シェーグレン症候群の新規自己抗原であるREG 蛋白の唾液導管細胞における発現誘導にはIL-6/STAT 経路が重要である

The regenerating gene, Reg, was originally isolated from a rat regenerating islet cDNA library, and its human homolog was named REG Iα. Recently, we reported that REG Iα mRNA as well as its product were overexpressed in ductal epithelial cells in the minor salivary glands of Sjögren׳s syndrome (SS) patients. This study was undertaken to elucidate the role of cytokines and the subsequent intracellular mechanism for induction of REG Iα in the salivary glands of SS patients. We prepared a reporter plasmid containing REG Iα promoter (−1190/+26) upstream of a luciferase reporter gene. The promoter plasmid was introduced by lipofection into human NS-SV-DC and rat A5 salivary ductal cells. The cells were treated with interleukin (IL)-6, IL-8, and a combination of the two. Thereafter transcriptional activity of REG Iα was measured by luciferase assay. We found that IL-6 stimulation, but not IL-8, significantly enhanced the REG Iα promoter activity in salivary ductal cells. Deletion analysis revealed that the region of −141 to −117 of the REG Iα gene was responsible for the promoter activation by IL-6, which contains a consensus sequence for signal transduction and activation of transcription (STAT). The introduction of siRNA for human STAT3 abolished IL-6-induced REG Iα transcription. These results showed that IL-6 stimulation induced REG Iα transcription through STAT3 activation and binding to the consensus sequence of REG Iα promoter in salivary ductal cells. This IL-6/STAT dependent REG Iα induction might play a role in the pathogenesis of SS.博士（医学）・甲第641号・平成27年11月27日Copyright © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Interleukin-6/STAT pathway is responsible for the induction of gene expression of REG Iα, a new auto-antigen in Sjögren׳s syndrome patients, in salivary duct epithelial cells

The regenerating gene, Reg, was originally isolated from a rat regenerating islet cDNA library, and its human homolog was named REG Iα. Recently, we reported that REG Iα mRNA as well as its product were overexpressed in ductal epithelial cells in the minor salivary glands of Sjögren׳s syndrome (SS) patients. This study was undertaken to elucidate the role of cytokines and the subsequent intracellular mechanism for induction of REG Iα in the salivary glands of SS patients. We prepared a reporter plasmid containing REG Iα promoter (−1190/+26) upstream of a luciferase reporter gene. The promoter plasmid was introduced by lipofection into human NS-SV-DC and rat A5 salivary ductal cells. The cells were treated with interleukin (IL)-6, IL-8, and a combination of the two. Thereafter transcriptional activity of REG Iα was measured by luciferase assay. We found that IL-6 stimulation, but not IL-8, significantly enhanced the REG Iα promoter activity in salivary ductal cells. Deletion analysis revealed that the region of −141 to −117 of the REG Iα gene was responsible for the promoter activation by IL-6, which contains a consensus sequence for signal transduction and activation of transcription (STAT). The introduction of siRNA for human STAT3 abolished IL-6-induced REG Iα transcription. These results showed that IL-6 stimulation induced REG Iα transcription through STAT3 activation and binding to the consensus sequence of REG Iα promoter in salivary ductal cells. This IL-6/STAT dependent REG Iα induction might play a role in the pathogenesis of SS

<Preliminary>An Enzymatic Study on Isocitrate Metabolism in the Ectomycorrhizal Fungus Laccaria amethystea

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K-Ar ages of biotite and muscovite from Pangong metamorphic complex, Shyok suture zone, India: Implications for the youngest post-collision metamorphic event in Ladakh Himalaya

The garnet-kyanite-staurolite and garnet-biotite-staurolite gneisses were collected from a locality within Lukung area that belongs to the Pangong metamorphic complex in Shyok valley, Ladakh Himalaya. The kyanite-free samples have garnet and staurolite in equilibrium, where garnets show euhedral texture and have flat compositional profile. On the other hand, the kyanite-bearing sample shows equilibrium assemblage of garnet-kyanite-staurolite along with muscovite and biotite. In this case, garnet has an inclusion rich core with a distinct grain boundary, which was later overgrown by inclusion free euhedral garnet. Garnet cores are rich in Mn and Ca, while the rims are poor in Mn and rich in Fe and Mg, suggesting two distinct generations of growth. However, the compositional profiles and textural signature of garnets suggests the same stage of P -T evolution for the formation of the inclusion free euhedral garnets in the kyanite-free gneisses and the inclusion free euhedral garnet rims in the kyanite-bearing gneiss. Muscovites from the four samples have consistent K-Ar ages, suggesting the cooling age (∼ 10 Ma) of the gneisses. These ages make a constraint on the timing of the youngest post-collision metamorphic event that may be closely related to an activation of the Karakoram fault in Pangong metamorphic complex

Surgical Approach to Pigmented Villonodular Synovitis and Synovial Osteochondromatosis in Pathological Expansion of the Popliteus Bursa

We orthopaedic surgeons are not familiar with the popliteus bursa. It is defined as the expansion in the synovial membrane of the posterolateral part of the knee that lies between the lateral meniscus and the tendon of the popliteus muscle. The popliteus bursa extends approximately 1 cm distal to the joint line and has 4 borders; the medial border is the peripheral margin of the lateral meniscus, the lateral border is the popliteus tendon, and the superior and inferior borders are formed by 2 fascicles. We very rarely observe cystic lesions that expand more distally, such as pigmented villonodular synovitis (PVNS) and synovial osteochondromatosis. We consider the distally expanded bursa as the pathologic expansion of the popliteus bursa. When this expansion is involved with PVNS, it may be the cause of recurrence of PVNS in the knee joint. Synovial osteochondromatosis in this expansion may cause pain in the posterolateral corner of the knee and may become a source of free bodies in the knee joint. In such conditions, these lesions should be surgically excised. The purpose of this Technical Note is to describe a surgical approach to the pathologic expansion of the popliteus bursa

A new Late Miocene great ape from Kenya and its implications for the origins of African great apes and humans

Extant African great apes and humans are thought to have diverged from each other in the Late Miocene. However, few hominoid fossils are known from Africa during this period. Here we describe a new genus of great ape (Nakalipithecus nakayamai gen. et sp. nov.) recently discovered from the early Late Miocene of Nakali, Kenya. The new genus resembles Ouranopithecus macedoniensis (9.6–8.7 Ma, Greece) in size and some features but retains less specialized characters, such as less inflated cusps and better-developed cingula on cheek teeth, and it was recovered from a slightly older age (9.9–9.8 Ma). Although the affinity of Ouranopithecus to the extant African apes and humans has often been inferred, the former is known only from southeastern Europe. The discovery of N. nakayamai in East Africa, therefore, provides new evidence on the origins of African great apes and humans. N. nakayamai could be close to the last common ancestor of the extant African apes and humans. In addition, the associated primate fauna from Nakali shows that hominoids and other non-cercopithecoid catarrhines retained higher diversity into the early Late Miocene in East Africa than previously recognized