A case report of acute dermatitis that developed during an experiment examining the bromination of 3-hexylthiophene

Occupational cases with allergic reaction to fragrance substances, which refer to various chemicals providing aroma characteristics, are arising with its recent usage diversification from pharmaceutical, perfume industry to aromatic remedies. However, chemicals responsible for fragrance allergy have hardly been identified because its component is complex and its sensitization is not frequent. This report will present a case of acute allergic dermatitis that is likely induced by 3-hexylthiophene, one of aromatic compounds often contained in fragrance substances. The case, who was a 27-year male researcher engaged in organic chemical synthesis for six years, was exposed to 3-hexylthiophene and its product (2-bromo-3-hexylthiophene) through an experiment in May 2004 and itching, swelling and eczema immediately developed from face to back. This case of sensitization to 3-hexylthiophene suggests that it be a possible allergen for fragrance allergy

Chronic Active Epstein–Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report

Chronic active Epstein–Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/μg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable

<i>In vitro</i> differentiated cells from <i>CKIδ</i> mutant and <i>CK2α</i> mutant ES cells show a longer period-length of the circadian clock than cells differentiated from wild type ES cells.

<p>After 28-day differentiation, the bioluminescence intensity in each well was monitored. (A, D) Averaged bioluminescence traces after <i>in vitro</i> 28-day differentiated <i>CKIδ</i> (A) or <i>CK2α</i> (D) mutant/revertant ES cells (<i>gray</i>, WT; <i>red</i>, homozygous mutant; <i>blue</i>, revertant). Data detrended by subtracting a 24-h moving average are means (<i>n</i> = 24). (B, C, E, F) Distributions and bar graphs of the period lengths of bioluminescence traces in each well. Error bars are SD. Statistical differences were evaluated using one-way ANOVA followed by Bonferroni post hoc test.</p

An <i>In Vitro</i> ES Cell-Based Clock Recapitulation Assay Model Identifies CK2α as an Endogenous Clock Regulator

<div><p>We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent <i>in vitro</i> circadian clock formation assay that recapitulates <i>in vivo</i> circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking <i>Casein Kinase I delta</i> (<i>CKIδ</i>) induced ∼3 hours longer period-length of circadian rhythm than the wild type, which was compatible with recently reported results using <i>CKIδ</i> null mice. In addition, this assay system also revealed that a <i>Casein Kinase 2 alpha</i> subunit (<i>CK2α</i>) homozygous mutant ES cell line developed significantly longer (about 2.5 hours) periods of circadian clock oscillations after <i>in vitro</i> or <i>in vivo</i> differentiation. Moreover, revertant ES cell lines in which mutagenic vector sequences were deleted showed nearly wild type periods after differentiation, indicating that the abnormal circadian period of the mutant ES cell line originated from the mutation in the <i>CK2α</i> gene. Since <i>CK2α</i> deficient mice are embryonic lethal, this <i>in vitro</i> assay system represents the genetic evidence showing an essential role of <i>CK2α</i> in the mammalian circadian clock. This assay was successfully applied for the phenotype analysis of homozygous mutant ES cells, demonstrating that an ES cell-based <i>in vitro</i> assay is available for circadian genetic screening.</p></div

Characterization of <i>CKIδ</i> and <i>CK2α</i> homozygous mutant ES cell clones and their revertant clones.

<p>(A) Design of the gene trap vector and its insertion sites in <i>CKIδ</i> and <i>CK2α</i> homozygous mutant ES cell clones. SA, splice acceptor; hyg, hygromycin-resistance gene; pA, polyadenylation signal; Pr, phosphoglycerate kinase-1 promoter; N, neomycin-resistance gene; P, fusion gene comprised of the puromycin-resistance gene and the herpes simplex virus thymidine kinase gene; LTR, long terminal repeat. Horizontal arrows below the gene trap vector indicate orientation of the N and P drug resistance genes. (B) Schematic representation of the removal of mutagenic vector sequence after FLPo/FRT recombination. Recombination events were identified by PCR primers (p1 and p2) at the flanking region of the vector insertion sites. Removal of vector sequences regenerate wild type transcripts in the revertant allele. Note that the size of the gene trap vector, exons, introns are not to scale. E, exon. (C) PCR screening for FLPo/FRT recombination events. Note that PCR product was not detected in non-recombinant clones because of the large intervening vector sequence between primers. M, 100-bp DNA ladder. (D) Relative expression level of <i>CKIδ</i> and <i>CK2α</i> mRNA in wild type, mutant and revertant ES cells. Error bars show SEM (n = 3).</p

<i>CKIδ</i> and <i>CK2α</i> mutant MEFs developed <i>in vivo</i> show a longer period-length of circadian clock oscillation than wild type ES cell-derived MEFs.

<p>(A) Preparation of mouse embryonic fibroblasts (MEFs) from E13.5 chimera embryos. MEFs were maintained in EFM and their bioluminescence was monitored. Only MEFs derived from injected ES cells, not the host blastocyst-derived MEFs, contain <i>Bmal1:luc</i> reporter and produce bioluminescence. (B) Averaged bioluminescence traces of MEFs from <i>CKIδ</i> and <i>CK2α</i> mutant chimeric mice (<i>gray</i>, WT; <i>red</i>, <i>CKIδ</i> mutant MEFs; <i>blue</i>, <i>CK2α</i> mutant MEFs). Data detrended by subtracting a 24-h moving average are means (<i>n</i> = 24). (C, D) Distributions and bar graphs of the period lengths of bioluminescences in MEFs from <i>CKIδ</i> and <i>CK2α</i> mutant chimeric mice. Arrowheads show the mean. Error bars are SD. Statistical differences were evaluated using one-way ANOVA followed by Bonferroni post hoc test. ***<i>P</i><0.001.</p

FTY720 Regulates Bone Marrow Egress of Eosinophils and Modulates Late-Phase Skin Reaction in Mice

Eosinophilia in the blood and skin is frequently observed in patients with certain inflammatory skin diseases, such as atopic dermatitis. However, the mechanism underlying eosinophil circulation and the role of eosinophils in cutaneous immune responses remain unclear. In repeated hapten application-induced cutaneous responses in BALB/c mice, the administration of FTY720 before the last challenge decreased the number of skin-infiltrating eosinophils and reduced the late-phase reaction. A similar reduction of the late-phase reaction was observed by a sphingosine-1-phosphate G protein-coupled receptor (S1P1)-selective agonist, SEW2871. We monitored numerous alterations of eosinophils in the blood, spleen, bone marrow, and lymph nodes of interleukin-5 transgenic mice, used as an eosinophilia model, following FTY720 administration. The number of circulating eosinophils was significantly decreased after treatment with FTY720, and eosinophils accumulated in the bone marrow. In addition, eosinophils expressed S1P1, S1P3, and S1P4 mRNAs, and their chemotactic response to S1P was abolished by FTY720 as well as by SEW2871. These findings suggest that FTY720 affects the number of eosinophils in both the blood and skin by inhibiting the egress of eosinophils from the bone marrow and thus downmodulating the late-phase reaction