非弁膜症性心房細動患者における経口第Xa因子阻害薬(リバーロキサバン)の凝固マーカーへの影響 : トラフ期を中心に

藤田保健衛生大

Highly sensitive chiral analysis in capillary electrophoresis with large-volume sample stacking with an electroosmotic flow pump.

To improve the sensitivity in chiral analysis by capillary electrophoresis without loss of optical resolution, application of large-volume sample stacking with an electroosmotic flow pump (LVSEP) was investigated. Effects of the addition of cyclodextrin (CD) into a running solution on the LVSEP preconcentration was theoretically studied, where the preconcentration efficiency and effective separation length would be slightly increased if the effective electrophoretic velocity (v(ep, eff, BGS)) of the analytes was decreased by interacting with CD. In LVSEP-CD-modified capillary zone electrophoresis (CDCZE) and LVSEP-CD electrokinetic chromatography with reduced v(ep, eff, BGS), up to 1000-fold sensitivity increases were achieved with almost no loss of resolution. In LVSEP-CD-modified micellar electrokinetic chromatography of amino acids with increased v(ep, eff, BGS), a 1300-fold sensitivity increase was achieved without much loss of resolution, indicating the versatile applicability of LVSEP to many separation modes. An enantio-excess (EE) assay was also carried out in LVSEP-CDCZE, resulting in successful analyses of up to 99.6% EE. Finally, we analyzed ibuprofen in urine by desalting with a C(18) solid-phase extraction column. As a typical result, 250ppb ibuprofen was well concentrated and optically resolved with 84.0-86.6% recovery in LVSEP-CDCZE, indicating the applicability of LVSEP to real samples containing a large amount of unnecessary background salts

Usefulness of central venous oxygen saturation monitoring during bidirectional Glenn shunt

A PediaSat(TM) oximetry catheter (PediaSat : Edwards Lifesciences Co., Ltd., Irvine, CA, U.S.A.), which facilitates continuous measurement of central venous oxygen saturation (ScvO2), may be useful for surgery for pediatric congenital heart disease. We used PediaSat during a bidirectional Glenn shunt. The patient was a 13-month-old boy. Under a diagnosis of left single ventricle (pulmonary atresia, right ventricular hypoplasia, atrial septal defect) and residual left aortic arch/left superior vena cava, a modified right Blalock- Taussig shunt was performed. Cyanosis deteriorated, so a bidirectional Glenn shunt was scheduled. After anesthesia induction, a 4.5 Fr double-lumen (8 cm) PediaSat was inserted through the right internal jugular vein for continuous ScvO2 monitoring. Furthermore, the probe of a near-infrared, mixed blood oxygen saturation-measuring monitor was attached to the forehead for continuous monitoring of the regional brain tissue mixed blood oxygen saturation (rSO2) (INVOS(TM) 5100C, Covidien ; Boulder, CO, U.S.A.). Blockage of the right pulmonary artery and right superior vena cava decreased the oxygen saturation, ScvO2, and rSO2, but increased the central venous pressure. Although changes in ScvO2 were parallel to those in rSO2, the former showed more marked changes. A combination of ScvO2 and rSO2 for monitoring during Glenn shunt may be safer

Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

<p>Abstract</p> <p>Background</p> <p>From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs). This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs.</p> <p>Methods</p> <p>Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A-LC and Child C-LC). Immunohistochemical (IHC), Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels.</p> <p>Results</p> <p>Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue.</p> <p>Conclusion</p> <p>It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.</p

An attenuated vaccinia vaccine encoding the severe acute respiratory syndrome coronavirus-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human angiotensin-converting enzyme 2 transgenic mice from severe acute respiratory syndrome coronavirus-2 and its variants

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2 S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected

Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment

The only curative treatment in biliary tract cancer is surgical treatment. Therefore, the suitability of curative resection should be investigated in the first place. In the presence of metastasis to the liver, lung, peritoneum, or distant lymph nodes, curative resection is not suitable. No definite consensus has been reached on local extension factors and curability. Measures of hepatic functional reserve in the jaundiced liver include future liver remnant volume and the indocyanine green (ICG) clearance test. Preoperative portal vein embolization may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50%–60% is planned. Postoperative complications and surgery-related mortality may be reduced with the use of portal vein embolization. Although hepatectomy and/or pancreaticoduodenectomy are preferable for the curative resection of bile duct cancer, extrahepatic bile duct resection alone is also considered in patients for whom it is judged that curative resection would be achieved after a strict diagnosis of its local extension. Also, combined caudate lobe resection is recommended for hilar cholangiocarcinoma. Because the prognosis of patients treated with combined portal vein resection is significantly better than that of unresected patients, combined portal vein resection may be carried out. Prognostic factors after resection for bile duct cancer include positive surgical margins, especially in the ductal stump; lymph node metastasis; perineural invasion; and combined vascular resection due to portal vein and/or hepatic artery invasion. For patients with suspected gallbladder cancer, laparoscopic cholecystectomy is not recommended, and open cholecystectomy should be performed as a rule. When gallbladder cancer invading the subserosal layer or deeper has been detected after simple cholecystectomy, additional resection should be considered. Prognostic factors after resection for gallbladder cancer include the depth of mural invasion; lymph node metastasis; extramural extension, especially into the hepatoduodenal ligament; perineural invasion; and the degree of curability. Pancreaticoduodenectomy is indicated for ampullary carcinoma, and limited operation is also indicated for carcinoma in adenoma. The prognostic factors after resection for ampullary carcinoma include lymph node metastasis, pancreatic invasion, and perineural invasion

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