ショクドウガン ジュツゴ ソウキ ニ キカン イカンロウ オ ガッペイ シタ 1レイ

The patient was a４５-year-old man. He had suffered from nephrotic syndrome at time of his twenties and had steroid salvage treatment. But he retired the treatment by himself. Esophageal tumor was suspected at the screening, and he was referred to our hospital. Preoperative diagnosis was the adenocarcinoma of the esophagogastric junction（cT２N０M０ stage Ⅱ）． Thoracoscopy assisted subtotal esophagectomy in prone position with D２dissection was performed. Gastric role was prepared in laparoscopic approach, and pulled up to the neck via posterior mediastinal route. Although early postoperative course was uneventful and esophageal fluoroscopy on the７th day showed no leakage, sudden dyspnea appeared on the８th day. CT examination and Bronchoscopy showed tracheoesophageal fistula. Unfortunately, the fistula didn’t get well, and we considered that it was difficult to close the fistula by only conservative treatment. Esophageal covered stent was inserted on the５６th day. After that, he could start ingestion intake and was discharged from hospital on the８５th day. Now, he is being followed up in our hospital

チュウスイ ゲンパツ フクゴウガタ セン シンケイ ナイブンピツ ガン ノ イチチケンレイ

A５２-year-old man visited our hospital because of epigastralgia. The colonoscopic examination revealed an about ４cm-protruded lesion like SMT on the appendix and findings of the biopsy specimen were compatible with the disgnosis of signet ring cell carcinoma. The primary lesion was unknown by upper gastrointestinal endoscopy, CT and PET, and the tumor markers were normal revel. At laparotomy, severe peritoneal metastasis was revealed in the abdominal cavity, especially appendix. Severe stenosis of ileocecum was found, so we conducted ileocecal resection. The histopathological diagnosis was primary signet ring cell caicinoma of appendix, SE, N２, M０, P３, pStage Ⅳ. Postoperatively mFOLFOX was started, but allergic reaction was seen after１cycle. We started Panitumumab/CPT-１１and the patient attended our emergency department with shivering chill and fever on treatment day１０. The next day he became shock state and CT revealed free air. Operation might not save his life and we started supportive care. He died on the day. The cause of his death was peritonitis by cancer perforation

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Formation of a PSI-PSII megacomplex containing LHCSR and PsbS in the moss Physcomitrella patens

Mosses are one of the earliest land plants that diverged from fresh-water green algae. They are considered to have acquired a higher capacity for thermal energy dissipation to cope with dynamically changing solar irradiance by utilizing both the "algal-type" light-harvesting complex stress-related (LHCSR)-dependent and the "plant-type" PsbS-dependent mechanisms. It is hypothesized that the formation of photosystem (PS) I and II megacomplex is another mechanism to protect photosynthetic machinery from strong irradiance. Herein, we describe the analysis of the PSI-PSII megacomplex from the model moss, Physcomitrella patens, which was resolved using large-pore clear-native polyacrylamide gel electrophoresis (lpCN-PAGE). The similarity in the migration distance of the Physcomitrella PSI-PSII megacomplex to the Arabidopsis megacomplex shown during lpCN-PAGE suggested that the Physcomitrella PSI-PSII and Arabidopsis megacomplexes have similar structures. Time-resolved chlorophyll fluorescence measurements show that excitation energy was rapidly and efficiently transferred from PSII to PSI, providing evidence of an ordered association of the two photosystems. We also found that LHCSR and PsbS co-migrated with the Physcomitrella PSI-PSII megacomplex. The megacomplex showed pH-dependent chlorophyll fluorescence quenching, which may have been induced by LHCSR and/or PsbS proteins with the collaboration of zeaxanthin. We discuss the mechanism that regulates the energy distribution balance between two photosystems in Physcomitrella

Substitution of Deoxycholate with the Amphiphilic Polymer Amphipol A8-35 Improves the Stability of Large Protein Complexes during Native Electrophoresis

Native polyacrylamide gel electrophoresis (PAGE) is a powerful technique for protein complex separation that retains both their activity and structure. In photosynthetic research, native-PAGE is particularly useful given that photosynthetic complexes are generally large in size, ranging from 200 kD to 1 MD or more. Recently, it has been reported that the addition of amphipol A8-35 to solubilized protein samples improved protein complex stability. In a previous study, we found that amphipol A8-35 could substitute sodium deoxycholate (DOC), a conventional electrophoretic carrier, in clear-native (CN)-PAGE. In this study, we present the optimization of amphipol-based CN-PAGE. We found that the ratio of amphipol A8-35 to alpha-dodecyl maltoside, a detergent commonly used to solubilize photosynthetic complexes, was critical for resolving photosynthetic machinery in CN-PAGE. In addition, LHCII dissociation from PSII-LHCII was effectively prevented by amphipol-based CN-PAGE compared with that of DOC-based CN-PAGE. Our data strongly suggest that majority of the PSII-LHCII in vivo forms C2S2M2 at least in Arabidopsis and Physcomitrella. The other forms might appear owing to the dissociation of LHCII from PS11 during sample preparation and electrophoresis, which could be prevented by the addition of amphipol A8-35 after solubilization from thylakoid membranes. These results suggest that amphipol-based CN-PAGE may be a better alternative to DOC-based CN-PAGE for the study of labile protein complexes

HAKKE: A Multi-Strategy Prediction System for Sequences

We developed a machine learning system HAKKE which is suitable for predicting functional regions from sequences, such as protein-coding region prediction, and transmembrane domain prediction. HAKKE is a hybrid system cooperated by a number of algorithms of a pool to make an accurate prediction. The system uses an extension of the weighted majority algorithm in order to fit the strength of each algorithm into given training examples. In this paper, we describe the core of the system and show some experimental results on transmembrane domain and ff-helix predictions

Cytoprotective effects of lysophospholipids from sea cucumber Holothuria atra

Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography- time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress

ROS generated by photo-excited carotenoids attacks tumor cells

A possibility of carotenoids as a photosensitizer in photodynamic therapy (PDT) was explored using fluorescence imaging.Singlet oxygen (1O2), one of the reactive oxygen species (ROS), is known to have toxicity to cells. Green plants use several carotenoids, which have n>10 length of the conjugated double bond, to relax 1O2 involuntarily generated by photosynthetic process. Some carotenoids have the T1 level (first triplet excited level) just below the energy level of 1O2 and can plunder energy from 1O2 by energy transfer and change the energy to heat by intersystem crossing. Conversely, some carotenoids with n<10 length of conjugated double bond, of which the T1 level is just above the energy level of 1O2, should generate 1O2. Additionally, carotenoids would have high affinity to cell membrane. We, therefore, anticipated carotenoids are useful as the photosensitizer in PDT.We performed in vitro experiments using neoxanthin (Neo) which has n=8 length of conjugated double bond. First, tumor cells were incubated in the medium containing 2 mu M Neo under the blue light (BL). After 24-hour incubation, cells changed to round morphology and the viability was remarkably decreased in contrast with controls. Second, ROS production of Neo excited by BL was investigated using HeLa cells expressing fluorescent protein activated by ROS (HeLa-R). HeLa-R were incubated in the medium containing 2 mu M Neo for 3h and additionally irradiated BL for 3h. We detected strong fluorescent signals from cytoplasm of HeLa-R. Moreover, the cells, in which carotenoids were removed before BL irradiation, showed the same results.We concluded from these results that carotenoids have high affinity to tumor membrane and they can produce 1O2 within tumor cells. ROS generated by photo-excited carotenoids and their toxicity to tumor cells were observed for the first time. We expect photosensitizing ability of carotenoids can be utilized in PDT.Joint Molecular Imaging Conferenc