1,720,963 research outputs found
CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule and marker of a regulatory subpopulation of dendritic cells, is involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis
No full textObjectives: The immunological effect of CD30 on dendritic cells ( DCs) was examined in a comparative study of patients with relapsing- remitting multiple sclerosis ( RRMS). The patients were divided into two groups on the basis of interferon ( IFN)beta-1a treatment: IFN beta-1a-treated patients and untreated patients. We have already shown that CD30 is a marker of cells involved in the regulation of the balance between TH1 and TH2 immune responses and so the aim of this study was to confirm this role in DCs and, consequently, to clarify the immunopathological mechanisms of MS and the causes of immunosuppressive drug failure. Methods: We studied network interactions between soluble ( s) CD30 and TH1/ TH2 cytokines in the supernatants of CD14+- derived immature DC ( IDC) and DC cultures from treated and untreated patients. Network interactions between the sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to TH1/ TH2 cytokine serum levels. Results: Our overall results show that CD30 is expressed on IDCs and DCs, indicating an immunological role in resting and activated physiological conditions. This role would appear to be the regulation of the resting and activated physiological balance between the TH1/ TH2 immune functions as abnormal increases in sCD30 levels result in impaired regulation. Further studies are undoubtedly required to clarify this situation. IFN beta-1a treatment was found to determine a fall in sCD30 levels, leading to the restoration of the normal functional selection of IDCs from progenitor cells and the regulation of the TH1/ TH2 network balance. However, IFN beta- 1a treatment may also be responsible for the in vivo suppression of CD30- mediated TH1- DC functions in immune activation. TH1- DC functions are involved in the induction of T- regulatory cells for the physiological deletion of self-aggressive cells. Conclusion: We conclude that CD30 is an important costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells involved in the maintenance of the physiological balance between TH1/ TH2 immune responses and tolerance. Elucidating the mechanisms restoring DC and T- regulatory cell function could lead to more effective therapy and strategies for the prevention and treatment of immunopathological conditions such as autoimmunity, transplant rejection, allergy and tumors. Copyright (C) 2005 S. Karger AG, Basel
Immunological study of IFNß-1a treated and untreated multiple sclerosis patients: clarifying IFNB mechanisms and establishing specific dendritic cell immunotherapy
No full textObjectives: A comparative immunological evaluation of multiple sclerosis ( MS) patients receiving IFNbeta treatment and patients who are not receiving treatment may help clarify IFNbeta neurological mechanisms and lead the way to an effective dendritic cell ( DC) immunotherapy. This type of study helps clarify the pathological function of T cells and DCs within the TH1/TH2/TH3 network as well as the specific interactions between TH1/TH2/TH3 cytokines implicated in MS pathological mechanisms and determine the best way of reestablishing the TH1/TH2/TH3 network equilibrium. Methods: We studied network interactions between TH1/TH2/TH3 cytokine levels in serum and supernatants of whole blood and CD14+ monocyte-derived DCs in the remission phase of the disease and in correlation to the Expanded Disability Status Scale (EDSS). Results: We found that TH1 dysregulation results in a disruption of the maturation and activation of dendritic and T cells, and a lack of T-regulating cells for the induction of self-tolerance; IFNbeta mechanisms restore regulation by reestablishing the network balance but fail to resolve the disease completely due to in vivo IL12p70 network interactions leading to the deletion of self-aggressive cells. Conclusions: Our results indicate that a specific DC immunotherapy could cure rather than treat MS. The best point to reestablish the normal physiological cycle is at the immature DC stage which can be done in vitro with treated peripheral blood CD14+ cells and used in vivo to stimulate the expansion of specific regulatory T cells. Copyright (C) 2005 S. Karger AG, Basel
P53 and H-RAS genomic analysis in oral squamous cell carcinoma
No full textWe examined p53 gene that has been detected in many gastrointestinal
tract neoplasms, in lO oral cancer patients.
The study consisted of a primer-mediated enzymatic
amplification (PCR) of two fragments (lll-319pb) included
in the exon5-intron5-exon6 region, and of a successive
digestion by two restriction enzymes, HhaI and Hae
III. No p53 alteration was evident in any of the samples
We also examined k-ras point mutations in codonl2. We
agree with other authors who point out there is no evidence
far alterations in the araI cavity, but these are
often found in malignancies of the lower digestive tract.
The absence of p53 gene modifications in oral squamous
carcinomas suggests that other codon mutation or other genetic events are implicated in etiopathogenesi
A gender-related action of IFNbeta-therapy was found in multiple sclerosis
No full textBackground: Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in
the regulation of T-helper (Th) cell network homeostasis.
Methods: We focused on sexually dimorphic changes in the immune response in multiple sclerosis (MS) patients in order to ascertain how these alterations relate to the pathway regulation of the cytokine homeostasis and the Th cell networks. We studied antigen presenting cell (APC)-dependent T cell activation in groups of healthy subjects, in patients under interferon (IFN) β-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded disability status scale (EDSS) were used as biomarkers for T cell differentiation and neurological deficit.
Results: The data confirm our belief that sexual dimorphism in autoimmune diseases is the result of differing pathways that regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and IFNγ pathways in men. Given the increased susceptibility of women to MS and the significance of IL6 in the autoimmune process compared to IFNγ, it is logical to assume that IL6 pathways are in some way implicated in the prevalence of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are also involved in T regulatory (Treg) cell imbalance and an increase in neurological deficit in both men and women groups of MS patients, underlining the autoimmune etiology of multiple sclerosis. In further support of differing cytokine pathways in men and women, we noted that the efficacy of IFNβ-treatment in the re-establishment of Th-network balance and in the delaying of the neurological disability progression is linked to the IL6 pathway in women, but to the IFNγ
pathway in men. Lastly, we also identified specific gender biomarkers for the use in therapy.
Conclusions: The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment
Oncogeni e metastasi linfonodali in tumori primitivi del cavo orale
No full textSulla base di precedenti ricerche di biologia molecolare eseguite su alcuni oncogeni (p53, Ha e Ki-ras, cErb) mediante estrazione di DNA gnomico da tessuto neoplastico di carcinomi del distretto oro-maxillo-facciale, gli AA hanno intrapreso uno studio degli stessi oncogeni su DNA estratto da tessuto linfonodale metastatico di forme primitive del cavo orale. Gli AA sottolineano come per questa indagine, a differenza di quelle precedenti, si siano dovute affrontare notevoli problematiche di ordine operativo, cui peraltro è verosimilmente da attribuire la estrema povertà di specifiche segnalazioni in letteratura. Le difficoltà sono legate essenzialmente al pattern istopatologico della metastasi linfonodale che rende in taluni casi indaginoso l’allestimento di speciments validi ai fini dello studio. Ciò ha comportato la ricerca di un percorso metodologico peculiare. Vengono riportati e discussi i primi dati ricavati dall’analisi genetica del tessuto linfonodale metastatico. Gli AA ritengono che tale ricerca possa, con i necessari approfondimenti, rappresentare il presupposto per un eventuale più mirato approccio al trattamento delle metastasi linfonodali
Soluble CD30: a biomarker for evaluating the clinical risk versus benefit of IFNß1A treatment in multiple sclerosis
No full textAberrant redox regulation occurs in immune and neurological pathologies, hence targeting the pathways involved in the regulation of the redox system could provide further insights into these diseases and open up new avenues for therapy. Soluble (s) CD30 is of key clinical importance in this respect, as its levels reflect the functionality of the CD30 receptor (CD30R), the specific lymphocyte receptor for thiol disulfide/oxidoreductase thioredoxin 1 (Trx1) which is known to regulate important immune and neurological processes. Increased levels of sCD30 appear to be a common element of oxidative stress, immunological alterations and neurological deficit, therefore these increases could be used as a clinical biomarker and target for therapy. We targeted sCD30 in our study of dendritic cell (DC) regulation of the T helper (Th) cell network in multiple sclerosis (MS) patients, as abnormalities in T regulatory (Treg)/Th1/Th17 pathways contribute to the pathogenesis of this immunological/neurological disease. DC profiles in Treg/Th1/Th2/Th17-types of cytokine production in culture supernatants were used as they determine the type of Th differentiation. Our results show that sCD30 levels increase significantly in MS patients, reflecting the disruption in the regulation of the Treg/Th1/Th17 cell network. A fall in the level of soluble CD30, induced by IFNbeta1a therapy, opposed the increase of neurological deficit through increasing IL10 and TGFbeta levels, thus re-establishing network homeostasis but only when this was accompanied by an increase in IL12p70 levels. Since IL12p70 cytokine production is regulated by Trx1, our results indicate that redox system alterations may be the cause of IFNbeta1a therapeutic inefficacy. We conclude that an increase in the level of IL10, TGFbeta and IL12p70 and a fall in the level of sCD30 represent a means of evaluating the clinical risk/benefit of IFNbeta1a treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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