Search results for "ALPHA"
showing 10 items of 3228 documents
Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease.
2019
Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. We conducted a phase 1 clinical trial with moss-aGal in six patients with confirmed diagnosis of Fabry disease during a 28-day schedule. All patients received a single dose of 0.2 mg/kg moss-aGal by i.v.-infusion. Primary endpoints of the trial were safety and pharmaco…
Functional profile of cytomegalovirus (CMV)-specific CD8+ T cells and kinetics of NKG2C+ NK Cells associated with the resolution of CMV DNAemia in al…
2011
Immune mechanisms involved in control of cytomegalovirus (CMV) infection in the allogeneic stem cell transplantation setting have not been fully disclosed. CMV pp65 and IE-1-specific CD8(+) T cells expressing IFN-γ, TNF-α, and CD107a, alone or in combination, and NKG2C(+) NK cells were prospectively enumerated during 13 episodes of CMV DNAemia. The expansion of monofunctional and polyfunctional CD8(+) T cells was associated with CMV DNAemia clearance. The size and functional diversity of the expanding CD8(+) T-cell population was greater in self-resolved episodes than in episodes treated with antivirals. These differences were related to the magnitude of expansion of cognate antigen IFN-γ C…
Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection
2005
Background/Aims Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. Methods Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNγ and TNFα production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. Results Intrahepatic CD8+T cells of HCV-infected patients…
Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients.
2012
Polymorphisms of genes encoding key factors for the control and activation of inflammatory response and coagulation cascade regulation may play a role in genetic susceptibility to acute myocardial infarction (AMI). This study sought to analyze the effect of TNF - 308G/A and pro-thrombin (FII) 20210G/A polymorphisms on the laboratory parameters of young patients affected by AMI. Results indicated that TNF - 308A positive genotype frequencies were increased in these patients and that a genetically determined higher production of TNF-alpha is associated in young subjects to a more severe cardiac damage as depicted by higher levels of troponin, Creatine kinase-MB Isoenzyme (mCK-MB) and a signif…
Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4
2008
We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antia…
De novo mutation in a male patient with Fabry disease: a case report
2014
Abstract Background Fabry disease is an X-linked inherited metabolic condition where the deficit of the α-galactosidase A enzyme, encoded by the GLA gene, leads to glycosphingolipid storage, mainly globotriaosylceramide. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD, including missense and nonsense mutations, small and large deletions. Such mutations are usually inherited, and cases of de novo onset occur rarely. Case presentation In this article we report an interesting case of a 44-year-old male patient suffering from a severe form of Fabry disease, with negative family history. The patient showed signs such as cornea verticillata, ang…
Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
2021
As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute…
Validation of the Italian version of the Burn Specific Health Scale-Brief
2014
Introduction A growing awareness of psychological and functional impairment due to burns have led to the development of specific instruments to evaluate Quality of Life in this population, such as the Burn Specific Health Scale - Brief (BSHS-B), whose psychometric properties have been consistently verified. The aim of this study was to translate the BSHS-B into Italian and to investigate its reliability and validity. Methods Translation procedures were carried out according to accepted standards. Internal reliability was assessed using Cronbach's alpha coefficient. Concurrent validity was evaluated through correlations between the BSHS-B and the Short-Form 36 Health Survey (SF-36), the Self…
Empathy in nurses: Spanish adaptation of the Jefferson scale of empathy (JSE) on nurses.
2020
Background: Empathy is a key skill for nurses for providing high-quality care. Aims: To adapt and explore the psychometric properties of the Jefferson Scale of Empathy (JSE) for nursing students in a sample of Spanish nurses, to analyse the empathy levels and to provide some percentiles for interpreting empathy levels. Methods: Factor structure was evaluated with exploratory and confirmatory factor analysis (EFA, CFA), and reliability was evaluated with Cronbach's alpha, composite reliability (CR), and average variance extracted (AVE) in a convenience sample of 500 Spanish nurses. Results: The definitive model composed of 15 items grouped into three factors presented good psychometric prope…
Reliability and Validity of a Further Tested Appreciative Management Scale
2020
Background and PurposeManagers need evidence-based methods to evaluate their management skills. To further test the appreciative management scale (AMS 1.0) to create a practical instrument to be used in evaluating appreciative management.MethodsFor further testing, a new survey was conducted among social and healthcare managers (n = 734) in Finland. Confirmatory factor analysis (CFA) was used to assess the scale validity and Cronbach's alpha coefficients the internal consistency.ResultsThe validated AMS 2.0 scale includes 24 items. The values measuring validity and reliability were good, with an Rool Mean Square Error of Approximation (RMSEA) of 0.072, Average Variance Extracted (AVE) value…