トルコ、アナトリア高原、トゥズ湖とコンヤ盆地における過去２４，０００年間の湖水位変動と扇状地の形成

Alluvial fans developed and lake levels fluctuated several times according to the climatic changes during the last 24,000 years. Alluvial fans developed in Lake Tuz in the cold, pluvial periods of increasing discharge during the Holocene around 5000 yr BP. and after 3500 yr BP. Lake expansion occurred at 23 ka., 18-20 ka., 14-15 ka., and 11ka. over the last 24,000 years in the Konya Basin. These expansions, shown by the raised lake terraces and beach ridges, were mainly due to cold and pluvial climatic changes. The lake level rose in the colder climate during marine oxygen isotope stage 2 and the Younger Dryas period. The lake level reached its highest level of 1013 to 1014 m during the last Glacial maximum before 18 ka

Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)–CC genotype caused by pegylated interferon (IFN)-α-2a with ribavirin therapy: a case report

BACKGROUND: Pegylated interferon combined with ribavirin treatment is an effective therapy for chronic hepatitis C viral infection. However, pegylated interferon combined with ribavirin is associated with various adverse reactions. Severe thrombocytopenia is a life-threatening side effect of interferon therapy that can lead to bleeding. It is generally understood that the inosine triphosphatase-CC genotype does not have a significantly lower reduction by pegylated interferon combined with ribavirin in the mean platelet counts compared with the AA/CA genotype. We report a case of severe thrombocytopenia that developed in a patient with chronic hepatitis C treated with pegylated interferon combined with ribavirin in spite of having the inosine triphosphatase-CC genotype. CASE PRESENTATION: A 57-year-old female had been diagnosed as having HCV infection in 2008. The inosine triphosphatase gene showed one single nucleotide polymorphism (rs1127354) C/C (major homozygous) and the IL28B gene showed single nucleotide polymorphism (rs8099917 T/T, rs11881222 T/T) (major homozygous). The patient was treated with pegylated interferon 180 μg once a week combined with ribavirin 600 mg per day from April 2011. The hepatitis c virus ribonucleic acid turned negative 9 weeks after treatment with pegylated interferon combined with ribavirin. During the therapy, the platelet count remained above 8.0 × 10(4)/μl for about 9 months. In January 2012, the platelet count was 6.8 × 10(4)/μl. In February 2012, the 44th week from the beginning of the treatment, a sudden decrease in the platelet count to 0.8 × 10(4)/μl was observed. After prednisolone was administered, the platelet count increased. Finally the platelet count had risen above normal range. CONCLUSION: We should pay careful attention in the differential diagnosis for patients with the inosine triphosphatase-CC genotype because, although rare, severe thrombocytopenia could occur

Franz Kafka und sein Nachfolger Milan Kundera

特集ゲルマン語の歴

Ochratoxin A, citrinin and deoxynivalenol decrease claudin-2 expression in mouse rectum CMT93-II cells.

Intestinal epithelial cells are the first targets of ingested mycotoxins, such as ochratoxin A, citrinin and deoxynivalenol. It has been reported that paracellular permeability regulated by tight junctions is modulated by several mycotoxins by reducing the expression of specific claudins and integral membrane proteins in cell-cell contacts, accompanied by increase in phosphorylation of mitogen-activated protein kinases, including extracellular signal-related kinase (ERK) 1/2, p38 and c-Jun NH2-terminal protein kinase. Claudin-2 is expressed in the deep crypt cells, but not in the villus/surface cells in vivo. While Caco-2, T84 and IPEC-J2 cells, which are widely used intestinal epithelial cell lines to assess the influence of mycotoxins, do not express claudin-2, CMT93-II cells express claudin-2. We previously reported that inhibition of the ERK pathway reduced claudin-2 levels in cell-cell contacts in CMT93-II cells. In this study, we examined whether ochratoxin A, citrinin and deoxynivalenol affect claudin-2 expression and ERK1/2 phosphorylation in CMT93-II cells. We found that all mycotoxins reduced claudin-2 expression in cell-cell contacts, with reduction (by citrinin and deoxynivalenol) or no change (by ochratoxin A) in phosphorylated ERK1/2. All mycotoxins increased transepithelial electrical resistance, but did not affect flux of fluorescein. While ochratoxin A and citrinin are known to be nephrotoxic, only deoxynivalenol reduced claudin-2 expression in MDCK II cells derived from the renal tubule. These results suggest that claudin-2 expression is regulated not only by the ERK pathway, but also by other pathways in an organ-specific manner.福岡歯科大学2017年

Anisomycin, a JNK and p38 activator, suppresses cell-cell junction formation in 2D cultures of K38 mouse keratinocyte cells and reduces claudin-7 expression, with an increase of paracellular permeability in 3D cultures.

Keratinocytes in the oral mucosal epithelium, which is a non-keratinized stratified epithelium, are exposed to various stimuli from the oral cavity. JNK and p38 are stress-activated mitogen-activated protein kinases (MAPKs) that are phosphorylated by various stimuli and are involved in the assembly and disassembly of tight junctions (TJs) in keratinocytes. Therefore, we investigated the effects of stress-activated MAPKs on TJs in a mouse keratinocyte cell line during cell-cell junction formation in two-dimensional (2D) cultures or stratification to form non-keratinized epithelium in 3D cultures. In 2D cultures, calcium induced zipper-like staining for ZO-1 at 2 h and string-like staining for ZO-1 at 12 h, which indicated immature and mature cell-cell junctions, respectively. Anisomycin (AM), a JNK and p38 activator, inhibited formation of string-like staining for ZO-1, whereas inhibition of JNK, but not p38, after AM treatment restored string-like staining for ZO-1, although claudins (CLDNs) 4, 6, and 7 did not completely colocalize to ZO-1-positive sites. In 3D cultures, AM treatment for 2 weeks activated only p38, suppressed flattening of the superficial cells, removed CLDN7 from ZO-1-positive spots on the surface of 3D cultures, which represent TJs, and decreased transepithelial electrical resistance. Thus, short-term AM treatment inhibited maturation of cell-cell junctions by JNK, but not p38, activation. p38 activation by long-term AM treatment affected morphology of stratified structures and paracellular permeability, which was increased by CLDN7 removal from TJs. Various chronic stimuli that activate stress-activated MAPKs may weaken the keratinocyte barrier and be involved in TJ-related diseases.福岡歯科大学2018年

Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact

Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-γ-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association