Key Points• IL-13 is an autocrine factor for CTCL.• IL-13 and its receptors represent novel markers of CTCL malignancy and potential therapeutic targets for intervention.Cutaneous T-cell lymphomas (CTCLs) primarily affect skin and are characterized by proliferation of mature CD4 1 T-helper cells. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCLs. Abnormal cytokine expression in CTCLs may be responsible for enhanced proliferation of the malignant cells and/or depression of the antitumor immune response. Here we show that interleukin-13 (IL-13) and its receptors IL-13Ra1 and IL-13Ra2 are highly expressed in the clinically involved skin of CTCL patients. We also show that malignant lymphoma cells, identified by the coexpression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. IL-13 induces CTCL cell growth in vitro and signaling through the IL-13Ra1. Furthermore, antibody-mediated neutralization of IL-13 or soluble IL-13Ra2 molecules can lead to inhibition of tumor-cell proliferation, implicating IL-13 as an autocrine factor in CTCL. Importantly, we established that IL-13 synergizes with IL-4 in inhibiting CTCL cell growth and that blocking the IL-4/IL-13 signaling pathway completely reverses tumor-cell proliferation. We conclude that IL-13 and its signaling mediators are novel markers of CTCL malignancy and potential therapeutic targets for intervention. (Blood. 2015;125(18):2798-2805
Growth signals drive hematopoietic progenitor cells to proliferate and branch into divergent cell fates, but how unequal outcomes arise from a common progenitor is not fully understood. We used steady-state analysis of in vivo hematopoiesis and Fms-related tyrosine kinase 3 ligand (Flt3L)-induced in vitro differentiation of dendritic cells (DCs) to determine how growth signals regulate lineage bias. We found that Flt3L signaling induced anabolic activation and proliferation of DC progenitors, which was associated with DC differentiation. Perturbation of processes associated with quiescence and catabolism, including AMP-activated protein kinase signaling, fatty acid oxidation, or mitochondrial clearance increased development of cDC2 cells at the expense of cDC1 cells. Conversely, scavenging anabolism-associated reactive oxygen species skewed differentiation toward cDC1 cells. Sibling daughter cells of dividing DC progenitors exhibited unequal expression of the transcription factor interferon regulatory factor 8, which correlated with clonal divergence in FoxO3a signaling and population-level bifurcation of cell fate. We propose that unequal transmission of growth signals during cell division might support fate branches during proliferative expansion of progenitors.
Distribution of Candida species was investigated by examining 245 samples from skin lesions and nails. The isolates were identified using standard laboratory methods including germ tube test, micromorphology of colonies on rice agar, the commercial kit, saccharide assimilation and fermentation tests. Eight species of Candida were identified: C. albicans accounted for 56.4% of the isolates, C. parapsilosis 29.1, C. tropicalis 7.8, C. pulcherrima 2.9, C. guilliermondii 1.5, C. krusei and C. zeylanoides for 0.9% each, and C. robusta for 0.5%. The factors significantly associated with colonization were prolonged antibiotic therapy, parenteral nutrition, low birth body mass of infants, intubation, duration of stay in hospital, indwelling intravenous catheter, malignancies, diabetes, surgery, and obesity.
Mycological analysis of swabs and scraping samples from the external ear canals of 40 patients with clinically diagnosed otomycosis (10 neonates, 30 adults) revealed the presence of fungi as etiological agents. They were investigated microscopically using 20 % potassium hydroxide, and by cultivation on Sabouraud's glucose agar. The Candida species were identified using the germ-tube test, micromorphology observations of colonies on rice agar, and particularly by the commercial kit AUXAcolor. The following Candida species were identified in the aural material examined: C. albicans (n = 21; 52.5 %), C. parapsilosis (11; 27.5), C. tropicalis (3; 7.5), C. krusei (3; 7.5), C. guilliermondii (2; 5.0). The above yeasts were present in samples together with Staphylococcus epidermidis (31), S. aureus (16), alpha-hemolytic streptococci (14), Neisseria spp. (14), Proteus mirabilis (3), Pseudomonas aeruginosa (3), Escherichia coli (1) and Haemophilus influenzae (1). The most frequent predisposing factors for otomycosis were swimming in public pools and/or bath, spa and diabetes mellitus.
Occurrence of Candida spp. was determined in a population of 60 infants, 1-15-month-old, with diaper dermatitis, admitted to a neonatal intensive care unit in Hospital Saca (Kosice, Slovakia). Specimens were obtained from the perianal, pubic, inguinal, or gluteal areas that showed signs of secondary infection as manifested by erythema, oozing, vesiculopustular lesions, and pus formation. The most frequently isolated species was C. albicans (41), followed by C. parapsilosis (8), C. tropicalis (4), C. pulcherrima (4), C. guilliermondii (2), and C. zeylanoides (1). Other organisms present in the mixed culture from the diaper area were Staphylococcus aureus (6), Escherichia coli (3), and 2 strains of each group B and D streptococci, and Proteus mirabilis. Infants diapered exclusively in disposable diapers showed less rash than those diapered exclusively or sometimes in cloth diapers.
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