Acute generalized exanthematous pustulosis: A retrospective study of 51 cases in Taiwan

AbstractBackground/ObjectiveAcute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse drug reaction characterized by fever and numerous sterile non-follicular pustules. It is mainly attributed to drugs, although other factors have been implicated. The objective of this study was to evaluate the clinical and histological features of AGEP in a Taiwanese population.MethodsIn this retrospective study, we reviewed patients diagnosed with AGEP with a EuroSCAR (RegiSCAR) validation score more than 4 (>4, probable to definite cases), between 1992 and 2012 at the Chang Gung Memorial Hospital in Taiwan. Demographic, clinical and laboratory data, pathologic findings, and disease causality were analyzed.ResultsA total of 51 patients were included in this study, with 34 (66.7%) patients being diagnosed with AGEP with drug causality, and 17 (33.3%) patients being diagnosed with AGEP without drug causality. Cases of AGEP with drug causality showed an older average age, and a significantly higher rate of previous drug hypersensitivity history compared to cases of AGEP without drug causality (p = 0.0018). None of the patients had a history of psoriasis or had developed psoriasis at the 1-year follow-up. A total of 12 cases (23.5%) had systemic involvement, including liver and kidneys. Penicillin or aminopenicillin (17.6%) and cephalosporins (17.6%) were the most common causative drug groups related to AGEP. In AGEP patients without drug causality, three cases of pathogen infections were identified (1 case of mycoplasma, Coxsackie virus, and Epstein-Barr virus, respectively).ConclusionWe found that beta-lactam antibiotics were the major drug class responsible for inducing AGEP in a Taiwanese population, but that some infectious pathogens may also contribute to AGEP development

Gene expression in early and progression phases of autosomal dominant polycystic kidney disease

<p>Abstract</p> <p>Background</p> <p>Little is known about the genes involved in the initial cyst formation and disease progression in autosomal dominant polycystic kidney disease (ADPKD); however, such knowledge is necessary to explore therapeutic avenues for this common inherited kidney disease.</p> <p>Findings</p> <p>To uncover the genetic determinants and molecular mechanisms of ADPKD, we analyzed 4-point time-series DNA microarrays from <it>Pkd1</it>^{<it>L</it>3/<it>L</it>3}mice to generate high resolution gene expression profiles at different stages of disease progression. We found different characteristic gene expression signatures in the kidneys of <it>Pkd1</it>^{<it>L</it>3/<it>L</it>3}mice compared to age-matched controls during the initial phase of the disease. By postnatal week 1, the <it>Pkd1</it>^{<it>L</it>3/<it>L</it>3}kidney already had a distinctive gene expression pattern different from the corresponding normal controls.</p> <p>Conclusion</p> <p>The genes differentially expressed, either induced or repressed, in ADPKD are important in immune defense, cell structure and motility, cellular proliferation, apoptosis and metabolic processes, and include members of three pathways (Wnt, Notch, and BMP) involved in morphogenetic signaling. Further analysis of the gene expression profiles from the early stage of cystogenesis to end stage disease identified a possible gene network involved in the pathogenesis of ADPKD.</p

Epidermal growth factor receptor regulates β-catenin location, stability, and transcriptional activity in oral cancer

<p>Abstract</p> <p>Background</p> <p>Many cancerous cells accumulate β-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of β-catenin in the nuclei of oral cancer cells.</p> <p>Results</p> <p>We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of β-catenin and GSK-3β, association of β-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, β-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of β-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation of β-catenin (tyrosine) and GSK-3β(Ser-(9), resulting in a loss of β-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates β-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of β-catenin in oral cancer.</p> <p>Conclusions</p> <p>EGFR signaling regulates β-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of β-catenin under EGFR activation is a malignancy marker of oral cancer.</p

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2\u27-deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation

8-Oxo-7,8-dihydro-2\u27-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2\u27-deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation

8-Oxo-7,8-dihydro-2\u27-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations