T helper (Th)1 insufficiency was recently found to be related to the pathogenesis of pemphigus vulgaris (PV). Decreased Th1 response was particularly noticed in the early stages of PV. Therefore, administration of interferon alpha in the early stages of aggressive PV may lead to rapid control of the acute stage of the disease.
View Article and Find Full Text PDFBackground: Global Burden of Disease Study is a research database containing systematically compiled information from vital statistics and epidemiologic literature to inform research, public policy, and resource allocation.
Objective: We sought to compare mortality among conditions with skin manifestations in 50 developed and 137 developing countries from 1990 to 2010.
Methods: This was a cross-sectional study to calculate mean age-standardized mortality (per 100,000 persons) across countries for 10 disease categories with skin manifestations.
Kallin syndrome (KS) is a variant of epidermolysis bullosa simplex (EBS), which, in addition to the classic features of EBS, also presents with deafness, alopecia, hypodontia and nail dystrophy. We report the case of a 17-year-old boy who presented to our clinic with trauma-induced skin blistering, alopecia, deafness, dental caries, nail dystrophy and vitiliginous areas. The skin blisters had been appearing since birth, and healed without scarring.
View Article and Find Full Text PDFBackground: The use of live attenuated varicella vaccine (Varilrix(®)) as an adjuvant treatment in severe cases of psoriasis has recently been postulated. Its efficacy raised questions regarding its possible mechanisms of action.
Objective: To compare the efficacy and safety of combining Varilrix(®) and cyclosporine to cyclosporine alone in the treatment of severe psoriasis.
Shigella flexneri, the etiological agent of bacillary dysentery, invades the human colonic epithelium and causes its massive inflammatory destruction. Little is known about the post-translational modifications implicated in regulating the host defense pathway against Shigella. Here, we show that SUMO-2 impairs Shigella invasion of epithelial cells in vitro.
View Article and Find Full Text PDFHigh-speed video stereo-microscopy relies on illumination from two distinct angles to create two views of a sample from different directions. The 3D trajectory of a microscopic object can then be reconstructed using parallax to combine 2D measurements of its position in each image. In this work, we evaluate the accuracy of 3D particle tracking using this technique, by extending the number of views from two to four directions.
View Article and Find Full Text PDFThe poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD(+) as substrate. Based on the composition of three NAD(+) coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms.
View Article and Find Full Text PDFImportance: Disease burden data helps guide research prioritization.
Objective: To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project.
Design: Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013.
Background: Acne vulgaris is a multifactorial disease of the skin. Several studies have shown that sebocyte proliferation and/or lipogenesis, as well as inflammatory reactions, may be regulated by peroxisome proliferator-activated receptor (PPAR)γ-mediated pathways.
Aim: To investigate whether the Pro12Ala polymorphism of the PPARγ gene might be associated with the risk of acne, and to assess the effect of this polymorphism on acne severity.
The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer.
View Article and Find Full Text PDFAggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell-cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach.
View Article and Find Full Text PDFFacial freckles are a cosmetic concern to Egyptians, particularly young females. Several therapeutic lines exist with variable response rates and limitations. Fractional carbon dioxide (FCO2) laser provides minimal ablation and therefore less down time and less side effects.
View Article and Find Full Text PDFPost-translational modification of proteins with ubiquitin and ubiquitin-like molecules (UBLs) is emerging as a dynamic cellular signaling network that regulates diverse biological pathways including the hypoxia response, proteostasis, the DNA damage response and transcription. To better understand how UBLs regulate pathways relevant to human disease, we have compiled a human siRNA "ubiquitome" library consisting of 1,186 siRNA duplex pools targeting all known and predicted components of UBL system pathways. This library can be screened against a range of cell lines expressing reporters of diverse biological pathways to determine which UBL components act as positive or negative regulators of the pathway in question.
View Article and Find Full Text PDFThe tumor suppressor p53 regulates the expression of genes involved in cell cycle progression, senescence and apoptosis. Here, we investigated the effect of single point mutations in the oligomerization domain (OD) on tetramerization, transcription, ubiquitylation and stability of p53. As predicted by docking and molecular dynamics simulations, p53 OD mutants show functional defects on transcription, Mdm2-dependent ubiquitylation and 26S proteasome-mediated degradation.
View Article and Find Full Text PDFImportance: Research prioritization should be guided by impact of disease.
Objective: To determine whether systematic reviews and protocol topics in Cochrane Database of Systematic Reviews (CDSR) reflect disease burden, measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 project.
Design, Setting, And Participants: Two investigators independently assessed 15 skin conditions in the CDSR for systematic review and protocol representation from November 1, 2013, to December 6, 2013.
Posttranslational modification with small ubiquitin-like modifiers (SUMOs) alters the function of proteins involved in diverse cellular processes. SUMO-specific enzymes conjugate SUMOs to lysine residues in target proteins. Although proteomic studies have identified hundreds of sumoylated substrates, methods to identify the modified lysines on a proteomic scale are lacking.
View Article and Find Full Text PDFBackground: Cryotherapy has been used in treatment of basal cell carcinoma (BCC). In 1993, Weshahy described his technique for applying cryotherapy in depth, i.e.
View Article and Find Full Text PDFEmerg Med Australas
April 2014
Objective: Describe the characteristics, reasons for leaving and outcomes of patients who did not wait (DNW) to be seen by a health practitioner in a regional Australian ED.
Methods: Prospective observational study of a convenience sample of ED DNW patients presenting to The Townsville Hospital between June 2011 and July 2012. Seven days from each month were selected, and DNW patients presenting on those days were enrolled.