Search results for "Major"
showing 10 items of 1120 documents
Bioinformatic methods for cancer neoantigen prediction
2019
Tumor cells accumulate aberrations not present in normal cells, leading to presentation of neoantigens on MHC molecules on their surface. These non-self neoantigens distinguish tumor cells from normal cells to the immune system and are thus targets for cancer immunotherapy. The rapid development of molecular profiling platforms, such as next-generation sequencing, has enabled the generation of large datasets characterizing tumor cells. The simultaneous development of algorithms has enabled rapid and accurate processing of these data. Bioinformatic software tools encoding the algorithms can be strung together in a workflow to identify neoantigens. Here, with a focus on high-throughput sequen…
Current advances in γδ T cell-based tumor immunotherapy
2017
γδ T cells are a minor population (~5%) of CD3 T cells in the peripheral blood, but abound in other anatomic sites such as the intestine or the skin. There are two major subsets of γδ T cells: those that express Vd1 gene, paired with different Vγ elements, abound in the intestine and the skin, and recognize the major histocompatibility complex (MHC) class I-related molecules such as MHC class I-related molecule A, MHC class I-related molecule B, and UL16-binding protein expressed on many stressed and tumor cells. Conversely, γδ T cells expressing the Vδ2 gene paired with the Vγ9 chain are the predominant (50-90%) γδ T cell population in the peripheral blood and recognize phosphoant…
Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells.
2017
ABSTRACT The B16F10 murine melanoma cell line displays a low expression of MHC class I molecules favoring immune evasion and metastases in immunocompetent C57 BL/6 wild-type mice. Here, we generated metastases to the liver, an organ that is skewed towards immune tolerance, by intrasplenic injection of B16F10 cells in syngeneic C57 BL/6 compared to allogeneic Balb/c mice. Surprisingly, Balb/c mice, which usually display a pronounced M2 macrophage and Th2 T cell polarization, were ∼3 times more susceptible to metastasis than C57 BL/6 mice, despite a much higher M1 and Th1 T cell immune response. The anti-metastatic advantage of C57 BL/6 mice could be attributed to a more potent NK-cell mediat…
Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis
2020
Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette–Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfecti…
Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.
2015
Antibiotic-associated diarrhea is an important clinical problem, associated with morbidity, mortality and healthcare costs. Our randomized, placebo controlled multicenter trial do not support the efficacy of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea.
Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort
2020
Abstract Background Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. Methods The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. Results Among 1336 definite cases of streptococcal IE, 823 were ca…
Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data from the PRESTIGIO Registry
2020
AbstractBackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Co…
Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors.
2021
Genetic deletion of cannabinoid CB1 receptors or diacylglycerol lipase alpha (DAGLa), the main enzyme involved in the synthesis of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG), produced profound phenotypes in animal models of depression-related behaviors. Furthermore, clinical studies have shown that antagonists of CB1 can increase the incidence and severity of major depressive episodes. However, the underlying pathomechanisms are largely unknown. In this study, we have focused on the possible involvement of astrocytes. Using the highly sensitive RNAscope technology, we show for the first time that a subpopulation of astrocytes in the adult mouse brain expresses Dagla, albeit at …
Aplasia of the lacrimal and major salivary glands (ALSG). First case report in spanish population and review of the literature
2018
Aplasia of the lacrimal and the major salivary glands (ALSG) is a rare disorder with scarce cases described in the recent literature. The pattern of genetic inheritance is autosomal dominant with variable expressivity. A 40 years male patient was referred to the Oral and Maxillofacial Service at the Hospital Universitario de A Coruna diagnosed with complete agenesis of all salivary glands. Our case it is the first of ALSG syndrome in the Spanish literature. Imaging tests are necessary to confirm the lack of formation of salivary glands and alteration of lacrimal system. A mutation of FGF10 has been proposed as the responsible of the syndrome. The management of the lacrimal alteration depend…
The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and a…
2021
The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VAL…