURMAN W A 
Published: July 2010

SUMMARYActivation of human umbilical vein endothelial (HUVE) cells with the inflammatory mediators tumour necrosis factor-alpha (TNF), interleukin-1 (IL-1), lipopolysaccharide (LPS) and phorbol esters enhanced their adhesiveness for leucocytes. The appearance of an activation antigen ELAM-1, recognized by a monoclonal antibody (MoAb) ENAI, parallels the kinetics of the enhanced adherence of leucocytes to endothelial cells. Adhesion of polymorphonuclear cells (PMN) to activated HUVE cells could be blocked by F(ab)2 fragments of MoAb ENA1 up to 60%. An additive inhibition of the adhesion was established by pre-incubation of the PMN with anti-CD18 MoAb and J. or leucocyte adhesion inhibitor (LAI), produced by endothelial cells. An opposite reaction, however, was observed when HUVE cells were pre-incubated with intact MoAb ENAI, resulting in an enhancement of the adhesion up to 200%. Apparently, the blocking effect of MoAb ENA1 could be bypassed by the strong interaction of the Fc part of the MoAb with the Fc receptor (FcR) on the PMN. Similarly, anti-CD 18 MoAb and J. or LAI reduced the adhesion observed if intact ENAI were used, and Fc-FcR interaction took place. The results presented in this study indicate that adhesion via ELAM-1, the CD18 antigen and via the receptor for LAI are different mechanisms. These mechanisms may act in concert to strengthen the binding of PMN to HUVE cells. Moreover, a strong adhesion could be established via the Fc part of MoAbs directed against HUVE cells with the FcR on the PMN. The phenomenon described may play a roie in graft rejection and in diseases where antibodies directed against endothelium are involved.