Perspectives. Use of telemedicine for home care ripe for experiment.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M G Jones.
Explore the source record for details and available documents.
The effect of 4 weeks' treatment with oral-L-carnitine (100 mg/kg per day) on carnitine status and metabolic parameters during an incremental ramp exercise test in a 12-year-old girl with isovaleric acidaemia was examined to determine its possible therapeutic role. The maximum work rate achieved increased from 110 to 120 watts; oxygen consumption at anaerobic threshold from 600 to 800 L/min; peak oxygen consumption from 1270 to 1450 L/min; and oxygen pulse, a measure of cardiac output, from 7.0 to 8.1 L/beat. These changes were associated with increases in plasma and urinary free and acyl carnitine concentrations but no change in physical activity. This observed effect of L-carnitine on exercise performance may be on cardiac or skeletal muscle function or both. We conclude that, in this single patient with isovaleric acid-aemia, L-carnitine supplementation had objective benefits and further studies on more patients are warranted.
We have used rats with streptozotocin-induced diabetes to investigate the effects of hyperglycaemia-mediated impaired nucleoside uptake on the actions of endogenous adenosine in hippocampal slices. In control tissue under conditions of anoxia and aglycaemia the rise in the extracellular adenosine concentration resulted in complete inhibition of synaptic activity in about 2 min. In slices from previously hyperglycaemic rats the inhibition of synaptically mediated responses occurred significantly faster, although this change could be prevented by insulin treatment. Application of the selective adenosine A1 receptor antagonist [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] prevented the anoxia/aglycaemia-mediated inhibition and, furthermore, abolished the differences in the electrophysiological responses between control and diabetic tissue. The effects of impaired nucleoside uptake could be mimicked in control slices by applying the nucleoside uptake blocker hydroxynitrobenzylthioinosine (HNBTI). This had the effect of speeding up the rate of anoxia/aglycaemia-induced synaptic inhibition in control tissue to that seen in diabetic tissue. However, such treatment had no effect on the responses in diabetic tissue as expected if the HNBTI-sensitive uptake process was already inhibited by the chronic hyperglycaemia. The impairment of nucleoside uptake by chronic hyperglycaemia results in the potentiation of the modulatory actions of endogenous adenosine in the central nervous system. Such an alteration in adenosine function may be important in explaining behavioural and pathological changes associated with diabetes mellitus.
Pseudouridine in urine and plasma has been proved to be a useful tumour marker in many malignant conditions. We studied its usefulness in pleural fluid for distinguishing malignant from non-malignant pleural effusions. Pleural fluid pseudouridine concentrations in different groups of patients with pleural effusion (31 malignant, 29 benign, 16 unknown, 1 double pathology) was measured and compared. Its usefulness in distinguishing malignant from non-malignant pleural effusions was analysed by receiver-operating characteristic (ROC) curve analysis. Pseudouridine concentrations in the malignant group were significantly higher than the non-malignant group (P < 0.017, Bonferroni adjustment) with values overlapping extensively at the lower end. The area-under-the curve (AUC) value in the ROC curve analysis was 0.675 (P < 0.05). We conclude that the pleural fluid pseudouridine is of limited clinical value in distinguishing malignant from non-malignant pleural effusion due to its extensive overlap. However, it is useful when the concentration is higher than 65 mumol/L, which indicates malignancy.
OBJECTIVE: To investigate whether the observed pathophysiological similarities that develop in both the collagen induced experimental model of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences in the relative activity of the glycosylation enzyme beta, 1-4 galactosyltransferase (GTase) within various tissues, and thus provide a new insight into the potential pathogenic mechanisms controlling glycosylation changes. METHODS: Lymphocytic membrane-bound GTase activity was examined in 30 mice with CIA, 30 age matched controls and 10 adjuvant treated non-arthritic DBA/1 mice. Tissue-specific changes were assessed by comparison of GTase activity in peripheral (P.GTase) and paired splenic lymphocytes. In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enzyme, by assaying serum GTase (S.GTase) activity in these and a further group of 27 arthritic and 20 control mice. To analyse this synthetic abnormality in greater depth and to investigate the relevance of these glycosylation changes to the pathogenesis of arthritis, we also examined the humoral regulatory component associated with this system by assaying for both anti-collagen as well as anti-GTase antibodies. RESULTS: The induction of arthritis in DBA/1 mice results in a marked reduction in P.GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P.GTase, splenic GTase activity was found to be similar in all the groups examined. Correspondingly, serum GTase activity was also found to be significantly lower in the collagen induced arthritic mice. This overall reduction in beta, 1-4 GTase activity reflects the clinical severity of arthritis and is associated with increased levels of naturally occurring anti-GTase antibodies. CONCLUSIONS: The GTase defect seen in the peripheral B and T cells in rheumatoid arthritis is also evident in the arthritic DBA/1 mouse model of RA. This may indicate a common pathological process in both rheumatoid disease and CIA, in which changes in glycosylation are dependent on the aberrant modulation of GTase in circulating, but not splenic lymphocytes. The relative expression and activity of glycosyltransferases within various tissues may not only contribute to immunoglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.
Several glycosides of calystegines B1 and B2 were synthesized by use of rice alpha-glucosidase and the whole cells of Rhodotorula lactosa, and their glycosidase inhibitory activities were investigated. Incubation of mixture of calystegine B1 and maltose with rice alpha-glucosidase gave 3-O-alpha-D-glucopyranosylcalystegine B1 (2, 11.3%). An enzymatic beta-transglucosylation reaction of calystegines B1 or B2 with cellobiose using the whole cells of R. lactosa gave 3-O-beta-D-glucopyranosylcalystegine B1 (1) (0.9%) or 4-O-beta-D-glucopyranosylcalystegine B2 (3, 11.2%), respectively, while similar beta-transgalactosylation of calystegine B2 from lactose gave 4-O-beta-D-galactopyranosylcalystegine B2 (4, 10.1%). The glycosylation of calystegines B1 and B2 markedly decreased or abolished their inhibition against beta-glucosidase, alpha- or beta-galactosidase. Compound 4 however retained more or less the potency of calystegine B2 against trehalase. Interestingly, compound 1 was a noncompetitive inhibitor of rice alpha-glucosidase, with a Ki value of 0.9 +/- 0.1 microM.
A subtractive hybridization method is described that allows the generation of a subtractive gene library from small amounts of plant or other eukaryotic tissues. The method uses paramagnetic oligo-dT beads to capture poly-adenylated mRNA and to synthesize the complementary cDNA on a solid support. The use of magnetic beads facilitates the change of reaction buffers and the removal of primers and minimizes yield losses. Subtracted material obtained from this method can either be cloned directly or used to screen a specific library.
Spatial learning abilities in younger adults and in healthy elderly adults were examined in 2 tasks. In the first task, participants were tested for their ability to recall relevant route information as well as to recognize and to order temporally landmark information observed along the route. Older participants had relatively greater difficulty retracing the route and temporospatially ordering landmarks but were equally good at recognition of landmarks occurring on the route. In the second task, participants memorized a 2-dimensional representation of a route and subsequently navigated the route from memory. Older participants had greater difficulty memorizing the route and navigating it. Errors of omission, commission, wrong, and forced choice were analyzed. Group differences in the pattern of errors differed by task.
Explore the source record for details and available documents.
BACKGROUND: Several studies have investigated water/salt soluble proteins which comprise 50% of the proteins in wheat. The remaining 50% of wheat proteins, are water/salt insoluble proteins of which there is limited information on their role in cereal hypersensitivity. OBJECTIVES: To investigate the allergenicity of the water/salt insoluble gliadin and glutenin proteins (prolamins). METHODS: RAST, electrophoresis and Western blotting were used to identify water/salt insoluble wheat allergens. Competitive RAST inhibition was conducted to investigate cross-reactivity between prolamins and water/salt soluble wheat proteins. RESULTS: Specific IgE to alpha-gliadin and to total glutenins were detected in all sera. IgE to beta-, gamma-, fast omega-, and slow omega-gliadin were present in lower numbers of sera. Prolamin allergens of 90-11 kDa were identified by immunoblotting. Water/salt soluble proteins crossreacted with alpha-gliadin and total glutenins. CONCLUSIONS: Individuals who are hypersensitive to water/salt soluble wheat proteins produce specific IgE to water/salt insoluble wheat proteins. Western blotting has shown that gliadins, glutenins and proteins with similar molecular weights as the endogenous water/salt soluble wheat enzyme inhibitors are important allergens. Alpha and fast omega- are the most allergenic gliadins. The water/salt insoluble proteins share cross-reacting epitopes with water/salt soluble proteins. These data show that the numbers of proteins involved in the development of cereal hypersensitivity is greater than previously believed and that the development of specific IgE to alpha-gliadin may in part depend on the presence of cross-reacting antibodies to water/salt soluble flour allergens.
The stereoselectivity and potency of 3N-substituted 2,3-benzodiazepines were examined in vivo against excitation of spinal neurones induced by electrophoretic ejection of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate in anaesthetised rats. AMPA receptor antagonist activity resided in the (-) isomers, LY300164 and LY303070, which were effective given electrophoretically, intravenously (2.5-5 mg/kg) or orally (10 mg/kg). The same stereoselectivity was observed in neuroprotection studies. Thus, systemic administration of the (-) isomer, but not the (+) isomer, of these 2,3-benzodiazepines before or immediately after bilateral carotid artery occlusion in the gerbil was neuroprotective. For example, 10 mg/kg of LY300164 intraperitoneally or orally provided survival of up to 25% of hippocampal CA1 neurones.
During brain ischaemia there is a sustained increase in extracellular glycine levels, and the potential role of these changes in modulating N-methyl-D-aspartate (NMDA) receptor-mediated activity following an anoxic/aglycaemic insult was studied in the rat hippocampal slice. Addition of large saturating concentrations of glycine (100 microM and 1 mM) to the superfusate resulted in increased extracellularly recorded NMDA receptor-mediated components of excitatory postsynaptic potentials (EPSPs) recorded in area CA1. The effects of added glycine were strychnine-insensitive and blocked by a competitive NMDA antagonist. Anoxic/aglycaemic insults to the tissue caused persistent increases in NMDA receptor-mediated EPSPs, but the magnitude of the observed upregulation was unaffected by the presence of added saturating concentrations of glycine. The data suggests that alterations in glycine levels after oxygen deprivation are not responsible for the long term modulation of NMDA receptor activity.
We have cloned and sequenced cDNA transcribed from the 3' 1,239 nucleotides of the genomic RNA of a Western Australian isolate (MI) of bean yellow mosaic potyvirus (BYMV). This sequence contains 246 nucleotides of the NIb (replicase) gene and 819 nucleotides representing the entire coding region of the viral coat protein gene, followed by a 3' non-coding region of 174 nucleotides. The coding region of the coat protein gene is identical in length (273 amino acids) to that already reported for other isolates of this virus. The sequence identities obtained for BYMV-MI and published sequences of BYMV isolates range between 85% and 92% for the coding region of the coat protein and 90% to 98% for the 3' non-coding region. Likewise, the region of the NIb gene sequenced shows 99% and 97% sequence identity in the deduced amino acid and the nucleotide sequences, respectively.
Explore the source record for details and available documents.
Five healthy male subjects were continuously infused subcutaneously with [14C]bicarbonate (12.3 microCi/day) using a mini pump for 5 days while in a whole body calorimeter. Energy expenditure was varied over a range of 1.35-1.75 times basal metabolic rate. Urine collections were obtained throughout the study and used to measure the specific activity of urea, from which CO2 production was estimated. It was assumed that the recovery of label in gaseous CO2 was 95% of that infused and that the specific activity of urea was 85% that of expired CO2. Continuous daily collections of calorimeter air revealed that 95.6 +/- 1.3% (SD) of infused label was recovered as gaseous CO2, with little daily variation. Another 1.5 +/- 0.4% was recovered as urinary urea. The estimated CO2 production, calculated from the specific activity of urea in 24-h urine samples corrected for the small effects due to changes in the size and specific activity of the urea pool, was found to be 100 +/- 5% of the calorimeter estimate for 1-day periods (20.80 +/- 1.44 mol CO2/day) and 100 +/- 2% for 4-day periods. This study suggests that, in healthy subjects, the labeled [14C]bicarbonate-urea method can provide reasonable estimates of net CO2 production over the range examined.
Explore the source record for details and available documents.
The pectinesterases in tomato pericarp were fractionated by cation exchange into four forms (A-D). Form A was the most abundant and C the second most abundant. Forms A-C were further purified by gel filtration, and antibodies were raised against A and C. Comparison of the different forms by dot blots and Western blots showed that although all three forms shared common immunological characteristics, there were also differences in their behaviour, indicative of structural differences. Form A had an N-terminal sequence identical to that published previously for the major pectinesterase in tomato fruit. In contrast, form C had a completely novel N-terminal sequence. Form A was absent from hypocotyls and roots. Forms B and C were present in comparable amounts in hypocotyls, while from C predominated in roots.
There are several sites on IgG Fc that have been reported to be the epitopes for binding rheumatoid factors (RF). It is now established that there are alterations in the oligosaccharides on IgG from patients with rheumatoid arthritis and it has been suggested that these changes may enhance immune complex and cryoglobulin formation. We have used a series of IgG preparations differing in their content of oligosaccharide chains lacking galactose from 18 to 86% to determine whether changes in sugar content affect the binding of rheumatoid factor. Five of 16 monoclonal rheumatoid factors prepared from synovial tissue, from patients with juvenile or adult rheumatoid arthritis, bound better to IgG which was deficient in galactose. Six of the 16 rheumatoid factors from the same patients bound independently of the galactose content. Four of the 16 rheumatoid factors could not be absolutely grouped in this manner but seemed to demonstrate a preference for agalactosyl IgG. One rheumatoid factor bound better to fully galactosylated IgG. There was an association between enhanced binding to galactose-deficient IgG and monoreactivity and a very strong association between the functional affinity of the rheumatoid factors and the dependent binding.