bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effect of intracolonically administered nuclear factorκB (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis
Authors: Murano M , Maemura K , Hirata I , Toshina K , Nishikawa T , Hamamoto N , Sasaki S , Saitoh O , Katsu K 
Published: March 2003

SUMMARYCytokines such as IL-1, tumour necrosis factor-alpha (TNF-α), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor κB (NF-κB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NF-κB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-α concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-κB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-κB antisense oligonucleotide may be effective in ulcerative colitis.
Absence of platelet CD40L identifies patients with X-linked hyper IgM syndrome
Authors: Inwald D P , Peters M J , Walshe D , Jones A , Davies E G , Klein N J 
Published: March 2003

SUMMARYCD40 ligand (CD40L), a membrane protein expressed on activated T cells, plays a pivotal role in B cell proliferation and differentiation. Mutations in the CD40L gene are associated with a rare immunodeficiency state, X-linked hyper IgM syndrome (XLHIGM). Recently, platelets have been described as capable of expressing CD40L within minutes of stimulation. We have developed a rapid technique to determine expression of CD40L on activated platelets by flow cytometry in whole blood. We have demonstrated that this technique is useful in neonatal screening, in rapid diagnosis and in determining reconstitution by donor bone marrow post-transplantation.
Inhibition of aromatic l-amino acid decarboxylase activity by human autoantibodies
Authors: Husebye E S , Bøe A S , Rorsman F , Kämpe O , Aakvaag A , Rygh T , Flatmark T , Haavik J 
Published: March 2003

SUMMARY
A full-length rat cDNA clone encoding aromatic l-amino acid decarboxylase (AADC) (E.C. 4.1.1.28) was used for in vitro transcription and translation. The enzyme had catalytic activity (0·2 pmol serotonin/μl lysate per min), and was stimulated 2·5-fold by the addition of excess pyridoxal phosphate. On size exclusion chromatography, AADC eluted as a single activity peak with an apparent mol. wt of 93 kD. This activity peak was immunoprecipitated by sera from patients with autoimmune polyendocrine syndrome type I (APS I) containing autoantibodies against AADC. Serum and purified IgG from these patients inhibited the enzyme activity (non-competitively) by 10–80%, while sera from APS I patients without autoantibodies and controls did not. This finding confirms and extends previous observations that APS I patients have inhibitory antibodies against key enzymes involved in neurotransmitter biosynthesis.
Disordered expression of inhibitory receptors on the NK1-type natural killer (NK) leukaemic cells from patients with hypersensitivity to mosquito bites
Authors: Seo N , Tokura Y , Ishihara S , Takeoka Y , Tagawa S , Takigawa M 
Published: March 2003

SUMMARYRecent studies have revealed the existence of a distinct type of NK cell leukaemia of the juvenile type, which presents with hypersensitivity to mosquito bites (HMB) as an essential clinical manifestation and is infected with clonal Epstein–Barr virus (EBV). This disorder is thus called HMB-EBV-NK disease and has been reported in Orientals, mostly from Japan. We investigated the profile of cytokine production and the expression of both types of NK inhibitory receptors, i.e. CD94 lectin-like dimers and killer-cell immunoglobulin-like receptors, in NK leukaemic cells from three patients with HMB-EBV-NK disease. It was found that freshly isolated NK leukaemic cells expressed mRNA for interferon-gamma (IFN-γ) and additionally produced IL-10 upon stimulation with IL-2, indicating that the NK cells were of NK1 type. More than 98% of NK cells from the patients bore CD94 at a higher level than did normal NK cells, whereas p70 or NKAT2, belonging to immunoglobulin-like receptor, was not expressed in those NK cells. Freshly isolated leukaemic NK cells transcribed mRNA for CD94-associated molecule NKG2C at an abnormally high level, and upon stimulation with IL-2 and/or IL-12 they expressed NKG2A as well. The disordered expression of these inhibitory receptors not only provides some insights into the pathogenesis of HMB-EBV-NK disease but also can be used as phenotypic markers for the diagnosis of this type of NK cell leukaemia.
Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)
Authors: Kadota Y , Okumura M , Miyoshi S , Kitagawa-Sakakida S , Inoue M , Shiono H , Maeda Y , Kinoshita T , Shirakura R , Matsuda H 
Published: March 2003

SUMMARYThymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4+ T cell development in thymoma and that IFN-γ-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-γ-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-γ in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3+ cells in the CD4+CD8− subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-γ. These results indicate that impaired up-regulation of HLA-DR in response to IFN-γ results from insufficient induction of CIITA, but not from the signal from IFN-γ receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4+ T cell development in thymoma.
Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and cysteine-rich domain (JD9) of the haemorrhagic metalloprotease, Jararhagin, inhibits the main lethal component of viper venom
Authors: Harrison R A , Moura-Da-Silva A M , Laing G D , Wu Y , Richards A , Broadhead A , Bianco A E , Theakston R D G 
Published: March 2003

SUMMARYEnvenoming by the Brazilian pit viper, Bothrops jararaca, induces extensive local and systemic haemorrhage in humans. The severe and occasionally lethal outcome of envenoming is prevented only by administration of antivenom which is conventionally prepared by hyperimmunization of large animals with an individual venom or a range of venoms. Since snake venoms typically consist of numerous molecules, only some of which are toxic, antivenoms are antigenically crude preparations whose therapeutic value would theoretically be enhanced by restricting antibody specificity to toxic venom molecules. We report here that high-titre IgG antibody from mice immunized by the GeneGun with DNA encoding the carboxy-terminal JD9 domain of Jararhagin, a haemorrhage-inducing metalloprotease in B. jararaca venom, extensively neutralized the main lethal component of B. jararaca venom. This is to our knowledge the first study to apply DNA-based methods to preparation of antivenom; it represents a novel approach with greater immunological specificity and fewer hazards than conventional systems of antivenom production.
Growth ofBrucella abortusin macrophages from resistant and susceptible mouse strains
Authors: Sathiyaseelan J , Jiang X , Baldwin C L 
Published: March 2003

SUMMARYC57Bl/10 mice have a superior ability to control chronic infections with virulent strains of the intracellular bacteria Brucella abortus compared with BALB/c mice. While a number of differences in the cytokines produced by lymphocytes following infection of these two strains of mice have been shown, macrophages have not been evaluated for their role in conveying relative resistance. The importance of macrophages in control of brucella infections is demonstrated by the observations that intracellular survival of various strains of B. abortus directly correlates with their virulence in vivo, and the ability of macrophages to control brucellae in vitro has been shown to correlate with a brucella-resistant phenotype in ruminants. While both BALB/c and C57Bl are Nramp-susceptible mouse strains, additional differences in macrophage function outside of the Nramp1 gene effects could influence susceptibility to brucellosis. The studies conducted here comparing the ability of macrophages from C57Bl/10 and BALB/c mice indicate that the macrophages from resistant mice did not control intracellular growth of B. abortus strain 2308 more efficiently than those from the susceptible mice, either in the absence of, or following, interferon-gamma activation or iron supplementation. A number of different conditions for culturing macrophages were evaluated to rule out the influence of antibiotics on the conclusions drawn from the results.
Cytomegalovirus infection in infants with autoimmune lymphoproliferative syndrome (ALPS)
Authors: Arkwright P D , Rieux-Laucat F , Le Deist F , Stevens R F , Angus B , Cant A J 
Published: March 2003

SUMMARYFas-mediated apoptosis may be one of the effector pathways leading to the elimination of virus-infected cells. Cytomegalovirus (CMV) infection in two brothers with Fas deficiency associated with autoimmunity and benign lymphoproliferation (ALPS) provided a unique opportunity to study the clinical course of CMV infection in children with defective apoptosis. The clinical courses of two brothers with autosomal dominant ALPS who were infected with CMV in the neonatal period are described. CMV was detected from throat and urine culture from the brothers. ALPS was confirmed by in vitro anti-CD95 MoAb-induced T lymphocyte apoptosis assay and subsequent sequencing and identification of mutations in the Fas gene. A de novo mutation in the Fas gene, leading to a truncated cytoplasmic Fas product, was associated with autosomal dominant ALPS in a mother and her two sons. Both boys had evidence of CMV infection acquired early in infancy which cleared by the age of 2–3 years. There were no neurodevelopmental sequelae. The natural history of CMV infection in two infants with ALPS was similar to that described in normal children.
Effects of IL-4 and IL-12 on experimental immune-mediated blepharoconjunctivitis in Brown Norway rats
Authors: Ozaki A , Fukushima A , Fukata K , Ueno H 
Published: March 2003

SUMMARYIL-12 and IL-4 are critical cytokines for Th1 and Th2 differentiation, respectively. To assess the roles of these cytokines in the development of experimental immune-mediated blepharoconjunctivitis (EC) in Brown Norway (BN) rats, their effects were tested either in vitro or in vivo. Draining lymph node cells from rats immunized with ragweed pollen (RW) in Al(OH)3 were collected and cultured for 3 days with RW in the presence of IL-4, IL-12, or PBS as a control. After harvesting the culture supernatants for cytokine ELISA and the cells for cytokine reverse transcriptase-polymerase chain reaction, 10 million cells were injected intravenously into syngeneic recipient rats (n = 12 per group). The rats were challenged with RW by eye drops 4 days after transfer. Eyes were harvested for histology 24 h later. Furthermore, IL-12 (500 ng per injection) or PBS was injected intraperitoneally every other day seven times from the day of active immunization (n = 6 per group). One day after the last injection, rats were challenged and EC was evaluated as above. Transfer of cells with IL-4 in vitro augmented eosinophilic infiltration in the conjunctiva compared with the other two groups, whereas IL-12 in vitro suppressed eosinophilic infiltration and increased lymphocytic infiltration. Interferon-gamma production was augmented by IL-12. IL-4 RNA expression was augmented by IL-4. IL-12 administration in vivo augmented lymphocytic infiltration in the conjunctiva without affecting infiltration of eosinophils. In conclusion, IL-4 and IL-12 either in vitro or in vivo augmented Th2 and Th1 immunity, respectively, thus leading to distinct histological features of EC.
A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Faslprcg/Faslprcgmice
Authors: Zhang Y , Yasuda T , Wang C R , Yoshimoto T , Nagase H , Takamoto M , Tsubura A , Kimura M , Matsuzawa A 
Published: March 2003

SUMMARYThe role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Faslprcg/Faslprcg (MRL-lprcg) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lprcg mice homozygous (CD4slprcg), heterozygous (CD4s/mlprcg), and wild-type (CD4mlprcg) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlprcg and CD4s/mlprcg mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4−CD8− (double-negative (DN)) T cells in CD4slprcg mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slprcg than CD4mlprcg mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.
Antibodies, directed towards Campylobacter jejuni antigens, in sera from poultry abattoir workers
Authors: Cawthraw S A , Lind L , Kaijser B , Newell D G 
Published: March 2003

SUMMARY
Occupational exposure of susceptible humans to Campylobacter jejuni appears to result in resistance to disease. This is believed to be due to acquired protective immunity. To support this hypothesis the levels of C. jejuni-specific IgG and IgM antibodies were determined in sera from poultry abattoir workers. Such individuals are persistently exposed to C. jejuni, but apparently rarely acquire campylobacteriosis. Sera from 43 short-term workers (employed ≤ 1 month), 78 long-term workers and 40 blood donors were investigated by ELISA. In 51 individuals a second serum sample, taken at least 1 month after the first, was also investigated. Eight workers had C. jejuni-positive faecal cultures and only one, a short-term worker, had symptoms of campylobacteriosis. There were significantly higher levels of specific IgG antibodies in long-term workers than in either of the other groups. There was no significant difference detectable in specific IgM antibody levels between any of the groups. The results provide supporting evidence that long-term exposure to C. jejuni induces circulating antibodies which reflect apparent reduced susceptibility to disease. Western blotting showed flagellin and polypeptides of 45, 40, 32 and 30 kD bound antibodies significantly more frequently by sera from long-term workers than short-term workers and blood donors. The most commonly detected antigens were the 40-kD (80%) and flagellin (55%). The results indicate that specific serum IgG responses induced by endemic exposure to C. jejuni might be directed towards a small number of protein antigens with apparently conserved epitopes.
HIV-1 Nef protein inhibits thein vitroinduction of a specific antibody response toCandida albicansby an early up-regulation of IL-15 production
Authors: Giordani L , Giacomini E , Quaranta M G , Viora M 
Published: March 2003

SUMMARYWe have previously demonstrated that exogenous Nef protein induced activation of normal human T cells up-regulating IL-15 production by monocytes. Since HIV-1 infection results in the early impairment of immune functions we decided to evaluate if Nef is able to modulate the induction of a specific antibody response. Human peripheral blood mononuclear cells from healthy donors were induced in vitro to mount a specific antibody response to the Candida albicans antigen. We show that Nef inhibited, in a dose-dependent manner, the induction of the anti-C. albicans antibody response. The ability of an anti-Nef antibody to prevent such inhibition indicates that the effect was indeed Nef-specific. In the Nef-treated cultures an early increase of IL-15 production was observed and the addition of anti-IL-15 antibody abrogated the Nef-induced inhibitory effect. Moreover the addition of IL-15 to the cultures inhibited, as well as Nef, the induction of the specific antibody response. Thus, our results suggest that Nef may inhibit the induction of a specific antibody response by an early up-regulation of IL-15 production. A better comprehension of this phenomenon may be important for unravelling some aspects of the B cell defects in HIV infection.
A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy
Authors: Tsuda H , Michimata T , Sakai M , Nagata K , Nakamura M , Saito S 
Published: March 2003

SUMMARYIt has been demonstrated that pregnancy induces the immunomodulation of cytokine responses away from the Th1 paradigm and towards the Th2 paradigm. In this study, we examined the expression of CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2) on decidual CD4+ and CD8+ T cells during the early stages of pregnancy. Examination of the cytokine profile revealed that CRTH2 was expressed on CD4+-type-2 T helper (Th2-type) and CD8+-type 2 T cytotoxic (Tc2-type) cells. The percentages of CRTH2+ cells in CD3+/CD4+ T cells and CD3+/CD8+ T cells were significantly higher in the decidua than in the peripheral blood. These results indicate the significance of Th2- and Tc2-type cells of the decidua in the maternal immune system, presumably through their production of cytokines which may contribute to the maintenance of pregnancy.
Treatment with ribavirin and interferon-αreduces interferon-γexpression in patients with chronic hepatitis C
Authors: Bergamini A , Bolacchi F , Cepparulo M , Demin F , Uccella I , Bongiovanni B , Ombres D , Angelico F , Liuti A , Hurtova M , Francioso S , Carvelli C , Cerasari G , Angelico M , Rocchi G 
Published: March 2003

SummaryRecent studies in vitro and in animals have suggested that ribavirin may potentiate the antihepatitis C virus (HCV) activity of interferon-α (IFN-α) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-γ, which play a key role in the cellular immune response against HCV. To study the immune-modulatory mechanisms of ribavirin further, cytokine production by activated T cells and circulating cytokine levels were studied by FACS analysis and ELISA testing in 25 patients with chronic hepatitis C unresponsive to IFN-α, before and after treatment with either ribavirin plus IFN-α or IFN-α alone. After 16 weeks of treatment, both the expression of IFN-γ by activated T cells and the blood levels of IFN-γ, were significantly reduced with respect to pretreatment values in patients treated with ribavirin and IFN-α but not in those undergoing treatment with IFN-α alone. The expression of IFN-γ was significantly lower in patients that gained normal ALT levels with respect to those that did not. No modification of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in either group of patients. In conclusion, the results of this study do not support up-modulation of IFN-γ and IL-2 production as the mechanism by which ribavirin potentiates IFN-α anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN-γ-driven T cell activation and liver damage.
Amphipathic variable region heavy chain peptides derived from monoclonal human Wegener's anti-PR3 antibodies stimulate lymphocytes from patients with Wegener's granulomatosis and microscopic polyangiitis
Authors: Peen E , Malone C , Myers C , Williams R C , Peck A B , Csernok E , Gross W L , Staud R 
Published: March 2003

SummaryAmphipathic variable-region heavy chain 11-mer peptides from monoclonal human IgM antiproteinase-3 antibodies were studied for peripheral blood lymphocyte stimulation in 21 patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), connective tissue disease controls and normal control subjects. Positive T-cell activation was observed in most experiments with WG patients' lymphocytes using amphipathic VH-region peptides from four different human monoclonal anti-PR3 antibodies. Control peptides of the same length but without amphipathic characteristics along with other amphipathic peptides not derived from monoclonal anti-PR3 sequence were employed as controls. No significant lymphocyte stimulation was observed with normal controls, but positive stimulation with amphipathic VH peptides was also recorded in other connective tissue disease controls mainly patients with rheumatoid arthritis. Amphipathic peptides not derived from anti-PR3 sequence did not stimulate WG lymphocytes. Our findings indicate that lymphocyte reactivity as an element of cell-mediated immunity may be activated by amphipathic VH-region amino acid sequences of autoantibodies which are themselves associated with diseases such as WG.