HLA-B*13:01 and the dapsone hypersensitivity syndrome.

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)-PCR. Two aberrant splice products were confirmed with RT-PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Vitexin, an inhibitor of hypoxia-inducible factor-1α, enhances the radiotherapy sensitization of hyperbaric oxygen on glioma.

PURPOSE: Vitexin, an inhibitor of hypoxia-inducible factor (HIF)-1α, has anti-tumor effect. However, whether it can enhance the radiotherapy sensitization of hyperbaric oxygen (HBO) on glioma is unclear. This study aimed to investigate the effect of vitexin. METHODS: The nude mice with paw-transplanted glioma were divided into four groups: control group, HBO + radiation group, HBO + vitexin group, and HBO + vitexin + radiation group. The mice of last two groups were daily given vitexin 75 mg/kg by intraperitoneal injection. 30 min after administration of vitexin, the HBO-treated mice were daily placed in HBO chamber for 60 min. The radiation-treated mice were given local tumor irradiation once every week during the HBO treatment, and the dose of irradiation was 10 Gy/time. The experimental treatment lasted for 21 days. RESULTS: Compared with the HBO + radiation group, the tumor volume, tumor weight, and tumor weight coefficient in the HBO + vitexin + radiation group were lower (p < 0.05). Importantly, the contents of reduced glutathione and glutathione peroxidase as well as expressions of HIF-1α, vascular endothelial growth factor, glucose transporter (GLUT)-1, and GLUT-3 proteins in tumor tissues were also lower in the HBO + vitexin + radiation group than in the HBO + radiation group (p < 0.01). CONCLUSIONS: Vitexin can cooperate with HBO to sensitize the glioma radiotherapy, and its mechanisms may be correlated to the inhibition of HIF-1α protein expression and subsequent decrements of its downstream protein expressions, which finally cause the reduction of antioxidant capacity.

Swelling behavior of organoclays in styrene and exfoliation in nanocomposites.

Organoclays were prepared by cationic exchange of montmorillonite (MMT) with three commercial surfactants: octadecylamine (ODA), hexadecyltrimethylammonium bromide (HTAB), benzalkonium chloride (BAC), and an in-house synthesized surfactant, vinylbenzylalkyldimethylammonium chloride (VDAC). The swelling behaviors of organoclays in styrene were compared by wettability and rheology measurements. VDAC-MMT had the slowest capillary rise rate in styrene. The Washburn equation was found not suitable for the swellable organoclay powders. All organoclay-styrene and organoclay-toluene mixtures demonstrated yield stress. However, VDAC-MMT-styrene and VDAC-MMT-toluene mixtures showed significant higher yield stresses than the other organoclay mixtures. The wettability and rheology measurements indicate that VDAC-MMT bearing a styryl functional group has the strongest interaction with styrene monomer and toluene. In order to further evaluate the extent of swelling and the microstructure, polystyrene (PS)-clay nanocomposites were prepared by in situ polymerization. X-ray diffraction (XRD) and transmission electron microscopy (TEM) indicate that ODA and HTAB-MMT led to intercalated PS-clay nanocomposites, while VDAC-MMT formed exfoliated PS-clay nanocomposites.