Effects of substitutions of glycine and asparagine for serine132 on activity and binding of human lipoprotein lipase to very low density lipoproteins

AbstractFor studying the role of Ser132 in the putative catalytic site of human lipoprotein lipase (LPL), mutant LPL cDNAs expressing LPLs with amino acid substitutions of Gly or Asn for Ser132 were obtained by site-directed mutagenesis, and were expressed in COS-1 cells. Considerable amounts of LPL enzyme protein mass were detected in the culture medium of COS-1 cells transfected with wild-type LPL, LPL-Gly132, or LPL-Asn132. LPL-Gly132 hydrolyzed Triton X-100-triolein and tributyrin as effectively as wild-type LPL, whereas LPL-Asn132 showed no activity. LPL-Asn132 bound to very low density lipoproteins as effectively as wild-type LPL

ジョウシン ニ ハッセイシタ タケイ センシュ ノ 1レイ

多形腺腫は唾液腺腫瘍の中で最も発生頻度が高い腫瘍である. 小唾液腺にも発生する多形腺腫の中であるが, 口唇に発生することはまれである. 今回われわれは口唇腺に発生した多形腺腫の1例を経験したので文献的考察を加えて報告する. 患者は52歳女性で, 上唇の腫瘤精査目的に当院皮膚科を受診し, 上唇良性腫瘍と診断され, 当科へ紹介され受診した. 左側上唇粘膜下に11×9 mm大の弾性硬, 可動性良好な腫瘤を認め, 全身麻酔下に摘出術を施行した. 腫瘍は被膜に包まれており, 周囲組織との境界は明瞭であった. 病理組織学的検査所見では, 腫瘍は薄い線維性被膜に覆われ, 大小の腺管構造とその周囲に筋上皮細胞の増殖, および軟骨様組織の形成を認め, 多形腺腫との診断であった. 術後1年6か月経過した現在, 口唇の機能的, 形態的異常はみられず, 腫瘍の再発は認めていない. 多形腺腫には悪性転化の報告もあり, 今後も注意深く経過観察を行う必要があると考えられる.Pleomorphic adenoma is the most common type of salivary gland tumor. The lip is a rare site of onset for pleomorphic adenomas that occur in the minor salivary glands. Here, we report our experience in the treatment of a patient with pleomorphic adenoma of the labial gland along with a review of the literature.The patient was a 52-year-old female who was referred to our department after consultation at the dermatology department of our institution for detailed examinations of a mass in the upper lip and being diagnosed with a benign tumor of the upper lip. A firm, elastic, highly movable mass of 11 × 9 mm was found under the mucosa of the left upper lip, which was excised under general anesthesia. The tumor was surrounded by a capsule, and the boundary of the surrounding tissue was well-delineated. Histopathological examinations revealed a thin fibrous capsule, and the proliferation of myoepithelial cells and formation of cartilage-like tissue were observed in and around the large and small ductal structures. Consequently, the tumor was diagnosed as a pleomorphic adenoma. At present, 1.5 years after surgery, no functional and morphological abnormalities of the lip have been observed, and there has been no recurrence of the tumor. Since there have been reports of malignant transformation of pleomorphic adenomas, careful follow-up will be necessary in the future

当科が報告したインシデントレポートの分析

当院では 2010年7月からコンピューターを用いたインシデント報告システムを導入し,職員が匿名でインシデントを報告できる体制となっている.本体制運用開始後10年間に当科で報告されたインシデントレポート55件を患者影響レベルに従って8段階に分類した.レベル0は6件(10.9%),レベル1は14件 (25.5%),レベル2は13件(23.6%),レベル 3a は10件(18.2%),レベル3bは8件(14.5%),レベル4aは0件(0%),レベ4bは3件(5.4%),レベ5は1 件(1.8%)であった.当科におけるレベル別報告件数の比率は，重大なアクシデントと中等度のエラーと300のヒヤリ・ハットの比率が1：29：300であるというハインリッヒの法則に則っていなかった.しかし当科では2010年から2020年にかけてヒヤリ・ハット報告数は増加しているため,インシデントを報告する習慣が身につきつつあると考えられた.今後,より積極的に報告を行うように，職員へのさらなる啓蒙活動が医療事故の防止のために重要であると考えられた.In July 2010,we introduced a computerized incident reporting system, which allows staff to report incidents anonymously. The 55 incidents reported in our department during the first 10 years of operation of this system were classified into 8 levels according to the patient impact level. Level 0 was 6 incidents (10.9%),level 1 was 14 incidents (25.5%),level 2 was 13 incidents (23.6%),level 3a was 10 incidents (18.2%),level 3b was 8 incidents (14.5%),level 4a was 0 incidents (0%),level 4b was 3 incidents (5.4%),and level 5 was 1 incident (1.8%).The ratio of the number of reports by level in our department did not follow Heinrich\u27s law, which states that the ratio of serious incidents to moderate errors and 300 near-misses is 1:29:300.However,the number of Hiyari-Hatto reports increased from 2010 to 2020 in our department, suggesting that the habit of reporting incidents is becoming more common. In the future, it will be important to educate the staff to report more actively in order to prevent medical accidents

Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects

Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration

シガ イカ ダイガク イガクブ フゾク ビョウイン ニオケル オーラル マネージメント システム ノ リンショウテキ ケントウ

当科では2014年から周術期口腔機能管理を目的に「オーラルマネージメントシステム」を稼働させている．2015年には患者に快適，安心，安全な周術期環境を提供することを目的とした，麻酔科医,薬剤師,歯科医師,歯科衛生士,看護師，管理栄養士,言語聴覚士など多職種からなる「周術期管理チーム」が発足し，当科はそのチームの一員として「オーラルマネージメントシステム」を使った口腔機能管理を担っている．今回われわれは，このシステムを利用して全身麻酔手術前の周術期口腔機能管理を実施した患者数の推移および依頼状況を把握するため臨床的検討を行った. 当院における2019年度の周術期口腔機能管理実施件数は1377件と2015年から比較して約1.6倍に増加し,実施率も34.5％と増加を認めた. 院内での啓蒙活動により,多職種における人々の口腔内に関する意識が高まり,周術期口腔機能管理実施件数や実施率の増加に繋がったと考えられた. その一方でマンパワーやチェア台数の不足などの課題も明らかとなった. 今回の調査結果を元に今後もシステムの発展に尽力する予定である.Since 2014, the Department of Oral and Maxillofacial Surgery at the Shiga University of Medical Science Hospital has been running an ‟Oral management system” specialized for oral management in the perioperative period. In 2015, the ‟Perioperative management team” was formed with the aim of providing a safe perioperative environment for patients. The team comprises anesthesiologists, pharmacists, dentists, dental hygienists, nurses, dietitians, speech pathologists, and other professionals, and manages the oral functions of patients. In this study, we report the statuses of requests and rate of adoption of the ‟Oral management system” in every department. In 2019, the number of cases of perioperative oral function management in our hospital was 1,377, an increase of about 1.6 times compared to 2015, and the implementation rate also increased to 34.5%. The educational activities in the hospital increased the awareness of the oral health of people in many professions, and led to an increase in the number and rate of perioperative oral function management. On the other hand, issues such as the lack of manpower and the number of chairs became apparent. Based on the results of this survey, we plan to continue our efforts to develop the system

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5

Protein homeostasis, including protein folding, refolding, and degradation, is thought to decline with aging. HSPB5 (also known as αB-crystallin) prevents target protein aggregation as a molecular chaperone and exhibits a cytoprotective function against various cell stresses. To elucidate the effect of HSPB5 on endoplasmic reticulum (ER) stress, we searched for novel binding proteins of HSPB5 using the proximity-dependent biotin labeling method. Proteins presumed to interact with HSPB5 in cells treated with the proteasome inhibitor MG132 were identified by a reversible biotin-binding capacity method combining tamavidin2-REV magnetic beads and mass spectrometry. We discovered a new binding protein for HSPB5, polo-like kinase 2 (PLK2), which is an apoptosis-related enzyme. The expression of PLK2 was upregulated by MG132 treatment, and it was co-localized with HSPB5 near the ER in L6 muscle cells. Inhibition of PLK2 decreased ER stress-induced phosphorylation of serine 19 in HSPB5 and increased apoptosis by activation of caspase 3 under ER stress. Overexpression of HSPB5 (WT) suppressed the ER stress-induced caspase 3 activity, but this was not observed with phospho-deficient HSPB5 (3A) mutants. These results clarify the role of HSPB5 phosphorylation during ER stress and suggest that the PLK2/HSPB5 pathway plays an essential role in cytoprotection against proteasome inhibition-induced ER stress

Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5

Protein homeostasis, including protein folding, refolding, and degradation, is thought to decline with aging. HSPB5 (also known as αB-crystallin) prevents target protein aggregation as a molecular chaperone and exhibits a cytoprotective function against various cell stresses. To elucidate the effect of HSPB5 on endoplasmic reticulum (ER) stress, we searched for novel binding proteins of HSPB5 using the proximity-dependent biotin labeling method. Proteins presumed to interact with HSPB5 in cells treated with the proteasome inhibitor MG132 were identified by a reversible biotin-binding capacity method combining tamavidin2-REV magnetic beads and mass spectrometry. We discovered a new binding protein for HSPB5, polo-like kinase 2 (PLK2), which is an apoptosis-related enzyme. The expression of PLK2 was upregulated by MG132 treatment, and it was co-localized with HSPB5 near the ER in L6 muscle cells. Inhibition of PLK2 decreased ER stress-induced phosphorylation of serine 19 in HSPB5 and increased apoptosis by activation of caspase 3 under ER stress. Overexpression of HSPB5 (WT) suppressed the ER stress-induced caspase 3 activity, but this was not observed with phospho-deficient HSPB5 (3A) mutants. These results clarify the role of HSPB5 phosphorylation during ER stress and suggest that the PLK2/HSPB5 pathway plays an essential role in cytoprotection against proteasome inhibition-induced ER stress

Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects

Abstract Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration