Oral administration of Ren-shen-yang-rong-tang \u27ninjin\u27yoeito\u27 protects against hematotoxicity and induces immature erythroid progenitor cells in 5-Fluorouracil-induced anemia

金沢大学医薬保健研究域薬学系The purpose of this study was to investigate the efficacy of four different Japanese and Chinese herbal prescriptions, Ren-Shen-Yang-Rong-Tang (Ninjin\u27yoeito, NYT), Chai-Hu-Gui-Zhi-Gan-Jiang-Tang (Saikokeishikankyoto, SKKT), Si-Jun-Zi-Tang (Shikunshito, SKT) and Si-Wu-Tang (Shimotsuto, SMT), which are traditionally used for anemia and fatigue, against hematotoxicity in mice treated with 5-fluorouracil (5-FU). NYT 1100 mg kg-1 day-1 injected orally for 7 consecutive days before and after 5-FU injection significantly suppressed reductions in red blood cell, white blood cell and platelet counts in peripheral blood, and accelerated their recovery. Administration of SKKT also produced a slight but significant improvement in 5-FU-induced erythrocytopenia, whereas SMT and SKT could not prevent anemia. Oral injection of NYT also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 10, and markedly hastened their recovery on day 20, in a dose-dependent manner. Erythroid progenitor colonies, such as colony forming units-erythroid and burst forming units-erythroid, formed by marrow cells from mice treated with 5-FU were significantly increased by oral administration of NYT. These findings suggest that NYT has the potential to protect against hematotoxicity, and also has hematopoietic activity, through stimulation of immature erythroid progenitor cell differentiation.出版者許諾要件により全文公開は2010年7月より

Lattice Formulation of Two-Dimensional N=(2,2) SQCD with Exact Supersymmetry

We construct a lattice model for two-dimensional N=(2,2) supersymmetric QCD (SQCD), with the matter multiplets belonging to the fundamental or anti-fundamental representation of the gauge group U(N) or SU(N). The construction is based on the topological field theory (twisted supercharge) formulation and exactly preserves one supercharge along the line of the papers [1]--[4] for pure supersymmetric Yang-Mills theories. In order to avoid the species doublers of the matter multiplets, we introduce the Wilson terms and the model is defined for the case of the number of the fundamental matters (n_{+}) equal to that of the anti-fundamental matters (n_{-}). If some of the matter multiplets decouple from the theory by sending the corresponding anti-holomorphic twisted masses to the infinity, we can analyze the general n_{+}\neq n_{-} case, although the lattice model is defined for n_{+} =n_{-}. By computing the anomaly of the U(1)_A R-symmetry in the lattice perturbation, we see that the decoupling is achieved and the anomaly for n_{+}\neq n_{-} is correctly obtained.Comment: 39 pages, no figures, LaTeX, (v2) some explanation added, (v3) misprint in eq.(3.19) corrected, (v4) version to be published in Nucl. Phys. B, (v5) a typo in eq.(A.12) fixe

Preoperative biliary drainage for biliary tract and ampullary carcinomas

We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ 1. Is preoperative biliary drainage necessary for patients with jaundice? The indications for preoperative drainage for jaundiced patients are changing greatly. Many reports state that, excluding conditions such as cholangitis and liver dysfunction, biliary drainage is not necessary before pancreatoduodenectomy or less invasive surgery. However, the morbidity and mortality of extended hepatectomy for biliary cancer is still high, and the most common cause of death is hepatic failure; therefore, preoperative biliary drainage is desirable in patients who are to undergo extended hepatectomy. CQ 2. What procedures are appropriate for preoperative biliary drainage? There are three methods of biliary drainage: percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) or endoscopic retrograde biliary drainage (ERBD), and surgical drainage. ERBD is an internal drainage method, and PTBD and ENBD are external methods. However, there are no reports of comparisons of preoperative biliary drainage methods using randomized controlled trials (RCTs). Thus, at this point, a method should be used that can be safely performed with the equipment and techniques available at each facility. CQ 3. Which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction? Unilateral biliary drainage of the future remnant hepatic lobe is usually enough even when intrahepatic bile ducts are separated into multiple units due to hilar malignancy. Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is difficult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. CQ 4. What is the best treatment for postdrainage fever? The most likely cause of high fever in patients with biliary drainage is cholangitis due to problems with the existing drainage catheter or segmental cholangitis if an undrained segment is left. In the latter case, urgent drainage is required. CQ 5. Is bile culture necessary in patients with biliary drainage who are to undergo surgery? Monitoring of bile cultures is necessary for patients with biliary drainage to determine the appropriate use of antibiotics during the perioperative period. CQ 6. Is bile replacement useful for patients with external biliary drainage? Maintenance of the enterohepatic bile circulation is vitally important. Thus, preoperative bile replacement in patients with external biliary drainage is very likely to be effective when highly invasive surgery (e.g., extended hepatectomy for hilar cholangiocarcinoma) is planned

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Intelligibility of Interrupted Japanese Vowels

In order to determine the role of the time factor in speech perception, and to apply this knowledge to the diagnosis of retrocochlear deafness, the intelligibility of periodically interrupted Japanese vowels was investigated. Interrupted speech sounds were produced by interruption synchronized with the fundamental frequency. Sound-time and silent-time fractions were controlled by an electronic switch. The results of two experiments showed that /a/, /e/ and /i/ are vowels of high redundancy, and /u/ and /o/ have low redundancy. No significant portion of the fundamental period needed to identify each vowel was found, but a duty cycle of above 0.5 was necessary for the identification of interrupted vowel sounds. The question of whether monosyllables or words are better test materials in the diagnosis of deafness is discussed with regard to their respective degrees of redundancy