bluuebunny/crossref_metadata_2025_split huggingface dataset:
GM-CSF, IL-1α, IL-β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α
Authors: PANG G , COUCH L , BATEY R , CLANCY R , CRIPPS A 
Published: July 2010

SUMMARYThe role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-lα, IL-1β, IL-6, IL-8, IL-10, intercellular adhesion molecule-I (ICAM-I) and vascular cell adhesion molecule-1 (VCAM-i) when stimulated with lipopolysaccharide (LPS) or IL-1α. The increased mRNA expression of GM-CSF, IL-1α IL-1β IL-6 and IL-α in response to IL-1α and LPS stimulation was time- and dose-dependent. In contrast. IL-10 was weakly expressed when fibroblasts were stimulated with LPS. IL-1α or tumour necrosis factor-alpha (TNF-α), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS. IL-1α or TNF-α. IL-1α was a more potent stimulator than LPS for GM-CSF. IL-6, IL-8 and I L-10 expression, but not for IL-1α and IL-1β. Increased GM-CSF. lL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1α and IL-1bL remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF. IL-6 and IL-8 when fibroblasts were exposed to IL-1α. TNF-α stimulated the release of GM-CSF. IL-6 and IL-8 and, combined with IL-1α. cytokine production was enhanced synergistically. Finally, both LPS and IL-1ã up-regulated ICAM-I and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.
Attenuation oflpr-graft-versus-host disease (GVHD) in MRL./lprspleen cell-injected SCID mice byin vivotreatment with anti-Vβ8.1,2 monoclonal antibody
Authors: HOSAKA N , NAGATA N , MIYASHIMA S , IKEHARA S 
Published: July 2010

SUMMARYWhen MKL/lpr (H-2k) spleen cells were intraperitoneally injected into C.B-17-scid/scid (severe combined immunodeficient (SCID)) (H-2d) mice, the SCID (SCID-MRL/lpr) mice manifested a severe wasting syndrome with weight loss, splenic atrophy, and lymphoid cell infiltration in the liver and lung, as seen in lpr-GVHD. In contrast. MRL/+ spleen cell-injected SCID (SCID-MRL/+) mice did not show Ipr-GVHD. The spleens of SCID-MRL/lpr mice showed progressive increases in donor CD4+ and CD8+ T cells from 4 to 12 weeks after injection and a decrease in B cells at 12 weeks. SCID-MRL/+ mice showed a stable engraftment of CD4+ and CD8+ T cells and a progressive increase in B cells. Analyses of T cell receptor (TCR) repertoires (Vβ6, Vβ8.1,2 and Vβ11) revealed that the Vβ8.1,2+ T cells were found more frequently in SCID-MRL/lpr mice than in SCID-MRL/+ mice. When SCID-MRL/lpr mice were treated with intraperitoneal injection of an anti-Vβ8.1,2+ (KJ16) MoAb, Vβ8.1,2+ T cells were markedly depleted, and the severity of/pr-GVHD was attenuated at 4 and 8 weeks after treatment, in contrast to normal rat IgG-injected SCID+MRL/lpr mice. However, the KJI6 MoAb-treated SCID-MRL/lpr mice suffered from severe lpr-GVHD 12 weeks after treatment, although Vβ8.1,2+ T cells were still maintained at a low level. These findings suggest that Vβ8.1,2+ T cells are a major T cell population (hat mediates lpr-GVHD in the early stage of lpr-GVHD. but that in the later stage, the other T cell populations may proliferate naturally or in accordance with the depletion of Vβ8.1,2+ T cells, and contribute to the development of lpr-GVHD.
IgG-mediated phagocytosis in regenerated splenic tissue
Authors: CLAYER M T R , DREW P A , LEONG A S-Y , JAMIESON G G 
Published: July 2010

SUMMARY
The risk of severe infections after splenectomy is well established. Operations such as auto-transplantation, splenic artery ligation or partial resection have been advocated for the retention or regeneration of splenic tissue following splenic trauma. The potential of such tissue to protect from infection is unclear. The ability of splenic tissue to phagocytose IgG opsonized syngeneic erythrocytes was measured in rats 6 months following splenectomy and splenic auto-transplantation, splenic artery ligation, total or partial splenectomy, and compared with eusplenic controls. In eusplenic and partially splenectomized rats 71% of the label was cleared at 3 h, compared with approximately 50% in rats following total splenectomy, splenectomy and splenic autotransplantation or splenic artery ligalion. The autotransplanted and the ligated splenic tissue cleared less than 10% compared with control spleen, but there was no difference between them when clearance was expressed as uptake per gram of tissue. Splenic autotransplants and ligated spleens were small and histologically abnormal, with an increase in the red pulp, significantly less white pulp and marginal zone, and the frequent absence of a central arteriole in the white pulp. The clearance of label was proportional to the amount of red pulp in the tissue, although the red pulp from the regenerated tissues was not as efficient at phagocytosis as control red pulp. The tissue which regenerated following autotransplantation or splenic artery ligation did not result in greater clearance of erythrocytes from the circulation than that which occurred in splenectomized rats.
Functional heterogeneity of mast cells isolated from different microenvironments within nasal polyp tissue
Authors: FINOTTO S , DOLOVICH J , DENBURG J A , JORDANA M , MARSHALL J S 
Published: July 2010

SUMMARYNasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, including mast cells, both in the epithelium and in the stroma. The aim of this work was to study human mast cells derived from two different anatomical sites within the same nasal polyp tissue. To this end, we isolated two distinct mast cell populations, one from the epithelial and the other from stromal layers of individual human nasal polyp tissues. We examined the mediator content of the two mast cell populations and found that stromal mast cells had a significantly higher content of tryptase compared with the epithelial mast cells from the same tissue. In addition, mast cells from the stromal compartment, but not those from the epithelium, released a significant amount of histamine after anti-IgE stimulation. By contrast, both populations released over 50% of the total histamine after non-specific stimuli (A231K7 10-6 M). The content of mediators and the response to immunological activation were not significantly altered in patients receiving topical steroid therapy. It remains to be determined if the observed differences are the result of an intrinsic characteristic of the mast cell populations localized to separate tissue compartments, or reflect a different in vivo exposure to stimuli such as antigens, or different surrounding structural or infiltrating cells. In conclusion, these data provide evidence of functional heterogeneity und differences in mediator content between mast cell subpopulations from a single human tissue. The failure of release of epithelial mast cell mediators from an immunologic stimulus may have implications concerning acute effects of antigen exposure in nasal polyposis.
High numbers of autoantigen-reactive mononuclear cells expressing interferon-gamma (IFN-γ), IL-4 and transforming growth factor-beta (TGF-β) are present in cord blood
Authors: YU M , FREDRIKSON S , LINK J , LINK H 
Published: July 2010

SUMMARYUmbilical cord blood of neonates and peripheral blood of healthy adults were analysed by in situ hybridization for numbers of mononuclear cells (MNC) expressing the cytokines IFN-γ, TGF-β and IL-4 mRNA without culture and after culture in the presence of acetylcholine receptor (AChR), myelin basic protein (MBP) and peripheral myelin protein P2. These antigens were chosen since they represent autoantigens in putatively immune-mediated neurological diseases, The numbers of cells expressing cytokine mRNA after 72 h culture in the presence of AChR, MBP and P2 were higher in cord blood than in peripheral blood of healthy adults. IFN-γ, TGF-β and IL-4 were always elevated in parallel. In cord blood there was a pronounced reactivity to several of the tested antigens, while such broad reactivity was not found in peripheral blood of healthy adults. No differences in cytokine mRNA expression were found between cord blood and peripheral blood of adults when cells were analysed without culture. The results show a capacity of cord blood cells to react to several autoantigens by the up-regulation of cytokine mRNA expression.
Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B
Authors: MICHALAK T I , LAU J Y N , McFARLANE B M , ALEXANDER G J M , EDDLESTON A L W F , WILLIAMS R 
Published: July 2010

SUMMARYThe susceptibility of hepatocytes from patients with chronic hepatitis B to complement-dependent cytotoxicity mediated by heterologous antibodies to hepatitis B virus core (anti-HBc) and surface (anti-HBc) antigens and to hepatic asialoglycoprotein receptor was examined using a micro-cytotoxicity assay. The anti-HBc-induced cytotoxicity was found to be markedly enhanced against hepatocytes isolated from patients with chronic active hepatitis (72·6 ± 9·5% (mean±s.e.m.); n= 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40·6 ± 18·6%; n= 4) (P= 0·019). Overall, values of the anti-HBc-directed cytotoxicity were higher in patients positive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg), Hepatocytotoxicity was also exerted by anti-HBs and anti-asialoglycoprotein receptor antibodies in the presence of complement, but it was not seemingly related to disease activity. These results indicate that hepatitis B virus core and surface antigens and asialoglycoprotein receptor at the hepatocyte surface can be recognized by antibodies, and raise the possibility that complement-dependent cytolysis may contribute to the injury of hepatitis B virus-infected hepatocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti-HBc antibody-directed complement-mediated cytotoxicity than those with inactive liver histology.
Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects
Authors: VINGERHOETS J H , VANHAM G L , KESTENS L L , PENNE G G , COLEBUNDERS R L , VANDENBRUAENE M J , GOEMAN J , GIGASE P L , DE BOER M , CEUPPENS J L 
Published: July 2010

SUMMARYThe CD28 receptor on CD4+ and CD8+ T cells interacts with B7 molecules on antigen-presenting cells (APC) to generate essential costimulatory signals. The cytolytic potential of CD8+ T cells could be linked to CD28 expression. Since HIV induces dysfunction of both CD4+ and CD8+ T cells, we evaluated CD28 expression and function in both subsets during HIV infection. CD28 expression on CD8+ T cells from HIV+ subjects was strongly reduced in a disease stage-related fashion. CD28-CD8+ T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2Rα. The CD8+ T cells from the patients showed a significantly reduced proliferative response to co-stimulation with cell-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixed anti-CD3, CD8+ T cells from HIV-infected subjects proliferated normally, and normal levels of IL-2Rα nod transferrin-receptor could be induced on CD28-CD8+ T cells from the patients. In addition, stimulation with plate-fixed anti-CD3 induced proliferative responses in highly purified CD28-CD8+ T cells from both HIV- and HIV+ persons. Furthermore, the increased cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 redirected assay, was predominantly exerted by CD28-CD57+ T cells. CD4+ T cells from the patients showed a slight but significant CD28 down-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8+ T cells from HIV+ subjects is associated with an impaired response to co-stimulation via B7. CD28-CD8+ T cells from seropositives, however, are not completely inert, since they contain in vivo activated CTL and they can be additionally activated through a B7-independent stimulation.
Fulminant meningococcal septic shock in a boy with combined inherited properdin and protein C deficiency
Authors: Fijen C A P , Derkx B H F , Kuijper E J , Mannens M , Poort S R , Peters M , Daha M R , Dankert J 
Published: July 2010

SUMMARY
A 7-year-old patient with fulminant septic shock, due to Neisseria meningitidis of the uncommon serogroup Y developed extensive gangrene of the limbs. Multiple amputations were necessary and a pulmonary embolism occurred within 2 days post-operatively. Complement and haemostatic system studies, done after recovery, showed a complete absence of properdin antigen and a low protein C antigen and activity level in plasma. Defective haemolytic activity in gel by the alternative pathway of complement activation could be restored with purified properdin, indicating a properdin deficiency type 1. Protein C antigen level as well as activity were in agreement with a protein C deficiency type I. The polymerase chain reaction (PCR) product of exon five of the protein C gene showed a substitution of 72Gly by Arg. Both deficiencies were traced among relatives of the patient. Serum of the father of the patient's mother was also properdin-deficient. Microsatellite haplotyping of the X-chromosome of the patient and his relatives showed that a distinct haplotype cosegregated with the properdin deficiency (Lodscore 2·25; four informative meioses). The protein C type I deficiency was present in the patient's mother and her mother and cosegregated with the mutation found. So far as is known, this is the first patient described with combined inherited properdin deficiency and protein C deficiency.
Cytotoxic T cell responses in patients with chronic hepatitis B virus infection undergoing HBe antigen/antibody seroconversion
Authors: Waters J A , O'rourke S , Schlict H-J , Thomas H C 
Published: July 2010

SUMMARY
Cytotoxic T cells have been identified in the peripheral blood of patients with acute hepatitis B virus infections for a short period after clinical presentation. However, in patients in whom the virus persists these have been difficult to demonstrate. In the chronic infection during HBe antigen clearance, when there has been an exacerbation of the disease, we have been able to demonstrate MHC class I-restricted cytolytic response directed against the nucleocapsid antigens. In an HLA-A2 patient this was induced in vitro with the peptide pl8-27, previously described as an HLA-A2-restricted T cell epitope. In patients of other HLA types, recombinant core antigen was used to induce antigen-specific lysis: statistical analysis of the cytolytic responses of chronically infected patients demonstrated a nucleocapsid antigen-specific lysis in patients who were seroconverting. Removal of CD4+ cells reduced non-MHC-restricted cytolysis, allowing an MHC class I-restricted cytolytic component to be demonstrated.
Antibody and clinical responses in volunteers to immunization with malaria peptide–diphtheria toxoid conjugates
Authors: Ramasamy R , Wijesundere DA , Nagendran K , Ramasamy MS 
Published: July 2010

SUMMARYTwenty residue peptides from the 185–200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphtheria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide–diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.
Tumour necrosis factor-alpha (TNF-α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions
Authors: Khanolkar-Young S , Rayment N , Brickell P M , Katz D R , Vinayakumar S , Colston M J , Lockwood D N J 
Published: July 2010

SUMMARYLeprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-α mRNA and TNF-α protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-α mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-α mRNA and TNF-α protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-α mRNA is more abundant than TNF-α protein; this may reflect the rapid turnover of TNF-α protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-α is generated as part of the host response to infection, but also produces local tissue damage.
Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after Bacillus Calmette—Guérin (BCG) immunotherapy
Authors: Jackson A M , Alexandroff A B , Kelly R W , Skibinska A , Esuvaranathan K , Prescott S , Chisholm G D , James K 
Published: July 2010

SUMMARYIntravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients’ urine. This study concerns the production of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, IFN-γ and sICAM-1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL-8 and IL-10) could be detected after the first instillation, whilst others (e.g. IL-2 and IFN-γ) were not detected until after the third or fourth instillation. Interestingly, IL-4 was not detected, perhaps suggesting a differential effect on Th2-like responses. Some patients produced particularly elevated or non-detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought t o be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data.
B cells from a distinct subset of patients with common variable immunodeficiency (CVID) have increased CD95 (Apo-1/fas), diminished CD38 expression, and undergo enhanced apoptosis
Authors: Saxon A , Keld B , Diaz-Sanchez D , Guo B-C , Sidell N 
Published: July 2010

SUMMARYWe investigated the role of apoptosis in the differentiation failure of B cells from a selected subpopulation of patients with CVID delineated by B cell surface marker analysis, in vitro. IgE response, and molecular markers of B cell VH gene repertoire. These patients had altered display of B cell surface molecules that play a role in apoptosis. The patients' ‘B cells had a 4.5 250-fold increase in CD95 (Apo-I. fas) expression and increased CD95 display on their T cells. CD38. a molecule important in preventing germinal centre B cell apoptosis. was reduced on the patients’ B cells. The expression of this molecule was inducible on the CVID lymphocytes with retinoic acid. Increased spontaneous apoptosis in vitro. was observed with the patients’B (23%) and T ceils (10%) compared with normal cells (13% and 3%, respectively). Stimulation in vitro. with IL-4 and CD40 rescued the B cells from apoptosis and allowed for their differentiation. However, IL-4 plus aCD40-driven immunoglobulin production was not quantitatively or qualitatively normal. Failure to overcome apoptosis, a normal step in germinal centre B cell development, may be involved in the lack of differentiation seen in this subset of CVID patients.
HLA-DR-restricted T cell lines from newly diagnosed type 1 diabetic patients specific for insulinoma and normal islet beta cell proteins: lack of reactivity to glutamic acid decarboxylase
Authors: Huang G C , Tremble J , Bailyes E , Arden S D , Kaye T , Mcgregor A M , Banga J P 
Published: July 2010

SUMMARYT cells reacting with pancreatic islet beta cell proteins play a pivotal role in the pathogenesis of type I diabetes in experimental animal models and man, although the islet cell autoantigens against which these T cells are directed remain to be characterized. We have previously shown the presence of disease-related antigens residing in the transplantable RIN insulinoma membranes which are recognized by T ceils from diabetic NOD mice. We now report on the establishment of CD4+, T cell lines reacting with insulinoma membranes from six newly diagnosed type 1 diabetic patients. Detailed examination of T cell lines from two patients revealed that both the lines continued to react with normal islet cell proteins and. interestingly, were also stimulated by antigens present in brain microsomes. The two T cell lines showed reactivity with different molecular weight proteins of the insulinoma membranes and both the lines were histocompatibility-linked antigen (HL A)-DR restricted. Although the insulinoma membrane preparation is known to contain glutamic acid decarboxylase (GAD), none of the six T cell lines proliferates in response to purified GAD. These T cell tines will be valuable in characterizing novel islet beta cell antigens which are likely to be implicated in type 1 diabetes.