bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the association between amyloid fibrils and glycosaminoglycans; possible interactive role of Ca2+ and amyloid P-component
Authors: STENSTAD T , MAGNUS J H , SYSE K , HUSBY G 
Published: July 2010

SUMMARYWe have previously reported the specific association of glycosaminoglycans (GAG) and proteogly-cans (PG) with amyloid fibrils and characterized the polysaccharides directly extracted from amyloid-laden tissues. In the present study we further elucidate the association between purified amyloid fibrils and GAG/PG with special reference to those GAG/PG associated with amyloid P-component (AP) and the interactive role of Ca2+ ions. Amyloid fibrils were isolated from human hepatic AA amyloid employing water extraction with and without preceding removal of AP. an extrafibrillar protein component of all amyloids, using sodium citrate. GAG/PG co-isolated with the amyloid extracts, with and without AP, were isolated and characterized. Agarose-affinity chromatography of extracts containing AP was performed, and the GAG associated with this extrafibrillary protein were characterized as well. Several different GA/GPG populations were demonstrated in the various extracts. The abolition of calcium-dependent binding markedly influenced the amount of GAG/PG recovered in the fibril extracts, as well as the total amount of amyloid material obtained. Thus, it seems that calcium plays an important role in the association between the fibrils and the sugar moieties, and that a significant fraction of the GAG found in amyloid exhibits a Ca2+-dependent fibril-GAG interaction. No significant difference in the proportion between galactosaminoglycans and glucosamines was, however, disclosed when the two extraction protocols were cbinpared, suggesting that no particular GAG species has a higher affinity for the fibrils themselves. Both dermatan/chondroitin sulphate and heparan sulphate identified in the present study exhibited a Ca2+ -dependent interaction with AP, supporting previous findings. However, the amyloid-associated galactosaminoglycans found, especially the large PG appearing in small amounts, seemed to have a higher affinity for the extrafibrillar AP than the other GAG.
Higher anti-heparan sulphate reactivity during systemic lupus erythematosus (SLE) disease exacerbations with renal manifestations; a long term prospective analysis
Authors: KRAMERS C , TERMAAT R M , ter BORG E J , van BRUGGEN M C J , KALLENBERG C G M , BERDEN J H M 
Published: July 2010

SUMMARYCross-reactive antibodies against heparan sulphate (HS) have been suggested to play a role in initiating renal disease in SLE. Recently, we found that HS-reactivity is mediated by anti-DNA antibodies complexed with DNA and histones. To evaluate the clinical significance of anti-HS reactivity, we studied prospectively a cohort of 72 consecutive SLE patients, of whom 22 experienced 40 exacerbations. In 20 of these exacerbations renal symptoms were present. In these 20 exacerbations significantly higher anti-DNA (median 1:160) and anti-HS (median 1:30) titres were detected compared with exacerbations without renal manifestations (median 1:60 for anti-DNA and negative for anti-HS). There were no correlations with other symptoms of SLE. Anti-HS titres showed a significant correlation with anti-DNA antibody titres (rs= 0·57, P &lt; 0·05). Anti-HS without anti-DNA reactivity was never detected. Some SLE patients showed a high anti-DNA titre without anti-HS reactivity, suggesting that not all anti-DNA antibodies are able to bind to histone/DNA complexes and thus to exhibit anti-HS reactivity. Our findings indicate that anti-HS reactivity is correlated with renal disease in SLE.
Dissociation of specific and total IgE antibody responses following repeated low-level infections withNippostrongylus brasiliensisin rats
Authors: YAMADA M , UCHIKAWA R , NAKAZAWA M , ODA M , ARIZONO N 
Published: July 2010

SUMMARYIgE, IgG and mast cell responses were studied in rats infected weekly with 10 larvae of Nippostrongylus brasiliensis (NB). Worm recovery at 8 weeks of repeated infections was six-fold greater than that of a single infection with 10 larvae, suggesting t he accumulation of worms during the repeated infections. Total serum IgE was increased after 2 weeks of infection, and further increased after repeated infections: at 6 weeks of infection the level was four to six times higher than that after a single infection. Anti-NB IgG1 levels were also significantly higher after repeated infections than after a single infection. On the other hand, there was no significant difference in the level of anti-NB IgE between single and repeated infections, as determined by ELISA, as well as by passive cutaneous anaphylaxis (PCA) reaction. Mastocytosis was induced in the small intestine after both single and repeated infections, but the levels did not differ between the two These results indicate that total IgE and specific IgG1 production are augmented by repeated helminth infections, but specific IgE and mast cell responses are not. This pattern of response may minimize the development of IgE-dependent hypersensitivity reactions with repeated helminth infections.
Cell-mediated pathology during murine malaria-associated nephritis
Authors: LLOYD C M , WOZENCRAFT A O , WILLIAMS D G 
Published: July 2010

SUMMARYWe have studied the cellular mechanisms involved in the development of nephritis during acute and chronic murine malaria infections induced by Plasmodium vinckei petteri and P. berghei respectively. Albuminuria and uraemia were observed during the early stages of both types of infeclio, and were associated with glomerular and interstitial hypercellularity. There was a gradual increase in numbers of CD45+ cells from the early stages of both infections onwards. These infitrates contained CD4+ and CDS cells and mononuclear phagocytes. The interstitial and glomerular hypercellularity was due to an influx of inflammatory cells rather than an increase in renal cell division. These findings indicate the importance of cell-mediated immune mechanisms in the development of nephritis during murine malaria and illustrate an example of naturally occurring infection-induced nephritis.
Increased proportion of responders to a murine anti-CD3 monoclonal antibody of the IgG1 class in patients with systemic lupus erythematosus (SLE)
Authors: BLASINI A M , STEKMAN I L , LEON-PONTE M , CALDERA D , RODRIGUEZ M A 
Published: July 2010

SUMMARYA group of Venezuelan patients with SLE showed an increased proportion of responders to Leu-4, an anti-CD3 Mo Ab of the IgG1 class, compared with ethnically matched non-SLE patients and healthy controls. The rate of proliferative responses or IL-2 production induced by Mo Ab Leu-4, and the helper effect of macrophages from Leu-4 responders on T cells from a third-party donor were comparable in patients and controls. No significant differences in the binding of murine IgG1 molecules by macrophages from SLE patients and controls were observed. The proportion of monocytes/macrophages expressing FcγRI was significantly higher in SLE patients. However, the expression of FcRII, the type capable of supporting Leu-4-mediated responses, and of FcγRIII was comparable in monocytes from SLE patients and controls. Our results suggest that Venezuelan patients with SLE may have a genetic predisposition for the expression of the phenotypic variant of FcγRII capable of binding murine IgG1 molecules.
Induction of neutrophil respiratory burst by tumour necrosis factor-alpha; priming effect of solid-phase fibronectin and intervention of CD 11b-CD18 integrins
Authors: DAPINO P , DALLEGRI F , OTTONELLO L , SACCHETTI C 
Published: July 2010

SUMMARYHuman neutrophils, added to fibronectin (FN)-coated polystyrene wells and exposed to tumour necrosis factor-alpba (TNF-α, were found to exhibit a prolonged production of superoxide anion (Q2) after a lag period of approx 30 min. The O2 production, but not the cell adherence to FN, was completely inhibited by two MoAbs against CD18 and by a MoAb against CD11b, suggesting the involvement of CD11b-CD18 integrins in the neutrophil oxidative response. When neutrophils were induced to adhere to FN by incubation for 30 min on FN-coated surfaces and then washed to remove non-adherent cells, FN-anchored cells exhibited a rapid onset of O2 production in response to TNF-α. This suggests that FN primes neutrophils for the TNF-α-mediated respiratory burst. The O2− production by adherent neutrophils could be inhibited by anti-CD11b and anti-CD18 MoAbs only when the MoAbs were present both during the induction of adherence and during the subsequent exposure of FN-bound cells to TNF-α. The incapacity of MoAbs, added to neutrophils during the induction of adherence, to modify the characteristics of the subsequent neutrophil response to TNF-α suggests that the FN-mediated cell priming is independent of the interaction of CD11b-CD18 integrins with the FN substrate. The results are consistent with the intervention of three classes of cell receptors in the TNF-α-induced oxidative burst of neutrophils plated on FN: (i) neutrophil FN-binding sites, distinct from CD11b-CD18 and responsible for the cell priming; (ii) CD11b-CD18 integrins, absolutely required for permitting the cell triggering; and (iii) TNF-α receptors, responsible for switching on a rapid cell response in primed cells. The requirement of multiple classes of receptors for the full expression of the cell function can be envisaged as a natural precautionary measure to control the neutrophil responsiveness to TNF-α and, in turn, the TNF-α-dependent neutrophil-mediated oxidative injury at sites of inflammation.
Early detection of the allogeneic effect in the mixed lymphocyte reaction (MLR) by anti-CD3 IgA mouse monoclonal antibody
Authors: MANZO C , FERRAIUOLO C 
Published: July 2010

SUMMARYMLR is a 6-day routine proliferation assay used to demonstrate HLA disparity between two individuals. However, on day 2 only a negligible proliferation can be detected. In contrast, we found a significant increase of the extent of proliferation if an anti-CD3 IgA antibody was present in the culture. Since the CD3 proliferation pathway cannot be triggered by an antibody of IgA isotype the result was interpreted as a consequence of a synergism between the allogeneic stimulus and the anti-CD3 antibody effect. The level of this proliferation well correlates with the HLA difference, thus suggesting the use of this methodology for a rapid detection of the allogeneic reaction.
In vivoexpression of human immunoglobulin germ-line mRNA in normal and in immunodeficient individuals
Authors: ISLAM K B , BASKIN B , CHRISTENSSON B , HAMMARSTRÖM L , SMITH C I E 
Published: July 2010

SUMMARYPrevious in vitro studies suggest that transcription of the unrearranged immunoglobulin switch region and its 5′ flanking region precedes isotype switching. These transcripts, which arc devoid of a variable region, contain unique exons and are called germ-line (GL) mRNA. A crucial point in this regard is whether such transcripts could be detected in vivo, and if their expression correlates with immunoglobulin class switching in health and disease. To understand the in vivo role of this transcriptional activity we have adapted the reverse transcription-polymerase chain reaction (PCR) to analyse the GL transcripts from unstimulated peripheral blood mononuclear cells (PBMC) in healthy individuals and in different immunological diseases. Furthermore, mononuclear cells from different human organs were also analysed. We report here that GL (Iα. Iγ and Iɛ used lo designate the GL mRNA for IgA. IgG and IgE, respectively) nRNA are expressed differentially during ontogeny of B cells. Unexpectedly, no difference of Iα mRNA expression between the PBMC and the secondary lymphoid organs was detected. Rather. the levels of GL transcripts were correlated to ihe number of sIgM+ cells. GL mKNA of all three isotypes could be detected in PBMC from healthy donors, whereas there was a decrease of specific GL transcript synthesis in individuals with Immunoglobulin deficiency. Furthermore, during the in vivo immune response in a parasitic infection, we could demonstrate an induction of GL k mRNA during in vivo immune response. Concomitantly. there was also increased synthesis of productive F. transcripts. These findings implicate a potential role of GL transcription during in vivo immunoglobulin class switching.
Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities
Authors: SHOEMAKER L R , SCHURMAN S J , DONALDSON V H , DAVIS A E 
Published: July 2010

SUMMARYThe mediator(s) responsible for localized enhanced vascular permeability that characterizes an exacerbation of hereditary angioneurotic oedema (HAE) is thought to be a product of either contact or complement system activation. In contrast to normal individuals, plasma from these patients generates both kinin and vascular permeability-enhancing activity following incubation at 37°C. Depletion of C1 inhibitor in both normal and C2-deficicnt plasma, but not in contact factor-deficient plasmas, resulted in generation of these activities. The kinin activity from incubated HAE plasma was susceptible to kininase inactivation and was blocked by a Bk2 receptor antagonist. Furthermore, this activity was isolated from HAE plasma; amino acid sequence analysis proved it to be bradykinin. Similarly, the vasopermeability-enhancing activity from ethanol-fractionated or boiled HAH plasma, collected during either attack or remission, co-eluted with bradykinin on reverse-phase high performance liquid chromatography (HPLC). These studies conclusively demonstrate that bradykinin is the major kinin and mediator of enhanced vascular permeability generated during incubation of HAE plasma. The role of other bioactive products, such as the C2 kinin, at local sites of oedema formation remains lo be further defined.
Human TcRγδ+ lymphocyte response on primary exposure toPlasmodium falciparum
Authors: ROUSSILHON C , AGRAPART M , GUGLIELMI P , BENSUSSAN A , BRASSEUR P , BALLET J J 
Published: July 2010

SUMMARYIn 29 patients experiencing their first P. falciparum malarial attack. blood levels of TcRγδ+ lymphocytes were studied from the onset of infection to up to 6-9 months later. Blood TcRγδ+ lymphocytes, revealed using the TcRδ1 monoclonal antibody (MoAb) were increased both in absolute and relative numbers. Alterations lasted for up to 3-4 months following the attack. A TiγA/ BB3 reactive Vγ/9 subset was preferentially amplified, in vitro, TcRγδ+ lymphocytes from both malaria-sensitized and unprimed donors responded to P. falciparum schizont extract (PFSE). PFSE-stimulated polyclonal T cell lines consisted principally in TcRγδ+ cells with a TiγAd+/BB-3+ phenotype. Several TcRγδ+ T cell clones obtained from patients recovering from acute malarial attack were maintained in the presence of PFSE and autologous irradiated PBL. They belong to the Vγ9 subset. In long-term cultures. TcRγδ+ clones progressively lost their capacity to react to PFSE antigen while they were able to proliferate and to exert cytotoxic activity in response to autologous TcRγδ+, PFSE-specific T lymphocyte clones. This suggests that regulatory interactions occur between activated TcRγδ+ and TcRγβ+ cells generated by P. falciparum. Sequential variations in blood TcRγδ+ and TcRγβ+ lymphocyte levels after primary exposure to P. falciparum suggest that such regulatory interactions may occur in vivo.
In vivotreatment with a monoclonal antibody to T helper cells in experimental autoimmune glomerulonephritis in the BN rat
Authors: REYNOLDS J , PUSEY C D 
Published: July 2010

SUMMARYExperimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti-GBM disease is characterized by the development, over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with MoAb W3/25 (anti-CD4) at different doses, starting at the time of immunization and continued for the duration of the study or for a limited period only. Continued treatment with W3/25, at a dose of 5 or 10 mg/kg intraperitoneally three times per week for 4 weeks. produced a marked reduction in circulating anti-GBM antibodies, absence of detectable deposited antibody and virtual absence of albuminuria. When W3/25 treatment, at 5 or 10 mg/kg, was stopped after 2 weeks, there was still a significant reduction in anti-GBM antibodies and albuminuria at 4 weeks. A similar effect on the disease was achieved when W3/25 was administered only three times during the first week at a dose of 30 mg/kg. Animals injected with W3/25 at a dose of 10 mg/kg through the course of disease showed &lt; 10% W3/25+ cells by KACS analysis of splenic lymphocytes at week 4, while controls and animals treated for shorter periods showed &gt;30% W3 25+ cells. These results demonstrate that W3/25 can prevent the development of EAG and that this effect is not dependent on persistent depletion of T cells. Further work is necessary to determine whether anti-T cell therapy is effective in established EAG and may be worth investigating in human anti-GBM disease.
Production of tumour necrosis factors by human T cells stimulated by a superantigen, toxic shock syndrome toxin-1
Authors: AKATSUKA H , IMANISHI K , INADA K , YAMASHITA H , YOSHIDA M , UCHIYAMA T 
Published: July 2010

SUMMARYThe capacity of human T cell subsets, CD4+ or CD8+ T cells, to produce tumour necrosis factors (TNF-α and TNF-β) upon stimulation with toxic shock syndrome toxin-l (TSST-I) and the requirement for MHC ctass II molecules on accessory cells (AC) in the response were investigated. The capacity of CD4+ T cells was much higher than that of CD8+ T cells in TSST-1-induced production of TNF-α and TNF-β. The expression of MHC class II molecules on AC was required in the response.
Intraglomerular expression of transforming growth factor-beta 1 (TGF-β1) mRNA in patients with glomerulonephritis: quantitative analysis by competitive polymerase chain reaction
Authors: IWANO M , AKAI Y , FUJII Y , DOHI Y , MATSUMURA N , DOHI K 
Published: July 2010

SUMMARYTGF-β1 is involved in the pathogenesis of glomerular sclerosis. We studied the intraglomerular expression of TGF-β1 mRNA in patients with glomerulonephritis using competitive polymerase chain reaction (PCR). This method is sensitive enough to quantify cDNA copies of mRNA present in small amounts of samples. Renal biopsy specimens were obtained from 42 patients with various kinds of glomerulonephritis. Ten glomeruli were dissected from renal biopsy specimens. Normal glomeruli were also obtained from the resected kidneys of eight patients with renal cell cancer. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of β-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of β-actin with a unique EcoRI site. Next, to measure TGF-β1 cDNA, we performed competitive PCR by co-amplifying mutant templates of TGF-β1. We observed a higher glomerular expression of TGF-β1 mRNA in cases of mesangial proliferative glomerulonephritis having a moderate increase in mesangial matrix, diabetic nephropathy and diffuse proliferative lupus nephritis, compared with normal glomeruli. Results suggest that the intraglomerular synthesis of TGF-β1 may be involved in the progression of glomerulonephritis in humans.
Expression of the gene for inducible nitric oxide synthase in experimental glomerulonephritis in the rat
Authors: COOK H T , EBRAHIM H , JANSEN A S , FOSTER G R , LARGEN P , CATTELL V 
Published: July 2010

SUMMARYNitrite, a stable product of nitric oxide (NO), is synthesized in vitro by glomeruli in experimental glomerulonephritis. We have now studied the expression of the gene for inducible NO synthase (iNOS) in accelerated nephrotoxic nephritis (NTN). The purpose of the study was to confirm in vivo induction of iNOS in this model of immune complex disease, and to relate the onset of induction and the level of expression to pathogenic events in the model. Glomeruli from rats with NTN were isolated at 6 h, 24 h and 2, 4 and 7 days and total RNA extracted. RNA (10/μg) was reverse transcribed and polymerase chain reaction (PCR) was performed with primers homologous to rat vascular smooth muscle iNOS and rat β actin. A 222-base PCR product corresponding to iNOS mRNA was present in all experimental animals. iNOS expression was also found in activated macrophages, neutrophils and IL-1-stimulated but not unstimulated mesangial cells. Quantitative competitive PCR was carried out on glomerular samples using a 514-bp mutant of a 735-bp PCR product. iNOS expression was present at low levels in normal glomeruli and was markedly enhanced at 6 h after the induction of glomerulonephritis and peaked at 24 h. Increased iNOS expression persisted to day 7. β actin mRNA levels were similar in all glomerular specimens. This study demonstrates that there is in vivo induction of iNOS in immune complex glomerulonephritis, corresponding to the generation of nitrite we have previously reported. iNOS gene expression is detectable within 6 h of induction of NTN, indicating the onset of gene transcription is closely related lo the initial formation of immune complexes.
Expression of the chemokine superfamily in rheumatoid arthritis
Authors: HOSAKA S , AKAHOSHI T , WADA C , KONDO H 
Published: July 2010

SUMMARYThe infiltration of leucocytes into the Joint of rheumatoid arthritis (RA) is believed to be mediated by chemotactic factors released by activated cells. In this study, examination was made of the gene expression and production of the chemokine superfamily in RA patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoprecipitation. Cultured synovial fibroblasts were found capable of expressing and producing IL-8, GRO, monocyte chemotactie and activating factor (MCAF), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and RANTES in response to IL-1α, The expression of IL-8, GRO. MCAF, MIP-1α, and MIP-1β was clearly shown to increase in freshly isolated synovial fluid mononuclear cells (SFMC) of RA patients, in contrast to peripheral blood mononuclear cells (PBMC) of RA patients and normal subjects. The gene expression of RANTES appeared to be the same for RA SFMC. RA PBMC, and normal PBMC. Thus, the over-expression of various chemokines may promote the recruitment of inflammatory cells into rheumatoid inflamed joints.