Checkpoint inhibition (CPI), particularly that targeting the inhibitory coreceptor programmed cell death protein 1 (PD-1), has transformed oncology. Although CPI can derepress cancer (neo)antigen-specific αβ T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αβ T cell recognition. In such settings, γδ T cells have been implicated, but the functional relevance of PD-1 expression by these cells is unclear.
View Article and Find Full Text PDFObjective: To characterize the presentation and outcomes of patients with atopic dermatitis (AD) who developed musculoskeletal symptoms after treatment with dupilumab, a human IgG4 monoclonal antibody that blocks the functions of interleukin-4 (IL-4) and IL-13, key pathologic pathways in AD.
Methods: This article reports an observational cohort of patients receiving dupilumab who developed new-onset musculoskeletal symptoms after dupilumab therapy at our center. All patients had a comprehensive rheumatologic history and examination, with imaging by ultrasonography (US) or magnetic resonance imaging (MRI) in most patients.
Background: Dupilumab is prescribed in one dosage across adult atopic dermatitis patients. Differences in drug exposure may explain variation in treatment response.
Objective: Investigating the clinical relevance of dupilumab serum concentration in atopic dermatitis in real-world practice.
Background: Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types.
Objective: To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type.
Methods: In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.
Innate-like tissue-resident γδ T cell compartments capable of protecting against carcinogenesis are well established in mice. Conversely, the degree to which they exist in humans, their potential properties, and their contributions to host benefit are mostly unresolved. Here, we demonstrate that healthy human breast harbors a distinct γδ T cell compartment, primarily expressing T cell receptor (TCR) Vδ1 chains, by comparison to Vδ2 chains that predominate in peripheral blood.
View Article and Find Full Text PDFThe spectrum of cosmogenic neutrons at Earth's surface covers a wide energy range, from thermal to several GeV. The flux of secondary neutrons varies with latitude, elevation, solar activity, and nearby material, including ground moisture. We report the results from a campaign to measure count rates in neutron detectors responding to three different energy ranges conducted near the geomagnetic North Pole at CFS Alert, Nunavut, Canada (82.
View Article and Find Full Text PDFExpert Rev Clin Immunol
November 2010
Psoriasis is a prevalent chronic inflammatory condition that affects the skin. There are many treatments available for psoriasis but they are not universally effective and some have associated toxicities. Pharmacogenetics and pharmacogenomics explore the relationship between individual genetic variation and drug effect to allow targeted 'personalized' therapy for patients.
View Article and Find Full Text PDFIntroduction: This is the first reported case of perforation and haemorrhage of a Meckel's diverticulum leading to the incidental finding of a gastrointestinal stromal tumour within the diverticulum. Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract, however, when symptomatic, it is often misdiagnosed at presentation. Common complications presenting in adults include bleeding, obstruction, diverticulitis and perforation.
View Article and Find Full Text PDFIntranasal administration of peptide Ac1-9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4(+) T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-T(Reg)) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo.
View Article and Find Full Text PDFOBJECTIVE: To assess the relationship between passive first metatarsophalangeal extension and rearfoot motion during walking on the windlass mechanism. DESIGN: An in vivo study of the windlass mechanism during passive extension of the first metatarsophalangeal joint and walking. BACKGROUND: Despite theoretical work regarding the windlass mechanism in cadavers, there is little research concerning its in vivo role.
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