{"title":"[The plant, which poisoned the World].","authors":"Jerzy Woy-Wojciechowski","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":94180,"journal":{"name":"Przeglad lekarski","volume":"72 8","pages":"414"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Ebola virus disease (EVD), formerly known as a hemorrhagic fever and discovered in 1976, is dangerous, highly infectious disease with very high mortality. There are no licensed therapeutics against EVD, although a range of medicines and therapies are currently being evaluated. During the 2014 Ebola outbreak, an experimental drug named ZMapp was administered on an emergency basis to seven patients of which five were recovered. Currently, since February 2015, ZMapp is tested in clinical trials. ZMapp is a mixture (named a cocktail) of three chimaeric monoclonal antibodies (mAbs) of IgG class, which bind to three different epitopes on Ebola surface glycoprotein (GP). ZMapp was created by systematic selection of antibodies from two other three-component cocktails--MB-003 and ZMab the components of which were produced by rapid transient expression method in tobacco species of Australian origin--Nicotiana benthamiana. The ZMapp antibodies of pharmaceutical grade are manufactured in green-house grown N.benthamiana according to the cGMP (current Good Manufacturing Practice), using RAMP platform (Rapid Antibody Manufacturing Platform) and MagnICON system, which utilizes transient expression by magnifection method using viral vectors delivered to plant tissue by a bacterium--Agrobacterium tumefaciens. The applied glycosylation mutant of N.benthamiana (delta XTFT) synthesizes human-like, biantennary N-glycans, with terminal N-acetylglucoseamine and without typical of plants, immunogenic sugar epitopes-beta1,2-linked xylose and alpha1,3-linked fucose. Due to an absence of fucose on N-glycans attached to the Fc domains, the plant-produced anti-Ebola mAbs elicited significantly stronger antibody-dependent cellular cytotoxicity (ADCC) than the analogous anti-Ebola mAbs with fucosylated (alpha1,6-linked fucose) N-glycans produced in a mammalian CHO cell line--the basic expression system for the industrial production of recombinant therapeutical glycoproteins. As far as a vaccine against Ebola virus disease is considered, so-called Ebola Immunogenic Complex (EIC) consisting of assembled molecules of a humanized IgG mAb--6D8 specific for Ebola GPI with GP1 fused to the C-terminus of the heavy chains, was obtained by transient expression in N. benthamiana.
埃博拉病毒病(EVD)以前被称为出血热,发现于 1976 年,是一种危险的高传染性疾病,死亡率非常高。目前还没有针对埃博拉病毒病的许可疗法,但正在对一系列药物和疗法进行评估。在 2014 年埃博拉疫情爆发期间,一种名为 ZMapp 的实验性药物被紧急用于 7 名患者,其中 5 人康复。目前,自2015年2月起,ZMapp开始接受临床试验。ZMapp是由三种嵌合型IgG类单克隆抗体(mAbs)组成的混合物(命名为鸡尾酒),可与埃博拉表面糖蛋白(GP)上的三个不同表位结合。ZMapp是从另外两种三成分鸡尾酒--MB-003和ZMab--中系统筛选出的抗体。ZMapp药物级抗体是根据cGMP(现行药品生产质量管理规范)要求,利用RAMP平台(快速抗体生产平台)和MagnICON系统在温室生长的烟草中生产的,MagnICON系统利用放大法瞬时表达病毒载体,通过肿瘤农杆菌(Agrobacterium tumefaciens)传递到植物组织中。所应用的 N.benthamiana(δ XTFT)糖基化突变体能合成类似人类的双年轮 N-聚糖,其末端为 N-乙酰葡萄糖胺,但没有典型的植物免疫原性糖表位--β1,2-连接的木糖和 α1,3-连接的岩藻糖。由于连接到 Fc 结构域的 N-聚糖上没有岩藻糖,植物生产的抗埃博拉 mAbs 所产生的抗体依赖性细胞毒性(ADCC)明显强于哺乳动物 CHO 细胞系(工业化生产重组治疗用糖蛋白的基本表达系统)生产的具有岩藻糖(α1,6-连接岩藻糖)N-聚糖的类似抗埃博拉 mAbs。就埃博拉病毒疫苗而言,所谓的埃博拉免疫原复合物(EIC)是在 N. benthamiana 中通过瞬时表达获得的,该复合物由针对埃博拉 GPI 的人源化 IgG mAb-6D8 和融合在重链 C 端的 GP1 组成。
{"title":"Tobacco against Ebola virus disease.","authors":"Jaromir Budzianowski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Ebola virus disease (EVD), formerly known as a hemorrhagic fever and discovered in 1976, is dangerous, highly infectious disease with very high mortality. There are no licensed therapeutics against EVD, although a range of medicines and therapies are currently being evaluated. During the 2014 Ebola outbreak, an experimental drug named ZMapp was administered on an emergency basis to seven patients of which five were recovered. Currently, since February 2015, ZMapp is tested in clinical trials. ZMapp is a mixture (named a cocktail) of three chimaeric monoclonal antibodies (mAbs) of IgG class, which bind to three different epitopes on Ebola surface glycoprotein (GP). ZMapp was created by systematic selection of antibodies from two other three-component cocktails--MB-003 and ZMab the components of which were produced by rapid transient expression method in tobacco species of Australian origin--Nicotiana benthamiana. The ZMapp antibodies of pharmaceutical grade are manufactured in green-house grown N.benthamiana according to the cGMP (current Good Manufacturing Practice), using RAMP platform (Rapid Antibody Manufacturing Platform) and MagnICON system, which utilizes transient expression by magnifection method using viral vectors delivered to plant tissue by a bacterium--Agrobacterium tumefaciens. The applied glycosylation mutant of N.benthamiana (delta XTFT) synthesizes human-like, biantennary N-glycans, with terminal N-acetylglucoseamine and without typical of plants, immunogenic sugar epitopes-beta1,2-linked xylose and alpha1,3-linked fucose. Due to an absence of fucose on N-glycans attached to the Fc domains, the plant-produced anti-Ebola mAbs elicited significantly stronger antibody-dependent cellular cytotoxicity (ADCC) than the analogous anti-Ebola mAbs with fucosylated (alpha1,6-linked fucose) N-glycans produced in a mammalian CHO cell line--the basic expression system for the industrial production of recombinant therapeutical glycoproteins. As far as a vaccine against Ebola virus disease is considered, so-called Ebola Immunogenic Complex (EIC) consisting of assembled molecules of a humanized IgG mAb--6D8 specific for Ebola GPI with GP1 fused to the C-terminus of the heavy chains, was obtained by transient expression in N. benthamiana.</p>","PeriodicalId":94180,"journal":{"name":"Przeglad lekarski","volume":"72 10","pages":"567-71"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Bazylewicz, Tomasz Kłopotowski, Mariusz Kicka, Łukasz Miśkiewicz, Sebastian Picheta
Unlabelled: Mercury is a heavy metal found in nature in three forms: metallic mercury, organic and inorganic compounds. It is a general protoplasmatic toxin. The pathophysiology of mercury toxicity is related to its binding to sulfhydryl groups of different receptor proteins and cellular enzymes, interrupting cellular metabolism and in this way causing cell death. In the paper we present a case of 57-year-old woman, who was admitted due to suspicion of metallic mercury parenteral poisoning. The computed tomography (CT) scan of abdomen accidentally revealed multiple disseminated tiny metallic densities. The blood mercury level was high (41.9 microg/l), as well as mercury urine level (85.7 microg/g creatinine which was 42.8 microg/l). Neurologic examination revealed unobtrusive symptoms of cerebellum affection. Psychological examination revealed disturbances of cognitive abilities reliant on the efficiency of vision organ. The results of A. Benton's organic test were abnormal. Psychiatric examination revealed no abnormalities. Results of pulmonary function tests were within normal limits.
Conclusions: The intravenous injection of metallic mercury did not cause serious clinical effects. Followup examination in order to reveal chronic toxic effects is necessary. Diagnostics and treatment of metallic mercury intoxications by parenteral injection should be carried out in the clinical toxicology departments.
{"title":"[Metallic mercury poisoning caused by intravenous injection in vague circumstances--a case report].","authors":"Anna Bazylewicz, Tomasz Kłopotowski, Mariusz Kicka, Łukasz Miśkiewicz, Sebastian Picheta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>Mercury is a heavy metal found in nature in three forms: metallic mercury, organic and inorganic compounds. It is a general protoplasmatic toxin. The pathophysiology of mercury toxicity is related to its binding to sulfhydryl groups of different receptor proteins and cellular enzymes, interrupting cellular metabolism and in this way causing cell death. In the paper we present a case of 57-year-old woman, who was admitted due to suspicion of metallic mercury parenteral poisoning. The computed tomography (CT) scan of abdomen accidentally revealed multiple disseminated tiny metallic densities. The blood mercury level was high (41.9 microg/l), as well as mercury urine level (85.7 microg/g creatinine which was 42.8 microg/l). Neurologic examination revealed unobtrusive symptoms of cerebellum affection. Psychological examination revealed disturbances of cognitive abilities reliant on the efficiency of vision organ. The results of A. Benton's organic test were abnormal. Psychiatric examination revealed no abnormalities. Results of pulmonary function tests were within normal limits.</p><p><strong>Conclusions: </strong>The intravenous injection of metallic mercury did not cause serious clinical effects. Followup examination in order to reveal chronic toxic effects is necessary. Diagnostics and treatment of metallic mercury intoxications by parenteral injection should be carried out in the clinical toxicology departments.</p>","PeriodicalId":94180,"journal":{"name":"Przeglad lekarski","volume":"69 8","pages":"575-9"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current opinions connected with HLA-E and HLA-F genes determining "nonclassical" (HLA-Ib) class I antigens of the Main Histocompatibility Complex MHC, and formed in the consequence of mutation or partial deletion of HLA-H pseudogene loci were presented. The expression of protein products of HLA-E and -F genes on some cells and tissues, their polymorphism, and also their biological functions in organisms were qualified by the use of molecular technics. The kind and frequency of occurrence of mutations 845 A (C282Y) and 187 G (H63D) in gene HLA-H were analysed, and in this context some genetic aspects of hereditary hemochromatozy (HH) were discussed.
{"title":"[Histocompatibility HLA system of man. Considerations in the light of current concepts. VII. Nonclassical HLA- E, F, and H loci].","authors":"A Kedzierska, G Turowski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Current opinions connected with HLA-E and HLA-F genes determining \"nonclassical\" (HLA-Ib) class I antigens of the Main Histocompatibility Complex MHC, and formed in the consequence of mutation or partial deletion of HLA-H pseudogene loci were presented. The expression of protein products of HLA-E and -F genes on some cells and tissues, their polymorphism, and also their biological functions in organisms were qualified by the use of molecular technics. The kind and frequency of occurrence of mutations 845 A (C282Y) and 187 G (H63D) in gene HLA-H were analysed, and in this context some genetic aspects of hereditary hemochromatozy (HH) were discussed.</p>","PeriodicalId":94180,"journal":{"name":"Przeglad lekarski","volume":"58 11","pages":"1009-12"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}