In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events.
View Article and Find Full Text PDFFlexible filamentous beds interacting with a turbulent flow represent a fundamental setting for many environmental phenomena, e.g., aquatic canopies in marine current.
View Article and Find Full Text PDFThe spreading of the virus-containing droplets exhaled during respiratory events, e.g., cough, is an issue of paramount importance for the prevention of many infections such as COVID-19.
View Article and Find Full Text PDFThe backreaction of dispersed rigid fibers to turbulence is analyzed by means of a state-of-the-art fully coupled immersed boundary method. The following universal scenario is identified: turbulence at large scales looses a consistent part of its kinetic energy (via a Darcy friction term), which partially reappears at small scales where a new range of energy-containing scales does emerge. Large-scale mixing is thus depleted in favor of a new mixing mechanism arising at the smallest scales.
View Article and Find Full Text PDFThis study used 2DE to investigate how Arabidopsis thaliana modulates protein levels in response to freezing stress after sub-lethal exposure at -10°C, both in cold-acclimated and in non-acclimated plants. A map was implemented in which 62 spots, corresponding to 44 proteins, were identified. Twenty-two spots were modulated upon treatments, and the corresponding proteins proved to be related to photosynthesis, energy metabolism, and stress response.
View Article and Find Full Text PDFParkinson's disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson's disease patients.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) a fatal degenerative disease that selectively affects motor neurons, likely results from a complex interplay among oxidative injury, excitotoxic stimulation, protein aggregation and genetic factors. Ceruloplasmin (Cp) protein is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form, protecting the central nervous system (CNS) from iron deposition. Cp is thus considered as one of the main systems dedicated to the protection of the CNS from oxidative stress damage.
View Article and Find Full Text PDFVAF347 is a low-molecular-weight compound, which activates the aryl hydrocarbon receptor (AhR). Herein, we report that oral administration of a water-soluble derivative of VAF347 (VAG539) promotes long-term graft acceptance and active tolerance in Balb/c mice that receive a transplant of MHC-mismatched pancreatic islet allografts. In vivo VAG539 treatment results in increased frequency of splenic CD4(+) T cells expressing CD25 and Foxp3, markers associated with regulatory T (Tr) cells, and in vitro VAF347 treatment of splenic CD4(+) T cells improved CD4(+)CD25(+)Foxp3(+) T-cell survival.
View Article and Find Full Text PDFEarly impairment of islet function and graft loss strongly limit the success of allogenic islet transplantation in insulin-dependent diabetes. Macrophages play a key role in this process thus the depletion of these cells may strongly affect islet survival. In this study, we have evaluated the effect of the depletion of macrophages in mouse allograft rejection using a new approach based on a single infusion of red blood cells loaded with the synthetic analogue of pyrophosphate clodronate.
View Article and Find Full Text PDFSera from colon carcinoma patients were used to identify tumor-associated antigens (TAAs) by screening tumor proteome resolved by 2D electrophoresis. A panel of six TAAs eliciting a serological immune response in colorectal cancer was identified, showing a modification in antigen recognition by B cells in patients as a function of colon cancer progression. The expression of these proteins was either confined or increased in tumor as compared to normal mucosa.
View Article and Find Full Text PDFMitochondrial ferritin (FtMt) is a novel ferritin type specifically targeted to mitochondria. It is highly expressed in the human testis and in sideroblasts from patients with sideroblastic anemia, but other organs have not been studied. To study its expression in the main organs of the mouse, we first used RT-PCR and then produced recombinant mouse FtMt and specific antibodies.
View Article and Find Full Text PDFThe immunoregulatory function of NKT cells is crucial for prevention of autoimmunity. The prototypical NKT cell Ag alpha-galactosylceramide is not present in mammalian cells, and little is known about the mechanism responsible for NKT cell recruitment and activation. Up-regulation of CD1d, the NKT cell restriction molecule, expressed on mononuclear cells infiltrating the target organ, could represent the physiological trigger for NKT cells to self-contain T cell immunity and to prevent autoimmune disease.
View Article and Find Full Text PDFRecent experimental evidence shows that vaccination with amyloid-beta peptide (Abeta) of transgenic mouse models of Alzheimer's disease protects from the pathological accumulation of amyloid within the CNS. Phase I/II clinical trials of Abeta vaccination in mild to moderate Alzheimer's disease have been undertaken. Un expectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation.
View Article and Find Full Text PDF