70 research outputs found
Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases
OBJECTIVE: To identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases. METHODS: Two distinct approaches (immunoprecipitation/mass spectrometry-based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples. RESULTS: Using the 2 methods as well as sera and CSF of patients with central and peripheral neurologic involvement, we identified Abs against the family of Argonaute proteins (mainly AGO1 and AGO2), which were already reported in systemic autoimmunity. AGO-Abs were mostly of immunoglobulin G 1 subclass and conformation dependent. Using CBA, AGO-Abs were detected in 21 patients with a high suspicion of autoimmune neurologic diseases (71.4% were women; median age 57 years) and only in 4/856 (0.5%) controls analyzed by CBA (1 diagnosed with small-cell lung cancer and the other 3 with Sjögren syndrome). Among the 21 neurologic patients identified, the main clinical presentations were sensory neuronopathy (8/21, 38.1%) and limbic encephalitis (6/21, 28.6%). Fourteen patients (66.7%) had autoimmune comorbidities and/or co-occurring Abs, whereas AGO-Abs were the only autoimmune biomarker for the remaining 7/21 (33.3%). Thirteen (61.9%) patients were treated with immunotherapy; 8/13 (61.5%) improved, and 3/13 (23.1%) remained stable, suggesting an efficacy of these treatments. CONCLUSIONS: AGO-Abs might be potential biomarkers of autoimmunity in patients with central and peripheral nonparaneoplastic neurologic diseases. In 7 patients, AGO-Abs were the only biomarkers; thus, their identification may be useful to suspect the autoimmune character of the neurologic disorder. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that AGO-Abs are more frequent in patients with autoimmune neurologic diseases than controls
Emulsion sheet doublets as interface trackers for the OPERA experiment
New methods for efficient and unambiguous interconnection between electronic
counters and target units based on nuclear photographic emulsion films have
been developed. The application to the OPERA experiment, that aims at detecting
oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is
reported in this paper. In order to reduce background due to latent tracks
collected before installation in the detector, on-site large-scale treatments
of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd)
packages, each made of a doublet of emulsion films, have been designed,
assembled and coupled to the OPERA target units ("ECC bricks"). A device has
been built to print X-ray spots for accurate interconnection both within the
CSd and between the CSd and the related ECC brick. Sample emulsion films have
been extensively scanned with state-of-the-art automated optical microscopes.
Efficient track-matching and powerful background rejection have been achieved
in tests with electronically tagged penetrating muons. Further improvement of
in-doublet film alignment was obtained by matching the pattern of low-energy
electron tracks. The commissioning of the overall OPERA alignment procedure is
in progress.Comment: 19 pages, 19 figure
Novel event classification based on spectral analysis of scintillation waveforms in Double Chooz
Liquid scintillators are a common choice for neutrino physics experiments, but their capabilities to perform background rejection by scintillation pulse shape discrimination is generally limited in large detectors. This paper describes a novel approach for a pulse shape based event classification developed in the context of the Double Chooz reactor antineutrino experiment. Unlike previous implementations, this method uses the Fourier power spectra of the scintillation pulse shapes to obtain event-wise information. A classification variable built from spectral information was able to achieve an unprecedented performance, despite the lack of optimization at the detector design level. Several examples of event classification are provided, ranging from differentiation between the detector volumes and an efficient rejection of instrumental light noise, to some sensitivity to the particle type, such as stopping muons, ortho-positronium formation, alpha particles as well as electrons and positrons. In combination with other techniques the method is expected to allow for a versatile and more efficient background rejection in the future, especially if detector optimization is taken into account at the design level
Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association
The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes
Study of the effects induced by lead on the emulsion films of the OPERA experiment
The OPERA neutrino oscillation experiment is based on the use of the Emulsion
Cloud Chamber (ECC). In the OPERA ECC, nuclear emulsion films acting as very
high precision tracking detectors are interleaved with lead plates providing a
massive target for neutrino interactions. We report on studies related to the
effects occurring from the contact between emulsion and lead. A low
radioactivity lead is required in order to minimize the number of background
tracks in emulsions and to achieve the required performance in the
reconstruction of neutrino events. It was observed that adding other chemical
elements to the lead, in order to improve the mechanical properties, may
significantly increase the level of radioactivity on the emulsions. A detailed
study was made in order to choose a lead alloy with good mechanical properties
and an appropriate packing technique so as to have a low enough effective
radioactivity.Comment: 19 pages, 11 figure
Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study.
PURPOSE: A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS: Forty-seven patients who were from 6 months to 16 years of age, with either relapsed (29) or primary resistant (18) NB, were included in a cooperative multicenter phase II study of the French Society of Pediatric Oncology (SFOP). The schedule consisted of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS: The response rate for the 39 assessable patients was 43%; there were four complete remissions and 13 partial remissions. Neither the status of the patients nor the total dose of CDDP that was received previously influenced response. Hematologic toxicity was marked and caused considerable delay between courses (median interval, 39 days). In these heavily pretreated patients, 16% had a more than 50% decrease in creatinine clearance and a 22% World Health Organization (WHO) grade 2 ototoxicity. CONCLUSION: This VP 16/CBDCA combination deserves further evaluation for efficacy and toxicity in newly diagnosed patients, and the combination of both drugs should be considered for high-dose therapy with bone marrow transplantation.Clinical TrialClinical Trial, Phase IIJournal ArticleMulticenter Studyinfo:eu-repo/semantics/publishe
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