Role Of Toxins Research Articles

Metabolites from Eutypa Species that Are Pathogens on Grapes

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Older and More Recent Observations on Esca : A Critical Overview

The main research findings of studies in esca carried out over the last few years in a number of laboratories are discussed. The topics include: the disease model; the relationship between black dead arm and esca; the role of toxins and xylem cavitation in the development of leaf symptoms; the artificial reproduction of leaf symptoms and wood rot; the inoculum sources of the fungi Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and Fomitiporia mediterranea, and the influence of climate on the incidence of esca. The purpose was to sum up the current state of esca research and where possible to present new suggestions and sometimes alternatives to the suggestions of other researchers. The ultimate aim was to draw attention to those questions in esca research that are open to differing and even opposing explanations because the hard data are still lacking.

Metabolites from Eutypa species that are pathogens on grapes

Structural and synthetic studies of the metabolites isolated from Eutypa lata are reviewed. This fungus is the causative agent of Eutypa dieback disease, also known as eutyposis or dying-arm disease, a perennial canker that affects grapevines and many other woody fruit plants. The review, which encompasses all the literature in this field up to the present and in which 76 references are cited, also includes a detailed study of the biological activity of the metabolites, especially the role of toxins in the development of the plant disease. Some aspects of the synthesis and biosynthesis of these metabolites and related compounds are discussed.

Susceptibility of two fishes ( Oreochromis niloticus and Cyprinodon variegatus) to Pfiesteria shumwayae and its associated toxin: Influence of salinity

Researchers examining the mechanisms of ichthyotoxicity of Pfiesteria shumwayae have come to different conclusions about the role of toxin in this process. Some attribute fish mortality solely to direct attack by these pedunculate dinoflagellates on exposed fish tissue while others have provided evidence for a role of a soluble toxin. Detection of toxin, especially in low concentrations, is a function of the sensitivity of the selected bioassay methods and the various groups addressing this question have utilized different methods. One notable difference in fish bioassay methods utilized to detect Pfiesteria-associated toxin (PfTx) is the species of fish tested. Studies that have not detected PfTx in bioassays generally have used Cyprinodon variegatus (sheepshead minnow) as the test fish while those that have detected toxin generally used Oreochromis spp. (Tilapia). In this study response of these two fish species was compared to determine their relative sensitivity to physical attack by P. shumwayae and to PfTx. The results indicate that Oreochromis niloticus is more susceptible to P. shumwayae and its associated toxin than C. variegatus and implicate differences in the ability these species to osmoregulate as a contributing factor for this phenomenon. Salinity stress enhanced susceptibility of O. niloticus to PfTx and thus improved the sensitivity of the bioassay. The observation that salinity stress enhances toxicity to O. niloticus provides additional information regarding the mechanism of PfTx toxicity although the conditions utilized are not representative of the natural habitat of these freshwater fish.

Structural Characterization of the Cell Wall Binding Domains of Clostridium difficile Toxins A and B; Evidence that Ca 2+ Plays a Role in Toxin A Cell Surface Association

Clostridium difficile (C.difficile) is a nosocomially acquired intestinal bacillus which can cause chronic diarrhea and life-threatening colitis. The pathogenic effects of the bacillus are mediated by the release of two toxins, A and B. The C-terminal portions of both toxins are composed of 20 and 30 residue repeats known as cell wall binding (CWB) domains. We have cloned and expressed the CWB-domains of toxins A and B and several truncated CWB-domain constructs to investigate their structure and function. The smallest CWB-domain that folded in a cooperative manner was an 11 repeat construct of toxin A. This differentiates the C-terminal domains of toxins A and B from the CWB-domain of Streptococcus pneumoniae LytA, which only requires six repeats to fold. The 11 repeat toxin A construct bound Ca2+ directly with millimolar affinity and interacted with mammalian cell surfaces in a concentration and Ca2+-dependent fashion. Millimolar Ca2+ levels also accelerated toxin mediated CHO cell killing in an in vitro cell assay. Together, the data suggest a role for extracellular Ca2+ in the sensitization of toxin A/cell-surface interactions.

Proposal for molecular mechanism of thionins deduced from physico‐chemical studies of plant toxins

We propose a molecular model for phospholipid membrane lysis by the ubiquitous plant toxins called thionins. Membrane lysis constitutes the first major effect exerted by these toxins that initiates a cascade of cytoplasmic events leading to cell death. X-ray crystallography, solution nuclear magnetic resonance (NMR) studies, small angle X-ray scattering and fluorescence spectroscopy provide evidence for the mechanism of membrane lysis. In the crystal structures of two thionins in the family, alpha(1)- and beta-purothionins (MW: approximately 4.8 kDa), a phosphate ion and a glycerol molecule are modeled bound to the protein. (31)P NMR experiments on the desalted toxins confirm phosphate-ion binding in solution. Evidence also comes from phospholipid partition experiments with radiolabeled toxins and with fluorescent phospholipids. This data permit a model of the phospholipid-protein complex to be built. Further, NMR experiments, one-dimensional (1D)- and two-dimensional (2D)-total correlation spectroscopy (TOCSY), carried out on the model compounds glycerol-3-phosphate (G3P) and short chain phospholipids, supported the predicted mode of phospholipid binding. The toxins' high positive charge, which renders them extremely soluble (>300 mg/mL), and the phospholipid-binding specificity suggest the toxin-membrane interaction is mediated by binding to patches of negatively charged phospholipids [phosphatidic acid (PA) or phosphatidyl serine (PS)] and their subsequent withdrawal. The formation of proteolipid complexes causes solubilization of the membrane and its lysis. The model suggests that the oligomerization may play a role in toxin's activation process and provides insight into the structural principles of protein-membrane interactions.

Women's Perspectives on Nutrition, Health, and Breast Cancer

Objective To explore women's beliefs about diet, health, and breast cancer. Design Individual interviews exploring women's perceptions of their eating habits, health status, and diet, health, and breast cancer beliefs. Setting Vancouver, British Columbia, Canada. Participants A culturally diverse convenience sample of women aged 40 to 60 years, including breast cancer survivors (n = 29) and women who had not had breast cancer (n = 32). Analysis Verbatim interview transcripts were coded and themes developed by sorting and summarizing coded transcript segments. Results Three perspectives on healthful eating were identified. A “traditional” perspective stressed regular meals of meat, potatoes, and vegetables and made no specific claims about the diet-breast cancer relationship. A “mainstream” perspective stressed increasing vegetables and fruits and decreasing fat intake to improve health, reduce cardiovascular disease risk, and, possibly, reduce breast cancer risk. An “alternative” perspective focused on the role of toxins, carcinogens, and protective factors in food in affecting cancer risk. Conclusions and Implications Although overall perspectives on healthful eating were not related to participants' breast cancer status, they were related to how participants thought about the relationships between diet and breast cancer. Specific diet-cancer beliefs, degree of conviction about those beliefs, and reasons why foods are believed to be protective or harmful are indicative of overall nutrition perspectives.

Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum

Background & Aims: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile, the causative agent of antibiotic-associated colitis. Methods: Ileal loops were injected with 10 μg of toxin A, and enterotoxic responses were measured at various time points. Results: Pretreatment of mice with 2.5 μg/kg of the CRH receptor antagonist α-helical CRH(9–41) that blocks both CRH receptor subtypes reduced toxin A–mediated ileal secretion, epithelial cell damage, mucosal edema, neutrophil infiltration, and mucosal content of interleukin 1β and tumor necrosis factor α. Pretreatment with the specific CRH1 receptor antagonist antalarmin (20 mg/kg, IP) also inhibited toxin A–induced fluid secretion and toxin A–associated histologic changes. CRH messenger RNA and protein were increased in mouse ileum 30 minutes after intraluminal toxin A administration. In situ hybridization and immunohistochemistry demonstrated that toxin A at 1 hour caused a substantial increase in the expression of both CRH receptor subtypes in the ileal mucosa. Conclusions: Peripheral CRH may play a proinflammatory role in toxin A–induced intestinal secretion and inflammation and that CRH1 receptor, at least in part, is important in the mediation of these responses.GASTROENTEROLOGY 2002;123:505-515

Reaction of Ptr ToxA-Insensitive Wheat Mutants to Pyrenophora tritici-repentis Race 1

ABSTRACT The host-selective toxin Ptr ToxA is produced by races 1 and 2 of Pyrenophora tritici-repentis, causal agent of tan spot of wheat. Ptr ToxA has been causally associated with pathogenicity by the race 2 phenotype in this system. However, the role of toxin in disease caused by race 1, the most prevalent form of the fungus in the central and northern Great Plains of North America, has not been rigorously investigated. Three independent wheat lines harboring mutations for insensitivity to Ptr ToxA were derived from ethylmethane sulfonate treatment of the hard red spring wheat cv. Kulm, possessing the single dominant gene for toxin sensitivity. Each of the three mutants was insensitive to Ptr ToxA in bioassays based on necrosis development and electrolyte leakage. Each mutant was crossed to each of the other mutants and to the wild-type Kulm. Segregation data indicate that each mutant line harbors a single recessive mutation for toxin insensitivity that maps to or near the same locus, possibly the toxin-sensitivity gene. Each toxin-insensitive mutant line was susceptible to two isolates of race 1 of P. tritici-repentis. F(2) and F(3) generations derived from crosses between Kulm and each mutant segregated for toxin reaction. However, segregation for fungal reaction was not evident, and all F(3) families were tan spot susceptible regardless of toxin reaction. Host insensitivity to Ptr ToxA is not necessarily equivalent to resistance to race 1. Ptr ToxA should not be used alone as a proxy for fungal inoculations by breeding programs aimed at developing tan spot-resistant wheat.

Role of Toxins in Intake of Varied Diets by Sheep

Herbivores foraging on toxic plants may consume a variety of foods that contain different toxins to increase food intake and to avoid toxicosis. We studied whether lambs offered two foods, each containing a different toxin, could ingest more food than lambs offered one food with a single toxin. Thirty-two lambs were allotted to four groups that received: (1) a ration with toxin A, (2) a ration with toxin B, (3) two rations, one with toxin A and the other with toxin B, and (4) a ration with no toxins. Toxin pairs used in the study were (1) amygdalin and lithium chloride (LiCl), (2) LiCl and LiCl, (3) sparteine and saponin, (4) oxalate and nitrate, and (5) tannin and saponin. For an hour each morning, lambs were offered their ration(s) and intakes were measured. Lambs were maintained on an alfalfa pellet or grass hay diet. Each trial lasted either five or six days. Whether or not lambs ate more when offered foods with different toxins depended on the kind and amount of toxin in the food. Lambs offered rations with amygdalin and LiCl or oxalate and nitrate consumed more food than lambs offered a ration with only one of these toxins. Lambs offered rations with sparteine and saponin or tannin and saponin did not eat more food than lambs offered a ration with either saponin or sparteine or tannin alone. Nor did lambs eat more when offered two rations both containing LiCl. In all trials, lambs offered toxins showed no signs of toxicosis, and they ate less food than lambs offered rations without toxins. Our results indicate that in some cases ruminants can increase intake of toxic foods by consuming foods containing different toxins. However, currently the only way to determine how specific toxins may interact in the body to influence intake would be to conduct feeding trials using plants or ground diets that contain toxins.

Effect of Clostridium difficile toxin A on human colonic lamina propria cells: early loss of macrophages followed by T-cell apoptosis.

We have previously shown that Clostridium difficile toxin A induces detachment of human colonic epithelial cells from the basement membrane and subsequent cell death by apoptosis. Because these cells require adhesion-dependent signalling from the extracellular matrix for survival, their detachment from the basement membrane by other means also induces apoptosis. The role of toxin A in the induction of apoptosis therefore remains to be determined. In addition, sensitivities to C. difficile toxin A of lamina propria lymphocytes, macrophages, and eosinophils, which lie below the surface epithelium, are not known. In contrast to epithelial cells, these lamina propria cells do not require adhesion-dependent signalling from the extracellular matrix for survival, and this may allow the mechanisms of toxin A-induced cell death to be further investigated. The aim of this study was to investigate the effect of purified C. difficile toxin A on human colonic lamina propria T cells, macrophages, and eosinophils. We show that C. difficile toxin A induces loss of viability in isolated colonic lamina propria cell preparations containing the three different cell types in a dose- and time-dependent fashion. Exposure to high concentrations of the toxin led to loss of macrophages within 72 h. T-lymphocyte and eosinophil cell death was prominent at later time points and occurred by apoptosis. Exposure to toxin A also induced the production of tumor necrosis factor alpha by the isolated colonic lamina propria cells. However, the presence of neutralizing antibodies to this cytokine did not influence C. difficile toxin A-induced T-cell apoptosis. Moreover, purified T cells also underwent apoptosis following exposure to toxin A, implying that apoptosis occurred as a consequence of a direct interaction between T cells and the toxin. Our studies suggest that C. difficile toxin A is capable of suppressing human colonic mucosal immune responses by inducing early loss of macrophages followed by T-cell apoptosis.

The role of toxins and virulence factors in hetero trophic bacteria present in drinking water supplies

Heterotrophic plate count (HPC) bacteria are ubiquitous in both man-made and natural water systems and consist of several bacterial species which rely on carbon molecules, generally pre-formed by other organisms, as a nutrient source. Previous studies have suggested that heterotrophs may be significant to human health if present in drinking water supplies and may be responsible for incidences of gastro intestinal disturbance. Bacteria which are associated with gastrointestinal (GI) illness may be classed as enterotoxigenic (ETEC), entero invasive (EIEC), enteropathogenic (EPEC) and/or entero haemorrhagic (EHEC). An overview of the literature, discussing both the proposed role of heterotrophs in causing GI symptoms and the known factors associated with entero toxicity, e.g. cytotoxic and cytotonic activity, invasiveness and haemolysin activity will be presented. The results of a recent UK study will also be discussed. In this study isolates were obtained from both pre-flush and post-flush drinking water samples taken from both houses and multi-occupancy buildings from several geographically unrelated sites. Studies to determine the occurrence of toxigenic/virulence factors in the heterotrophs isolated were undertaken, by assessing their potential to cause GI upset, by determination of their invasiveness and cytotonic and cytotoxic effects using three different cell lines, together with haemolysin activity. The results of this study concur with others and suggest that the frequency of isolation of heterotrophic species with the capability to cause GI symptoms is too low to be of significant concern to health authorities or water companies. Furthermore, where a positive result was obtained with respect to the possession of virulence characteristics, the bacteria in question usually displayed more than one type of virulence factor.

Book reviews

Book reviewed in this article:The Future of Play Theory: A Multidisciplinary Inquiry into the Contributions of Brian Sutton‐Smith. Edited by Anthony D. Peligrini.Mothers, Babies, and Cocaine: The Role of Toxins in Development. Edited by M. Lewis & M. Bendersky.Children with Language Impairments: An Introduction. By Morag A. Donaldson.Race, Evolution, and Behaviour: A Life History Perspective. By J. Philippe Rushton.Children's Mental Health Services. Edited by Leonard Bickman & Debra J. Rog.Interaction in Cooperative Groups. Edited by Rachel Hertz‐Lazarowitz & Norman Miller.Gestalt Psychology and the Cognitive Revolution. By David J. Murray.Levels of Cognitive Development. By Tracy S. KendlerPhonological Development—The Origins of Language in the Child. By Marilyn May Vihman.Trouble Talking. A Guide for the Parents of Children with Speech and Language Difficulties. By J. Law & J. Elias.Emotional Development. By L. A. Sroufe.The Computational Infant. By Julie C. Rutkowska.Children Talk about the Mind. By K. Bartsch & H. M. Wellman.Language, Thought and Consciousness: An Essay in Philosophical Psychology. By Peter Carruthers.Latent Variables Analysis: Applications for Developmental Research. Edited by A. Von Eye & C. C. Clogg.Changing Times: Challenges to Identity. 12‐year‐olds in Belfast 1981 and 1992. By Jean Whyte.Children's Numbers. By Catherine Sophian

Mothers, Babies, and Cocaine: The Role of Toxins in Development

From the Department of Developmental and Behavioral Pediatrics University of California Davis, California

Mothers, babies, and cocaine: the role of toxins in development

Contents: C.L. Jones, Foreword. Preface. Part I:Models. D.L. Dow-Edwards, Developmental Toxicity of Cocaine: Mechanisms of Action. B.M. Lester, K. Freier, L. LaGasse, Prenatal Cocaine Exposure and Child Outcome: What Do We Really Know? B. Weiss, Incipient Hazards of Cocaine: Lessons from Environmental Toxicology. D.E. Hutchings, A.C. Zmitrovich, Methadone During Pregnancy: A Brief Review of Clinical Outcome and a New Animal Model. Part II:Methods. C.V. Vorhees, A Review of Developmental Exposure Models for CNS Stimulants: Cocaine. D.R. Neuspiel, The Problem of Confounding in Research on Prenatal Cocaine Effects on Behavior and Development. J.L. Jacobson, S.W. Jacobson, Strategies for Detecting the Effects of Prenatal Drug Exposure: Lessons from Research on Alcohol. H.C. Olson, T.M. Grant, J.C. Martin, A.P. Streissguth, A Cohort Study of Prenatal Cocaine Exposure: Addressing Methodological Concerns. M. Bendersky, S.M. Alessandri, M.W. Sullivan, M. Lewis, Measuring the Effects of Prenatal Cocaine Exposure. E.M. Ostrea, Jr., Meconium Drug Analysis. Part III:Outcomes. L.P. Spear, Alterations in Cognitive Function Following Prenatal Cocaine Exposure: Studies in an Animal Model. R. Needlman, D.A. Frank, M. Augustyn, B.S. Zuckerman, Neurophysiological Effects of Prenatal Cocaine Exposure: Comparison of Human and Animal Investigations. L.C. Mayes, M.H. Bornstein, Developmental Dilemmas for Cocaine-Abusing Parents and Their Children. S.M. Alessandri, M.W. Sullivan, M. Bendersky, M. Lewis, Temperament in Cocaine-Exposed Infants. L. Beckwith, S. Crawford, J.A. Moore, J. Howard, Attentional and Social Functioning of Preschool-Age Children Exposed to PCP and Cocaine in Utero. N.S. Woods, M. Behnke, F.D. Eyler, M. Conlon, K. Wobie, Cocaine Use Among Pregnant Women: Socioeconomic, Obstetrical, and Psychological Issues. Part IV:Intervention. A. Baxter, L.S. Butler, R.P. Brinker, W.A. Frazier, D.M. Wedgeworth, Effective Early Intervention for Children Prenatally Exposed to Cocaine in an Inner-City Context. T. Field, Cocaine Exposure and Intervention in Early Development.

Neurotoxicity induced by prenatal exposure to MPTP on the monoaminergic and peptidergic systems of the marmoset brain

The neurotoxicity induced by incidental prenatal exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in three marmosets. The baby marmosets exposed in utero to MPTP looked normal in the first few weeks of life but around 8 to 10 weeks of life they started to behave abnormally and were sacrificed when they were 20 weeks old. A marked reduction in DA levels was found in the baby marmosets prenatally exposed to MPTP as compared to the corresponding age-matched controls and this was highly significant in the caudate nucleus, putamen, and nucleus accumbens. Serotonin content was normal in the caudate and putamen and was only significantly reduced in the nucleus accumbens, hypothalamus, and cingulate cortex. Met-enkephalin levels were reduced in the caudate nucleus, putamen, and globus pallidus. Substance P content tended to be lower in all regions examined; however, the decrease was only statistically significant in the substantia nigra. These results indicate that prenatal exposure to MPTP induces a marked and long-lasting alteration in monoaminergic and peptidergic systems of the primate brain. This observation may provide a new insight into the role of toxins in the etiology of Parkinson's disease.

The Role of Toxin(s) Produced by Germinating Spores of Pyricularia oryzae in Pathogenesis

AbstractPyricularia oryzae produced toxin(s) during spore germination which induced susceptibility to infection by non‐pathogenic Alternaria alternata of rice leaves. The induced susceptibility was independent of the compatibility between the races of blast fungi used for obtaining the toxin(s) and the rice cultivars used for bioassay. Susceptibility was also induced in other susceptible species (e.g. barley, Italian ryegrass, perennial ryegrass and wheat), results suggesting that the toxin(s) are host‐selective and determine the host specificity at plant species level.

The Role of Toxin(s) Produced by Germinating Spores of Pyricularia oryzae in Pathogenesis

Abstract Pyricularia oryzae produced toxin(s) during spore germination which induced susceptibility to infection by non‐pathogenic Alternaria alternata of rice leaves. The induced susceptibility was independent of the compatibility between the races of blast fungi used for obtaining the toxin(s) and the rice cultivars used for bioassay. Susceptibility was also induced in other susceptible species (e.g. barley, Italian ryegrass, perennial ryegrass and wheat), results suggesting that the toxin(s), are host‐selective and determine the host specificity at plant species level.

Magnolia virginiana Neolignan compounds as chemical barriers to swallowtail butterfly host use

The role of toxins and deterrents in preventingtroilus group species (Lepidoptera, Papilionidae) from feeding on magnoliaceous hosts was investigated using bioassay-directed isolation ofMagnolia virginiana allelochemicals. A fraction consisting of three neolignan compounds significantly reduced survival of first instarP. palamedes, atroilus group member. Two of these compounds, magnolol and a biphenyl ether, were tested individually and were both toxic toP. palamedes. The larval survival ofP. troilus, anothertroilus group species, was also significantly reduced by magnolol but not by the biphenyl ether. In contrast,P. glaucus, a polyphagousglaucus group species that feeds on magnoliaceous hosts, was not affected by either compound. The effect of these compounds against a. polyphagous nonpapilionid was examined using the fall webworm (Hyphantria cunea, Lepidoptera: Arctiidae). The biphenyl ether but not magnolol significantly lowered webworm first-instar survival, demonstrating that polyphagy does not preadapt lepidopterans to feeding on this neolignan. These results demonstrate that although phagostimulants play a role in the specialization of thetroilus group on the Lauraceae, the presence of toxins and/or deterrents in nonhosts is also important in determining food plant patterns in these species.

Abstracts of Papers Presented at the Annual Meeting of the Canadian Phytopathological Society Banff, Alberta June 1991

Abstracts of Papers Presented at the Annual Meeting of the Canadian Phytopathological Society Banff, Alberta June 1991