bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of lymphocyte function-associated antigen (LFA-1) on peripheral blood leucocytes from individuals with Down's syndrome
Authors: BARRENA M J , ECHANIZ P , GARCIA-SERRANO C , ZUBILLAGA P , CUADRADO E 
Published: July 2010

SUMMARYWe analysed the expression of lymphocyte function-associated antigen LFA-1 on the cell surface peripheral blood lymphocytes, monocytes and granulocytes from 20 children wilh Down's syndrome. No differences in LFA-1 expression was found within monocytes or granulocytes from either normal or Down's syndrome children: however, a clear-cut difference was observed on lymphoid cells: Both normal and Down's syndrome lymphocytes displayed a bimodal pattern of LFA-1 staining by flow cytometry, with a predominance of cells with low expression in normal population, and an increased proportion of lymphocytes with high level of LFA-1 expression in Down's syndrome children. This difference correlates well with the abnormal proportion of T cell subsets and inversion of CD4/CD8 observed in a majority of our cases, and therefore, it could merely reflect the increase of certain T cell subsets nonnaily expressing higher number ofLFA-1 molecules. Taken together, our results do not support an abnormally increased expression of leucocytes integrins in trisomy 21 cells, and raise some doubt about the suggested role of the abnormal cellular expression of LFA-1 in the pathogensis of secondary immunodeficiency associated to Down's syndrome.
Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptorin vitro
Authors: LÖHR H , TREICHEL U , PORALLA T , MANNS M , ZUM BÜSCHENFELDE K H MEYER , FLEISCHER B 
Published: July 2010

SUMMARYAutoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera orpaticnts with autoimmune liver disorders. Live-nfiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (A-AH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclcar cells (PBMC) from patients with A-AH or PBC but not chronic viral hepatitis secreted ant-SGPR antibodies in vitro. In this study we characterized the influence of live-nfiltrating T cells on the secretion of ASGP-pecific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with A-AH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibod-ecrcting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supematants and showed a proliferative response to ASGPR. T cel-epleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+ CD8− live-nfiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous ant-SGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8− and two CD4−CD8+ T cell clones no-esponding to ASGPR provided this help for antibody secretion. Ant-SGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclona-ctivating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGP-pecific antibodies. This help can be provided by ASGP-esponsive T helper cells via cellular interactions.
Immunization of mice with the antigen A60 oi Mycobacterium bovis BCG
Authors: HUBBARD R D , FLORY C M , COLLINS F M , COCITO C 
Published: July 2010

SUMMARY
Antigen 60 (A60) is a thermostable component of the cytoplasm of Mycobacterium tuberculosis and BCG which can be fractionated into at least 15 protein bands when analysed by Western blot. Normal B6D2 mice were immunized subcutaneously with 20 μg of the A60 protein suspended in Freund's incomplete adjuvant (FIA) or in saline. Three weeks later the mice received a second dose of vaccine followed 2 weeks later by an aerogenic challenge with approximately 103 CFU of M. tuberculosis Erdman. The mice receiving the adjuvanled A60 showed a significant reduction (P &lt; 0·05) in the number of viable organisms recovered from the lungs and the spleen 3 weeks after challenge. However, this response was less than that seen in BCG vaccinated controls.
B cell responses to HIV and the development of human monoclonal antibodies
Authors: BOYD J E , JAMES K 
Published: July 2010

SUMMARYIn this review B cell responses in HIV-infected individuals are summarized together with the techniques used to date to produce human monoclonals to HIV and the properties of these antibodies. Profound disturbances in B cell responses are apparent both in vivo and in vitro. While there is evidence in vivo of marked polyclonal B cell activation, primary and secondary antibody responses are impaired. Similarly these cells exhibit spontaneous immunoglobulin secretion upon in vitro culture but do not readily respond to B cell mitogens and recall antigens including HIV. Furthermore, certain of these defects can be reproduced in normal B cells in vitro by incubation with HIV or HIV coded peptides. Individuals infected with HIV develop antibodies to HIV structural proteins (e.g. p17, p24, gp41 and gp120) and regulatory proteins (e.g. vif, nef, RT). Autoantibodies against a number of immunologically important molecules are also frequently observed. The anti-HIV antibodies are predominantly of the IgG1 isotype and exhibit a variety of effects on the virus in vitro. To date, using conventional immortalization strategies, an appreciable number of human monoclonals to HIV have been developed. These have been specific for gp41, gp120 and gag with antibodies of the former specificity predominating. The majority of these antibodies have been of the IgGl isotype. Only a small number of the antibodies neutralize virus in vitro and most of these react with gp120. The neutralizing antibodies recognize conformational and carbohydrate epitopes or epitopes in amino acid positions 306–322. The predominant epitopes recognized by the anti-gp41 antibodies were in amino acid positions 579–620 and 644–662. A high percentage (≏ 25%) of these antibodies enhance viral growth in vitro. The problems relating to the production of human monoclonals to HIV are discussed together with strategies that could be used in the future.
Treatment of patients with chronic granulomatous disease with recombinant human interferon-gamma does not improve neutrophil oxidative metabolism, cytochrome b558 content or levels of four anti-microbial proteins
Authors: MÜHLEBACH T J , GABAY J , NATHAN C F , ERNY C , DOPFER G , SCHROTEN H , WAHN V , SEGER R A 
Published: July 2010

SUMMARY
Recombinant interferon-gamma (rIFN-γ) has been described to enhance phagocyte functions in vitro and in vivo in several patients with chronic granulomatous disease (CGD). To demonstrate the clinical usefulness of this treatment. 128 patients were treated in a randomized, double-blind multi-centre study with a placebo preparation or with rIFN-γ. We analysed parameters of neutrophil oxidative and non-oxidative metabolism in 16 patients enrolled in this study. No enhanced superoxide-release was observed in patients treated with rIFN-γ compared to placebo-treated patients. Phagocyte cytochrome b558 content also remained unchanged. Levels of four nonoxidative antimicrobial proteins (cathepsine G. azurocidine, p29b, lactoferrin) rose, fell, or remained unchanged, irrespective of treatment with rIFN-γ or placebo.
IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2
Authors: YANAGAWA H , SONE S , MUNEKATA M , ATAGI S , NII A , OGURA T 
Published: July 2010

SUMMARYThe levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1β was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.
T and B cell reactivity to adrenal antigens in autoimmune Addison's disease
Authors: FREEMAN M , WEETMAN A P 
Published: July 2010

SUMMARYAutoimmune Addison's disease is a rare condition of uncertain pathogcncsis. To delineate potential autoantigens. an adrenal homogenate was fractioned by SDS-gel clectrophoresis and used in immunoblotting and T cell proliferation assays. Antibodies specific for adrenal proteins with approximate molecular weights of 70, 55 and 45 were found in five out of 20 consecutive Addison's disease patients at routine follow-up. Five sera also reacted with a 52-kD protein shared with liver. T cells from six out of 10 Addison's disease patients proliferated in response to a range of adrenal-specific antigens including one, in particular, with a molecular weight of 18–24 kD. T and B cell reactivity to adrenal antigens did not appear to correlate and there was no relationship with time since diagnosis, associated autoimmunity or HLA-DR type. These results show that the autoimmune response to adrenal antigens in Addison's disease is heterogeneous and that such autoreactivity can only be inconsistently documented using these techniques and circulating antibodies or T cells.
Monocyte heterogeneity in angiotensin-converting enzyme induction mediated by autologous T lymphocytes
Authors: RYU J H , VUK-PAVLOVIC Z , ROHRBACH M S 
Published: July 2010

SUMMARYThe ability of monocyte subpopulations to be induced selectively by T lymphocytes to synthesize enhanced levels of angiotensin-converting enzyme (ACE) was examined using an in vitro model employing normal peripheral blood monocytes and T lymphocytes. Separation of monocytes into subpopulations on the basis of buoyant density indicated no difference in the ability of the resulting monocyte subpopulations to produce basal levels of ACE when cultured in the absence of T lymphocytes. However, the subpopulations differed significantly in their ability to synthesize enhanced levels of ACE in response to the presence of autologous T lymphocytes; low-density monocytes were induced by T lymphocytes to synthesize three-fold more ACE than were highdensity monocytes. Surface antigen labelling using MoAbs demonstrated that the low-density monocyte subpopulations also had a significantly higher percentage of Leu-M2+ monocytes compared with the high-density monocyte subpopulations. When monocytes were separated on the basis of the presence of the Leu-M2 antigen using an immune rosetting technique, T lymphocytes were able to induce significantly elevated levels of ACE in the Leu-M2+ enriched monocyte subpopulation but were unable to induce ACE beyond basal levels in the Leu-M2+-depleted monocyte subpopulation. These results demonstrate that monocytes are heterogeneous with respect to their ability to be induced by T lymphocytes to synthesize ACE. This raises the possibility that selective accumulation of a monocyte subpopulation in the granulomatous inflammation of sarcoidosis may be one of the factors required for elevated ACE synthesis in the resulting granuloma epithelioid cells.
Involvement of platelet-activating factor and tumour necrosis factor in the pathogenesis of joint inflammation in rabbits
Authors: ZARCO P , MAESTRE C , HERRERO-BEAUMONT G , GONZÁLEZ E , GARCIA-HOYO R , NAVARRO F J , BRAQUET P , EGIDO J 
Published: July 2010

SUMMARYWe have studied the participation of platelet-activating factor (PAF) in antigen-induced arthritis in rabbits, as well as the possible co-operation between PAF and tumour necrosis factor (TNF) in their ability to induce joint inflammation when injected into the knees of healthy rabbits. The administration of two structurally different PAF receptor antagonists, BN52021 and Alprazolam, from 4 h before the intra-articular injection of ovalbumin in preimmunized rabbits, induced an important reduction in the synovial fluid volume, in the amount of cells infiltrating the articular cavity and the synovial membrane, as well as in the prostaglandin E2 (PGE2) concentration. Furthermore, proteoglycans of the articular cartilage, which were found diminished in animals with non-treated arthritis, were well preserved in rabbits treated with PAF antagonists. All the synovial fluids from joints with arthritis had detectable amounts of PAF. The injection of either TNFor PAF into the joints of normal rabbits induced a mild inflammation. When TNF was administered 1 h before PAF, a synergistic response was noted in the synovial fluid volume, in the accumulation of leucocytes, and in the amount of PGE2. The administration of BN50726, a hetrazepine with a potent PAF-receptor antagonist effect, induced a diminution in those parameters. Our results suggest that PAF may be an early and important mediator of joint damage, and that TNF can amplify the inflammatory response induced by PAF. PAF receptor antagonists could play some role in the treatment of inflammatory joint diseases.
A human monoclonal autoantibody to a nucleolar structure
Authors: GONZALEZ M F , WICHMANN I , YELAMOS J , MELERO J , MAGARIÑO R , SANCHEZ-ROMAN J , NUÑEZ-ROLDAN A , SANCHEZ B 
Published: July 2010

SUMMARYPeripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supematants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supematants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens. CDC-1 reacted against Ro/SS-A, Ul (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 k D. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to delect three bands at 60,55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A.
Phospholipid-containing toxic malaria antigens induce hypoglycaemia
Authors: TAYLOR K , BATE C A W , CARR R E , BUTCHER G A , TAVERNE J , PLAYFAIR J H L 
Published: July 2010

SUMMARYHypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytcs infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed lime course compared with insulin: some, though weaker, activity could also be obtained by overnight incubation of uninfected crythrocytes. The active component shares many properties with (he phospholipid-containing molecules which we have previously shown to be toxic and to induce the release of tumour necrosis factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity of tumour necrosis factor in vitro did not prevent this induction of hypoglycaemia, whereas antiscrum against the toxic antigens did, as did immunization of normal (but not the immunoglobulin-deficient SCID) mice with the same material. Furthermore, normal mice injected with the antigens after immunization with phosphatidyl inositol or inositol monophosphale did not develop hypoglycaemia; the latter compound was also inhibitory when mixed with the antigens before injection. These compounds were previously shown to block the induction of TNF by the antigens and to induce the production of inhibilory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.
Anti-endothelial cell antibodies in nephropathia epidemica and other viral diseases
Authors: WANGEL A G , TEMONEN M , BRUMMER-KORVENKONTIO M , VAHERI A 
Published: July 2010

SUMMARY
Increased capillary permeability is a central feature of the severe forms of haemorrhagic fever with renal syndrome (HFRS) and occurs also, though less frequently, in ncphropaihia epidemica (NE). one of the milder forms of this syndrome, caused by Puumala virus. We therefore searched for anti-cndothclial cell antibodies (AECA) in patients with NE and in those with other presumed or serologically proven acute viral illnesses. By enzyme immunoassay. using human umbilical vein endothelial cells (HUVEC) as the substrate. IgG class AECA were detected significantly more frequently in patients with NE and with influenza A than in Red Cross blood donors. A lesser degree of reactivity could be shown with a human alveolar cell carcinoma line and with human and mouse embryonic fibroblasts. Prelreatment of HUVEC with interferon-gamma (IFN-y). but not with II.-I or tumour necrosis factor-alpha (TNF-a), increased their ability to bind IgG of sera from patients with NE and acute febrile illnesses. We conclude that, although AECA can be demonstrated in NE. they occur also in other acute viral illnesses and. unless cytopathic by a mechanism not shared by the AECA of these other illnesses, are unlikely to be causally related to the capillary leak in HFRS.
Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity?
Authors: SPRONK P E , ter BORG E J , LIMBURG P C , KALLENBERG C G M 
Published: July 2010

SUMMARYTo investigate the possible role of IL-6 in the activation of the autoimmune process in systemic lupus erythematosus (SLE), we serially measured concentrations of IL-6, IgG, and anti-dsDN A antibodies before and during exacerbations in patients with SLE. In addition, we serially related the IL-6 response to the generation of the acute phase reactant C-reaclive protein (CRP). Sixteen consecutive patients who developed an exacerbation were analysed in this study. Blood samples were drawn in EDTA monthly. At the time of maximal disease activity during exacerbation, IL-6 plasma concentrations were increased (≥6 pg/ml) in 12 out of the 16 cases. Concentrations of IL-6 correlated with the concentrations of CRP(P&lt;0·01) and the score of the disease activity index (P &lt;0·05). No correlation was found between IL-6 concentrations and concentrations of anti-dsDNA or IgG. The course of changes in IL-6 concentrations before the exacerbation was variable. Five out of the 16 exacerbations studied were characterized by a prominent rise of IL-6 at the time of maximum disease activity. In this subgroup serositis as well as elevated concentrations of CRP were observed more frequently (P&lt;0–02). Seven exacerbations were not accompanied or preceded by changes in IL-6 concentrations and showed generally low IL-6 concentrations. In this latter subgroup cerebral involvement was seen more frequently (P&lt;0·02). Our data do not suggest a pathogenic role for IL-6 in the generation of IgG and/or anti-dsDNA antibodies before exacerbations. Rises of IL-6 concentrations before exacerbations in SLE seem only to occur in a subgroup of patients with SLE characterized by the presence of serositis and elevated concentrations of CRP during exacerbation.
Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone
Authors: BAKER D , O'NEILL J K , DAVISON A N , TURK J L 
Published: July 2010

SUMMARY
Mitoxantrone was used as an immunosuppressive probe to elucidate a means for the control of experimental allergic enccphalomyelitis (EAE) induced in Biozzi AB/H mice following injection of spinal cord homogenate emulsified in Freund's adjuvant. A single i.p. injection of 2·5 mg/kg of mitoxantrone, 1–2 days before the anticipated onset of EAE, failed to prevent the majority of animals from developing clinical disease, whereas when the compound was injected directly into the central nervous system (CNS), at this time point, significantly increased therapeutic benefit was evident, with most animals failing to develop clinical EAE. Although the clinical use of intrathecal mitoxantrone is strongly contraindicated, these data suggest that increased therapeutic benefit may be achieved in immune-mediated disease of the CNS by targeting immunosuppressive doses of suitable agents, on lymphocyte activation within the CNS. In addition, direct administration of immunosuppressive doses into the CNS may reduce potentially unwanted (side) effects in the periphery.
Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (αCD3/αCD19)
Authors: HAAGEN I A , van de GRIEND R , CLARK M , GEERARS A , BAST B , de GAST B 
Published: July 2010

SUMMARYBispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD 19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL). expressing TCRαβ or TCRγδ were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CDI9 target cells were not killed. Fresh CDI9* leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD. Vactivatcd IL-2 expanded peripheral blood mono-nuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.
Deficiency of complement component C3 is associated with accelerated removal of soluble 123I-labelled aggregates of IgG from the circulation
Authors: HALMA C , DAHA M R , CAMPS J A J , EVERS-SCHOUTEN J H , PAUWELS E K J , VAN ES L A 
Published: July 2010

SUMMARYComplement and erythrocyte complement receptors CR1 (CD35) play an important role in the clearance of immune complexes. We studied the elimination of soluble 123I-labelled aggregates of human immunoglobulin G (123I-AIgG), used as a model for immune complexes, in two patients with a congenital and two patients with an acquired deficiency of complement component C3, and compared these with 10 healthy controls. The first disappearance halflife of 123I-AIgG was shorter (3.3 ± 04 versus 70 ± 0.4 min in the controls, P= 0.005) and maximal hepatic uptake of aggregates was increased in the C3 deficient patients (maximal liver/background ratio 3.6 ± 0.4 versus 2.7 ± 0.2 in controls, P= 0.04). Apparently, in the absence of C3, removal of circulating immune complexes by the liver is accelerated, probably through Fc receptor-dependent mechanisms.