Review Article Immunogenetic Analysis of Severe Forms of Parasitic Diseases

Malaria and Schistosomiasis are the major endemic parasitic diseases in the world. The former is killing over one million children in Africa per year, and the latter suffers several millions in the endemic areas in Asia, Africa and South America. Collaborative studies were performed to identify some genetic factors contributing to the development of fatal forms of these infectious diseases. In Thailand, TNF-ﾎｱ 5\u27- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc <0.0001, OR=124.86) and Burma (Pc <0.0001, OR = 34.50). In China, we have identified two major genes related to severity of liver fibrosis, one was HLA-class II and the other was IL-13 gene. The allele frequencies of HLA-DRB5*0101 and IL-13 promoter A/A homozygote were both increased in the fibrotic group although the two genes are located in the different chromosomes, Chromosome 6p and 5q. The person who had both genotypes showed much higher Odds Ratio (OR=24.5) compared with sum of either genotype positive persons (OR=5.1 for HLA-DRB5*0101, OR=3.7 for IL-13P A/A). The observation that the effect of the two susceptible markers were synergistic rather than additive, strongly suggested that the pathogenic Th2 response directly influence the prognosis of post-Schistosomal liver fibrosis

Host genetic susceptibility to severe dengue infection

Epidemiological evidence indicates that host genetic factors are relevant and predispose DHF/DSS development. Here, we review the host genetic studies concerning human leucocyte antigens, antibody receptors, immune/inflammatory mediators, attachment molecules, cytokines and other factors exerting an immunoregulatory effect as well as the current genome-wide association studies. We also discuss some viewpoints on future challenges related to the design of safe and effective prevention and treatment options

Enzymatic one-step ring contraction for quinolone biosynthesis.

The 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities. Here we report in vitro and computational analyses leading to the discovery of a hemocyanin-like protein AsqI from the Aspergillus nidulans aspoquinolone biosynthetic pathway that forms viridicatins via a conversion of the cyclopenin-type 6,7-bicyclic system into the viridicatin-type 6,6-bicyclic core through elimination of carbon dioxide and methylamine through methyl isocyanate

Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

<p>Abstract</p> <p>Background</p> <p>Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)_nrepeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated.</p> <p>Methods</p> <p>Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated <it>Plasmodium falciparum </it>malaria (UM) and 80 cases with <it>Plasmodium vivax </it>malaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand.</p> <p>Results</p> <p>The number of (GT)_nrepeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GT_nrepeats. The genotype of (GT)_nrepeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed.</p> <p>Conclusions</p> <p>Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With this limited sample size, the finding of the lack of association between malaria disease pathogenicity/severity genetic polymorphisms of HO-1 (GT)_nrepeat as well as TNF observed in this study may not entirely exclude their possible link with malaria disease pathogenicity/severity. Further study in larger sample size is required.</p

Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.

Epoxides are highly useful synthons and biosynthons for the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a reaction that is notably missing, in regard to the synthetic toolbox, is cationic rearrangement that takes place under strong acid. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis

経営管理におけるＫＰＩプールを活用した業務プロセス改革に関する研究

本論文は、経営管理に役立つ業務プロセス改革を効率的かつ効果的に進めるために、①業務レベルの課題として、効率的かつ効果的な現状業務の可視化、②管理レベルの課題として、業務プロセス改革に最適なＫＰＩ（Key Performance Indicator:重要業績指標）の設定、③戦略レベルの課題として、戦略・戦術にひもづいた業務プロセス改革対象業務の抽出の３つに分けて探究し、それぞれに新手法を考案した上で、実務での適用効果を確認したものである。第１章では、本研究の目的とフレームワークを明確にしている。すなわち、業務レベル、管理レベル、および、戦略レベルにおける業務プロセス改革の課題を整理し、課題解決の考え方と新手法について考察し、実務での適用と結論に至る筋道を示している。第２章では、業務機能の可視化について考察している。すなわち、加工組立型製造業の業務機能調査表を基にして、自己チェックで現状業務を可視化する新手法「業務機能プール」を考案し、その詳細について検討している。さらに、「業務機能プール」で可視化された現状業務を、業務フローで表現する新手法「Stream+」を考案し、その詳細についても検討している。新手法を実際に製造業の国内業務、および、海外生産拠点における業務プロセス改革プロジェクトに適用し、いずれも効率的かつ効果的に活用できることを確認している。第３章では、最適なＫＰＩの設定について考察している。まず、多くの業務プロセス改革事例から１，１８７のＫＰＩを収集整理している。つぎに、ＫＰＩの設定を支援する新手法「ＫＰＩプール」を考案し、その詳細について検討している。さらに、「ＫＰＩプール」を実際に業務プロセス改革プロジェクトで適用し、経営管理の改善に役立つＫＰＩを抽出できることを提示している。第４章では、戦略・戦術に役立つ業務プロセス改革について考察している。まず、「ＫＰＩプール」の改修を行っている。つぎに、「業務機能プール」と「ＫＰＩプール」を使って、戦略・戦術と業務プロセス改革対象の業務機能候補およびＫＰＩ候補を同時に抽出できる新手法「戦略展開フロー」を考案し、その詳細について検討している。さらに、「戦略展開フロー」を業務プロセス改革研修に適用しその効果を検証した上で、中堅機械製造企業の経営計画策定に実際に適用し、その効果を確認している。第５章では、本論文の結びとして、本論文の発見事実と貢献、今後の研究の展望について取りまとめられている。甲南大学平成26年(2014年度

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

ABSTRACT: INTRODUCTION: Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. METHODS: Electronic searches in PubMed, Scopus, the MEDION database and Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. RESULTS: Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square p = 0.1009, I2 = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers