: Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. ...The response of neurological symptoms and antibody titers to a gluten‐free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten‐free diet.Thirty‐five CD patients (9 males, 26 females, mean age 37.1 ± 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten‐free diet, 12 were not. At recruitment and during follow‐up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti‐ganglioside antibodies were assayed by ELISA; anti‐neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten‐free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti‐ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow‐up (mean duration of follow‐up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow‐up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.
This article describes a custom VHDL firmware implementation of a two-dimensional cluster-finder architecture for reconstructing hit positions in the new vertex pixel detector (VELO) that is part of ...the LHCb Upgrade. This firmware has been deployed to the existing FPGA cards that perform the readout of the VELO, as a further enhancement of the DAQ system, and will run in real time during physics data taking, reconstructing VELO hits coordinates on-the-fly at the LHC collision rate. This pre-processing allows the first level of the software trigger to accept an 11% higher rate of events, as the ready-made hit coordinates accelerate the track reconstruction and consumes significantly less electrical power. It additionally allows the raw pixel data to be dropped at the readout level, thus saving approximately 14% of the DAQ bandwidth. Detailed simulation studies have shown that the use of this real-time cluster finding does not introduce any appreciable degradation in the tracking performance in comparison to a full-fledged software implementation. This work is part of a wider effort aimed at boosting the real-time processing capability of HEP experiments by delegating intensive tasks to dedicated computing accelerators deployed at the earliest stages of the data acquisition chain.
Coeliac disease is an autoimmune enteropathy characterized by an enhanced permeability of the intestinal epithelial barrier. In epithelial cells paracellular permeability is regulated by ...intercellular tight junction. The cytoplasmic protein ZO-1 interacts directly with F-actin and plays a pivotal role in the structural and functional organization of tight junction.
Aim. The aim of this study was to investigate the expression and localization of ZO-1 in the intestinal mucosa of coeliac patients.
Patients and methods. Twenty patients with active coeliac disease, seven of whom underwent a repeat biopsy following a gluten-free diet and 27 control subjects, were studied. In all subjects, three biopsies were obtained from distal duodenum during upper gastrointestinal endoscopy. ZO-1 protein localization and levels were detected by immunofluorescence followed by confocal microscopy analysis and immunoblotting. ZO-1 mRNA expression was assessed by RT-PCR. F-actin distribution was also investigated.
Results. In patients with active coeliac disease, both ZO-1 protein levels and mRNA were clearly reduced. Cytoskeletal organization was disrupted with F-actin staining concentrated at the subcortical and basal surface regions. Abnormalities in ZO-1 expression and actin organization were reversed after a gluten-free diet.
Conclusions. In active coeliac disease, ZO-1 protein expression is downregulated at the transcriptional level in association with F-actin redistribution. These changes are completely reversed after a gluten-free diet and could contribute to the increased intestinal paracellular permeability observed in this disorder.
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