A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

Association of Fas Ligand gene polymorphism with Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute severe blistering diseases of the skin and also two of the most devastating ocular surface diseases leading to corneal damage and loss of vision. The extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. SJS/TEN patients in the acute stage were reported to manifest increased serum levels of Fas Ligand (FasL). Thus, we performed SNP association analysis of the FasL gene. METHODS: In 76 Japanese SJS/TEN patients with ocular surface complications and 160 Japanese healthy controls, we examined four SNPs of FasL reported in the Japanese Single Nucleotide Polymorphisms (JSNP) database by sequencing. RESULTS: The SNP rs.3830150 A/G showed a significant strong inverse association with SJS/TEN. Analysis of the genotype pattern of SNPs rs.3830150 and rs.2639614 (rs.3830150 A/A-rs.2639614 G/G) also manifested a strong inverse association with SJS/TEN. CONCLUSION: FasL gene polymorphisms might be associated with SJS/TEN.

Human conjunctival epithelial cells express functional Toll-like receptor 5.

PURPOSE: The expression and function of Toll-like receptor 5 (TLR5) was analysed in human conjunctival epithelial cells (HCjEC). METHODS: The expression of TLR5 in HCjEC was studied by reverse transcriptase (RT) PCR and flow cytometry. The amount of interleukin (IL) 6 and IL-8 proteins was determined by ELISA. Messenger RNA expression elicited by stimulation with flagellins derived from Pseudomonas aeruginosa, Serratia marcescens, Salmonella typhimurium, and Bacillus subtilis was assayed by quantitative RT-PCR. The localisation of TLR5 protein in human conjunctival epithelium was detected immunohistochemically. RESULTS: HCjEC expressed TLR5-specific mRNA and TLR5 protein. In HCjEC stimulated with flagellins derived from P. aeruginosa and S. marcescens, IL-6 and IL-8 production was increased and IL-6 and IL-8 mRNA was upregulated. Flagellins from S. typhimurium and B. subtilis did not induce the upregulation of these genes and proteins. TLR5 protein was detected on the basolateral but not the apical side of human conjunctival epithelium. CONCLUSIONS: Human conjunctival epithelium harbours functional TLR5. Considering the spatially selective basolateral localisation of TLR5 protein, it was postulated that flagellins from ocular pathogenic bacteria induce inflammatory responses when disruption of the epithelial barrier permits their transmigration to the basolateral side but not under healthy physiological conditions on the ocular surface.

Inmunodiagnóstico de las infecciones por Strongloides stercoralis en Chile utilizando la prueba de ELISA / Immunodiagnosis of Strongyloides stercoralis infections in Chile using ELISA test

BACKGROUND: Strongyloides stercoralis is a world wide distributed small intestinal nematode parasite. In immunocompetent individuals S stercoralis can produce asymptomatic infections or a moderate clinical picture of diarrhea, some cases become chronic. In immunocompromised patients, a disseminated disease may appear, sometimes fatal. In Chile, there is little epidemiological information about S stercoralis infections and appropriate diagnostic techniques are usually not used. AIM: To evaluate the yield of an ELISA test for the diagnosis of strongyloidiasis in Chilean patients. MATERIAL AND METHODS: Ten serum samples from patients with S stercoralis infections confirmed by a positive stool examination, 66 samples from individuals with other infections by tissue helminthes (24 toxocariasis, 15 trichinellosis, 11 hydatidosis, 12 fascioliasis and 4 cysticercosis), 13 samples from subjects with autoimmune diseases and 49 samples from apparently healthy individuals with a normal eosinophil count, were studied. ELISA antigen was prepared using a filariform larval extract obtained from a murine species of Strongyloides, maintained in laboratory animals. RESULTS: Using 0.33 optical density units as a cut off value, 9 of 10 sera of S stercoralis infected individuals, had a positive ELISA test. No cross reactions were observed with sera of patients with other helminthic infections, autoimmune diseases or in healthy individuals. Thus, specificity, positive and negative predictive values were 100 per cent. CONCLUSIONS: The results obtained are similar with those found by other investigators. ELISA test for strongyloidiasis is a useful tool for the diagnosis of clinical cases and for seroepidemiological studies of this nematode infection in Chile.

Three-dimensional sonographic features of fetal central nervous system anomaly.

OBJECTIVE: To visualize an intracranial structure of the fetal central nervous system (CNS) anomaly using transabdominal three-dimensional (3D) sonography. METHODS: A total of 12 cases with fetal CNS anomalies (one unilateral ventriculomegaly; three hydrocephalus; three anencephaly; three holoprosencephaly; one Dandy-Walker cyst; and one enlarged cisterna magna) from 17 to 37 weeks of gestation were studied with transabdominal 3D sonography (3.5 MHz). RESULTS: In unilateral ventriculomegaly, insight view of dilated lateral ventricle, especially dilated atrium was depicted. In hydrocephalus, severely dilated bilateral ventricles and thin brain mantle were very clearly shown. In anencephalus, an absence of the brain and defect of the vault of the skull was clearly noted. In holoprosencephaly, absent interhemispheric fissure, common ventricle, and the extent of thalamic fusion were evident. In Dandy-Walker cyst, cerebellar hemisphere was clearly depicted due to the agenesis of cerebellar vermis. In enlarged cisterna magna, posterior intracranial view of the fetus showed a large space of cisterna magna. Although the diagnosis of each CNS anomaly was made using conventional two-dimensional sonography, 3D sonography proved most helpful delineating the exact nature and anatomic level of the anomaly. CONCLUSIONS: These results suggest that 3D sonography provides a novel means of visualizing fetal CNS anomalies in utero. However, it should be noted that our 3D sonography cannot depict intracranial brain structures in normal fetuses or some CNS anomaly such as intracranial tumor.

[Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix].

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.

Studies on the influence of age in the infection of caged chickens by Raillietina laticanalis and on the susceptibility to reinfection.

The aim of the experiments was to explain the high number of worms found in chickens from a poultry facility. Infections by Raillietina laticanalis were achieved in chickens kept in the laboratory. Thirty cysticercoids obtained from beetles (Dermestes ater) caught at the poultry facility were administered by pipette to each chicken. The rate of recovered worms was employed to evaluate the persistence of the infection, the influence of bird age on susceptibility to infection, and the possibility of reinfection. To verify the persistence of the infection, a group of ten chickens was infected. At each of five different intervals, two chickens were necropsied. Tapeworms were recovered up to the 46th day. To verify the influence of bird age on susceptibility to infection, three different age groups were used in the experimental design: 3-4 weeks, 6-9 weeks, and 17-20 weeks. There was no difference in susceptibility to the infections across the groups. To investigate the possibility of reinfection, a group of birds received an additional dose of cysticercoids a few days after the first doses. Another group received the second dose only after the worms had already been established. There was a significant increase in the number of recovered worms in both groups when compared with the control. The short worms found in some experiments may be due to natural destrobilization. Thus, the high number of worms found in chickens from the poultry facility could result from both infections being acquired earlier and infections acquired at the laying stage, since we demonstrated the possibility of reinfection and the long lifespan of the worm.(ABSTRACT TRUNCATED AT 250 WORDS)