bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why do patients develop reactions to streptokinase?
Authors: LYNCH M , PENTECOST B L , LITTLER W A , STOCKLEY R A 
Published: July 2010

SUMMARY
Minor reactions to streptokinase are not uncommon, although the etiology is unknown. It is widely presumed, however, that these, like the more serious immune reactions, are antibody-mediated. We measured specific anti-streptokinase IgG. subclasses IgG1, IgG2, IgG3, IgG4 and IgE by ELISAs, haemagglutination, indirect Coombs' test and immunoblotting in six patients who developed reactions to streptokinase. Evidence of complement activation by streptokinase was sought by a haemolytic complement assay and by measurement of C3, C4 and C3d. The patients who reacted to streptokinase presented with low titres of anti-streptokinase IgG (median = 5; range 0–32) and IgG1 (median = 3; range 0–14). No evidence of any other IgG subclass was found, nor of specific anti-streptokinase IgE. Anti-streptokinase IgG1 was found to fix complement; patients who reacted to streptokinase were found to have low levels of total complement 1 year post reaction. Probable aggregates and fragments of human albumin (added stabiliser) were found in the streptokinase preparation and proved to be antigenic in some patients, but were not found to be related to the development of reactions. The findings suggest that patients who develop reactions to streptokinase cannot be predicted on the basis of antibody titres at presentation. Minor reactions to streptokinase would not appear to be antibody-mediated, although complement activation may be involved.
Common idiotypes expressed on human, monoclonal, abnormal immunoglobulins and cryoglobulins with polyreaetive autoantibody activities
Authors: BARBOUCHE M R , GUILBERT B , MAKNI S , GORGI Y , AYED K , AVRAMEAS S 
Published: July 2010

SUMMARYSeveral hutiian monoclonal immunoglobtilins with the same auloatitibody activity have been shown to have cross-reactive idiotypes (CRI). In this study, using polyclonal anti-idiotypic antibodies, we fotind that 28% of hutnan monoclonal immunoglobulins with polyreaetive autoantibody activity from myeloma. Waldenstrom's macroglobulinaemia and eryoglobulinaemia patients shared common idiotype(s). Furthermore, the latter were expressed on human and murine natural MoAbs (respectively in 12% and 22% of the clones tested) and on human IgG preparations used for therapeutic intravenous injections (IVlg) and which contain natural antibodies. These findings suggest that monoclonal immunoglobulins could arise from the proliferation of a clotie that normally produces a natural antibody. The existenee of common idiotype(s) between monoclonal immunoglobulins and IVIg could be relevant to the improvement noted after treatment with IVIg in patients suffering from peripheral neuropathies associated with monoclonal gammopathy.
Elevated expressionin situof selectin and immunoglobulin superfamily type adhesion molecules in retroocular connective tissues from patients with Graves' ophthalmopathy
Authors: HEUFELDER A E , BAHN R S 
Published: July 2010

SUMMARYActivation of certain adhesion molecules within vascular endothelium and the surrounding extravascular space is a critical event in the recruitment and targeting of an inflammatory response or autoimmune attack to a particular tissue site. We have recently demonstrated that the adhesion of lymphocytes to cultured retroocular fibroblasts obtained from patients with Graves’ ophthalmopathy (GO) is mediated predominantly by the interaction of lymphocyte function-associated antigen-1 (LFA-1), expressed on lymphocytes, with intercellular adhesion molecule-1 (ICAM-I), expressed by these cells following exposure to interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), IL-lα or purified thyroid-stimulating immunoglobulins. We now report the expression and localization in situ of several adhesion molecules. ICAM-1, endothelial leucocyte adhesion molccule-l (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and LFA-3 in retroocular tissues derived from patients with severe GO (n=4) and normal individuals (n = 3). Serial cryostat sections of tissue specimens were processed for immunoperoxidase staining using various MoAbs against ICAM-1, ELAM-1, VCAM-1 and LFA-3. In addition, consecutive sections were stained with MoAbs against LFA-1, CD45RO (UCHL-1)DR-human leucocyte antigen (HLA-DR), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). In GO-retroocular tissues, strong immunoreactivity for ICAM-1 and LFA-3 was detected in blood vessels (&gt;90%), in perimysial fibroblasts surrounding extraocular muscle fibres, and in connective tissue distinct from extraocular muscle. No ICAM-1 or LFA-3 immunoreactivity was present in extraocular muscle cells themselves. ICAM-1 and LFA-3 immunoreactivity in normal tissues was minimal or absent both in connective and muscle tissues. Vascular endothelium was strongly positive for ELAM-1 and VCAM-1 in GO-retroocular tissues, while VCAM-1 immunoreactivily was minimal (&lt;5% of blood vessels) and ELAM-1 immunoreactivity was generally absent in normal retroocular tissue. LFA-1-expressing, activated mononuclear cells and memory T lymphocytes (CD3+/CD45RO+) were only detected in GO-retrocular tissues, and were mainly localized around blood vessels and in areas of ICAM-1-expressing connective and perimysial tissue. HLA-DR expression was restricted to GO-tissue specimens, with strong immunoreactivity detected in blood vessels, macrophages and connective tissue and perimysial fibroblasts. No HLA-DR was detectable in extraocular muscle cells. In conclusion, infiltration of the orbit in GO by mononuclear cells, and their targeting within the orbit, may depend upon the coordinate expression of certain adhesion and MHC molecules. Activation of appropriate adhesion molecules in mononuclear cells, endothelial cells and fibroblasts in response to various cytokines and inflammatory mediators may be involved in the evolution and perpetuance of GO.
Comparative analysis of biological activities ofDer p I-derived peptides on Fc receptor-bearing cells fromDermatophagoides pteronyssinus-sensitive patients
Authors: JEANNIN P , PESTEL J , BOSSUS M , LASSALLE P , TARTAR A , TONNEL A-B 
Published: July 2010

SUMMARYThe ability of Tour uncoupled synthetic peptides (p52–71, p117–133, p176–187, p188–199) derived from Der p I, a major allergen from the house dust mite Dermatophagoides pteronyssinus (Dpt) to stimulate FcεR+ cells from Dpt-sensitive patients was comparatively analysed. Each free peptide may specifically stimulate basophils (FcεRI+ cells) and platelets (FcεRII+ cells) from patients with significant levels of anti-Der p I IgE antibodies; p52–71 and p 117–133 appear the best cell stimulation inducers. Both concentration-dependent biological activities of Der p I-peptide on FcεR+ cells are enhanced by coupling peptide to a carrier (as human serum albumin). Interestingly each Der p I sensitive patient tested presents an individual pattern of response to peptide. Thus, from our results it appears that different Der p I sequences could be involved in the immune response to Der p I.
Antibodies to EYRKK vesicular stomatitis virus-related peptide account only for a minority of anti-Ro60kD antibodies
Authors: ROUTSIAS J G , SAKARELLOS-DAITSIOTTS M , DETSIKAS E , TZIOUFAS A G , SAKARELLOS C , MOUTSOPOULOS H M 
Published: July 2010

SUMMARY
Previous studies demonstrated a possible antigenic relation between the carboxyl terminal portion of anti-Ro60kD autoantigen and a nucleocapsid protein (N) of vesicular stomatitis virus (VSV). In order to investigate whether anti-Ro60kD autoantibodies react with the VSV homologous region of the Ro60kD protein we synthesized, according to Merrifield's method, the EYRKKMDI octapeptide (8p) sharing a common sequence with the N protein of VSV. Sera from 61 patients with autoimmune rheumatic diseases (34 systemic lupus erythematosus (SLE), 21 Sjögren's syndrome (SS) and six rheumatoid arthritis (RA)) as well as 59 from normal blood donors were tested for the presence of anti-Ro60kD autoantibodies by ELISA and immunoblot (IB) and anti 8p antibodies by ELISA. Antibodies to 8p were found in 9/31 of anti-Ro60kD IB-positive sera, 5/30 of anti-Ro60kD-negative sera and 2/59 of normal control sera. The concordance between the anti-8p ELISA and the anti-Ro60kD IB was very poor (χ2= 0·71 P= 0·4) in contrast to the anti-Ro60kD ELISA and the anti-Ro IB(χ2= 27·6, P= 10-7). Subsequent affinity purification of the anti-8p antibodies from a strong positive anti-8p and anti-Ro60kD SLE serum yielded 95% depletion of the anti-8p activity and 37% reduction of the anti-Ro60kD activity. Inhibition assays with the affinity-purified anti-8p antibodies demonstrated that the octapeptide gave 94·5% inhibition of the anti-Ro60kD activity, while Ro60kD protein led to 420% inhibition of the anti-8p. Preincubation of the serum with the octapeptide produced 4% inhibition of anti-Ro60kD ELISA. These results indicate that the anti-8p antibodies account only for a minority of the anti-Ro60kD autoantibodies.
MHC-associated immunopotentiation affects the embryo response to teratogens
Authors: Torchinsky A , Fein A , Carp HJA , Toder V 
Published: July 2010

SUMMARYThe present study was performed to evaluate whether the effect of environmental teratogens can be modified by maternal immunostimulation. Two chemicals, cyclophosphamide (CP) and 2,3-quinoxalinedimetanol,1,4-dioxide (QD) were used as the reference teratogens (RT), The response to these RT was investigated in two animal models: (i) primigravid C57B1 6 mice who underwent intrauterine immunization with allogeneic paternal (CBA/J), third-party (BALB c) or syngeneic male splenocytes 21 days before mating; (ii) C57B1 6 and CBA/J mice who were treated with RT during the second pregnancy only, after a different mating combination (syngeneic or allogeneic) in the first and the second pregnancy. Different doses of CP and QD were injected on days 12 and 9 of pregnancy, respectively. On day 19 of pregnancy implantation sites, resorptions, live and dead fetuses were recorded and live fetuses were examined for external and internal malformations with methods routinely used in teratological study. It was shown that intrauterine immunopotentiation with allogeneic paternal splenocytes clearly enhances the tolerance of F| embryos to RT, Thus, in CP-treated females the resorption rate and the proportion of malformed fetuses were significantly reduced. It was followed by an almost two-fold increase in fetal weight. The protective effect of such immunization in QD-treated females was manifested as a dramatic decrease of the proportion of malformed fetuses and the resorption rate, Syngeneic splenocytes could not significantly influence an embryo's sensitivity to RT, The response to RT was also significantly weaker in the second pregnancy of female mice mated twice allogeneically than that observed in allogeneically mated primigravid mice. These results show that the embryo's response to environmental teratogens may be influenced by fetomaternal immune interactions.
Intraglomerular expressions of IL-1α and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis
Authors: AKAI Y , IWANO M , KITAMURA Y , SHIIKI H , DOHI Y , DOHI K , MORIYAMA T , YONEMASU K 
Published: July 2010

SUMMARYBoth PDGF and IL-I play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1α mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-lα mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1α mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.
Neonatal capsaicin pretreatment suppresses intramedullary inflammation in adjuvant-induced spondylitis
Authors: IMAI S , HUKUDA S , MAEDA T 
Published: July 2010

SUMMARYIn order to investigate the proposed involvement of neuropeptides in musculoskeletal inflammation we pretreated rats, in an adjuvant spondylitis model, with capsaicin, a neurotoxin. Immunohistochemistry showed that administration of capsaicin to newborn rats depicted irreversibly the neuropeptide substance P. Elimination of capsaicin-sensitive fibres by the neonatal injection of capsaicin did not suppress the peridiscitis of rats in which adjuvant spondylitis was induced at 7 weeks of age. However, elimination of capsaicin-sensitive fibres did suppress the inflammation usually seen in the bone marrow. We speculate that this intramedullary inflammation is normally induced or sustained by capsaicin-sensitive fibres.
Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma
Authors: MITROPOULOS D , KOOI S , RODRIGUEZ-VILLANUEVA J , PLATSOUCAS C D 
Published: July 2010

SUMMARYFresh (uncultured) TIL from 12 untreated patients with primary renal cell carcinoma were prepared from tumour specimens by enzymatic digestion, and were characterized by immunotluorescence using MoAbs recognizing leucocyte differentiation antigens or particular Va or Vα segments of the T cell receptor (TCR). These fresh TIL comprised CD3+ (20–84%); CD4+ (3–15%); CD8+ (13–35%); α/βTCR+ (20–50%); γδTCR+ (3–17%); CD16+ (1–18%) and CD56+ (3–10%) cells. Significant proportions of Vα2+, Vβ5.1+ and Vβ6+ cells were found in TIL of certain patients with renal cell carcinoma, suggesting that they comprised oligoclonal T cells. T cell lines were developed in low concentrations of rIL-2 (200 U/ml) from TIL from II patients with renal cell carcinoma, and were characterized by immunofluorescence and cell-mediated cytotoxicity. These T cell lines consisted primarily of CD3+ (51–94%); CD4+ (1–80%); CD8+ (0–84%); αβ/3TCR+ (65–87%); γδTCR+ (0–25%); CDI6+ (0–16%) and CD56+ (2–57%) cells. These Tcell lines exhibited non-specific cytotoxicity against autologous and aliogeneic renal tumour cells, with the exception of one T cell line that exhibited preferential cytotoxicity against autoiogous renal tumour cells. These results suggest that fresh TIL from patients with renal cell carcinoma contain significant proportions of oligoclonal T cells that may have accumulated at the tumour site as a result of a clonal expansion.
Hereditary C6 deficiency in a strain of PVG/c rats
Authors: LEENAERTS P L , STAD R K , HALL B M , VAN DAMME B J , VANRENTERGHEM Y , DAHA M R 
Published: July 2010

SUMMARYA chance observation has led to the discovery of a strain of PVG rats (PVG/c−) which are deficient in complement (C) component C6. Analysis of total haemolytic activity (CH50) of PVG/c− serum revealed an absent CH50 activity compared with serum of other rat strains and of a PVG/c rat (PVG/c-) that showed normal C activity. Thus, the PVG/c− rat was unable to activate the C5b-9 membrane attack complex. To gain insight into the complement abnormalities, analysis of individual C components was performed. Testing the PVG/c− serum in a C6 haemolytic assay and using deficient human sera showed a deficiency of C6 in the PVG/c− rat. Highly purified human C6 and human sera deficient in other components were able to reconstitute the CH50 activity of the PVG/c+ rat. The possibility that an inactivator of C was present in PVG/c− serum was excluded. The deficiency was found to be inheritable and under the control of an autosomal recessive gene, Furthermore tissue antigens and immunity of the PVG/c+ rat were found to be identical to those determined in the PVG/c+ rat. With regard to their health status, the PVG/c− animals seem to have no disadvantages compared with PVG/c+ rats when held under the same conditions within the protected environment of animal facilities. Taken together, both rat strains provide an unique animal model for studying the biological role of C, particularly the C5b-9 membrane attack complex in experimental medicine.
Glycation of monoclonal antibodies impairs their ability to bind antigen
Authors: KENNEDY D M , SKILLBN A W , SELF C H 
Published: July 2010

SUMMARY
As elevated levels of glycated IgG have been detected in the plasma of patients with diabetes mellitus, a disease associated with increased susceptibility to infection, we have investigated whether glycation of MoAbs affects the kinetics and/or affinity of antigen binding. Three mouse MoAbs were incubated with 0.5 M glucose at pH 7.4 for 14-1 days at 37°C. Control MoAbs were incubated using identical conditions but with no added glucose. Using a surface plasmon resonance technique we found that glycation significantly increased the rate of dissociation (kdiss) of the antigen-antibody complex for all three MoAbs (P &lt; 0.05, n= 4), but had no significant effect on the rate of association (kass). For one of the MoAbs, against human IgG (Fab), we also measured kdiss by an alternative method utilizing radiolabelled antigen, which confirmed that glycation of the antibody significantly increases kdiss (P &lt; 0.001. n = 8). We also found using an ELISA-based method that glycation of the same MoAb significantly increased (he equilibrium dissociation constant (kd) (P &lt; 0.05, n = 6). A significant increase in kd was observed after glycation using glucose concentrations consistent with those found in poorly controlled diabetics (P &lt; 0.02, n = 5). We conclude that in vitro glycation can significantly lower the affinity of an antibody for its antigen, and significantly increases the rate of dissociation of the antigen antibody complex.
Elevated tumour necrosis factor-alpha (TNF-α) biological activity in psoriatic skin lesions
Authors: ETTEHADI P , GREAVES M W , WALLACH D , ADERKA D , CAMP R D R 
Published: July 2010

SUMMARYLesions of the common inflammatory skin disease psoriasis are characterized by epidermal hyperproliferation, leucocyte adhesion molecule expression and leucocyte infiltration. The local release of proinflammatory cytokines. such as TNF-α, may play an important role in the induction of these events. We have, therefore, analysed aqueous extracts of lesional and uninvolved (clinically normal) stratum corneum for the presence of TNF-α immunoreactivity and biological activity. TNF-α immunoreactivity and bioactivity were consistently higher in lesional compared with uninvolved samples. By using an anti-TNF-α neutralizing antibody it was demonstrated that the biological activity measured was due to the presence of TNF-α alone. Concentrations of soluble TNF receptors (p55 and p75) were also higher in lesional stratum corneum extracts, with the p55 form predominating. The plasma of psoriatic patients was also found to contain elevated concentrations of soluble p55 compared with normal controls. These results confirm the presence of immunoreactive TNF-α and, for the first time, conclusively demonstrate TNF-α biological activity and quantifiable concentrations of soluble TNF receptors (p55 and p75) in lesional psorialic samples. TNF-α recovery from stratum corneum probably reflects synthesis in deeper, viable layers, where il is likely lo exert its biological effects. Local and systemic release of soluble TNF receplors, in particular p55, may serve to regulate the effects of TNF-α in psoriasis.
Apparent killing of Mycobacterium tuberculosis by cytokine-activated human monocytes can be an artefact of a cytotoxic effect on the monocytes
Authors: WARWICK-DAVIES J , DHILLON J , O'BRIEN L , ANDREW P W , LOWRIE D B 
Published: July 2010

SUMMARY
A protocol using combined exposure to interferon-gamma (IFN-γ), calcitriol and tumour necrosis factor-alpha (TNF-α) has been reported to activate human monocytes in vitro to kill Mycobacterium tuberculosis. We have attempted to repeat the findings in two laboratories, with negative results: treated cells were no different from untreated cells in this respect. However, the treated cells were more sensitive to a toxic effect of the bacteria. We suggest that the reported dramatic mycobacterial killing may have been an illusory consequence of the toxicity leading to cell lysis and loss of the liberated bacteria from the assay.
Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis
Authors: EBERHARD B A , LAXER R M , ANDERSSON U , SILVERMAN E D 
Published: July 2010

SUMMARYThe production of tumour necrosis factor-alpha (TNF-α), TNF-β and IL-6 in synovial fluid was studied in 50 samples of synovial fluid from 44 children with juvenile rheumatoid arthritis (JRA) by identifying cytokine production al a single-cell level. Post Ficoll-separated synovial fluid mono-nuclear cells were permeabilized and then intracellular TNF-α, TNF-β and IL-6 protein production was examined using indirect immunofluorescence and murine anti-cytokine MoAbs. All three cytokines were measured in 37 of the 50 samples. In 25 of the 37 samples there was complete concordance: all three cytokines were present in six and absent in 19 samples. At least one cytokine was present in 27/50 (54%) of synovial fluid samples. Overall, TNF-α was detected in 22/49 (45%) samples. TNF-β in 15/41 (37%) and IL-6 in 16/45 (36%) samples. Five patients had serial arthrocentesis, and in these samples there were two patients who had initially positive cytokine production, which on subsequent measurement was negative; in the other three patients there was no change from the previous cytokine production. We provide evidence that synovial fluid mononuclear cells produce monocyte and T cell cytokines in JRA. These findings suggest a role for both T cell and macrophage products in the pathogenesis of JRA, and the potential for modulation of cytokine production as a target for therapeutic intervention.