bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 co-receptor expression on trophoblastic cells from early placentas and permissivity to infection by several HIV-1 primary isolates
Authors: Mognetti B , Moussa M , Croitoru J , Menu E , Dormont D , Roques P , Chaouat G 
Published: March 2003

SUMMARYWe examined CD4 and major HIV-1 co-receptor expression by trophoblast cells (TC) from early placentas, and the permissiveness of TC for infection by several natural HIV-1 isolates in vitro. Ten early placentas (4–6 weeks of gestation) from HIV−women were obtained after elective abortion. CD4 and HIV-1 co-receptor expression by TC was examined in terms of both mRNA and protein. The same TC were then challenged with three clinical HIV isolates of known phenotype, two originating from mothers who transmitted the virus to their child and one from a vertically infected newborn. TC infection was detected by polymerase chain reaction. CD4 expression was detected in five of the 10 placentas, while membrane protein expression of CCR3, CXCR4 and CCR5 was detected in every case, despite quantitative differences among individuals. Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations. TC from seven out of eight placentas were permissive to HIV entry, but no productive viral replication was detected (reverse transcriptase activity in culture supernatants). Interestingly, the addition of chemokine(s) or a CD4-blocking antibody to the cultures failed to inhibit TC virus entry. These data point to marked interindividual variability in HIV co-receptor expression by trophoblast cells and show that TC from early placentas can be infected in vitro by clinical HIV-1 isolates. They also suggest that viral entry in vitro might occur through a mechanism independent of both CD4 and chemokine receptors.
Chemokine synthesis and cellular inflammatory changes in lungs of mice bearing p40taxof human T-lymphotropic virus type 1
Authors: Miyazato A , Kawakami K , Iwakura Y , Saito A 
Published: March 2003

SUMMARYTo elucidate the pathogenic mechanisms of human T-lymphotropic virus type 1 (HTLV-1)-associated lung inflammation, we conducted a histopathological and molecular analysis study using transgenic mice bearing pX region of this virus. In these mice, accumulations of inflammatory cells consisting mainly of lymphocytes were present in peribronchiolar and perivascular areas and alveolar septa, while control littermate mice did not show such changes. In situ hybridization showed that the anatomic distribution of p40tax mRNA was similar to that of inflammatory cells, typically in peribronchiolar areas and to a lesser extent in perivascular and alveolar septa. Inflammatory cytokines, including IL-1β, tumour necrosis factor-alpha and interferon-gamma, and several chemokines, such as monocyte chemotactic protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1α (MIP-1α) and IP-10, were detected in lungs of transgenic mice but not control mice. Semiquantitative analysis using reverse transcription-polymerase chain reaction showed a significant correlation between MCP-1 mRNA expression and p40tax mRNA, but not with other chemokines. The gene expression of the above chemokines, with the exception of MIP-1α, correlated with the severity of histopathological changes in the lung. Considered together, our results suggested that p40tax synthesis may be involved in the development of lung lesions caused by HTLV-1 through the induction of local production of chemokines.
Identification and immune regulation of 25-hydroxyvitamin D-1-α-hydroxylase in murine macrophages
Authors: Overbergh L , Decallonne B , Valckx D , Verstuyf A , Depovere J , Laureys J , Rutgeerts O , Saint-Arnaud R , Bouillon R , Mathieu C 
Published: March 2003

SUMMARYReceptors for 1,25(OH)2vitaminD3 are found in most immune cells and important immunological effects have been described in vitro, reflected by its capacity to prevent autoimmunity and to prolong graft survival. The aim of this study was to examine the presence and nature of the enzyme responsible for final activation of the molecule, 1-α-hydroxylase, in murine macrophages and to analyse its regulation and possible role in the immune system. Peritoneal macrophages from C57Bl/6 mice were incubated with lipopolysaccharide (LPS; 100 μg/ml), interferon-gamma (IFN-γ; 500 U/ml) or a combination of both. By quantitative reverse transcriptase-polymerase chain reaction, using primers based on the murine renal cDNA sequence, low levels of 1-α-hydroxylase mRNA were detected in freshly isolated cells (18 ± 7 × 10−6 copies/β-actin copies). Analysis of the cDNA sequence of the gene revealed identical coding sequences for the macrophage and renal enzymes. mRNA levels rose three-fold with LPS (NS), but a six-fold increase was seen after IFN-γ stimulation (P &lt; 0·05). Combining LPS and IFN-γ did not result in a major additional increase, but addition of cyclosporin A further increased levels 2·5-fold both in IFN-γ- and combination-stimulated cells (P &lt; 0·05). Time course analysis revealed that up-regulation of 1-α-hydroxylase was a late phenomenon, preceded by the up-regulation of activating macrophage products such as IL-1 and tumour necrosis factor-alpha. Finally, a defect in 1-α-hydroxylase up-regulation by immune stimuli was found in autoimmune non-obese diabetic mice. In conclusion, we propose that the up-regulation of 1-α-hydroxylase in activated macrophages, resulting in the synthesis of 1,25(OH)2D3, might be a negative feedback loop in inflammation. A defect in this system might be an additional element in tipping the balance towards autoimmunity.
Cryofibrinogenaemia: a study of 49 patients
Authors: Blain H , Cacoub P , Musset L , Costedoat-Chalumeau N , Silberstein C , Chosidow O , Godeau P , Frances C , Piette J C 
Published: March 2003

SUMMARY
The purpose of this study was to characterize the clinical features and components of 30 patients with isolated cryofibrinogen (CF) versus those of 19 patients with combined CF and cryoglobulins (CG). Secondary forms of cryofibrinogenaemia associated with collagen disorders, infectious or malignant diseases, were significantly more frequent in patients with combined CF and CG than those with isolated CF (79 versus 47%, P = 0.02). Both groups of CF patients presented predominantly cutaneous symptoms (77% in isolated CF; 58% in combined CF + CG), and less frequently venous and/or arterial thrombosis (13% in isolated CF; 3% in combined CF + CG). Patients with idiopathic forms of CF, and particularly those without CG, suffered essentially from recurrent painful skin ulcers, mainly triggered by cold exposure. Patients with isolated CF had higher mean plasma concentrations of CF than those with combined CF + CG (1.61 ± 1.26 versus 0.82 ± 1.18 g/l, respectively; P = 0.004), but there was no correlation between the CF plasma level and either the severity of symptoms or the sensitivity to cold. In patients with isolated CF, fibronectin was suggested (by precipitation analysis) to be a major component of the cryoprecipitate, whereas immunoglobulins were rarely present (in only three out of 30 patients). By contrast, in the majority of patients (78%) with combined CF and CG, the CF consisted mainly of immunoglobulins of the same class as those characterizing the associated CG. Analysis of the CG precipitate revealed the presence of fibronectin but not fibrinogen, α1-antitrypsin and α2-macroglobulin. In conclusion, isolated and combined cryofibrinogenaemia are associated with different clinical signs requiring different clinical management, but there is no evidence as yet for a causal role of the cryoprecipitates in the differences observed.
The 19-kD antigen and protective immunity in a murine model of tuberculosis
Authors: Yeremeev V V , Lyadova I V , Nikonenko B V , Apt A S , Abou-Zeid C , Inwald J , Young D B 
Published: March 2003

SUMMARYThe 19-kD antigen is a cell wall-associated lipoprotein present in Mycobacterium tuberculosis and in bacille Calmette–Guérin (BCG) vaccine strains. Expression of the 19-kD antigen as a recombinant protein in two saprophytic mycobacteria—M. vaccae and M. smegmatis—resulted in abrogation of their ability to confer protection against M. tuberculosis in a murine challenge model, and in their ability to prime a DTH response to cross-reactive mycobacterial antigens. Induction of an immune response to the 19-kD antigen by an alternative approach of DNA vaccination had no effect on subsequent M. tuberculosis challenge. These results are consistent with a model in which the presence of the 19-kD protein has a detrimental effect on the efficacy of vaccination with live mycobacteria. Targeted inactivation of genes encoding selected antigens represents a potential route towards development of improved vaccine candidates.
Anti-β2-glycoprotein I (GPI) autoantibodies, annexin V binding and the anti-phospholipid syndrome
Authors: Hanly J G , Smith S A 
Published: March 2003

SUMMARYWe examined the role of autoantibodies to β2-GPI and prothrombin (PT) in the inhibition of annexin V binding to cardiolipin (CL) and the association with clinical manifestations of the anti-phospholipid syndrome (APS). Plasma samples from 59 patients with anti-phospholipid (aPL) antibodies were studied. Affinity purification of total IgG and IgG anti-ß2-GPI antibodies was performed using staphylococcal protein A and phospholipid liposomes. Annexin V binding to CL was significantly inhibited by 31/59 (53%) aPL+ plasma samples. There was a significant association between annexin V inhibition and elevated levels of IgG anti-cardiolipin (aCL) (r = −0.62; P &lt; 0.001), IgG anti-ß2-GPI (r = −0.67; P &lt; 0.001) and a weaker association with lupus anti-coagulant (r = −0.27; P = 0.05). There was no association with other isotypes of aCL and anti-ß2-GPI or with anti-PT of any isotype. In patients with clinical manifestations of the APS there were higher levels of IgG aCL (median (range) Z score): 10.0 (0–17.6) versus 5.0 (0–16.1); P = 0.03), IgG anti-ß2-GPI (4.5 (0–11.3) versus 0.9 (0–9.7); P = 0.02) and greater inhibition of annexin V binding to CL (−3.4 (−11.4–0.6) versus−1.1 (−10.8–1.2); P = 0.22). Odds ratios for the laboratory assays and the presence of clinical manifestations of the APS varied between 0.38 and 4.16, with the highest values for IgG aCL (4.16), IgG anti-ß2-GPI (3.28) and annexin V inhibition (2.85). Additional experiments with affinity-purified IgG antibodies indicated that inhibition of annexin V binding was dependent upon the concentration of ß2-GPI and anti-ß2-GPI antibodies. These results indicate that inhibition of annexin V binding to procoagulant phospholipid surfaces is dependent upon anti-ß2-GPI antibodies and suggest a role for annexin V in the pathogenesis of the APS.
Dysregulation in IL-12 secretion by neutrophils from HIV-infected patients
Authors: Vecchiarelli A , Monari C , Palazzetti B , Bistoni F , Casadevall A 
Published: March 2003

SUMMARYIt is generally believed that neutrophils from HIV-infected patients are functionally competent, but several studies have shown impairment in neutrophil fungal killing and cytokine production. In this study we evaluated the ability of neutrophils from healthy donors and HIV-infected patients to produce IL-12 in response to stimulation with Candida albicans, lipopolysaccharide (LPS) and Cryptococcus neoformans (acapsular and encapsulated), with and without MoAb opsonization. Neutrophils from healthy donors secreted IL-12 in response to LPS or C. albicans but not in response to encapsulated or acapsular C. neoformans, regardless of MoAb opsonization. Surprisingly, neutrophils from HIV-infected patients demonstrated constitutive IL-12 production, although these cells were not responsive to LPS stimulation. The inability of MoAb to C. neoformans capsular polysaccharide to promote IL-12 production by neutrophils excludes phagocytosis and/or CD16 cross-linking in this process, and distinguishes neutrophils from monocytes. Our results provide additional evidence for cytokine dysregulation in neutrophils from HIV-infected patients. Furthermore, the IL-12 response of neutrophils and monocytes to CD16 stimulation appears to be different, suggesting differences in the role of these phagocytic cells during the inflammatory response.
Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis
Authors: Tontsch D , Pankuweit S , Maisch B 
Published: March 2003

SUMMARYThe concept of antigenic mimicry in autoimmune diseases such as rheumatic fever has been under investigation for decades and the range of cross-reactive tissue antigens for streptococcal-induced antibodies identified in rheumatic heart disease is still expanding. To identify heart tissue-reactive antigens which may be implicated in the secondary immunopathogenesis of rheumatic fever, sera from 56 patients with acute rheumatic heart disease were probed in two-dimensional Western blots for reactivity against heart tissue antigens. After two-dimensional immunoblot analysis, proteins were submitted to N-terminal amino acid sequence analysis. This analysis identified creatine kinase, two mitochondrial proteins and, at a low level, various stress proteins as cross-reactive myocardial antigens. Therefore, in addition to myosin, creatine kinase may represent another major antigen for autoreactive antibodies in rheumatic heart disease. Mitochondrial proteins have been implicated in the pathogenesis of inflammatory heart disease for some years, and in this study we have identified two mitochondrial proteins as relevant antigens in rheumatic heart disease.
Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection?
Authors: Bianco A , Whiteman S C , Sethi S K , Allen J T , Knight R A , Spiteri M A 
Published: March 2003

SUMMARYSince clinical experimental studies indicate that upper respiratory tract viral infections may exacerbate acute asthma symptoms in atopic/asthmatic individuals, we have investigated the expression and modulation of ICAM-1 on human nasal epithelial cells (HNEC) from normal and atopic subjects. ICAM-1 is the attachment molecule for the majority of serotypes of human rhinovirus (HRV), including HRV-14, and is also critical for the migration and activation of immune effector cells. Basal ICAM-1 expression was significantly higher in HNEC obtained by brushings from atopic compared with non-atopic subjects (P = 0.031), and was also significantly increased on atopic HNEC harvested in season compared with out of season (P &lt; 0.05). Atopic HNEC showed further up-regulation in ICAM-1 expression when cultured with clinically relevant allergen (P = 0.032). ICAM-1 levels on normal HNEC were also increased by infection with HRV-14 (P &lt; 0.05). Basal expression of ICAM-1 on atopic nasal polyp epithelial cells (EC) was significantly higher than on both normal and atopic nasal HNEC. This elevated nasal polyp ICAM-1 level was not increased further by allergen, although HRV infection resulted in a small significant increase. Recovered viral titres from HRV-infected nasal polyp EC were 1.5-fold higher than from infected normal nasal HNEC. The data are consistent with the hypothesis that allergen, by enhancing expression of the HRV attachment target on host cells, facilitates viral infection in atopic subjects; simultaneously HRV-induced increases in ICAM-1 levels would favour migration and activation of immune effector cells to the airway, resulting in enhanced atopic inflammation.
Autoantigen-pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats
Authors: Huang Y-M , Yang J-S , Xu L-Y , Link H , Xiao B-G 
Published: March 2003

SUMMARYDendritic cells (DC) can modulate the nature of immune responses in a stimulatory or tolerogenic fashion. Great attention has been given to the induction of immunity to tumour and infection. In this study, bone marrow-derived DC from healthy Lewis rats were pulsed in vitro with encephalitogenic myelin basic protein peptide 68–86 (MBP 68–86), and injected subcutaneously (1 × 106/rat) into normal Lewis rats. Upon observation of the rats pretreated in this way for 4 weeks, when no clinical signs of EAE occurred, these rats were immunized with MBP 68–86 and Freund's complete adjuvant. The pretreated rats failed to develop clinical EAE. This tolerance was associated with augmented proliferative responses, interferon-gamma secretion, inducible nitric oxide synthase (iNOS) expression and NO production. The frequency of apoptotic cells was increased in the rats receiving MBP 68–86-pulsed DC compared with unpulsed control DC. Few infiltrating inflammatory cells were observed in spinal cord sections from rats that had received MBP 68–86-pulsed DC. The data are compatible with the interpretation that MBP 68–86-pulsed DC induce tolerance to EAE possibly through up-regulation of iNOS expression and NO production, which mediate cell apoptosis, thereby reducing infiltration of inflammatory cells within the central nervous system.
Pathogenic function of IL-1βin psoriasiform skin lesions of flaky skin (fsn/fsn) mice
Authors: Schön M , Behmenburg C , Denzer D , Schön M P 
Published: March 2003

SummaryIL-1 acts on many cells as an inflammatory mediator. Its two forms, IL-1α and IL-1β, are regulated differentially within hyperproliferative inflammatory skin conditions, such as psoriasis. While IL-1α is down-regulated within psoriatic lesions, the levels of IL-1β are increased. However, some investigators have described an inactive form of IL-1β in psoriasis, while others have detected increased IL-1β activity within these lesions. Thus, its in vivo role remains unclear. We have assessed expression and function of IL-1β within psoriasiform skin lesions of the spontaneous mouse mutation flaky skin (fsn/fsn). It was found that IL-1β was increased by 357% within psoriasiform lesions of fsn/fsn mice compared with their wild-type or heterozygous (+/?) littermates (P &lt; 0·00001). When the IL-1β function was inhibited by i.p. injection with a neutralizing MoAb, no effects were seen in +/? mice. In contrast, psoriasiform features in fsn/fsn mice were alleviated dramatically, as demonstrated by a 40% decrease of the epidermal thickness and a diminished number of intra-epidermal microabscesses. In addition, infiltrating epidermal CD4+ and CD8+ T cells were decreased by 68% and 81%, respectively (P &lt; 0·05), and epidermal Langerhans cells also were reduced by 36% (P &lt; 0·005). In contrast, mast cells were not affected, suggesting differential responses of various cutaneous cell types. Our results demonstrate an important in vivo role of IL-1β for the generation of hyperproliferative inflammatory skin lesions in the fsn/fsn model.
CD4+ and CD8+ T cell responses inHelicobacter pylori-infected individuals
Authors: Quiding-Järbrink M , Lundin B S , Lönroth H , Svennerholm A-M 
Published: March 2003

SUMMARYIn order to characterize T cell responses in human Helicobacter pylori infection, we have examined proliferative responses and cytokine production by CD4+ and CD8+ T cells isolated from duodenal ulcer patients and asymptomatic H. pylori carriers, after activation with some H. pylori antigens that may be important in disease development. For control purposes, T cells from uninfected volunteers were also examined. The different H. pylori antigens induced only modest proliferative responses in circulating CD4+ and CD8+ T cells from both H. pylori-infected and uninfected individuals. However, circulating T cells from H. pylori-infected subjects produced larger amounts of interferon-gamma (IFN-γ) in response to the Helicobacter antigens than did T cells from uninfected volunteers. Furthermore, CD8+ T cells produced larger amounts of IFN-γ than did CD4+ T cells, on a per cell basis. Most IFN-γ-producing cells from both infected and uninfected volunteers appeared to be naive T cells expressing CD45RA. Increased production of IL-4 and IL-5 was, on the other hand, only seen in a few instances after stimulation of isolated CD4+ and CD8+ T cells. Stimulation of freshly isolated gastric T cells with the different H. pylori antigens did not result in increased proliferation or cytokine production. In conclusion, our results show that several different purified H. pylori antigens induce production of IFN-γ, preferentially by CD8+ cells. Therefore, they suggest that IFN-γ-secreting CD8+ cells contribute significantly to the cytokine response induced by H. pylori infection.
Recombinant bacille Calmette–Guérin (BCG) expressing human interferon-alpha 2B demonstrates enhanced immunogenicity
Authors: Luo Y , Chen X , Han R , O'Donnell M A 
Published: March 2003

SUMMARYTo increase its immunostimulatory properties, BCG was genetically engineered to secrete recombinant human interferon-alpha 2B (rhIFN-α) under control of the mycobacterial heat shock protein (hsp)60 promoter and the α antigen signal sequence. Expression of rhIFN-α was readily detectable by ELISA and on Western blotting. When compared with control BCG, rhIFN-α BCG was substantially more active in inducing the production of IFN-γ and IFN-inducible protein 10 (IP-10) from human peripheral blood mononuclear cells, while IL-10 production was correspondingly decreased. These effects were reversible upon antibody neutralization of rhIFN-α. Among 10 patients tested, rhIFN-α BCG enhanced IFN-γ production in all patients ranging from 1·4- to 23·7-fold with a general trend toward greatest enhancement among those with weakest baseline responses to control BCG. Correspondingly, rhIFN-α BCG decreased IL-10 production in all patients by 1·2–4·8-fold. The onset of IFN-γ production induced by rhIFN-α BCG was also more rapid, occurring within 4 h after stimulation versus &gt; 24 h with wild-type BCG. The observation that the maximum IFN-γ induction depends on the simultaneous presence of both IFN-α and BCG highlights the advantages of rhIFN-α BCG. Taken together, these immunostimulatory properties of rhIFN-α BCG suggest that it may be a superior agent for immunotherapeutic protocols involving live BCG in humans.
Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression
Authors: Flieger D , Hoff A S , Sauerbruch T , Schmidt-Wolf I G H 
Published: March 2003

SUMMARYMoAbs against tumour-associated antigens (TAA) may be useful for the treatment of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody-dependent cellular cytotoxicity we examined whether the cytokines IL-2, IL-4, IL-6, IL-10, IL-12, interferon-alpha (IFN-α), IFN-γ, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and tumour necrosis factor-alpha can influence EpCAM and LewisY expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN-α increased significantly whereas IL-4 decreased both EpCAM and LewisY expression. IFN-γ significantly increased LewisY expression only. When tumour cells were treated with MoAb, the LewisY-specific MoAb BR55-2 down-regulated LewisY antigen expression, whereas MoAb 17-1A, which binds to EpCAM, up-regulated this TAA after 3 days of culture. The cytokines IFN-α or IFN-γ combined with MoAb 17-1A enhanced further slightly the expression of EpCAM. In additional experiments with chemotherapeutic drugs commonly used for the treatment of colorectal cancer, we found that 5-fluorouracil, mitomycin-C and oxaliplatin up-regulated EpCAM and LewisY antigen expression. Raltitrexed enhanced LewisY and down-regulated EpCAM expression, whereas CPT-11 had no influence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN-α, 5-fluorouracil and MoAb 17-1A. Our results may be useful for defining combinations of biological and chemotherapeutic drugs for the treatment of colorectal cancer. Further trials should evaluate to what extent these combinations enhance antibody-dependent cellular cytotoxicity.