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Biomedical subjects

B B Jarvis

Publications and source records attributed to B B Jarvis.

At least 37 records · Page 2Linked to original sources

Experimental lung mycotoxicosis in mice induced by Stachybotrys atra.

Stachybotrys atra is often isolated from building materials in houses with moisture problems. Spores of S. atra can contain mycotoxins which may lead to various symptoms in exposed residents in damp houses. The pathogenesis of S. atra-induced lung diseases has not been elucidated. The purpose of the present study was to investigate lung mycotoxicosis experimentally in mice after an intranasal exposure to spores of S. atra-fungus. One group of mice received one intranasal injection of spores of a toxic strain of S. atra (1 x 10(6) spores) and the other group spores of a less toxic strain. Spores of both strains contained spirolactones and spirolactams while the highly toxic strain contained also trichothecene mycotoxins, satratoxins. The spores containing satratoxins caused severe intra-alveolar, bronchiolar and interstitial inflammation with haemorrhagic exudative processes in the alveolar and bronchiolar lumen. A significant difference was observed in the severity of the lung damage caused by the two strains of S. atra. The spores without satratoxins induced a milder inflammation, so that the toxic compounds of S. atra-spores are most likely responsible for the severity of the lung injury.

Animals↗

Stachybotrys toxins. 1.

Cultures of several isolates of Stachybotrys chartarum have produced a series of cytotoxic macrocyclic trichothecenes including two newly characterized congeners: isosatratoxin G and S-isosatratoxin H. Nine immunosuppressant phenylspirodrimanes (1-9) were isolated and characterized, the majority of which are newly reported compounds.

Crystallography, X-Ray↗

Secondary metabolites and their role in evolution.

The role of secondary metabolites in evolution will be examined with the view that they are chemicals released within a system by one component which have evolved to affect other component(s) within the system. Secondary metabolites are a natural outgrowth and consequence of an increase in complexity, and they are a critical part of the chemical "glue" that holds a system together. An analysis of secondary metabolites from a broad perspective (e.g. genetics, ecology, evolution, etc.) suggests that the nature of secondary metabolism can be viewed as a critical component of an emergent system (ecological) arising from a host of interlocking cycles and feedback processes.

Animals↗

Homogentisic acid is the product of MelA, which mediates melanogenesis in the marine bacterium Shewanella colwelliana D.

Shewanella colwelliana D is a marine procaryote which produces a diffusible brown pigment that correlates with melA gene expression. Previously, melA had been cloned, sequenced, and expressed in Escherichia coli; however, the reaction product of MelA had not been identified. This report identifies that product as homogentisic acid, provides evidence that the pigment is homogentisic acid-melanin (pyomelanin), and suggests that MelA is p-hydroxyphenylpyruvate hydroxylase. This is the first report of pyomelanin in an obligate marine bacterium.

4-Hydroxyphenylpyruvate Dioxygenase↗

A biological assay for the detection of Myrothecium spp. produced macrocyclic trichothecenes.

A rapid, inexpensive bioassay to detect Myrothecium spp.-produced macrocyclic trichothecenes was developed. Media containing Myrothecium isolates were inoculated with Chlorella vulgaris, Ustilago maydis and Trichoderma viride. Based on width of the inhibition zone, isolates could be classified as highly toxigenic, non-toxigenic and intermediate. Whereas, C. vulgaris and U. maydis showed significant differences in their response to toxigenic and non-toxigenic isolates, T. viride did not. Production of roridins and verrucarins by the toxigenic isolates (by bioassay) was confirmed by thin layer chromatography and high performance liquid chromatography. This bioassay system, combined with confirmation chemical analyses, increases our ability to detect toxigenic fungal isolates.

Biological Assay↗

The toxicity of macrocyclic trichothecenes administered directly into the rat brain.

The tested macrocyclic trichothecenes are produced by Myrothecium fungi and by the plant Baccharis megapotamica. The toxicity of five macrocyclic trichothecenes has been measured by intracerebral and subcutaneous injection into rats. It is assumed that the toxic effects are based on inhibition of protein synthesis. Intoxication of rats by these compounds finds expression in slowly progressing respiratory depression and paralysis of skeletal muscles. The macrocyclics are derived from verrucarol, which lacks ring D and exhibits only low toxicity. The high toxicity of the macrocyclics, established by intracerebral and subcutaneous applications, may thus be attributed to the presence of the large ring D.

Animals↗

Macrocyclic trichothecenes produced by Stachybotrys isolated from Egypt and eastern Europe.

Twenty seven isolates of Stachybotrys chartarum, S. albipes, S. kampalensis and S. microspora from Egypt and Eastern Europe were tested for production of macrocyclic trichothecenes. Twenty of the 27 isolates, grown on rice seeds, were toxic to brine shrimp larvae. Based on TLC and HPLC analyses, 5 macrocyclic trichothecenes (verrucarin J, roridin E, satratoxins F, G & H) as well as trichoverrols were identified. When grown in liquid culture on rice extract medium, only 3 isolates were toxic and produced verrucarin J, roridin E and satratoxins G & H. Extracts from mycelial mats were more toxic than culture filterates of two isolates grown on rice extract and both contained the same macrocyclic trichothecenes (285.5 mg/4 L), in addition to trichoverrols A & B (31 mg/4 L) found in mycelial mats only. When grown on 3% sucrose Czapek's medium supplemented with peptone and yeast extract (still cultures), all isolates were non-toxic to brine shrimp and no trichothecenes could be detected in the extracts.

Animals↗

Effects of macrocyclic trichothecene congeners on the viability and mitogenesis of murine splenic lymphocytes.

The effects of several congeners of the macrocyclic class of trichothecene mycotoxins on murine splenic cells in vitro were investigated. The mycotoxins were roritoxin B, myrotoxin B, roridins A, D and E, baccharinoids B4, B5 and B12, 16-hydroxyverrucarin A, and verrucarins A and J. Lymphocytes from CD-1 mice were cultured with each of the mycotoxins for 48 h to assess cytotoxicity. The maximum effect of various trichothecenes produced on cells occurred at concentrations ranging from 10(-6) to 10(-4) M. Mycotoxins had no effect at concentrations ranging from 10(-12) to 10(-7) M. The mitogenic stimulants concanavalin A, lipopolysaccharide, phytohemagglutinin, and pokeweed mitogen were added to splenic lymphocyte cultures along with varying concentrations of selected mycotoxins. Blastogenesis was inhibited at concentrations 2-5 orders of magnitude lower than those which produced lethality on resting lymphocytes.

Animals↗

Mass spectral investigations on trichothecene mycotoxins. VII. Liquid chromatographic-thermospray mass spectrometric analysis of macrocyclic trichothecenes.

Thermally labile, polar toxic roridins and biologically active, isomeric baccharinoids were separated on a reversed-phase high-performance liquid chromatography column and effectively ionized under thermospray ionization conditions. The mass spectra indicated the formation of corresponding molecular ion-ammonium adducts in great abundance. Experiments designed for monitoring specific ions of these analytes at predesignated intervals were utilized for the accurate analysis of these macrocyclic trichothecenes in real, crude samples. A synthetically modified macrocyclic trichothecene, 8-ketoverrucarin A, was used as the internal standard for the detection and quantification of these compounds. Minimum detectable limits, during this first reported method for the unambiguous analysis of these structurally related macrocyclic trichothecenes, were determined to be 2-5 ng.

Chemical Phenomena↗

Toxicology of novel macrocyclic trichothecenes, baccharinoid B4, myrotoxin B, and roritoxin B.

Baccharinoid B4, Myrotoxin B and Roritoxin B, some recently identified macrocyclic trichothecenes, were tested in Swiss mice with respect to their toxicity after oral and topical application. For oral dosing, the mycotoxins were dissolved in propylene glycol, and doses from 0 to 8.0 mg/kg body weight (BW) were employed. For topical application, toxins were dissolved in DMSO. A dose of 40 mg/kg BW was applied, except for Roritoxin B, where a dose of 10 mg/kg BW was also utilized. Animals were observed until death, or until 14 days after application and histopathological examinations were performed. It was found that Baccharinoid B4 was only moderately toxic, but this macrocyclic trichothecene appeared to exert its toxicity particularly on the intestine. Myrotoxin B was found to be quite toxic, and Roritoxin B was determined to be the most potent and toxic macrocyclic trichothecene of the three investigated. Oral administration of Roritoxin B resulted in death of 70-90% of mice at doses up to 1.0 mg/kg BW, and topical application of 10 or 40 mg/kg BW caused 100% death within 18 hours after application.

Administration, Oral↗

Mycotoxin production by Fusarium oxysporum and Fusarium sporotrichioides isolated from Baccharis spp. from Brazil.

Fusarium oxysporum isolated from roots of and soil around Baccharis species from Brazil produced the trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol, and 3'-OH T-2 (TC-1), whereas Fusarium sporotrichioides from the same source produced T-2 toxin, HT-2 toxin, acetyl T-2, neosolaniol, TC-1, 3'-OH HT-2 (TC-3), iso-T-2, T-2 triol, T-2 tetraol, and the nontrichothecenes moniliformin and fusarin C. Several unknown toxins were found but not identified. Not found were macrocyclic trichothecenes, zearalenone, wortmannin, and fusarochromanone (TDP-1).

Brazil↗

Trichothecene mycotoxins in aerosolized conidia of Stachybotrys atra.

Stachybotrys atra is the etiologic agent of stachybotryotoxicosis, and this fungus and its trichothecene mycotoxins were recently implicated in an outbreak of unexplained illness in homes. S. atra was grown on sterile rice, autoclaved, dried, and then aerosolized by acoustic vibration. The distribution of particles (mass and number) was monitored on an aerodynamic particle sizer interfaced with a computer. Dust was collected on preweighed glass-fiber filters and extracted with 90% aqueous methanol. Extracts were tested for the ability to inhibit protein synthesis in rat alveolar macrophages, the ability to inhibit the proliferation of mouse thymocytes, and the presence of specific trichothecene mycotoxins. Virtually all of the particles were less than 15 micron in aerodynamic diameter, and the mass median diameter was 5 micron. Thus, most of the particles were respirable. Microscopic analysis of the generated dust revealed that ca. 85% of the dust particles were conidia of S. atra, another 6% were hyphal fragments, and the remainder of the particles were unidentifiable. Thus, greater than 90% of the particles were of fungal origin. The extracts strongly inhibited protein synthesis and thymocyte proliferation. Purified satratoxin H was also highly toxic in the same systems. Each of the individual filters contained satratoxin H (average, 9.5 ng/mg of dust). Satratoxin G and trichoverrols A and B were found in lesser amounts in some, but not all, of the filters. The limit of analysis is ca. 50 ng. These results establish that the conidia of S. atra contain trichothecene mycotoxins. In view of the potent toxicity of the trichothecenes, the inhalation of aerosols containing high concentrations of these conidia could be a potential hazard to health.

Aerosols↗

Trichothecenes produced by Stachybotrys atra from Eastern Europe.

A total of 17 isolates of Stachybotrys atra isolated from various parts of Hungary and Czechoslovakia were grown on rice, and the toxin production of each isolate was analyzed by high-performance liquid chromatography. Of the 17 isolates, 14 produced macrocyclic trichothecenes (satratoxins F, G, and H, roridin E, and verrucarin J) as well as trichoverrols A and B. Most isolates produced satratoxins G and H in higher quantities than the other trichothecenes. The yield (in milligrams) of trichothecenes produced by one isolate grown on 800 g of rice was as follows: roridin E, 12; satratoxin F, 10; satratoxin G, 75; satratoxin H, 100; trichoverrol A, 15; and trichoverrol B, 30.

Chromatography, High Pressure Liquid↗

Antileukemic compounds derived by chemical modification of macrocyclic trichothecenes. 2. Derivatives of roridins A and H and verrucarins A and J.

Various 8 beta-hydroxy, 16-hydroxy, and 9 beta,10 beta-epoxy derivatives of roridins A and H and verrucarins A and J have been prepared and tested in vivo against P388 mouse leukemia. The 9 beta,10 beta-epoxy derivatives and 16-hydroxy derivatives consistently exhibit very high activity. The 8 beta-hydroxy-9 beta,10 beta-epoxy and 16-hydroxy-9 beta,10 beta-epoxy derivatives of verrucarin A and roridin A exhibit extraordinary activity against P388. The 8 beta-hydroxy-9 beta,10 beta-epoxy and 16-hydroxy-9 beta,10 beta-epoxy derivatives of verrucarin A and roridin A exhibit extraordinary against P388.

Animals↗

Production of verrucarol.

Verrucarol was obtained from a simple procedure that involved the hydrolysis of a crude extract of a culture of Myrothecium verrucaria ATCC 24571.

Journal Article↗