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Biomedical subjects

M J Sweeney

Publications and source records attributed to M J Sweeney.

At least 19 recordsLinked to original sources
PubMed2000

The use of reverse transcription-polymerase chain reaction (RT-PCR) for monitoring aflatoxin production in Aspergillus parasiticus 439.

A detection system based on reverse transcription PCR (RT-PCR) has been developed to monitor aflatoxin gene expression in Aspergillus parasiticus. Total RNAs of aflatoxigenic A. parasiticus 439 grown in aflatoxin permissive and non-permissive media were amplified and monitored over time by RT-PCR with specific primers designed from two genes of the aflatoxin biosynthetic pathway. Gene transcription in both media was assessed by monitoring the house keeping beta-tubulin gene and aflatoxin production was correlated with transcription by thin layer chromatography. This RT-PCR technique has the potential to be employed as a tool to investigate the effects of a variety of physiological factors on the transcription of the aflatoxin genes.

Aflatoxins↗
PubMed1999

Molecular biology of mycotoxin biosynthesis.

Mycotoxins are secondary metabolites produced by many important phytopathogenic and food spoilage fungi including Aspergillus, Fusarium and Penicillium species. The toxicity of four of the most agriculturally important mycotoxins (the trichothecenes, and the polyketide-derived mycotoxins; aflatoxins, fumonisins and sterigmatocystin) are discussed and their chemical structure described. The steps involved in the biosynthesis of aflatoxin and sterigmatocystin and the experimental techniques used in the cloning and molecular characterisation of the genes involved in the pathway are described in detail. The biosynthetic genes involved in the fumonisin and trichothecene biosynthetic pathways are also outlined. The potential benefits gained from an increased knowledge of the molecular organisation of these pathways together with the mechanisms involved in their regulation are also discussed.

Cloning, Molecular↗
PubMed1989

Anaerobic biosynthesis of unsaturated fatty acids in the cyanobacterium, Oscillatoria limnetica.

The mechanism for synthesis of monounsaturated fatty acids under aerobic and anaerobic conditions was studied in the facultative anaerobic cyanobacterium, Oscillatoria limnetica. The hexadecenoic acid (C16:1) of aerobically grown O. limnetica was shown to contain both the delta 7 (79%) and delta 9 (21%) isomers, while the octadecenoic (C18:1) acid was entirely the delta 9 acid. Incorporation of [2-14C] acetate into the fatty acids under aerobic conditions resulted in synthesis of the delta 7 and delta 9 C16:1 and the delta 9 C18:1. Synthesis of unsaturated fatty acids in the presence of DCMU required sulfide. Anaerobic incubations in the presence of DCMU and sulfide (less than 0.003% atmospheric oxygen) resulted in a two-fold increase in monounsaturated fatty acids of both delta 7 and delta 9 C16:1 and delta 9 and delta 11 C18:1. The synthesis of these is characteristic of a bacterial-type, anaerobic pathway.

Acetates↗
PubMed1988

Allergenic cross-reactivity between Callistemon citrinis and Melaleuca quinquenervia pollens.

Aqueous extracts of both Callistemon citrinis (bottlebrush) and Melaleuca quinquenervia (melaleuca) were analyzed for allergenic cross-reactivity. Inhibition analysis using the radioallergosorbent test (RAST) was performed on the ammonium bicarbonate extracts of bottlebrush (NH4B) and melaleuca (NH4M) pollens. RAST inhibition analysis demonstrated that the extracts contained allergenically cross-reactive components. Sephadex G-100 column chromatography of NH4B and NH4M extracts resulted in at least 4 distinct peaks for each extract analyzed. These fractions were designated NH4B1-NH4B4 and NH4M1-NH4M4. A modified dot-blot assay for detection of allergenic components was utilized to show that the first elution peaks of bottlebrush and melaleuca, NH4B1 and NH4M1, respectively, contained allergenic components. These allergenic components, NH4B1 and NH4M1, had estimated molecular weights of 50,000 and 35,000 daltons, respectively.

Animals↗
PubMed1986

Isolation and characterization of cross-reactive allergenic components in Callistemon citrinis and Melaleuca quinquenervia pollen by trans-blot enzyme-linked crossed immunoelectrophoresis.

Antigenic extracts obtained from Callistemon citrinis (bottle brush) and Melaleuca quinquenervia (melaleuca) pollen were analyzed by crossed immunoelectrophoresis (CIE), tandem-crossed immunoelectrophoresis (TCIE), and trans-blot enzyme-linked crossed immunoelectrophoresis (TECIE). CIE analysis detected 14 and 12 antigenic components in bottle brush and melaleuca, respectively. TCIE analysis of bottle brush pollen, employing rabbit anti-melaleuca serum in the intermediate gel, demonstrated that all of the antigenic components detected were cross-reactive. Similar analysis of melaleuca using rabbit anti-bottle brush serum in the intermediate gel also showed that all of the antigenic components were cross-reactive. At least three bottle brush and two melaleuca cross-reactive pollen components were demonstrated to be allergenic by TECIE analysis of CIE and TCIE gels.

Animals↗
PubMed1982

Dopaminergic properties of nomifensine.

Nomifensine and a proposed dihydroxy metabolite produced stimulation of motor behavior in mice with nomifensine being more potent. Weak cage-climbing behavior (stereotypy) was also produced. The stimulatory effects were greater in mice in which dopamine receptor sensitivity was increased by long-term haloperidol. Both of the analogs were potent inhibitors of dopamine and norepinephrine uptake in vitro with nomifensine approximately 3 times more potent than the metabolite. In contrast, the two analogs had weak affinity for the post-synaptic dopamine receptor (as measured by displacement of ligand binding in vitro) with dihydroxynomifensine approximately 6 times more potent than nomifensine. These results suggest that the behavioral effects of nomifensine are largely dependent on presynaptic catecholamine mechanisms but that weak direct dopamine agonist properties do exist, particularly in vivo where the drug may be metabolized to a more active form.

Animals↗
PubMed1982

Systemic anaphylaxis immediately following delayed hypersensitivity skin tests.

Delayed hypersensitivity skin tests are performed frequently for other than primary immunologic disorders. Systemic anaphylaxis occurred during delayed hypersensitivity skin testing on a healthy, non-atopic individual. This reaction appeared to be IgE mediated. Anaphylactic recovery sets must be readily available whenever such testing is performed.

Anaphylaxis↗
PubMed1981

An IgE inhibition assay for the detection of allergen specific IgE.

A method for the detection of specific IgE in human serum is described, using a modified radioimmune assay termed the Inhibition Assay Technique (IAT) The technique is based on the ability of specific IgE to bind with allergen. The difference in total IgE before incubation with the allergen and after incubation with the allergen gives a relative concentration of specific IgE to that particular allergenic substance. The assay has been shown to correlate with both the intradermal skin test as well as the standard RAST now used to determine specific IgE.

Allergens↗
PubMed1978

Structure-activity relationships of dimeric Catharanthus alkaloids. 1. Deacetylvinblastine amide (vindesine) sulfate.

Exploration of the effects of "minor" structural differences on the antitumor activity and toxicity of dimeric Catharanthus alkaloids resulted in the preparation of deacetylvinblastine amide (vindesine, VDS) from either vinblastine (VLB) or deacetylvinblastine. Adequate amounts of vindesine for biological testing were prepared by preferential hydrazinolysis of the C23-ester in the vindoline moiety of VLB, followed by hydrogenolysis of the resulting deacetylvinblastine hydrazide. Vindesine in its activity spectrum against rodent tumor systems resembles vincristine (VCR) rather than its parent VLB, while its neurotoxic potential appears to be less than that of VCR. The experimental models developed to estimate this potential include in vitro measurements of axoplasmic transport effects in the cat sciatic nerve and the estimation of neuromuscular disturbances in chickens and monkeys by vindesine in comparison with VCR. A radioimmunoassay for VLB, VCR, and VDS, developed by means of deacetylvinblastine acid azide, has been used to study the pharmacokinetics of vindesine in man. The clinical investigation of vindesine is in progress. Deacetylvinblastine, in contrast to earlier reports, showed activity against several murine tumor systems.

Animals↗
PubMed1977

Mycophenolic acid and its mechanism of action in cancer and psoriasis.

Mycophenolic acid is active against fungi, bacteria, and viruses in vitro and is active against some viruses and tumors in experimental animals. Mycophenolic acid is not effective in the treatment of cancer in man, but it is effective in treating psoriasis. In all of the various diseases MA presumably inhibits the synthesis of GMP resulting in decreased synthesis of RNA and DNA. The direct inhibition of GMP synthesis is the result of MA activity against the IMPDHase and GMP synthetase as determined in experimental tumors. The inhibition of GMP synthesis can be circumvented by the guanine salvage pathway which is controlled by PRTase activity. PRTase may be the sole factor in preventing the inhibition caused by MA in the biosynthesis of GMP (Fig. 3). However, before MA can stop GMP synthesis, MA must enter the cell. The current data show that MA is almost completely detoxified in man and circulates in the plasma as the glucuronide, MAG, Glucuronides are normally inactive forms of active drugs. Due to their bivalent and non-lipophilic nature, glucuronides do not normally cross the cell membranes. Therefore, MAG is extracellular and beta-Gase intracellular, and this prevents hydrolysis of MAG to the active MA in cancer patients.

Animals↗
PubMed1975

Activity of 6-methyl-8-substituted ergolines against the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma.

The ability of a series of 8-beta-carboxamido ergolines, 8-formamido ergolines, and 8-methyl ergolines to cause regressions of established dimethylbenz[a]anthracene-induced mammary carcinomas was compared to some ergot alkaloids. Although most of the ergoline derivatives depressed serum prolactin concentrations in rats, only a few had pronounced effects against the dimethylbenz[a]anthracene-induced mammary carcinoma in rats. Some derivatives from each of the three groups of substituted ergolines gave comparable activities against the dimethylbenz[a]anthracene-induced mammary carcinoma.

Animals↗