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Biomedical subjects

J M Yeung

Publications and source records attributed to J M Yeung.

At least 19 recordsLinked to original sources

Management of intermittent claudication: the importance of secondary prevention.

Atherosclerotic peripheral arterial disease (PAD) is a common disorder usually associated with silent or symptomatic arterial disease elsewhere in the circulation and a cluster of cardiovascular risk factors inducing atheroma progression and/or thrombotic complications. Because of these strong clinical associations, especially with coronary heart disease, the ankle-brachial pressure index (ABPI) is of prognostic significance. The clinical management of IC should include relief of symptoms combined with prevention of secondary cardiovascular complications, e.g. acute thrombotic events causing limb- or life-threatening ischaemia, which are often due to atherosclerotic plaque rupture leading to thrombotic vessel occlusion. Many patients with PAD do not receive an optimum package of secondary prevention, tailored to include maximum cholesterol reduction, BP and glycaemic control, ACE inhibition and single or combination anti-platelet therapy. This review considers recent information from large secondary prevention trials, e.g. the PAD subgroups within the HOPE, CAPRIE and statin studies. Slowing progression of atherosclerosis, and inducing stabilisation and regression of atheromatous plaques, is now feasible using long-term combination drug therapy. The phrase angle quotation mark, leftangle quotation mark, leftconservative therapyangle quotation mark, rightangle quotation mark, right, popular among vascular surgeons, implies a passive minimal-intervention strategy of surveillance and lifestyle advice; such terminology is perhaps no longer appropriate since considerable improvements in survival are likely to accrue if all patients with PAD, especially those with low ABPI, receive vigorous, titrated medical therapies, tailored to individual patients, as part of an evidence-based secondary prevention regime.

Angiotensin-Converting Enzyme Inhibitors↗

Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon.

Coordinated expression of Hoxa2, Hoxd1 and Pax6 proteins were found to coincide with the three developmental stages of the diencephalon, as described for the mouse brain. In the first stage (embryonic day (E) 10-12) Hoxa2, Hoxd1 and Pax6 (an early marker gene of the diencephalon) were expressed as early as E10.5 in prosomeres (p), p2 and p3. All three proteins continue to exhibit overlapping domains of expression at E12.5-13 (beginning of the second stage) when the primitive dense cell layer begins to differentiate into the internal germinal, external germinal and mantle layers. Towards the end of the second stage (E15), Pax6 expression was down-regulated whereas Hoxa2 and Hoxd1 continued to exhibit overlapping domains of expression for both protein and mRNA. Hoxd1 expression decreased significantly in the third stage of diencephalic development (E16-postnatal) such that only Hoxa2 expression persisted in the diencephalon of newborn mice. The temporal and spatial expression of these three proteins imply that coordinated waves of Hoxa2, Hoxd1 and Pax6 expression may be required to provide positional information for the specification of the diencephalon.

Animals↗

Surface plasmon resonance-based immunoassays.

Surface plasmon resonance (SPR) has been successfully incorporated into an immunosensor format for the simple, rapid, and nonlabeled assay of various biochemical analytes. Proteins, complex conjugates, toxins, allergens, drugs, and pesticides can be determined directly using either natural antibodies or synthetic receptors with high sensitivity and selectivity as the sensing element. Immunosensors are capable of real-time monitoring of the antigen-antibody reaction. A wide range of molecules can be detected with lower limits ranging between 10(-9) and 10(-13) mol/L. Several successful commercial developments of SPR immunosensors are available and their web pages are rich in technical information. This review highlights many recent developments in SPR-based immunoassay, functionalizations of the gold surface, novel receptors in molecular recognition, and advanced techniques for sensitivity enhancement. Furthermore, it describes the challenge of current problems and provides some insights toward the future technologies.

Antibodies↗

Criteria to determine food allergen priority.

The emergent health issue of food allergens presents an important challenge to the food industry. More than 170 foods have been reported in the scientific literature as causing allergic reactions. Clearly, it would be impossible to deal with the presence of trace amounts of all these in the context of food labeling. If the decision to classify major allergens is based solely on the knowledge and experience of allergists and food scientists in the field, without scientifically defined criteria, it is likely to lead to a proliferation of lists. Such practices may lead to an unnecessary elimination of foods containing important nutrients. This paper defines food allergy, food intolerance, and food anaphylaxis and identifies criteria for classifying food allergens associated with frequent allergic reactions. A practical list of food allergens that may result in potentially life-threatening allergic reactions is provided. A mechanism-based (i.e., immunoglobulin E mediated), acute life-threatening anaphylaxis that is standardized and measurable and reflects the severity of health risk is proposed as the principal inclusion criterion for food allergen labeling. Where available, prevalence in the population and threshold levels of allergens should be used as an additional guide to identify possible future labeling needs.

Allergens↗

Immunoassay of fumonisins by a surface plasmon resonance biosensor.

A surface plasmon resonance (SPR) immunosensor is developed to determine concentrations of the mycotoxin, fumonisin B1 (FB1), in spiked samples. Polyclonal antibodies produced against FB1 are adsorbed onto a thin gold film substrate, which is coupled to a glass prism in the Kretschmann configuration. The output beam of a planar light-emitting diode is focused through the prism to excite SPR at the surface of the gold film. When a sample containing FB1 is added to a cell on the outside of the gold film, the angular profile of reflected light intensity shifts. This changes the resonance angle and the reflected beam intensity at a selected angle, both of which are proportional to the FB1 concentration. After optimization of the antibody overlayer, a detection limit of 50 ng/mL is obtained for the direct assay with an analysis time under 10 min. Multiple sample additions and large-volume sample circulation can be used with the high-affinity antibodies to achieve lower detection limits.

Biosensing Techniques↗

Evaluation of enzyme-linked immunosorbent assay for analysis of beer for fumonisins.

A recently developed sensitive indirect competitive enzyme-linked immunosorbent assay (ELISA) was applied to the determination of fumonisins in beer. Intra-assay and inter-assay recoveries averaged 98.7-102.8% at added fumonisin B1 (FB1) levels of 0.5-50 ng/ml beer, and coefficients of variation were 2.8-4.4 and 4.7-8.6%, respectively. Cross-reactivity of fumonisin B2 (FB2) compared with FB1 averaged 67% in beer. Two experiments were carried out to compare ELISA with liquid chromatography (LC) for determination of fumonisins in beer. In the first experiment, 19 samples (five previously known positive, nine other samples and five spiked samples) were passed through commercial immunoaffinity columns (ICs) and analysed by LC before conducting blind ELISA determinations on the extracts and beers directly. The known positive beers and extracts were used as blind duplicates. The second comparative experiment screened 46 beer samples by ELISA and then 22 positive and three of the negative samples were analysed by LC; the highest level found was 64.3 ng total fumonisins/ml measured by LC (24.7 ng/ml by ELISA). Regression analyses showed good correlation between ELISA and LC in the first experiment but low level interferences (equivalent to up to 5.35 ng fumonisin/ml) were observed by ELISA in the IC extracts. Five of nine beers negative by LC showed < 1 ng/ml ELISA responses on direct beer analysis. The second comparative experiment indicated underestimation by ELISA. However, there were two samples which tested positive by ELISA (0.2 ng/ml) but were found negative by LC (results close to the detection limits of both methods, which were 0.1 or 0.2 ng/ml by ELISA and 0.1-0.15 ng each fumonisin/ml by LC). There were no false negatives. It is concluded that ELISA has considerable value in rapid screening of beer directly for fumonisins.

Beer↗

Fumonisin B1 induces protein kinase C translocation via direct interaction with diacylglycerol binding site.

Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to evaluate whether FB1 affects PKC activation. Similar to tumor-promoting phorbol ester, phorbol 12-myristate-13-acetate (PMA), PKC is also catalytically activated by FB1. Protein kinase C activity and its redistribution in response to FB1 were determined in rat cerebrocortical slices. Cytosolic and membranous PKC activities were determined by histone phosphorylation in the presence of [gamma-32P]ATP, phosphatidyl-L-serine, PMA, and Ca2+. Distribution of gamma PKC isozyme in the presence of FB1 was also assessed by immunoblotting using affinity purified anti-peptide antibodies. Similar to PMA, FB1 added in vitro to rat cerebrocortical slices facilitated PKC translocation from cytosol to membrane in a concentration-dependent manner. This FB1-induced PKC translocation was inhibited by incubation with the inactive 4 alpha-phorbol 12,13-didecanoate. The effects of FB1 and PMA were neither additive nor synergistic. In addition, PMA and FB1-induced PKC enzyme redistribution were inhibited by pretreating tissues with sphingosine. A concentration-related FB1 attenuation of specific phorbol dibutyrate, [3H]PDBu, binding was also observed when cortical membranes were incubated with either PMA or sphingosine. This is the first report of FB1-induced PKC translocation via a direct action on the diacylglycerol site that also binds phorbol esters. Because phorbol esters are well known tumor promoters, we provide a plausible cellular mechanism to explain the carcinogenicity of FB1.

Animals↗

Biological fate of fumonisin B1 in food-producing animals.

The presence of mycotoxins in grains and feedstuffs causes not only animal health problems, but also a valid concern about the transmission of potentially toxic residues into animal-derived products intended for human consumption. In a series of studies at Agriculture and Agri-Food Canada, we investigated the biological fate of fumonisin B1 (FB1) in several food-producing animals (grower pigs, laying hens, dairy cattle), as well as monitored various parameters for evidence of toxicity in these species. In several experiments involving either single-dose protocols (iv, po) or longer-term feeding trials, the pharmacokinetic profiles of FB1 (purity > 95%) in these species were determined, including tissue accumulation and transmission of residues. Toxicological (and economical) implications such as performance (feed consumption, growth), productivity, and carcass quality were also measured when appropriate.

Absorption↗

Prenatal cocaine exposure selectively reduces mesocortical dopamine release.

The effect of prenatal exposure to cocaine on the release of [3H]dopamine and on presynaptic dopamine autoreceptor regulation of [3H]dopamine release in prelabeled frontal cortical, cingulate cortical and striatal slices was investigated. The release of [3H]dopamine that is evoked by high K+ was reduced by 20 to 28% in the cortical regions but not in striatum. This effect was observed at 10 days of age and persisted up to postnatal day 120 in rabbits that were exposed to cocaine during gestational days 8 to 29. Spontaneous [3H]dopamine release was increased by 18 to 22% in frontal and cingulate cortices but not in striatum of the 10- but not the 50- or 120-day-old rabbit that was exposed to cocaine during gestational days 8 to 29. Total [3H]dopamine accumulated in brain slices examined on postnatal days 10, 50 or 120 was not affected by prenatal cocaine exposure. Incubation of slices with dopamine dose-dependently inhibited K(+)-evoked [3H]dopamine release in both cortical and striatal slices. Prenatal cocaine exposure enhanced the responsiveness to in vitro dopamine in the two cortical regions but not in striatum. Fetal cocaine exposure did not affect the levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in frontal cortex or striatum. Similarly, no apparent differences in dopamine metabolism, as indicated by the ratio of 3,4-dihydroxyphenylacetic acid + homovanillic acid/dopamine, were observed in these brain areas. These findings demonstrate that prenatal cocaine exposure selectively affects depolarization-evoked [3H]dopamine release and its regulation by presynaptic dopamine autoreceptor in cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of deoxynivalenol on neurotransmitters in discrete regions of swine brain.

The effect of deoxynivalenol (DON, vomitoxin) on brain amine levels was investigated in swine. DON, a trichothecene mycotoxin, causes suppression of feed intake (anorexia) in susceptible species. Following acute administration of DON to pigs (0.25 mg/kg, IV), concentrations of endogenous catecholamines norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), and homovanillic acid (HVA), and the indoleamines, 5-hydroxytryptamine (5HT, serotonin) and 5-hydroxyindoleacetic acid (5HIAA) were determined in five brain regions, periodically during the 24 h post-dosing. Analysis was carried out by high performance liquid chromatography, using electrochemical detection. Effects of DON in the swine brain were transmitter, time and region-specific. It was observed that levels of the major transmitters (NE, DA and 5HT) were statistically different from controls in the hypothalamus (Hypo), frontal cortex (FCX) and cerebellum (Cb) up to 8 h post-dosing. Overall, DON administration elevated NE and depressed DA concentrations in these regions, and levels of 5HT which increased initially in Hypo (1 h), had dropped significantly below controls in both Hypo and FCX at 8 h. These alterations, however, were not indicative of known neurochemical changes associated with chemical-induced anorexia. Instead, this data suggested that the neurochemical effects of acute DON exposure might be due to peripheral toxicological events (i.e., vomiting), which overwhelmed its more subtle feed refusal activity.

Animals↗

Effects of the antidepressant phenelzine on brain levels of gamma-aminobutyric acid (GABA).

Time- and dose-response studies were carried out on the effects of the monoamine oxidase-inhibiting antidepressant and antipanic drug phenelzine on GABA levels in rat whole brain. At a dose of 15 mg/kg i.p., phenelzine significantly elevated GABA levels at all time intervals studied (1, 2, 4, 8, 16, and 24 h). A further investigation indicated that this was a dose-dependent effect. The possible importance of GABA in the etiology and pharmacotherapy of depression and panic disorder is discussed.

Animals↗

Effect of aging and diet restriction on monoamines and amino acids in cerebral cortex of Fischer-344 rats.

The effect of chronic diet restriction on amino acids and monoamines in cerebral cortex was studied in young and old male Fischer-344 rats. The effect of restricted feeding (60% of ad lib diet) was compared at 6 and 24 months of age. The results indicate that aging did not significantly alter the levels of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in frontal (FCX), parietal (PCX) and occipital cortices (OCX). On the other hand, the effect of age on serotonin (5HT) was found to be regionally specific. The level of 5HT was 43% higher, while the ratio of 5HIAA/5HT was decreased 26% in OCX of 24 months old animals. In the FCX 5HIAA/5HT ratio was increased 27%. Diet restriction in old rats increased DA level markedly in FCX, and attenuated the age-related increase of 5HT level in OCX. The ratios of 5HIAA/5HT in FCX and OCX of DR animals were maintained at those found in the young ad lib (AL) group. The cortical neurotransmitter amino acids (aspartate, glutamate, gamma-aminobutyric acid, glycine and taurine) were well maintained during aging and dietary manipulation. Age-related reduction of cortical tryptophan and plasma ratio of tryptophan to large neutral amino acids in old animals were attenuated by chronic DR. The results suggest that serotonergic neurons are more susceptible to change during aging than are the catecholaminergic neurons. Diet restriction during the life of the animals appears to protect or attenuate the age-related changes in cortical serotonergic system while FCX dopamine concentrations were dramatically increased.

3,4-Dihydroxyphenylacetic Acid↗

Analysis of the antidepressant phenelzine in brain tissue and urine using electron-capture gas chromatography.

A novel gas chromatographic method for the analysis of the antidepressant phenelzine has been developed. The procedure involves extraction with a liquid ion-pairing compound, back-extraction with HCl, basification, and derivatization with pentafluorobenzoyl chloride. The dipentafluorobenzoyl derivative (structure confirmed by mass spectrometry) is separated and analyzed on a gas chromatograph equipped with a fused silica capillary column and an electron-capture detector. The procedure has been utilized for quantitation of phenelzine in brain of phenelzine-treated rats and in urine from human subjects receiving phenelzine.

Animals↗

Rapid analysis of beta-phenylethylamine in tissues and body fluids utilizing pentafluorobenzoylation followed by electron-capture gas chromatography.

A rapid, sensitive gas chromatographic procedure for analysis of beta-phenylethylamine is reported. The procedure involves extraction with a liquid ion-pairing compound, back-extraction with HCl, basification and reaction with pentafluorobenzoyl chloride under aqueous conditions. The pentafluorobenzoyl derivative of beta-phenylethylamine is then separated and analyzed on a gas chromatograph equipped with a capillary column and an electron-capture detector. The procedure produces a derivative which has good chromatographic properties and a high degree of stability. The method has been applied to analysis of beta-phenylethylamine in a variety of tissues and body fluids.

Animals↗

Synthesis of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides with hyperglycemic-hypoglycemic activity.

A group of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides 7 were synthesized to determine the effect that the position and physicochemical properties of substituents attached to the heterocyclic ring have on blood glucose levels. 5-Methyl-N-(3,6-dihydro-1(2H)-pyridinyl)benzamide 7b was the most active hyperglycemic agent, elevating blood glucose 124% and 116% at 2 and 4 h, respectively, after a 100 mg/kg po dose. The most active hypoglycemic agent was the 4-acetyl analogue 7o, which was about 50% as active as chlorpropamide, lowering blood glucose 19% at 4 h after a 100 mg/kg po dose. A correlation between blood glucose levels and the partition coefficient P was not observed.

Animals↗

Simple automated gas chromatographic analysis of amino acids and its application to brain tissue and urine.

The separation of 21 free amino acids as their isobutyl N(O,S)-pentafluorobenzoyl derivatives by capillary gas chromatography with electron-capture detection is described. This method has been successfully applied to routine analysis of most of these amino acids in brain tissue and urine. The amino acids are converted to their isobutyl N(O,S)-pentafluorobenzoyl derivatives by acid-catalysed esterification followed by aqueous extractive pentafluorobenzoylation. The 21 amino acids can be separated on a single capillary column in 21 min. The high sensitivity permits analysis in minute quantities of sample and the high stability permits the use of an automatic sample injector at ambient temperatures. Thus, over 50 samples can be readily analyzed in a single day.

Amino Acids↗

Synthesis of N-(carbonylamino)-1,2,3,6-tetrahydropyridines with analgesic, antiinflammatory, and hyperglycemic activity.

A group of N-(carbonylamino)-1,2,3,6-tetrahydropyridines was synthesized to investigate the effects that changes in functionality at the carbonyl group have on analgesic, antiinflammatory, and hyperglycemic activities. One of the most active analgesic compounds was N-[(ethoxycarbonyl)amino]-1,2,3,6-tetrahydropyridine (5o), which was comparable to that of morphine. Pretreatment with naloxone did not alter the activity of 5o or 5q. N-[(2-Furanylcarbonyl)amino]-1,2,3,6-tetrahydropyridine (5q) was the most potent hyperglycemic agent, elevating blood glucose 181% at 2 and 4 h after a 100 mg/kg po dose.

Analgesics↗