Biomedical subjects
J W Bennett
Publications and source records attributed to J W Bennett.
Na+/Ca2+ exchange activity is increased in Alzheimer's disease brain tissues.
These studies were performed to determine the changes that occur in Na+/Ca2+ exchange activity in Alzheimer's disease (AD) brain tissues. Cerebral plasma membrane vesicles were purified by sucrose density gradient centrifugation from frozen postmortem hippocampal/temporal cortex tissue slices derived from age matched brains of normal, AD and non-Alzheimer dementia (NAD) origin (autopsy confirmed). Membrane marker assays (Na/K ATPase, muscarinic receptor, cytochrome c oxidase) revealed no change in membrane purity across different preparations. Thin-section electron microscopy revealed predominantly intact unilamellar vesicles. Vesicles were preincubated for 15 min (37 degrees C) in buffer containing 132 mM NaCl, 5 mM KCl, 1.3 mM MgCl2, 10 mM glucose and 10 mM HEPES (pH 7.4). Ca2+ uptake was initiated by diluting vesicles 20-fold with buffer containing either 132 mM NaCl or 132 mM choline chloride and 45CaCl2 then terminated by addition of 200 microM LaCl3 and rapid filtration. Ca2+ content increased rapidly at first and then maintained a steady plateau for up to 5 min. When the Ca2+ ionophore A23187 (10 microM) with 100 microM EGTA was added after 4 min, Ca2+ content was reduced to 10% of its original value. Ruthenium red (10 microM) had no effect on Ca2+ content. Na(+)-dependent Ca2+ uptake (Ca2+ content measured in choline chloride minus that measured in NaCl) was increased in AD brains as evidenced by both an increase in the initial rise in Ca2+ content and in elevated values of peak plateau Ca2+ content.(ABSTRACT TRUNCATED AT 250 WORDS)
Na(+)-Ca2+ exchange activity is increased in Alzheimer's disease brain tissues.
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Sterigmatocystin production on complex and defined substrates.
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Biosynthetic origin of aflatoxin G1: confirmation of sterigmatocystin and lack of confirmation of aflatoxin B1 as precursors.
The origin of aflatoxin G1 was studied using mutant strains of Aspergillus parasiticus blocked early in the pathway and by tracing 14C-labelled aflatoxin B1 (AFB1) in wild-type A. flavus and A. parasiticus strains. Sterigmatocystin (ST) was a precursor of AFB1, AFG1 and AFG2 in the four mutants examined. The identity of AFG1 was confirmed by mass spectrometry. No evidence for conversion of AFB1 to AFG1 was found. A rigorously controlled study of conversions of radioactivity based on preparative thin-layer chromatography of aflatoxins demonstrated that low levels of aflatoxin interconversions previously reported in the literature might actually be artifacts.
Mycotoxins, mycotoxicoses, mycotoxicology and Mycopathologia.
Mycotoxins are fungal poisons. This definition does not stipulate whether fungi are the targets of poisoning or are the producers of the poisons. The following is suggested as a useful working definition: Mycotoxins are natural products produced by fungi that evoke a toxic response when introduced in low concentration to higher vertebrates and other animals by a natural route. Some mycotoxins have multiple effects, and may cause phytotoxic and antimicrobial syndromes in addition to animal toxicity. By convention, mushroom and yeast poisons are usually excluded from discussions of mycotoxins. The eclectic nature of the discipline and the international scope of the problem has attracted scientists from many different backgrounds. The publishers and editors of Mycopathologia intend for this journal to become a major forum for mycotoxin research.
Fast neutron spectrum measurements in anthropomorphic phantoms using an NE213 scintillation spectrometer.
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Nonrandom chromosome structural aberrations and oncogene loci in human malignant melanoma.
Short-term cultures of 10 malignant melanomas derived from 8 patients were analyzed cytogenetically. The chromosome composition of the tumors was found to be similar in terms of modal number and structural and numerical aberrations, especially the nonrandom nature of breakpoints. Six chromosomes were consistently involved in marker formation. Aberrations of chromosomes #1 and #9 were identified in every tumor, whereas structural alterations of chromosome #2 were found in 9 tumors. In contrast, aberrations of chromosomes #6, #3, and #7 were identified in 7, 7, and 8 of the tumors, respectively. The nonrandom breakpoints on these chromosomes frequently coincided with known oncogenic loci and resulted in morphologically identical marker chromosomes. Consecutive lesions were obtained for two patients. Common markers were identified in both cases, indicating the clonal origin of the tumors. In addition, many marker chromosomes characteristic of the individual lesions were also identified. The presence of these lesion-specific markers indicates the nonrandom selective nature of the metastatic process and suggests the possible heterogeneity of the original tumor cell population.
Effect of selected inhibitors on growth, pigmentation, and aflatoxin production by Aspergillus parasiticus.
We have treated a wild type strain of Aspergillus parasiticus with several known aflatoxin inhibitors in hopes of finding specific metabolic blocks in the aflatoxin biosynthetic pathway. In defined medium, benzoic acid (2 and 3 mg/ml), cinnamon (1 mg/ml), and sodium acetate (5 mg/ml) were fungitoxic. Benzoic acid (0.5 and 1 mg/ml), chlorox (5 microliters/ml), and dimethyl sulfoxide (5 microliters/ml) did not affect dry weight or mycelial pigmentation. Sodium benzoate (1, 2, 4 and 8 mg/ml) added after 2 days growth inhibited aflatoxin production in two defined media. We were unable to confirm previously published reports that an uncharacterized yellow pigment accumulates with benzoate-inhibition of aflatoxin biosynthesis.
Biosynthetic relationship among aflatoxins B1, B2, M1, and M2.
Aflatoxins are a family of toxic, acetate-derived decaketides that arise biosynthetically through polyhydroxyanthraquinone intermediates. Most studies have assumed that aflatoxin B1 is the biosynthetic precursor of the other aflatoxins. We used a strain of Aspergillus flavus which accumulates aflatoxin B2 to investigate the later stages of aflatoxin biosynthesis. This strain produced aflatoxins B2 and M2 but no detectable aflatoxin B1 when grown over 12 days in a low-salt, defined growth medium containing asparagine. Addition of dichlorvos to this growth medium inhibited aflatoxin production with concomitant accumulation of versiconal hemiacetal acetate. When mycelial pellets were grown for 24, 48, and 72 h in growth medium and then transferred to a replacement medium, only aflatoxin B2 and M2 were recovered after 96 h of incubation. Addition of sterigmatocystin to the replacement medium led to the recovery of higher levels of aflatoxins B2 and M2 than were detected in control cultures, as well as to the formation of aflatoxins B1 and M1 and O-methylsterigmatocystin. These results support the hypothesis that aflatoxins B1 and B2 can arise independently via a branched pathway.
Droplet enrichment factors of pigmented and nonpigmented Serratia marcescens: possible selective function for prodigiosin.
Drops produced by bursting bubbles provide a mechanism for the water-to-air transfer and concentration of matter. Bacteria can adsorb to air bubbles rising through bacterial suspensions and enrich the drops formed by the bubbles upon breaking, creating atmospheric biosols which function in dispersal. This bacterial enrichment can be quantified as an enrichment factor (EF), calculated as the ratio of the concentration of bacteria in the drop to that of the bulk bacterial suspension. Bubbles were produced in suspensions of pigmented (prodigiosin-producing) and nonpigmented cultures of Serratia marcescens. EFs for pigmented cultures were greater than EFs for nonpigmented cells. Pigmented cells appeared hydrophobic based on their partitioning in two-phase systems of polyethylene glycol 6000 and dextran T500. The surface hydrophobicity of pigmented cells may result from the hydrophobic nature of prodigiosin and could account for the greater ability of these bacteria to adsorb to air bubbles and enrich airborne droplets. Enhancement of the aerosolization of S. marcescens may be a selective function of the bacterial secondary metabolite prodigiosin.
Influence of trace elements and nitrogen sources on versicolorin production by a mutant strain of Aspergillus parasiticus.
A mutant strain of Aspergillus parasiticus blocked in aflatoxin biosynthesis accumulates versicolorin A and versicolorin C. The effect of trace elements on the growth and versicolorin production by this strain was studied in a defined medium. The omission of manganese was slightly stimulatory to versicolorin production; when zinc was omitted from the medium, no detectable versicolorins were produced. Experiments on nitrogen sources in a high-sucrose medium indicated that fourfold to fivefold increases in versicolorin yields could be obtained by substituting 3 ml/l corn steep liquor or 0.1 M NH4NO3 for the 0.023 M (NH4)2SO3 used previously as the nitrogen source in studies on versicolorin production by this strain. These improved yields will facilitate attempts to accumulate enough versicolorin A and versicolorin C for toxicity and carcinogenicity testing. Chromatographic profiles of mycelial extracts of cultures grown in a defined medium with 0.1 M NH4NO3 as the nitrogen source revealed 2 previously unrecognized compounds. The accumulation of these new metabolites in a mutant blocked in aflatoxin production may indicate that they are biosynthetically related to aflatoxin.
Gametogenesis and incidence of Down syndrome.
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Aflatoxins and anthraquinones from diploids of Aspergillus parasiticus.
Three spore colour, two mycelial colour and 12 auxotrophic mutants were isolated from an aflatoxigenic strain of Aspergillus parasiticus. These mutants and heterozygous diploids formed by pairwise combinations of auxotrophs were assayed for aflatoxin production; norsolorinic acid and versicolorin A production were also assayed in the diploids. In general, introduction of an auxotrophic marker lowered aflatoxin production in haploids. The green-spored, prototrophic diploids resembled haploid wild-type strains in that they produced high levels of aflatoxin, low levels of versicolorin A, and no detectable norsolorinic acid. Parasexual analysis of segregants from four heterozygous diploids was hampered by the uniform conidiospore diameter of haploids and diploids and by the non-random recovery of genotypes among somatic segregants with and without treatment with p-fluorophenylalanine. Nevertheless, this technique is useful for recombinational analysis of mutants blocked in aflatoxin synthesis. The fortuitous association of mycelial pigmentation with certain blocked aflatoxin mutants should prove useful in future analyses of the genetics and biosynthesis of these economically important secondary metabolites.
Changing perspectives on Down's syndrome.
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Thermal control of blood flow through capillaries and arteriovenous anastomoses in skin of sheep.
Using radioactive microsphere and electromagnetic techniques, hindleg vascular responses were studied in 38 conscious, chronically prepared sheep subjected to either exposure to a warm environment, and/or local warming of the hypothalamus, spinal cord, forelegs of hindlegs. The total proportion of cardiac output passing through AVA's was increased by all treatments. AVA flow in hindleg skin was increased but capillary flow was unchanged by warming the hypothalamus, spinal cord or forelegs. AVA flow was unchanged but capillary flow was increased by warming the ambient air or the hindlegs alone. Equivalent cooling treatments resulted in AVA and capillary flow changes converse to warming. It is concluded that, in sheep, blood flow through cutaneous AVA's is controlled by specific thermoregulatory reflexes, whereas capillary flow is the target of local temperature effects. A significant role for the direction of the thermal gradient across the skin is implicated.
Radioactive microsphere partitioning of blood flow between capillaries and arteriovenous anastomoses in skin of conscious sheep.
Using radioactive plastic microspheres in conscious sheep, cardiac output is measured by dose injection into a vein, and sampling from the pulmonary artery. Partition of organ blood flow between capillaries and arteriovenous anastomoses is derived from cardiac output and the radioactivity in pulmonary artery blood sampled after dose injection into the artery supplying the organ. Validation tests are presented. The hindlimb is shown to be a suitable model for studying thermal influences on skin blood flow. In contrast to other techniques or previous applications of microspheres: (a) conscious, chronically prepared animals are used, (b) there is no need to kill the animal to obtain results, (c) only small doses are necessary, (d) the one nuclide label can be used repeatedly, and (e) there is no need for precisely matched doses.