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Biologically Active Polypeptides of Anemonia sulcata—and of Other Sea Anemones—Tools in the Study of Exitable Membranes 海葵及其他海葵的生物活性多肽——可分泌膜研究的工具
Pub Date : 2005-01-01 DOI: 10.1081/TXR-200038380
L. Béress
During the past thirty years sea anemones turned out to be important producer of biologically highly active polypeptides acting on Na+ and K+ ion channels. They are compoused from 27 to 59 aminoacids having molecular weights from 3000 to 7000 Da. All contain six cystein molecules which are interconnected to three sisulfide bridges. Because of their specifique mode of action on nerve cell exitation and on the mammalian heart muscle they became very important tools in neurophysiology and pharmacology. In the present review the research on sea anemone polypeptid toxins is summarized from a historical point of view, focussed on the polypeptides of Anemonia sulcata, Condylactis gigantea and Anthopleura elegantissima.
在过去的三十年里,海葵被证明是作用于Na+和K+离子通道的生物高活性多肽的重要生产者。它们由27到59个氨基酸组成,分子量在3000到7000 Da之间。它们都含有6个半胱氨酸分子,它们与3个硫化物桥相连。由于它们对神经细胞兴奋和哺乳动物心肌的特殊作用方式,它们成为神经生理学和药理学的重要工具。本文从历史的角度对海葵多肽毒素的研究进行了综述,重点介绍了海葵、巨乳和细胸的多肽。
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引用次数: 5
Special Section on Bacterial Phospholipases C as Exotoxins 细菌磷脂酶C外毒素专题
Pub Date : 2005-01-01 DOI: 10.1081/TXR-200038404
H. Ikezawa
More than 60 years ago, studies on bacterial phospholipases C started with the monumental work of Macfarlane and Knight (1941). According to their study, Clostridium perfringens a-toxin having lethal, necrotic, and hemolytic activities, proved to be an enzyme ‘‘lecithinase’’ that hydrolyzes lecithin, i.e., phosphatidylcholine, into diacylglycerol and phosphorylcholine. From various points of view, this discovery was epoch-making. First, it indicates that a single enzyme can be a major lethal toxin of C. perfringens. Afterward, several other toxins, such as diphtheria toxin, proved to be enzymes. Therefore, C. perfringens a-toxin is the first bacterial toxin recognized as an enzyme. Second, this discovery poses an inevitable question. How does this enzyme exert its toxic action against host cells, leading to the
60多年前,对细菌磷脂酶C的研究始于麦克法兰(Macfarlane)和奈特(Knight)(1941)的不朽著作。根据他们的研究,产气荚膜梭菌毒素具有致死、坏死和溶血活性,被证明是一种酶“卵磷脂酶”,可以将卵磷脂,即磷脂酰胆碱水解成二酰基甘油和磷酰胆碱。从各个角度来看,这一发现都是划时代的。首先,这表明一种单一的酶可以成为产气荚膜梭菌的主要致死毒素。后来,其他几种毒素,如白喉毒素,被证明是酶。因此,产气荚膜梭菌a-毒素是第一个被确认为酶的细菌毒素。其次,这一发现提出了一个不可避免的问题。这种酶是如何对宿主细胞发挥毒性作用,从而导致
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引用次数: 0
Bacterial Phosphatidylinositol‐Specific Phospholipases C as Membrane‐Attacking Agents and Tools for Research on GPI‐Anchored Proteins 细菌磷脂酰肌醇特异性磷脂酶C作为膜攻击剂和研究GPI锚定蛋白的工具
Pub Date : 2005-01-01 DOI: 10.1081/TXR-200038412
H. Ikezawa
Bacterial phosphatidylinositol‐specific phospholipases C have been shown not only to cause breakdown of phosphatidylinositol but also to release GPI‐anchored proteins from the plasma membranes of eucaryotes. Several enzymes in this group have been sequenced by cloning genomic DNA, and the enzymes of Bacillus cereus and Listeria monocytogenes were analyzed for their structures by X‐ray crystallography. In the active sites of enzymes from Bacillus genera and L. monocytogenes, the roles of component amino acid residues in catalysis have been mostly clarified. The enzyme of Bacillus thuringiensis exhibited cytotoxicity against some cultivated cells. The enzyme of L. monocytogenes was shown to contribute to listerial infection of epithelial cells and macrophages as a virulence factor cooperating with other factors such as listeriolysin O and phosphatidylcholine‐preferring phospholipase C. Recently, this enzyme proved to stimulate the signal‐transduction system of host cells in listeriosis. The requirements for effective utilization of bacterial phosphatidylinositol‐specific phospholipases C should be considered in research on GPI‐anchored proteins, cellular transduction, and so forth, given the unique properties of these enzymes.
细菌磷脂酰肌醇特异性磷脂酶C已被证明不仅能导致磷脂酰肌醇的分解,还能从真核生物的质膜上释放GPI锚定蛋白。通过克隆基因组DNA对该组酶进行了测序,并用X射线晶体学分析了蜡样芽孢杆菌和单核增生李斯特菌的酶的结构。在芽孢杆菌属和单核增生乳杆菌的酶活性位点中,氨基酸残基的催化作用已基本阐明。苏云金芽孢杆菌酶对部分培养细胞表现出细胞毒性。单核增生乳杆菌酶作为一种毒力因子,与李斯特菌溶素O和磷脂酰胆碱偏好磷脂酶c等其他因子协同作用,参与上皮细胞和巨噬细胞的李斯特菌感染。最近,该酶被证明在李斯特菌病中刺激宿主细胞的信号转导系统。考虑到细菌磷脂酰肌醇特异性磷脂酶C的独特性质,在研究GPI锚定蛋白、细胞转导等方面应考虑有效利用这些酶的要求。
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引用次数: 1
The Bacterial Zinc‐Metallophospholipases C 细菌锌-金属磷脂酶C
Pub Date : 2005-01-01 DOI: 10.1081/TXR-200038417
R. Titball, A. Basak
The bacterial zinc‐metallophospholipases C are produced only by gram‐positive bacteria and are characterised on the basis of the presence of up to three zinc ions in the active site. Some zinc‐metallophospholipases C, like the α‐toxin of Clostridium perfringens, are potent toxins and play key roles in the pathogenesis of disease. Toxicity appears to be related to the ability of the enzyme to interact with phospholipids in host cell membranes and to the hydrolysis of both phosphatidylcholine and sphingomyelin. Significant insight into the mode of action of the zinc‐metallophospholipases has been gained from knowledge of the crystal structures of several members of this group. All of the enzymes possess an enzymatic domain, but only some zinc‐metallophospholipases possess a domain that can play a key role in the recognition of membrane phospholipids. The presence of this domain appears to be necessary for toxicity, but not all enzymes that possess this domain are toxic. Several studies have indicated that membrane active toxins, such as C. perfringens α‐toxin, might be exploited for the treatment of oncogenic disease.
细菌锌金属磷脂酶C仅由革兰氏阳性细菌产生,其特征是在活性位点存在多达三个锌离子。一些锌-金属磷脂酶C,如产气荚膜梭菌的α -毒素,是强效毒素,在疾病的发病机制中起关键作用。毒性似乎与酶与宿主细胞膜磷脂相互作用的能力以及磷脂酰胆碱和鞘磷脂的水解有关。锌-金属磷脂酶的作用方式的重要见解已经从这组成员的晶体结构的知识中获得。所有的酶都具有酶结构域,但只有一些锌-金属磷脂酶具有在膜磷脂识别中起关键作用的结构域。这个结构域的存在似乎对毒性是必要的,但并非所有拥有这个结构域的酶都是有毒的。一些研究表明,膜活性毒素,如产气荚膜梭菌α毒素,可能被用于治疗癌性疾病。
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引用次数: 7
Use of a Novel Peripheral Biomarker, Urine Trans, Trans, Muconic Acid, for Benzene Toxicity Monitoring 使用一种新的外周生物标志物,尿反式,反式,粘膜酸,苯毒性监测
Pub Date : 2005-01-01 DOI: 10.1081/TXR-200038389
V. Wiwanitkit
Benzene is a colorless poisonous toxic liquid with a sweet odor. Benzene exposure is of particular concern because recent research indicates that benzene exposure can result in chronic toxicity. Potential metabolic mechanisms underlying the hemopoietic toxicity of benzene include bioactivation of phenolic metabolites of benzene by myeloperoxidases in bone marrow, which results in hydroquinolone, a major leukemogen. In exposure and risk evaluations, the monitoring of benzene by peripheral biomarker has several advantages over a technical assessment of exposure. Of several monitoring methods, the peripheral urine biomarker, urine trans, trans‐muconic acid (ttMA) level is accepted as a novel and useful monitoring tool for early diagnosis of exposure. Presently, it is introduced as an alternative to the classical biomarker, urine phenol. Here, some previous reports on the use of ttMA as biomarker have been reviewed.
苯是一种无色的有毒液体,有一种甜味。苯暴露尤其令人担忧,因为最近的研究表明,苯暴露可导致慢性毒性。苯的造血毒性的潜在代谢机制包括骨髓中髓过氧化物酶对苯的酚类代谢物的生物活化,从而产生氢喹诺酮,一种主要的白血病原。在暴露和风险评估中,通过外周生物标志物监测苯比技术暴露评估有几个优点。在几种监测方法中,外周尿液生物标志物尿反式,反式粘膜酸(ttMA)水平被认为是早期诊断暴露的一种新颖而有用的监测工具。目前,它被介绍为经典生物标志物尿酚的替代品。本文对近年来有关ttMA作为生物标志物的报道进行了综述。
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引用次数: 1
The Economic Impact of Bt Corn Resulting from Mycotoxin Reduction 减少霉菌毒素对Bt玉米的经济影响
Pub Date : 2004-01-01 DOI: 10.1081/TXR-200027872
Felicia Wu, J. Miller, Elizabeth A. Casman
The insecticidal proteins in genetically modified hybrid Bt corn (Zea mays spp.) reduce insect damage, which in turn can reduce infection of the grain by mycotoxigenic fungi. Lower levels of Fusarium mycotoxins, fumonisin, and deoxynivalenol in Bt corn could have significant market and health impacts, both in the United States and around the world. These impacts are foregone losses through market rejection, human health losses, and animal health losses. We estimate that at current planting levels, Bt corn saves farmers in the United States about $17 million annually through reduced fumonisin and deoxynivalenol damage alone. Though not extensively grown in developing countries, the benefits there in mycotoxin reduction could be even more significant, particularly in regions where corn is a staple in the human diet.
转基因杂交Bt玉米(Zea mays spp.)中的杀虫蛋白减少了昆虫的伤害,从而减少了产霉毒素真菌对谷物的感染。在Bt玉米中较低水平的镰刀菌毒素、伏马菌素和脱氧雪腐镰刀菌醇可能对美国和世界各地的市场和健康产生重大影响。这些影响是由于市场排斥造成的损失、人类健康损失和动物健康损失。我们估计,在目前的种植水平下,仅通过减少伏马菌素和脱氧雪腐镰刀菌醇的危害,Bt玉米每年就为美国农民节省了1700万美元。虽然在发展中国家没有广泛种植,但在减少霉菌毒素方面的好处可能更为显著,特别是在玉米是人类饮食主食的地区。
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引用次数: 58
Risk of Exposure to and Mitigation of Effect of Aflatoxin on Human Health: A West African Example 黄曲霉毒素对人体健康的影响:西非的一个例子
Pub Date : 2004-01-01 DOI: 10.1081/TXR-200027817
K. Cardwell, S. Henry
The purpose of this chapter is to examine the relative risk of exposure of different human populations to food‐borne aflatoxins; the types of health impact that may be incurred by dietary exposure to aflatoxins; and possible strategies likely to mitigate risks to human health. Risk of exposure is examined in a global context comparing risk of toxin exposure by levels of national socioeconomic development. Then risk of exposure is reexamined in the context of agro‐ecology, distribution of toxigenicity of Aspergillus flavus, and social factors that influence food management practices. The effects of aflatoxin exposure on human health are explored in three sections: human disease and nutritional status, carcinogenicity, and child growth and development. The section concerning mitigation of the effects of aflatoxin on human health contrasts efficacy of regulation, food basket modification, and production‐side agriculture intervention. It is concluded that risk of hepatocellular carcinoma in developing countries, such as West Africa, may be addressed by vaccination for hepatitis B virus (HBV) and other public health options. Young children in West Africa who are chronically exposed to aflatoxin in foods and who consume nutritionally deficient diets have been shown to be stunted and underweight, as measured by World Health Organization (WHO) Z‐scores.
本章的目的是检查不同人群暴露于食源性黄曲霉毒素的相对风险;饮食中接触黄曲霉毒素可能造成的健康影响类型;以及可能减轻对人类健康风险的策略。在全球范围内审查接触风险,按国家社会经济发展水平比较毒素接触风险。然后在农业生态学、黄曲霉的毒性分布和影响食品管理实践的社会因素的背景下重新检查暴露风险。黄曲霉毒素暴露对人类健康的影响分为三个部分:人类疾病和营养状况、致癌性和儿童生长发育。关于减轻黄曲霉毒素对人类健康影响的部分对比了监管、食品篮子改造和生产侧农业干预的效果。结论是,西非等发展中国家的肝细胞癌风险可通过乙型肝炎病毒(HBV)疫苗接种和其他公共卫生选择来解决。根据世界卫生组织(世卫组织)Z - score的测量,西非长期暴露于食物中的黄曲霉毒素和饮食营养不足的幼儿已被证明发育迟缓和体重不足。
{"title":"Risk of Exposure to and Mitigation of Effect of Aflatoxin on Human Health: A West African Example","authors":"K. Cardwell, S. Henry","doi":"10.1081/TXR-200027817","DOIUrl":"https://doi.org/10.1081/TXR-200027817","url":null,"abstract":"The purpose of this chapter is to examine the relative risk of exposure of different human populations to food‐borne aflatoxins; the types of health impact that may be incurred by dietary exposure to aflatoxins; and possible strategies likely to mitigate risks to human health. Risk of exposure is examined in a global context comparing risk of toxin exposure by levels of national socioeconomic development. Then risk of exposure is reexamined in the context of agro‐ecology, distribution of toxigenicity of Aspergillus flavus, and social factors that influence food management practices. The effects of aflatoxin exposure on human health are explored in three sections: human disease and nutritional status, carcinogenicity, and child growth and development. The section concerning mitigation of the effects of aflatoxin on human health contrasts efficacy of regulation, food basket modification, and production‐side agriculture intervention. It is concluded that risk of hepatocellular carcinoma in developing countries, such as West Africa, may be addressed by vaccination for hepatitis B virus (HBV) and other public health options. Young children in West Africa who are chronically exposed to aflatoxin in foods and who consume nutritionally deficient diets have been shown to be stunted and underweight, as measured by World Health Organization (WHO) Z‐scores.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82578952","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}
引用次数: 73
Introduction to Aflatoxin and Food Safety—Part II 黄曲霉毒素与食品安全简介-第二部分
Pub Date : 2004-01-01 DOI: 10.1081/txr-200027807
Mycotoxins are secondary metabolites produced by fungi that have deleterious effects on animals and/or humans. Aflatoxins are a very toxic group of mycotoxins produced by Aspergillus species such as A. flavus Link, A. parasiticus Speare, and A. nomius Kurtzman, Horn, and Hesseltine. These fungal species are found on many food and feed crops, especially corn (Zea mays L.), cottonseed (Gossypium hirsutum L.), peanuts (Arachis hypogaea L.), and tree nuts. Aflatoxins are of great threat to food safety around the world. The Council for Agricultural Science and Technology (CAST, 2003) lists aflatoxins as a major group of mycotoxins of concern, along with fumonisins, trichochothecenes, and ochratoxins. Recently, several studies have reported cocontamination of field samples by aflatoxins along with various other mycotoxins. Recently, fumonisins have been reported to be carcinogenic to animals. The presence of multiple toxins in food raises additional safety concerns. Thus, this second issue devoted to aflatoxin food safety also will address the significance of aflatoxins in relation to other mycotoxins to give us a better understanding of their total impact. The first special issue, Aflatoxin and Food Safety—Part I, was published as Journal of Toxicology–Toxin Reviews, Vol. 22, Nos. 2 & 3, pages 139 to 459, 2003. That issue covered a variety of topics ranging from the financial impact of mycotoxin contamination in the U.S. and other parts of the world to strategies for reducing aflatoxin contamination in several crops and with multiple modalities. Also considered were molecular genetic techniques to study aflatoxin biosynthesis, and techniques for measuring aflatoxin in food, feed, and other biological specimens. The current issue expands the
真菌毒素是真菌产生的次生代谢物,对动物和/或人类有有害影响。黄曲霉毒素是一种毒性很强的真菌毒素,由曲霉产生,如a . flavus Link、a . parasiticus Speare和a . nomius Kurtzman、Horn和Hesseltine。这些真菌存在于许多食物和饲料作物上,尤其是玉米(Zea mays L.)、棉籽(Gossypium hirsutum L.)、花生(Arachis hypogaea L.)和树坚果上。黄曲霉毒素在世界范围内对食品安全构成重大威胁。农业科学技术理事会(CAST, 2003)将黄曲霉毒素与伏马菌素、曲霉菌素和赭曲霉毒素一起列为值得关注的一大类真菌毒素。最近,几项研究报告了黄曲霉毒素与各种其他真菌毒素共同污染现场样品。最近,有报道称伏马菌素对动物具有致癌性。食品中多种毒素的存在引发了额外的安全担忧。因此,专门讨论黄曲霉毒素食品安全的第二期也将讨论黄曲霉毒素与其他真菌毒素的重要性,以使我们更好地了解其总体影响。第一期特刊《黄曲霉毒素与食品安全——第一部分》于2003年在《毒理学-毒素评论杂志》第22卷第2、3期第139页至第459页上发表。该问题涵盖了各种主题,从霉菌毒素污染对美国和世界其他地区的经济影响到以多种方式减少几种作物中黄曲霉毒素污染的战略。还考虑了研究黄曲霉毒素生物合成的分子遗传技术,以及测量食品、饲料和其他生物标本中黄曲霉毒素的技术。当前的问题扩展了
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引用次数: 0
Toxicity of Ricin 蓖麻毒素的毒性
Pub Date : 2004-01-01 DOI: 10.1081/TXR-120030648
C. Winder
Ricin is a potent protein toxin derived from the beans of the castor plant (Ricinus communis). Castor beans are found in many parts of the world, and the toxin can be produced simply. Ricin's significance as a potential terrorist weapon relates in part to its wide availability and ease of extraction. Ricin comprises a number of polypeptide chains that act to assist cellular uptake of the ricin molecule, cause membrane damage, and once in the cell, inhibit protein synthesis. The toxic dose in animals is low, although there is little toxicity data in humans. Most probable exposure in humans would be from inhalation of aerosols or mists containing ricin, or by ingestion. There is one established case of assassination by injection. Signs and symptoms of toxicity in humans would probably include weakness, fever, cough and pulmonary edema occuring within 18–24 hours of inhalation exposure, followed by severe respiratory distress and death from hypoxemia in 36–72 hours.
蓖麻毒素是从蓖麻植物(Ricinus communis)的豆类中提取的一种有效的蛋白质毒素。世界上许多地方都有蓖麻,毒素的产生很简单。蓖麻毒素作为一种潜在的恐怖主义武器的重要性部分与它的广泛可用性和易于提取有关。蓖麻毒素由许多多肽链组成,这些多肽链的作用是帮助细胞吸收蓖麻毒素分子,造成膜损伤,一旦进入细胞,就会抑制蛋白质合成。对动物的毒性剂量很低,但对人类的毒性数据很少。人体接触蓖麻毒素的最可能途径是吸入含有蓖麻毒素的气雾剂或雾剂,或吞食蓖麻毒素。有一个已确定的注射暗杀案例。人体中毒的体征和症状可能包括在吸入接触18-24小时内出现虚弱、发烧、咳嗽和肺水肿,随后在36-72小时内出现严重呼吸窘迫和低氧血症死亡。
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引用次数: 13
Identifying Sources of Resistance to Aflatoxin and Fumonisin Contamination in Corn Grain 玉米对黄曲霉毒素和伏马菌素污染的抗性来源鉴定
Pub Date : 2004-01-01 DOI: 10.1081/TXR-200027865
M. J. Clements, D. G. White
Researchers at the University of Illinois seek to identify sources of genetic resistance that contribute alleles for low aflatoxin and low fumonisin accumulation in grain and low severity of Aspergillus and Fusarium ear rots to commercial corn (Zea mays L.) inbreds. Studies of resistance to aflatoxin accumulation in grain and Aspergillus ear rot began in 1988 with experiments designed to address fundamental needs of a new breeding program. Through the 1990s, diverse inbred lines, test crosses, and segregating populations were developed and evaluated for resistance in numerous environments. Concerns of industry inspired researchers to initiate an accelerated program for resistance to fumonisin accumulation in grain and Fusarium ear rot in the late 1990s. Present research in both programs is directed with the latest molecular marker technology, and is focused on incorporating novel genes for resistance from diverse sources into elite inbred lines that impart high yield to hybrid performance. With continued funding, agronomically superior sources of resistance along with information on molecular markers associated with resistance soon may be released.
伊利诺斯大学的研究人员试图确定对商品玉米(Zea mays L.)自交系的低黄曲霉毒素和低伏马毒素积累以及低曲霉和镰刀菌穗腐病严重程度的等位基因的遗传抗性来源。小麦抗黄曲霉毒素积累和抗穗腐曲霉的研究始于1988年,当时的实验是为了满足一项新的育种计划的基本需要。在20世纪90年代,开发了多种自交系、试验杂交和分离群体,并在许多环境中评估了抗性。20世纪90年代末,工业的担忧促使研究人员启动了一项加速计划,以抵抗伏马菌素在谷物和穗腐镰刀菌中的积累。目前,这两个项目的研究都以最新的分子标记技术为指导,重点是将来自不同来源的新型抗性基因整合到优秀的自交系中,从而提高杂交性能的产量。随着持续的资金投入,农艺学上优越的抗性来源以及与抗性相关的分子标记信息可能很快就会公布。
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引用次数: 46
期刊
Journal of Toxicology-toxin Reviews
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