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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Consumption of food contaminated with Fusarium moniliforme causes leucoencephalomalacia and hepatotoxicity in horses, pulmonary edema in pigs and liver cancer in rats, and has been correlated with esophageal cancer in humans. The causative agents are thought to be a family of compounds called fumonisins, which have recently been shown to be potent inhibitors of sphingosine (sphinganine) N-acyltransferase. Because inhibition at this step blocks the formation of complex sphingolipids while leading to accumulation of sphinganine, we hypothesized that exposure of animals to fumonisin-contaminated feed might be detected by analyses of serum sphingolipids. Within days of giving ponies feed contaminated with 15 to 44 micrograms/g fumonisin B1, there was an increase in the amount of free sphinganine (and sometimes sphingosine) and a reduction in complex sphingolipids. Free sphinganine and sphingosine decreased when ponies consumed less of the contaminated feed, and increased again when they consumed more fumonisin. When toxicosis was evident as indicated by other serum markers, complex sphingolipids as well as free sphingosine and sphinganine were elevated, probably due to loss of sphingolipids from dying cells. These findings establish that consumption of fumonisin-contaminated feed disrupts sphingolipid metabolism. Because the changes in sphinganine and sphingosine were seen before liver enzymes were noticeably elevated, they may be an early marker of exposure to fumonisins.
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PMID:Increases in serum sphingosine and sphinganine and decreases in complex sphingolipids in ponies given feed containing fumonisins, mycotoxins produced by Fusarium moniliforme. 164 Feb 65

Culture materials and grains contaminated with certain isolates of Fusarium moniliforme cause equine leucoencephalomalacia, porcine pulmonary edema syndrome, and liver cancer in rats. The causative agents are thought to be a family of compounds called fumonisins, which bear considerable structural similarity to the long-chain (sphingoid) base backbones of sphingolipids. Incubation of rat hepatocytes with fumonisins inhibited incorporation of [14C]serine into the sphingosine moiety of cellular sphingolipids with an IC50 of 0.1 microM for fumonisin B1. In contrast, fumonisin B1 increased the amount of the biosynthetic intermediate sphinganine, which suggests that fumonisins inhibit the conversion of [14C]sphinganine to N-acyl-[14C]sphinganines, a step that is thought to precede introduction of the 4,5-trans double bond of sphingosine (Merrill, A.H., Jr. and Wang, E. (1986) J. Biol. Chem. 261, 3764-3769). In agreement with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes with 50% inhibition at approximately 0.1 microM and reduced the conversion of [3H]sphingosine to [3H]ceramide by intact hepatocytes. As far as we are aware, this is the first discovery of a naturally occurring inhibitor of this step of sphingolipid metabolism. These findings suggest that disruption of the de novo pathway of sphingolipid biosynthesis may be a critical event in the diseases that have been associated with consumption of fumonisins.
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PMID:Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. 186 Aug 57

Fusarium moniliforme is one of the predominant fungi associated with corn intended for human and animal consumption world-wide. Fumonisins, food-borne carcinogens that occur naturally in corn, were first isolated and chemically characterized in South Africa in 1988. The major metabolite, fumonisin B1 (FB1), was subsequently shown to cause leukoencephalomalacia (LEM) in horses, pulmonary edema syndrome (PES) in pigs, and liver cancer in rats. FB1 is also a cancer promoter and initiator in rat liver; hepatotoxic to horses, pigs, rats, and vervet monkeys; cytotoxic to mammalian cell cultures; and phytotoxic to several plants. Fumonisins in home-grown corn have been associated with an elevated risk for human esophageal cancer in Transkei and China. There is a close structural similarity between fumonisin and sphingosine, and fumonisins are the first known naturally occurring inhibitors of sphingolipid biosynthesis. The natural occurrence of FB1, together with FB2 and FB3, has been reported in commercial corn and/or corn-based feeds and foods from Argentina, Australia, Brazil, Botswana, Bulgaria, Canada, China, Egypt, France, Italy, Japan, Kenya, Hungary, Nepal, Peru, South Africa, Switzerland, United States, and Zimbabwe. It is imperative that safe levels of fumonisins in human foods and animal feeds should be determined and realistic tolerance levels established as soon as possible.
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PMID:Fumonisins: their implications for human and animal health. 758 16

Fumonisins are a class of mycotoxins produced by Fusarium moniliforme and other Fusarium spp. These compounds are widely distributed in corn. Equine leukoencephalomalacia, pulmonary oedema in swine, and nephrotoxicity, hepatotoxicity and liver cancer in male rats, all of which are caused by toxic F. moniliforme, have been experimentally reproduced using fumisin B1 (FB1) (ca 90-94% purity). To investigate the effect of purified (> or = 99% purity) FB1, to compare the effects of FB1 in males and females, and to obtain dose-response information for FB1, three rats per sex were fed diets containing 0, 15, 50 or 150 FB1 for 4 weeks. Serum chemical, organ weight and histopathological evidence showed that 150 mg/kg FB1 was hepatotoxic in both sexes. Nephrosis was found in males fed > or = 15 mg/kg and females fed > or = 50 mg/kg FB1. Altered sphingolipid profiles, specifically increased free sphinganine concentrations and increased sphinganine:sphinogosine ratios, were found in the liver, kidney, serum and urine of FB1-fed rats. These findings support the hypothesis that in vivo toxicity caused by fumonisins may result from altered sphingolipid metabolism.
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PMID:Subchronic toxicity of fumonisin B1 to male and female rats. 766 45

Fusarium moniliforme (FM) is a major fungal pathogen of corn and is involved with stalk rot disease. FM is widely spread throughout the world, including the United States. Most strains of FM produce several mycotoxins, the most prominent of which is called fumonisin. Recent epidemiological studies indicated that ingestion of fumonisin correlates with a higher incidence of esophageal cancer in Southern and Northern Africa and China. Furthermore, fumonisin causes a neurodegenerative disease in horses, induces hepatic cancer in rats, and induces pulmonary edema in swine. Considering that high levels of fumonisin have been detected in healthy and diseased corn grown in the United States, fumonisin may pose a health threat to humans and livestock animals. Structurally, fumonisin resembles sphingolipids which are present in the membranes of animal and plant cells. At the present time, very little is known concerning the mechanism by which fumonisin elicits its carcinogenic effect. Our studies indicate that fumonisin represses expression of protein kinase C and AP-1-dependent transcription. In contrast, fumonisin stimulated a simple promoter containing a single cyclic AMP response element. Since fumonisin did not alter protein kinase A activity, it appears that cyclic AMP response element activation was independent of protein kinase A. It is hypothesized that the ability of fumonisin to alter signal transduction pathways plays a role in carcinogenesis.
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PMID:Repression of protein kinase C and stimulation of cyclic AMP response elements by fumonisin, a fungal encoded toxin which is a carcinogen. 771 70

Fusarium moniliforme Sheldon is a common fungal contaminant of corn and produces a variety of mycotoxins. Among these are the recently discovered fumonisins, which are now known to cause certain animal diseases, namely leukoencephalomalacia in horses and pulmonary edema in swine. There is a significant association between their presence in corn and human esophageal cancer in southern Africa. Fumonisin B1 causes liver cancer in rats. Five other fumonisins--B2, B3, B4, A1 and A2, have been isolated; the last two are N-acetates of fumonisins B1 and B2 and do not appear to be toxic. Several other Fusarium species are now known to produce fumonisins. Procedures for detection and determination of fumonisins include thin layer chromatography, liquid chromatography (with fluorescence derivatization), post-hydrolysis gas chromatography, immunochemical assay, and mass spectrometry. In addition to their natural occurrence in corn-based animal feeds and in home-grown African corn used for food, fumonisins are frequently found in commercial corn-based foods. Fumonisins are moderately heat-stable. No effective detoxification process has yet been developed for use with fumonisin-contaminated feeds.
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PMID:Fumonisins. 834 25

The fumonisins (FBs) are a group of closely related mycotoxins that are prevalent in maize. They were isolated from strains of Fusarium moniliforme (Sheldon), which were implicated in the aetiology of human oesophageal cancer in the Transkei, South Africa. Their discovery explained the cause of equine encephalomalacia, or "hole in the head" syndrome, when it was found by feeding trials in horses that they elicited the disease. Subsequently, they were found to cause hepatic cancer in rats and pulmonary oedema in pigs, with most animal species tested showing liver and kidney damage. FB1 is the most important of the group and, although poorly absorbed from the gastrointestinal tract, its action is at the cellular level, affecting sphingolipid metabolism. Ceramides derived from sphingosine metabolism are cell regulatory factors affecting, among other things, DNA synthesis. Because FB1 has a close molecular resemblance to sphinganine, it interferes with ceramide biosynthesis and, hence, the processes that it regulates, which is thought to explain its carcinogenic properties. Studies on the FBs are still at a relatively early stage, but it is already clear that they play an important role in animal mycotoxicoses and, by implication, in human disease. A more positive aspect is that they will be used in elucidating the role of sphingolipids in cellular regulation.
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PMID:Fumonisins, mycotoxins of increasing importance: their nature and their effects. 884 66

Fusarium moniliforme is a widespread fungal pathogen which primarily infects corn, but can also infect rice or wheat. Fusarium moniliforme produce several mycotoxins, the most prominent of which is called fumonisin B1 (FB1). Epidemiological studies have indicated that ingestion of fumonisins correlates with a higher incidence of oesophageal cancer in Africa and China. Fumonisins also cause a neurodegenerative disease in horses, induce hepatic cancer in rats, are nephrotoxic in rats, or cause pulmonary oedema in swine. Structurally, fumonisins resemble sphingolipids and can alter sphingolipid biosynthesis. suggesting that sphingolipid alterations play a role in disease and carcinogenesis. Previous studies determined that FB1 blocked cell-cycle progression in CV-1 cells but not COS-7 cells. Herein, we have examined the effects that FB1 treatment has on cell-cycle regulatory proteins. Our studies established that FB1 treatment of CV-1 cells, but not COS-7 cells, leads to dephosphorylation of the retinoblastoma (Rb) protein. Cyclin dependent kinase 2 (CDK2) activity was repressed five- to 10-fold and cyclin E protein levels were lower in CV-1 cells after fumonisin treatment. Two CDK inhibitors, Kip1 and Kip2, were induced within 3 hours after fumonisin treatment of CV-1 cells, suggesting these two proteins mediate cell-cycle arrest induced by FB1. This mycotoxin caused large increases in sphinganine within 3 hours after addition of FB1. As sphingoid bases are known to induce Rb phosphorylation, this increase in sphinganinie might be the stimulus for the suppression of cyclin dependent kinase activities via Kip1 and Kip2. The ability of FB1 to accumulate sphingosine or sphinganine and arrest the cell cycle in some cells but not others may play an important role in carcinogenesis or disease.
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PMID:Characterization of cell-cycle arrest by fumonisin B1 in CV-1 cells. 973 26

This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.
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PMID:Discovery and occurrence of the fumonisins: a historical perspective. 1135 91

Fumonisins are a group of mycotoxins produced by Fusarium verticillioides (synonym Fusarium moniliforme Sheldon). Fumonisin B1 has acute toxicity and potential carcinogenicity to some animals, causing leukoencephalomalacia in horses, porcine pulmonary edema (PPE) and liver cancer in rats. It was considered to be epidemiologically associated with high incidence of Human Esophageal Cancer (EC) in human. At present, the study on fumonisins has reached molecular levels. 4 clustered and coregulated genes fum1, fum2, fum3 and fum4 associated with Fumonisin biosynthesis were identified through genetics study on Fumonisin producing strains of Fusarium verticillioides. The result of PCR with degenerate primers based on polyketide synthase (PKS) gene proved that fum5 was PKS gene required for fumonisin biosynthesis. Study on molecular biology of Fumonisin producing strains was also performed. Furthermore, transgenic strategies were used for ear mold resistance to Fusarium and reducing Fumonisin contamination in plants, to decrease the hazard to the health of both human and animals, as well as food safety.
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PMID:[Molecular genetics on fumonisin-producing strains of Fusarium verticillioides]. 1595 76


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