bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pigeon fanciers' lung: identification of disease-associated carbohydrate epitopes on pigeon intestinal mucin
Authors: Baldwin C I , Todd A , Bourke S J , Allen A , Calvert J E 
Published: March 2003

SUMMARY
Pigeon intestinal mucin, a complex high molecular weight glycoprotein, is a key antigen in the development of pigeon fanciers' lung (PFL). We have studied the specificity of antibodies to mucin in patients with PFL and asymptomatic antibody-positive individuals. Extensive papain digestion, which removes the non-glycosylated regions of the mucin leaving the heavily glycosylated ‘bottle brush’ regions, resulted in a 600-fold decrease in IgG3 antibody titres with little effect on IgG1 and IgG2 titres. This suggests that IgG1 and IgG2 are directed against the region rich in O-linked sugar chains whilst the majority of the IgG3 is directed against epitopes which are proteinase-sensitive. Lectin mapping of the carbohydrates present on pigeon intestinal mucin demonstrated high levels of exposed n-acetyl neuraminic acid, n-acetyl galactosamine and n-acetyl glucosamine, with lower levels of fucose and some galactose. Sera from pigeon fanciers inhibited binding of lectins specific for n-acetyl neuraminic acid, n-acetyl galactosamine, internal n-acetyl glucosamine and fucose. Sera from people with PFL, compared with sera from asymptomatic antibody-positive fanciers, had significantly higher titres of antibody that inhibited binding of four lectins specific for n-acetyl galactosamine and one fucose-specific lectin, suggesting that these sugars may play a dominant role in disease-associated epitopes. The results suggest that different IgG subclasses recognize different epitopes on mucin and that the epitopes recognized by the major subclasses are present on the O-linked oligosaccharides. Further, the carbohydrate-specific anti-mucin antibodies produced by PFL patients may differ in their specificity from those found in asymptomatic individuals.
Colony-stimulating factor-1 (CSF-1) expression in the uteroplacental unit of mice with spontaneous and induced pregnancy loss
Authors: Gorivodsky M , Torchinsky A , Shepshelovich J , Savion S , Fein A , Carp H , Toder V 
Published: March 2003

SUMMARYCSF-1 plays an important role in female reproduction and normal embryo development. To understand further CSF-1 function in normal and, especially, in compromised pregnancy, we studied the pattern of its mRNA expression as well as expression of its receptor (c-fms) in the uteroplacental units of mice with induced (cyclophosphamide (CY)-treated) and spontaneous (CBA/J × DBA/2J mating combination) pregnancy loss. RNase protection analysis demonstrated the presence of two forms of CSF-1 mRNA in the uteroplacental unit corresponding to 1400- and 263-bp protective fragments. Densitometric analysis demonstrated that the level of 1400-bp mRNA form was decreased by 40% in the uteroplacental units of mice with CY-induced pregnancy loss compared with the control mice. About 20% decrease in 263-bp protective fragment was registered in resorbing versus non-resorbed placenta of CBA/J females mated to DBA/2J males. As judged by in situ hybridization assay, CSF-1 mRNA transcripts were localized in the uterine epithelium and stroma, while c-fms mRNA was found mainly in the trophoblast. The number of metrial gland cells as well as the number of uterine leucocytes expressing CSF-1 and c-fms mRNAs was substantially lower in the uteroplacental unit of mice with pregnancy loss than in control animals. Maternal immunostimulation, while significantly decreasing the resorption rate in mice with CY-induced pregnancy loss, also strengthened CSF-1 mRNA expression at the fetomaternal interface and resulted in reconstitution in the number of CSF-1+ uterine leucocytes and metrial gland cells. These data suggest a role for uterine CSF-1 in the physiology of normal and compromised pregnancy and demonstrate a possible involvement of CSF-1-associated signalling in mechanisms of placenta and endometrium repair following immunopotentiation.
Induction of HIV-1-specific T cell responses by administration of cytokines in late-stage patients receiving highly active anti-retroviral therapy
Authors: Imami N , Hardy G O D , Nelson M R , Morris-Jones S , Al-Shahi R , Antonopoulos C , Gazzard C , Gotch F M 
Published: March 2003

SUMMARYHighly active anti-retroviral therapy (HAART) is associated with reduction in the morbidity and mortality of patients with advanced HIV-1 disease. The ability of such treatment to improve immune responses against HIV-1 and opportunistic pathogens is variable and limited. Addition of cytokine immunotherapy to this treatment may improve immune responses. IL-2 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to HIV-1+ individuals receiving HAART with undetectable viral loads, and CD4 counts &lt; 100 cells/μl. In one patient presenting with Mycobacterium avium complex (MAC) infection, we evaluated the effect of cytokine immunotherapy on lymphocyte phenotype; plasma viral load; proliferative responses to mitogens, recall and HIV-1 antigens; cytokine production and message in response to non-specific and specific stimuli; and natural killer (NK) cell activity. Proliferation assays were performed in two similar patients. Before cytokine immunotherapy the predominant CD8+ population was mainly CD28−. No proliferation or IL-2 production was seen in response to mitogens, recall or HIV-1 antigens; and no HIV-1 peptide-specific interferon-gamma (IFN-γ)-secreting cells were present. Low levels of IL-4 were detected in response to antigens to which patients had been exposed, associated with up-regulated expression of costimulatory molecules influenced by IL-4. Following IL-2 administration, loss of IL-4 was associated with increased NK cell activity and HIV-1 peptide-specific and non-specific IFN-γ-producing cells. Proliferative responses associated with IL-2 production and responsiveness were only seen after subsequent concomitant administration of GM-CSF with IL-2. These changes mirrored clinical improvement. An imbalance of lymphocyte subsets may account for immune unresponsiveness when receiving HAART. Restoration of responses following immunotherapy suggests a shift towards a lymphocyte profile with anti-pathogen activity.
Cytokine gene expression in peripheral blood mononuclear cells (PBMC) from patients with pharmacologically treated cystic echinococcosis
Authors: Riganò R , Profumo E , Buttari B , Teggi A , Siracusano A 
Published: March 2003

SUMMARYThe influence of pharmacological treatment on the immune response of patients with Echinococcus granulosus infection was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to determine mRNA expression for IL-12 p35, IL-12 p40, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-4 in PBMC from 12 patients before and after chemotherapy and from seven uninfected controls. Most patients’ PBMC showed measurable amounts of IL-12 p35, IL-4, IFN-γ and TNF-α mRNA in parasite antigen-stimulated and unstimulated cultures. Conversely, IL-12 p40 mRNA was detected almost exclusively in successfully treated patients (86%) after therapy. In these patients semiquantitative analysis of RT-PCR products showed a significant difference between IL-12 p40 mRNA mean levels before and after therapy (P = 0.03 in parasite antigen-stimulated cultures; P = 0.001 in unstimulated cultures). IL-4 mRNA was weakly expressed before therapy and more highly so after treatment in both groups of patients and under both culture conditions; IL-4 mRNA reached its highest level in post-therapy PBMC from patients in whom therapy failed (stimulated cultures). IFN-γ and TNF-α mRNA expression increased in patients who responded to therapy and decreased in patients who did not. In contrast to IL-12 p35, IFN-γ and TNF-α mRNAs, IL-12 p40 and IL-4 mRNAs were detected exclusively in patients, suggesting a close relationship between these two cytokines and cystic echinococcosis. Our findings indicate that chemotherapy influences the immune response, thus determining changes in Th1/Th2 cytokine mRNA patterns, predominantly in IL-12 p40 and IL-4 mRNA expression.
CCR5 and CXCR4 chemokine receptor expression and β-chemokine production during early T cell repopulation induced by highly active anti-retroviral therapy
Authors: Giovannetti A , Ensoli F , Mazzetta F , De Cristofaro M , Pierdominici M , Muratori D S , Fiorelli V , Aiuti F 
Published: March 2003

SUMMARYExpression of chemokine receptors and β-chemokine production by peripheral blood mononuclear cells (PBMC) were determined in HIV-1-infected individuals before and after highly active anti-retroviral therapy (HAART) and their relationship to viral load, T cell phenotype and the expression of immunological activation markers was examined. We found that the expression of CCR5 is up-regulated in HIV-1-infected individuals while CXCR4 appears down-regulated on both CD4 and CD8 T cells compared with normal controls. These alterations are associated with the high levels of viral load. In addition, a relationship was observed between the degree of immune activation and chemokine receptor expression on T cells. However, after 3 months of combined anti-retroviral regimen, expression of CXCR4 significantly increased while CCR5 decreased when compared with pretherapy determinations. This was seen in strict association with a dramatic decrease of viral load and an increase of both CD45RA+/CD62L+ (naive) and CD45RA−/CD62L+ or CD45RA+/CD62L− (memory) T cells accompanied by a significant decrease of the expression of immune activation markers such as HLA-DR and CD38. At enrolment, both spontaneous and lectin-induced RANTES, macrophage inflammatory protein-1α (MIP-1α) and MIP-1β production by PBMC were higher in HIV-1-infected individuals compared with normal controls, although differences for MIP-1β were not statistically significant. However, RANTES and MIP-1α production decreased during HAART at levels closer to that determined with normal controls, while MIP-1β production was less consistently modified. These data indicate that the expression of chemokine receptors CCR5 and CXCR4 and the production of β-chemokines are altered in HIV-infected individuals, and suggest that their early modifications during HAART reflect both the peripheral redistribution of naive/memory T cell compartments and the decrease in levels of T cell activation. Such modifications in the expression of host determinants of viral tropism and the production of anti-viral molecules may play a role in the emergence of virus variants when a failure of HAART occurs.
The matrix metalloproteinase inhibitor BB-1101 prevents experimental autoimmune uveoretinitis (EAU)
Authors: Wallace G R , Whiston R A , Stanford M R , Wells G M A , Gearing A J H , Clements J M 
Published: March 2003

SUMMARYEAU is characterized by breakdown of the blood–retinal barrier and extravasation of leucocytes into retinal tissue leading to destruction of photoreceptor cells. Matrix metalloproteinases (MMP) have been implicated in trafficking of cells into tissues, but their role in inflammatory eye disease is unclear. A synthetic MMP inhibitor, BB-1101, was administered subcutaneously, from either day 0 or day 7, to Lewis rats challenged with bovine S-antigen to induce EAU. When given up to day 14, BB-1101 reduced the incidence of disease and delayed the day of onset of clinical disease. When administered from day 7 until day 21, EAU was completely abrogated. A quantitative polymerase chain reaction (PCR) assay showed an increase of both matrilysin (MMP-7), neutrophil collagenase (MMP-8) and macrophage metalloproteinase (MMP-12) in retinas from EAU animals compared with naive controls. These enzymes are produced by activated leucocytes and act on components of the basement membrane. These results therefore implicate these MMP as integral to the development of pathology in EAU.
Th1-biased immune responses induced by DNA-based immunizations are mediated via action on professional antigen-presenting cells to up-regulate IL-12 production
Authors: Asakura Y , Liu L-J , Shono N , Hinkula J , Kjerrström A , Aoki I , Okuda K , Wahren B , Fukushima J 
Published: March 2003

SUMMARYThe efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-γ cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by a codelivery of an ectopic IFN-γ expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL-12 production. Taken together, it appears likely that Th1-biased immune responses induced by DNA-based immunization are mediated via action on professional antigen-presenting cells to produce IL-12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram-positive bacterium that induces strong Th1-biased immune responses. The result suggests that DNA-based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA-based immunization so efficiently induces protective immunity against these microbial pathogens.
Adrenaline-induced mobilization of T cells in HIV-infected patients
Authors: Søndergaard S R , Cozzi Lepri A , Ullum H , Wiis J , Hermann C K , Laursen S B , Qvist J , Gerstoft J , Skinhøj P , Pedersen B K 
Published: March 2003

SUMMARYThe present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV− controls received a 1-h adrenaline infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45RO+CD45RA− and CD8+CD28−cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect induced an impaired ability to mobilize immune-competent cells in response to stress stimuli. Furthermore, the study does not support the idea that CD4+ T cells are trapped in lymph nodes by HIV antigens, because untreated and HAART-treated HIV-infected patients mobilized similar numbers of CD4+ T cells. Finally, no evidence was found for the existence of a HAART-induced non-circulating pool of CD4+ T cells.
Osteoblasts and stromal cells isolated from femora in rheumatoid arthritis (RA) and osteoarthritis (OA) patients express IL-11, leukaemia inhibitory factor and oncostatin M
Authors: Lisignoli G , Piacentini A , Toneguzzi S , Grassi F , Cocchini B , Ferruzzi A , Gualtieri G , Facchini A 
Published: March 2003

SUMMARYWe investigated both in vitro and ex vivo the role of mature osteoblasts (OB) and bone marrow stromal cells (BMSC) in RA and OA by analysing the expression of the following IL-6-type cytokines: IL-11, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and IL-6. OB and BMSC were isolated from femora of RA, OA and post-traumatic (PT) patients, cultured in vitro in the presence or absence of IL-1β and tumour necrosis factor-alpha (TNF-α), and assessed for the production and mRNA expression of IL-6-type cytokines. Trabecular bone biopsies were obtained from the inner portions of femoral heads and used for cytokine in situ immunostaining. Cultured OB and BMSC from different patients constitutively secreted IL-11 and IL-6 but not OSM. LIF was secreted only by BMSC, at very low levels. Interestingly, IL-11 basal production was significantly higher in BMSC than in OB in all three groups tested. IL-1β and TNF-α strongly stimulated IL-6-type cytokine release (except for OSM) by both OB and BMSC. OSM was expressed only at mRNA levels in all groups studied. Cytokine immunostaining on bone biopsies confirmed the data obtained on cultured cells: IL-11, IL-6 and LIF proteins were detected both in mesenchymal (BMSC and OB) and mononuclear cells; OSM was found only in mononuclear cells. These data demonstrate that IL-6-type cytokines are constitutively expressed in the bone compartment in RA, OA and PT patients and can be secreted by bone cells at different stages of differentiation (BMSC and OB). This suggests that these cytokines may be involved in the mechanisms of bone remodelling in OA and RA.
Circulating,Mycobacterium tuberculosis-specific lymphocytes from PPD skin test-negative patients with tuberculosis do not secrete interferon-gamma (IFN-γ) and lack the cutaneous lymphocyte antigen skin-selective homing receptor
Authors: Magnani Z I , Confetti C , Besozzi G , Codecasa L R , Panina-Bordignon P , Lang R , Rossi G A , Pardi R , Burastero S E 
Published: March 2003

SUMMARYIndividuals with a negative intradermal reaction to tuberculin PPD have long been described in the Mycobacterium tuberculosis exposed, immune-competent population. Here, we studied PPD-specific blood T lymphocytes from these subjects for phenotypic markers relevant to skin migration, including the expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen (CLA). Out of 82 patients with active tuberculosis we identified four subjects who were repeatedly PPD skin test-negative. CD4 T lymphocytes specific to mycobacterial antigens were derived from these individuals, which (i) proliferated in vitro to M. tuberculosis antigens comparably to those from PPD+ patients; (ii) secreted comparable amounts of IL-2 but lower amounts of IFN-γ; (iii) were confined within the CLA-negative T cell subset. We conclude that the negative tuberculin reaction in a small subset of patients exposed to mycobacteria is associated with impaired production of IFN-γ by circulating PPD-specific T cells that are lacking CLA expression. On this basis in vitro proliferation to PPD can discriminate bona fide non-responders from infected patients with a deficit in the margination of M. tuberculosis-specific T lymphocytes.
Development of antibodies against tetravalent meningococcal polysaccharides in revaccinated complement-deficient patients
Authors: Drogari-Apiranthitou M , Fijen C A P , Van De Beek D , Hensen E F , Dankert J , Kuijper E J 
Published: March 2003

SUMMARY
Individuals deficient in C3 or a late complement component are susceptible to recurrent meningococcal infections. Since they experience meningococcal episodes mostly with uncommon meningococcal serogroups, vaccination with a tetravalent vaccine containing A, C, Y and W135 polysaccharides has been suggested. We vaccinated a cohort of two C3 and 17 late complement component-deficient (LCCD) patients, revaccinated them 7 years later and investigated the development of their IgG antibodies to the capsular polysaccharides of the meningococcal vaccine. Seven years after the first vaccination levels of IgG antibodies declined compared with the levels present at 6 months after the first vaccination, but were still at least four times higher than before vaccination. Levels of antibodies to Y polysaccharide in serum of complement-deficient patients were rather low but they did not differ significantly from those in serum of healthy non-related controls (P = 0.07). Three months after the second vaccination IgG antibodies against all polysaccharides increased, exceeding those measured at 6 months after the first vaccination. In the 8 years of observation after the first vaccination two new meningococcal infections with strains related to the vaccine (serogroup Y strains) occurred in two patients, 3.5 and 5 years after the first vaccination. Our findings show that high IgG antibody levels against the tetravalent meningococcal polysaccharide vaccine were reached after revaccination of two C3 and 17 LCCD individuals 7 years after the first vaccination. Whether revaccination should be required within a period shorter than 7 years is discussed, since two vaccinees developed meningococcal disease to vaccine serogroup Y.
IL-10 enhances IL-2-induced proliferation and cytotoxicity by human intestinal lymphocytes
Authors: Ebert E C 
Published: March 2003

SUMMARYIL-10 modulation of human intestinal T lymphocyte functions was studied for the first time. Lymphocyte proliferation was determined by 3H-thymidine incorporation; cytokine production, by ELISA; expression of surface markers, by immunofluorescence and flow cytometric analysis; and cytotoxicity, by lysis of 51Cr-labelled target cells. IL-10 blocked phytohaemagglutinin (PHA)-induced activation and proliferation of CD8+ T cells from the epithelium and lamina propria. It was a greater inhibitor of IL-2, interferon-gamma, and tumour necrosis factor-alpha production than were IL-4 or transforming growth factor-beta. In contrast, IL-10 enhanced IL-2-stimulated proliferation of both CD4+ and CD8+ T cells by increasing cell division after activation. It also augmented IL-2- but not IL-15-induced cytotoxicity of intestinal lymphocytes against colon cancer by a mechanism independent of natural killer cells. In conclusion, IL-10 blocking of proinflammatory cytokine secretion probably reduces intestinal inflammation. IL-10 augmentation of IL-2-induced cytotoxicity may help to maintain host defence.
Nuclear factor-κB activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin
Authors: Herfarth H , Brand K , Rath H C , Rogler G , Schölmerich J , Falk W 
Published: March 2003

SUMMARYIn acute DSS-induced colitis nuclear factor (NF)-κB-dependent inflammatory cytokines including IL-1 and tumour necrosis factor-alpha (TNF-α) are up-regulated. Here we examined the effects of gliotoxin, a fungal metabolite known to inhibit NF-κB activity, on cytokine production by a mouse cell system in vitro and on intestinal inflammation and NF-κB activation in vivo. In vitro gliotoxin decreased TNF-α gene expression and protein production by RAW-264.7 mouse macrophage-like cells stimulated with lipopolysaccharide. In vivo, gliotoxin treatment of mice was begun on day 3 of 5% DSS application dissolved in the drinking water and continued until day 8. Gliotoxin treatment dose-dependently down-regulated colonic inflammation as assessed histologically and in parallel there was a suppression of colonic TNF-α and IL-1α mRNA expression on day 8 as analysed by semiquantitative reverse transcriptase-polymerase chain reaction (P &lt; 0·01). Furthermore, colonic NF-κB DNA-binding activity was increased in DSS-induced colitis and was suppressed by gliotoxin. These results demonstrate the essential role of NF-κB in DSS-induced colitis and indicate a molecular approach to the treatment of intestinal inflammatory disorders.