Anti-phospholipid-antibodies in patients with relapsing polychondritis

Relapsing polychondritis (RP) is an extremly rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM-and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG-and IgM-isotypes) and anti-β-2-glycoprotein I-antibodies (aβ2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated aβ2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP

Ba3Ga3N5 - A Novel Host Lattice for Eu2+ - Doped Luminescent Materials with Unexpected Nitridogallate Substructure

The alkaline earth nitridogallate Ba3Ga3N5 was synthesized from the elements in a sodium flux at 760°C utilizing weld shut tantalum ampules. The crystal structure was solved and refined on the basis of single-crystal X-ray diffraction data. Ba3Ga3N5 (space group C2/c (No. 15), a = 16.801(3), b = 8.3301(2), c = 11.623(2) Å, β = 109.92 (3)°, Z = 8) contains a hitherto unknown structural motif in nitridogallates, namely, infinite strands made up of GaN4 tetrahedra, each sharing two edges and at least one corner with neighboring GaN4 units. There are three Ba2+ sites with coordination numbers six or eight, respectively, and one Ba2+ position exhibiting a low coordination number 4 corresponding to a distorted tetrahedron. Eu2+ - doped samples show red luminescence when excited by UV irradiation at room temperature. Luminescence investigations revealed a maximum emission intensity at 638 nm (FWHM =2123 cm−1). Ba3Ga3N5 is the first nitridogallate for which parity allowed broadband emission due to Eu2+ - doping has been found. The electronic structure of both Ba3Ga3N5 as well as isoelectronic but not isostructural Sr3Ga3N5 was investigated by DFT methods. The calculations revealed a band gap of 1.53 eV for Sr3Ga3N5 and 1.46 eV for Ba3Ga3N5

CD95/CD95L interactions and their role in autoimmunity

CD95 (Fas/Apo-1) is a broadly expressed death receptor involved in a variety of physiological and pathological apoptotic processes. Since its discovery, defects in CD95/CD95L system have been proposed as major pathogenic factors responsible for impaired immunological tolerance to self antigens and autoimmunity. Later, analysis of altered sensitivity to CD95-induced apoptosis in cells targeted by the immune response has revealed an unexpected role for CD95 and CD95L in organ-specific autoimmunity. CD95 has been shown to be expressed and functional in virtually all cell types that are target of the organ-specific autoimmune response. Here we review some of the major findings concerning the role of CD95 in autoimmunity, in dysfunctions due to increased or decreased CD95-induced apoptosis

Death in 2000 ways

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Prevention of Chemotherapy-Induced Anemia and Thrombocytopenia by Constant Administration of Stem Cell Factor

Purpose: Chemotherapy-induced apoptosis of immature hematopoietic cells is a major cause of anemia and thrombocytopenia in cancer patients. Although hematopoietic growth factors such as erythropoietin and colony-stimulating factors cannot prevent the occurrence of drug-induced myelosuppression, stem cell factor (SCF) has been previously shown to protect immature erythroid and megakaryocytic cells in vitro from drug-induced apoptosis. However, the effect of SCF in vivo as a single myeloprotective agent has never been elucidated. Experimental Design: The ability of SCF to prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia was tested in a mouse model of cisplatin-induced myelosuppression. To highlight the importance of maintaining a continuous antiapoptotic signal in immature hematopoietic cells, we compared two treatment schedules: in the first schedule, SCF administration was interrupted during chemotherapy treatment and resumed thereafter, whereas in the second schedule, SCF was administered without interruption for 7 days, including the day of chemotherapy treatment. Results: The administration of SCF to cisplatin-treated mice could preserve bone marrow integrity, inhibit apoptosis of erythroid and megakaryocytic precursors, prevent chemotherapy-induced anemia, and rapidly restore normal platelet production. Treatment with SCF increased the frequency of Bcl-2/Bcl-XL\u2013 positive bone marrow erythroid cells and sustained Akt activation in megakaryocytes. Myeloprotection was observed only when SCF was administered concomitantly with cisplatin and kept constantly present during the days following chemotherapy treatment. Conclusions: SCF treatment can prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia in mice, indicating a potential use of this cytokine in the supportive therapy of cancer patients

Repeated exposure to subinfectious doses of sars-cov-2 may promote t cell immunity and protection against severe covid-19

Europe is experiencing a third wave of COVID-19 due to the spread of highly transmissible SARS-CoV-2 variants. A number of positive and negative factors constantly shape the rates of COVID-19 infections, hospitalization, and mortality. Among these factors, the rise in increasingly transmissible variants on one side and the effect of vaccinations on the other side create a picture deeply different from that of the first pandemic wave. Starting from the observation that in several European countries the number of COVID-19 infections in the second and third pandemic wave increased without a proportional rise in disease severity and mortality, we hypothesize the existence of an additional factor influencing SARS-CoV-2 dynamics. This factor consists of an immune defence against severe COVID-19, provided by SARS-CoV-2-specific T cells progressively developing upon natural exposure to low virus doses present in populated environments. As suggested by recent studies, low-dose viral particles entering the respiratory and intestinal tracts may be able to induce T cell memory in the absence of inflammation, potentially resulting in different degrees of immunization. In this scenario, non-pharmaceutical interventions would play a double role, one in the short term by reducing the detrimental spreading of SARS-CoV-2 particles, and one in the long term by allowing the development of a widespread (although heterogeneous and uncontrollable) form of immune protection

Non-perturbative electron dynamics in crossed fields

Intense AC electric fields on semiconductor structures have been studied in photon-assisted tunneling experiments with magnetic field applied either parallel (B_par) or perpendicular (B_per) to the interfaces. We examine here the electron dynamics in a double quantum well when intense AC electric fields F, and tilted magnetic fields are applied simultaneously. The problem is treated non-perturbatively by a time-dependent Hamiltonian in the effective mass approximation, and using a Floquet-Fourier formalism. For B_par=0, the quasi-energy spectra show two types of crossings: those related to different Landau levels, and those associated to dynamic localization (DL), where the electron is confined to one of the wells, despite the non-negligible tunneling between wells. B_par couples parallel and in-plane motions producing anti-crossings in the spectrum. However, since our approach is non-perturbative, we are able to explore the entire frequency range. For high frequencies, we reproduce the well known results of perfect DL given by zeroes of a Bessel function. We find also that the system exhibits DL at the same values of the field F, even as B_par non-zero, suggesting a hidden dynamical symmetry in the system which we identify with different parity operations. The return times for the electron at various values of field exhibit interesting and complex behavior which is also studied in detail. We find that smaller frequencies shifts the DL points to lower field F, and more importantly, yields poorer localization by the field. We analyze the explicit time evolution of the system, monitoring the elapsed time to return to a given well for each Landau level, and find non-monotonic behavior for decreasing frequencies.Comment: REVTEX4 + 11 eps figs, submitted to Phys. Rev.

Associative Stimulation of the Supraorbital Nerve Fails to Induce Timing-Specific Plasticity in the Human Blink Reflex

BACKGROUND: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006). METHODOLOGY/PRINCIPAL FINDINGS: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment. CONCLUSION/SIGNIFICANCE: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex

Intact Organization of Tactile Space Perception in Isolated Focal Dystonia

Background: Systematic perceptual distortions of tactile space have been documented in healthy adults. In isolated focal dystonia impaired spatial somatosensory processing is suggested to be a central pathophysiological finding, but the structure of tactile space for different body parts has not been previously explored. Objectives: The objective of this study was to assess tactile space organization with a novel behavioral paradigm of tactile distance perception in patients with isolated focal dystonia and controls. Methods: Three groups of isolated focal dystonia patients (cervical dystonia, blepharospasm/Meige syndrome, focal hand dystonia) and controls estimated perceived distances between 2 touches across 8 orientations on the back of both hands and the forehead. Results: Stimulus size judgments differed significantly across orientations in all groups replicating distortions of tactile space known for healthy individuals. There were no differences between groups in the behavioral parameters we assessed on the hands and forehead. Conclusions: Tactile space organization is comparable between patients with isolated focal dystonia and healthy controls in dystonic and unaffected body parts

Chemotherapy resistance of glioblastoma stem cells [2]

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