Oral lichenoid drug reaction with autoantibodies in peripheral blood: Case report

AbstractA 51-year-old man complained of oral roughness and pain. At the age of 49 years, he was admitted for 8 months for bipolar emotional disorder. Oral administration of lithium carbonate was started. Extensive, hemorrhagic, erythema-mixed white lace-like patches were noted on the lip, buccal mucosae, and lingual margins. On biopsy, all lesions were consistent with oral lichen planus. A drug lymphocyte stimulation test showed a positive reaction to lithium carbonate. Blood examination revealed marked increases in the peripheral blood levels of antinuclear antibodies. To relieve the symptoms, the systemic administration of prednisolone was performed while continuing the lithium carbonate

Endoscopic ultrasound-guided immunotherapy

AbstractAnti-tumoral endoscopic ultrasound-guided fine-needle injection (EUS-FNI), with its minimally invasive access for anti-tumoral agent delivery, is the most exciting field of intervention EUS. Pancreatic cancer is regarded as a systemic disease even if imaging modalities reveal no visible metastasis. From that perspective, immunological therapy is performed. To date, several reports have described immunotherapy under EUS-guidance. The first report of EUS-FNI intended for immunotherapy for advanced pancreatic cancer was published in 2000. In that study, an allogeneic mixed-lymphocyte culture was injected into tumors of eight patients with unresectable local pancreatic adenocarcinoma. The study of dendritic cells (DCs) for cancer has continued to develop in recent years. Actually, DCs are potent antigen-presenting cells for the induction of primary T-cell dependent immune response. When injected intratumorally, DCs acquire and process tumor antigens in situ, migrate to regional lymphoid organs, and initiate a strong tumor-specific immune response. To date, three reports have described EUS-FNI of DCs into pancreatic cancer: two for unresectable and one for pre-surgical operations. Every study has indicated the feasibility and safety. Furthermore, these reports showed that EUS-guided DCs injection might be an important option for treating advanced pancreatic cancer. EUS-guided immunotherapy is a very exciting field in interventional EUS for obstinate cancers

MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice

Commensal bacterial sensing by Toll-like receptors is critical for maintaining intestinal homeostasis, but can lead to colitis in the absence of interleukin-10. Although Toll-like receptors are expressed in multiple cell types in the colon, the cell type(s) responsible for the development of colitis are currently unknown. Here we generated mice that are selectively deficient in MyD88 in various cellular compartments in an interleukin-10[superscript −/−] setting. Although epithelial expression of MyD88 was dispensable, MyD88 expression in the mononuclear phagocyte compartment was required for colitis development. Specifically, phenotypically distinct populations of colonic mononuclear phagocytes expressed high levels of interleukin-1β, interleukin-23 and interleukin-6, and promoted T-helper 17 responses in the absence of interleukin-10. Thus, gut bacterial sensing through MyD88 in mononuclear phagocytes drives inflammatory bowel disease when unopposed by interleukin-10.Howard Hughes Medical InstituteNational Institutes of Health (U.S.) (NIH grant DK071754)National Institutes of Health (U.S.) (NIH grant AI046688)National Institutes of Health (U.S.) (NIH grant AI055502)National Institutes of Health (U.S.) (NIH grant RO1OD011141)National Institutes of Health (U.S.) (Training grant)National Cancer Institute (U.S.) (Irvington Fellowship

Signaling pathway for phagocyte priming upon encounter with apoptotic cells

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocytespecific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.Embargo Period 12 month

ダイズ β コングリシニン ブンシシュ ノ ニュウカ トクセイ ニ ツイテ

　大豆β-コングリシニン分子種のB0 (β3), B1 (α′1β2), B3(α1α′1β1), B5 (α2α′1）コングリシニンについて、乳化活性、油滴界面への吸着率、吸着サブユニット成分、表面疎水性、および表面張力の測定を行い、乳化機能発現におよぼす各サブユニットの寄与について検討し、以下の結果を得た。　(1) α,α′のα系サブユニットを2 個以上含む分子種の乳化活性が高かった。一方、吸着率と表面疎水性はα系サブユニット含量とともに高くなった。　(2) サブユニット間のアミノ酸配列の相同性が高いコア領域のN末端側に結合したエクステンション領域の存在が乳化機能発現にとって重要であった。　(3) β-コングリシニンは、サブユニット構造を保ったまま、多分子層を形成しながら油滴界面に吸着するものと考えられた。　(4) 平衡表面張力値は、4分子種間で差異はなかった。また、界面形成後の表面張力の低下速度もB0が遅かった以外、ほぼ同様の挙動を示し、乳化特性との相関はなかった

NEUTROPHILIC MYOSITIS ASSOCIATED WITH PYODERMA GANGRENOSUM IN A BREAK-DANCER

Neutrophilic myositis is an extremely rare condition, cases of which have been reported in association with neutrophilic dermatosis, inflammatory bowel disease and malignant hematological disease. The disorder is histologically characterized by a sterile infiltration of neutrophils throughout muscle, with necrosis of muscle fibres. We here report the case of a young male who also had associated pyoderma gangrenosum, and who presented with necrotizing fasciitis-like manifestations. In this case, although there were no other underlying disorders, compulsive exertional stress due to break-dancing was thought to be a precipitant. Debridement of the necrotic tissues combined with oral corticosteroid treatment was effective

Design and Synthesis of 8-Hydroxyquinoline-based Radioprotective Agents

In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn2+ in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against g-ray radiation (10 Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and –independent apoptotic pathways