834 research outputs found
Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.
CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy
Structural properties in Sr0.61a0.39Nb2O6 in the temperature range 10 K to 500 K investigated by high-resolution neutron powder diffraction and specific heat measurements
We report high-resolution neutron powder diffraction on Sr0.61Ba0.39Nb2O6,
SBN61, in the temperature range 15-500 K. The results indicate that the
low-temperature anomalies (T<100K) observed in the dielectric dispersion are
due to small changes in the incommensurate modulation of the NbO6-octahedra, as
no structural phase transition of the average structure was observed. This
interpretation is supported by specific heat measurements, which show no latent
heat, but a glass-like behavior at low temperatures. Furthermore we find that
the structural changes connected with the ferroelectric phase transition at Tc
approx. 350K start already at 200K, explaining the anisotropic thermal
expansion in the temperature range 200-300K observed in a recent x-ray
diffraction study.Comment: Accepted by PRB (2006
Long-Term Results at 10 Years of Pouch Resizing for Roux-en-Y Gastric Bypass Failure
Background: Roux-en-Y gastric bypass (RYGB) is currently one of the most performed bariatric procedures and it is associated with rapid weight loss. However, weight loss failure and weight regain after RYGB occurs in approximately 30% and 3-5% of patients, respectively, and represent a serious issue. RYGB pouch resizing is a surgical option that may be offered to selected patients with RYGB failure. The aim of this study is to assess long-term results of pouch resizing for RYGB failure. Materials and Methods: From February 2009 to November 2011, 20 consecutive patients underwent gastric pouch resizing for RYGB failure in our tertiary bariatric center. The primary outcome was the rate of failure (%EWL < 50% with at least one metabolic comorbidity) after at least 10 years from pouch resizing. Gastroesophageal Reflux Disease (GERD) was also assessed. Results: Twenty patients (18 women (90%)) were included and seventeen (85%) joined the study. The failure rate of pouch resizing was 47%. Mean %EWL and mean BMI were 47%, and 35.1 kg/m(2), respectively. Some of the persistent co-morbidities further improved or resolved after pouch resizing. Seven patients (41%) presented GERD requiring daily PPI with a significantly lower GERD-HQRL questionnaire score after pouch resizing (p < 0.001). Conclusion: Pouch resizing after RYGB results in a failure rate of 47% at the 10-year follow-up while the resolution of comorbidities is maintained over time despite a significant weight regain
The internal structure of the velvet worm projectile slime : a small-angle scattering study
For prey capture and defense, velvet worms eject an adhesive slime which has been established as a model system for recyclable complex liquids. Triggered by mechanical agitation, the liquid bioâadhesive rapidly transitions into solid fibers. In order to understand this mechanoresponsive behavior, here, the nanostructural organization of slime components are studied using smallâangle scattering with neutrons and Xârays. The scattering intensities are successfully described with a threeâcomponent model accounting for proteins of two dominant molecular weight fractions and nanoscale globules. In contrast to the previous assumption that high molecular weight proteinsâthe presumed building blocks of the fiber coreâare contained in the nanoglobules, it is found that the majority of slime proteins exist freely in solution. Only less than 10% of the slime proteins are contained in the nanoglobules, necessitating a reassessment of their function in fiber formation. Comparing scattering data of slime reâhydrated with light and heavy water reveals that the majority of lipids in slime are contained in the nanoglobules with homogeneous distribution. Vibrating mechanical impact under exclusion of air neither leads to formation of fibers nor alters the bulk structure of slime significantly, suggesting that interfacial phenomena and directional shearing are required for fiber formation
Dark matter effective field theory scattering in direct detection experiments
We examine the consequences of the effective field theory (EFT) of dark matterânucleon scattering for current and proposed direct detection experiments. Exclusion limits on EFT coupling constants computed using the optimum interval method are presented for SuperCDMS Soudan, CDMS II, and LUX, and the necessity of combining results from multiple experiments in order to determine dark matter parameters is discussed. We demonstrate that spectral differences between the standard dark matter model and a general EFT interaction can produce a bias when calculating exclusion limits and when developing signal models for likelihood and machine learning techniques. We also discuss the implications of the EFT for the next-generation (G2) direct detection experiments and point out regions of complementarity in the EFT parameter space
Sepsis-induced long-term immune paralysis â results of a descriptive, explorative study
Background: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. Methods: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4+, CD8+ T cells; CD25+ CD127- regulatory T cells; CD14+ monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. Results: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8+ cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4+ T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. Conclusions: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage
Reducing the positional modulation of NbO6-octahedra in SrxBa1-xNb2O6 by increasing the Barium content: A single crystal neutron diffraction study at ambient temperature for x=0.61 and x=0.34
We report on the influence of the Barium content on the modulation amplitude
in SrxBa1-xNb2O6 compounds by comparing Sr0.61Ba0.39Nb2O6 (SBN61) and
Sr0.34Ba0.66Nb2O6 (SBN34). Our single crystal neutron diffraction results
demonstrate that the amplitude of the positional modulation of the NbO6
octahedra is reduced with increasing barium content, indicating that the origin
of the modulation is the partial occupation of the pentagonal channels by Sr
and Ba atoms. By increasing the Sr content the bigger Ba atoms are replaced by
the smaller Sr atoms, which leads to a larger deformation of the surrounding
lattice and hence to a larger modulation amplitude. The more homogeneous the
filling of these channels with one atomic type (Ba) the lower the modulation
amplitude. Our results also show that the structure can be described with a
two-dimensional incommensurate harmonic modulation. No second order modulation
has been observed, both by single crystal diffraction measurements and q-scans.
The positional modulation of the Nb atoms is much smaller than that of the
oxygen atoms, such that the modulation can be seen as a rotational modulation
of almost rigid NbO6-octahedra
Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome
Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases
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