Biosynthesis and Toxicological Effects of Patulin

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects

Polycystic kidney disease: an unrecognized emerging infectious disease?

Polycystic kidney disease (PKD) is one of the most common genetic diseases in humans. We contend that it may be an emerging infectious disease and/or microbial toxicosis in a vulnerable human subpopulation. Use of a differential activation protocol for the Limulus amebocyte lysate (LAL) assay showed bacterial endotoxin and fungal (1-->3)-beta-D-glucans in cyst fluids from human kidneys with PKD. Fatty acid analysis of cyst fluid confirmed the presence of 3-hydroxy fatty acids characteristic of endotoxin. Tissue and cyst fluid from three PKD patients were examined for fungal components. Serologic tests showed Fusarium, Aspergillus, and Candida antigens. IgE, but not IgG, reactive with Fusarium and Candida were also detected in cyst fluid. Fungal DNA was detected in kidney tissue and cyst fluid from these three PKD patients, but not in healthy human kidney tissue. We examine the intertwined nature of the actions of endotoxin and fungal components, sphingolipid biology in PKD, the structure of PKD gene products, infections, and integrity of gut function to establish a mechanistic hypothesis for microbial provocation of human cystic disease. Proof of this hypothesis will require identification of the microbes and microbial components involved and multifaceted studies of PKD cell biology

Identification and characterization of the maize arogenate dehydrogenase gene family

In plants, the amino acids tyrosine and phenylalanine are synthesized from arogenate by arogenate dehydrogenase and arogenate dehydratase, respectively, with the relative flux to each being tightly controlled. Here the characterization of a maize opaque endosperm mutant (mto140), which also shows retarded vegetative growth, is described The opaque phenotype co-segregates with a Mutator transposon insertion in an arogenate dehydrogenase gene (zmAroDH-1) and this led to the characterization of the four-member family of maize arogenate dehydrogenase genes (zmAroDH-1–zmAroDH-4) which share highly similar sequences. A Mutator insertion at an equivalent position in AroDH-3, the most closely related family member to AroDH-1, is also associated with opaque endosperm and stunted vegetative growth phenotypes. Overlapping but differential expression patterns as well as subtle mutant effects on the accumulation of tyrosine and phenylalanine in endosperm, embryo, and leaf tissues suggest that the functional redundancy of this gene family provides metabolic plasticity for the synthesis of these important amino acids. mto140/arodh-1 seeds shows a general reduction in zein storage protein accumulation and an elevated lysine phenotype typical of other opaque endosperm mutants, but it is distinct because it does not result from quantitative or qualitative defects in the accumulation of specific zeins but rather from a disruption in amino acid biosynthesis

Real and Perceived Risks for Mycotoxin Contamination in Foods and Feeds: Challenges for Food Safety Control

Mycotoxins are toxic compounds, produced by the secondary metabolism of toxigenic moulds in the Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys genera occurring in food and feed commodities both pre- and post-harvest. Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. When ingested, mycotoxins may cause a mycotoxicosis which can result in an acute or chronic disease episode. Chronic conditions have a much greater impact, numerically, on human health in general, and induce diverse and powerful toxic effects in test systems: some are carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic and neurotoxic. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. However, in developing countries, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. Therefore both producers and governmental control authorities are directing their efforts toward the implementation of a correct and reliable evaluation of the real status of contamination of a lot of food commodity and, consequently, of the impact of mycotoxins on human and animal health

Cryoprecipitation Properties and Structural Analysis of a High Affinity Anti-Fluorescein Immunoglobulin-M Antibody

212 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1988.A high affinity (K\sb{\rm a} = 2.9 \times 10\sp M\sp{-1}) murine monoclonal anti-fluorescein IgM antibody (18-2-3) exhibiting low temperature insolubility in the absence of bound ligand has served as a model to study cryoprecipitation. Insolubility of 18-2-3 at low temperature (4\sp\circC) had been shown to be reversible at higher temperatures and in the presence of fluorescyl ligand, indicating antigen binding site involvement. The primary objectives were to isolate and identify structural component(s) responsible for insolubility at low temperature. Procedures were developed for production and isolation of the monomeric subunit (IgM\sb{\rm s}) and Fab and (Fc)\sb5 fragments. Electrostatic interactions were implicated as being responsible for atypical low temperature insolubility of 18-2-3 since self-aggregation was sensitive to pH, ionic strength, temperature and protein concentration. Results indicated that interactions involving 18-2-3 antibody-combining sites with interactive sites in the Fc region of homologous IgM were responsible for the phenomenon of cryoprecipitation.The complete V region sequences of 18-2-3 were determined by Edman degradation and nucleotide sequence analysis. The V\sb{\rm H} region of 18-2-3 was encoded by a gene (V\sb{\rm H}IB) of the Q52 V\sb{\rm H} family that had 96% homology with that of anti-oxazolone antibody NQ7.5.3, but appeared to utilize a larger D region (D\sb{\rm Q52} plus N region). The V\sb\kappa region of 18-2-3 was encoded by a gene (V\sb\kappaIV) that had an amino acid sequence 97% homologous to that of anti-oxazolone antibody NQ11.1.18. J gene usage was J\sb{\rm H}4 and J\sb\kappa5. This was the first variable region sequence of a murine IgM that self-aggregates at low temperature.Solid phase analyses showed that 18-2-3 was not idiotypically related to prototypic anti-fluorescein antibodies 4-4-20 and 9-40, but that 18-2-3 could bind to other IgM antibodies, both murine and human. Hemagglutination assays indicated that 18-2-3 was not a cold agglutinin. Preferential binding of fluorescein to 18-2-3 heavy chain occurred as determined by affinity labeling with fluorescein isothiocyanate isomer I.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD