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Biomedical subjects

M G Jones

Publications and source records attributed to M G Jones.

At least 19 recordsLinked to original sources
PubMed2006

IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis.

Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection, unresolving inflammation and progressive lung damage. Bronchiectasis can be associated with autoimmune diseases including ulcerative colitis. Defects of both innate and adaptive immunity have been proposed. The airway inflammation is characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils and T cells. Here we investigated two candidate gene polymorphisms that may contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that is implicated in IL-8 binding and neutrophil trafficking as well as the interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of IFNgamma production. These polymorphisms were distributed similarly in the idiopathic bronchiectasis group and controls, suggesting that these two candidate gene polymorphisms are not associated with disease susceptibility.

Alleles↗
PubMed2005

L-carnitine and exercise tolerance in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency: a pilot study.

Skeletal muscle function may be impaired in patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, but the value of L-carnitine in their long-term management is not clear. This study was designed as a pilot to examine the effects of L-carnitine on exercise tolerance in patients with MCAD deficiency. Four clinically asymoptomatic MCAD-deficient patients, aged 8 to 20 years, were studied. Incremental ramp exercise tests were carried out before and after 4 weeks' treatment with oral L-carnitine (100 mg/kg per day). During exercise without L-carnitine supplementation, plasma carnitine concentrations fell, associated with an increased excretion of urinary acylcarnitines, notably acetylcarnitine, hexanoylcarnitine and octanoylcarnitine. L-carnitine treatment prevented this fall in plasma carnitine and resulted in greater increases in excretion of acylcarnitines. All four patients showed biologically significant improvement in peak oxygen uptake (peak VO2, 18-32% improvement), VO2 at a heart rate of 170 beats/min (15-23% improvement), VO2 at anaerobic threshold (27-42% improvement), and/or oxygen pulse (10-32% improvement). Exercise tolerance in MCAD-deficient patients may be improved by short-term L-carnitine supplementation. This may be the direct result of improved intramitochondrial homeostasis induced by L-carnitine in removing accumulating acyl moieties.

3-Hydroxybutyric Acid↗
PubMed2005

Synthesis of the flavour precursor, alliin, in garlic tissue cultures.

The path of synthesis of alkyl cysteine sulphoxides, or flavour precursors, in the Alliums is still speculative. There are two proposed routes for alliin biosynthesis, one is from serine and allyl thiol while the other is from glutathione and an allyl source via gamma glutamyl peptides. The routes have been investigated by exposing undifferentiated callus cultures of garlic and onion to potential pathway intermediates. After a period of incubation of 2 days the callus was extracted, and analysed for flavour precursors and related compounds by HPLC. Standards of alliin, isoallin and propiin were synthesised and their identity confirmed by HPLC and NMR. Putative intermediates selected included the amino acids serine and cysteine, as well as more complex intermediates such as allylthiol, allyl cysteine and glutathione. Both garlic and onion tissue cultures were able to synthesize alliin following incubation with allylthiol, and cysteine conjugates such as allyl cysteine. The ability of the tissue cultures to form alliin from intermediates was compatible with the proposed routes of synthesis of alliin.

Cysteine↗
PubMed2005

Automated quantitative volumetric breast ultrasound data-acquisition system.

This paper describes the development and initial testing of an automated ultrasound imaging technique to acquire quantitative volumetric breast data; the clinical application being breast cancer diagnosis and management. A novel mechanical scanner has been designed and constructed to constrain the breast tissue without compromising the image, to acquire images of the majority of the breast using a conventional B-mode scanner and to maintain patient comfort. An algorithm to improve upon simple depth-dependent amplification by compensating for tissue-dependent attenuation is applied to the images, making the grey-scale values represent local scattering properties more closely. Registration techniques have been developed to correct for geometric errors arising in the data set because of tissue movement and variations in speed of sound in the tissues. The data sets are reconstructed into volumes and viewed interactively. A pilot study of seven patients was performed and selected results are presented to illustrate lesion features. The automated scan reduces operator-dependence, provides clear information on the 3-D tissue boundaries and provides a full record for monitoring or surgical planning.

Algorithms↗
PubMed2004

Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acid anhydrides.

BACKGROUND: Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. OBJECTIVE: We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. METHODS: We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. RESULTS: The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1(*)0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). CONCLUSION: DQB1(*)05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1(*)0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.

Adult↗
PubMed2002

Total daily energy expenditure in wasted chronic obstructive pulmonary disease patients.

OBJECTIVES: To investigate total daily energy expenditure in chronic obstructive pulmonary disease (COPD) patients during a rehabilitation programme. DESIGN: Observational study involving a case and a control group. SUBJECTS: Ten COPD patients (six with body mass index (BMI) <18.5 kg/m(2) and four with BMI >18.5 kg/m(2)) were evaluated for their energy expenditure profile. Four additional healthy age-matched volunteers were also included for methodology evaluation. INTERVENTIONS: Measurements of total daily energy expenditure (TEE), resting energy expenditure (REE) and diet-induced thermogenesis (DIT) and energy intake were undertaken by indirect calorimetry and bicarbonate-urea methods and dietary records. RESULTS: REE in COPD patients was not significantly different from that predicted by the Harris-Benedict equation. Before the exercise day the mean TEE was 1508 kcal/day and physical activity level (PAL as calculated by TEE/REE) was 1.52. On the exercise day the TEE increased to 1568 kcal/day and PAL was 1.60, but neither of these changes were significant. The energy cost of increased physical activity during rehabilitation exercise was estimated to be 191 kcal/day. No significant change was found in DIT between the two patient groups. However, overall energy balances were found to be negative (-363 kcal/day). CONCLUSION: The rehabilitation programme did not cause a significant energy demand in COPD patients. TEE in COPD patients was not greater than in free-living healthy subjects. Patients, who were underweight, did not have a higher TEE than patients with normal weight. This suggested that malnutrition in COPD patients was not due to an increased energy expenditure. On the other hand, a significant negative energy balance due to insufficient energy intake was found in seven out of 10 patients.

Aged↗
PubMed2002

Micellar casein gelation at high sucrose content.

This article investigates the effect of sucrose addition on the formation of casein gels by acidification and/or renneting of pure micellar casein. Gelation kinetics and gel properties were followed by rheological methods, and microscopy and syneresis measurements were used to obtain a more complete characterization of the structures formed. Sucrose content has been identified as a key parameter for controlling the kinetics of aggregation and the strength of the final gels. Results have shown that the effect of sucrose on gelation can vary such that effects can be completely reversed depending on the gelation route used. During acid gelation, addition of up to 30% (wt/wt) sucrose causes gels to form more rapidly and at higher pH values, and to have higher viscoelastic moduli and a more homogeneous microstructure than those without sucrose. By contrast, gels formed by renneting in the presence of sucrose are weaker and have longer gelation times. It is proposed that sucrose reduces solvent quality and causes the collapse of the "hairy" kappa-casein brush on the surface of the casein micelles. This may explain why sucrose increases the possibility of gel formation during acidification and reduces the degree of kappa-casein hydrolysis during renneting.

Caseins↗
PubMed2001

Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation.

Brain-derived neurotrophic factor (BDNF) is synthesized by small neuron cell bodies in the dorsal root ganglia (DRG) and is anterogradely transported to primary afferent terminals in the dorsal horn where it is involved in the modulation of painful stimuli. Here we show that BDNF is released in the rat isolated dorsal horn after chemical stimulation by capsaicin or electrical stimulation of dorsal roots. Capsaicin superfusion (1-100 microm) induced a dose-dependent release of BDNF, measured using ELISA. The highest dose of capsaicin also induced a depletion of BDNF protein in the dorsal horn. BDNF release was also seen after electrical stimulation of the dorsal roots at C-fiber strength. This release was encoded by specific patterns of afferent fiber stimulation. Neither continuous low-frequency (480 pulses, 1 Hz) nor tetanic high-frequency (300 pulses in 3 trains, 100 Hz) stimulation evoked release of BDNF, although substance P (SP) release was observed under both of these conditions. However, BDNF was released after short bursts of high-frequency stimulation (300 pulses in 75 trains, 100 Hz) along with SP and glutamate. The NMDA antagonist d-AP-5 inhibited electrically evoked BDNF release. BDNF release was also measured after systemic or intrathecal NGF treatment. This upregulated BDNF content in the DRG and increased the capsaicin-evoked release of BDNF. Similarly, the amount of BDNF released by burst stimulation was increased after NGF treatment. This activity-dependent release continued to be encoded solely by this stimulation pattern. These experiments demonstrate that BDNF release in the dorsal horn is encoded by specific patterns of afferent fiber stimulation and is mediated by NMDA receptor activation.

Animals↗
PubMed2001

The Aspergillus nidulans GATA transcription factor gene areB encodes at least three proteins and features three classes of mutation.

In Aspergillus nidulans, the principal transcription factor regulating nitrogen metabolism, AREA, belongs to the GATA family of DNA-binding proteins. In seeking additional GATA factors, we have cloned areB, which was originally identified via a genetic screen for suppressors of areA loss-of-function mutations. Based on our analysis, areB is predicted to encode at least three distinct protein products. These arise from the use of two promoters, differential splicing and translation initiating at AUG and non-AUG start codons. All the putative products include a GATA domain and a putative Leu zipper. These regions show strong sequence similarity to regulatory proteins from Saccharomyces cerevisiae (Dal80p and Gzf3p), Penicillium chrysogenum (NREB) and Neurospora crassa (ASD4). We have characterized three classes of mutation in areB; the first are loss-of-function mutations that terminate the polypeptides within or before the GATA domain. The second class truncates the GATA factor either within or upstream of the putative Leu zipper but retains the GATA domain. The third class fuses novel gene sequences to areB with the potential to produce putative chimeric polypeptides. These novel gene fusions transform the putative negative-acting transcription factor into an activator that can partially replace areA.

Amino Acid Sequence↗
PubMed2001

Characterization of nitrogen metabolite signalling in Aspergillus via the regulated degradation of areA mRNA.

AreA is the principal transcription factor involved in determining nitrogen utilization in Aspergillus nidulans. NH4+ and Gln are utilized preferentially but in their absence, AreA acts to facilitate the expression of genes involved in metabolizing alternative nitrogen sources. It is crucial to the function of AreA that its expression is tightly modulated by the quality and availability of nitrogen sources. One signalling mechanism involves regulated degradation of the areA transcript in response to NH4+ and Gln, which provides the first direct means of monitoring nitrogen signalling in this fungus. Here we assess the specificity of the transcript degradation response, determining that it responds qualitatively to a variety of additional nitrogen sources including Asn. Furthermore, the response to Gln and NH4+ requires the same discrete region of the areA 3'-UTR but both NH4+ and Asn need to be metabolized to Gln before they are effective as a signal. However, NH4+ signalling is independent of AreA activity, unlike Gln and Asn signalling. A mutation in the structural gene for NADP-linked glutamate dehydrogenase, gdhA, which disrupts metabolism of NH4+ to Glu, is additive with mutations in two distinct regions of areA that disrupt the previously identified signalling mechanisms. The triple mutant is both strongly derepressed and expresses very high levels of nitrate reductase activity. These data suggest nitrogen metabolism in A. nidulans is in part regulated in response to the intracellular levels of Gln via the regulated degradation of areA mRNA, but the intracellular Gln level is not the sole determinant of nitrogen metabolite repression.

Aspergillus nidulans↗
PubMed2001

Nitric oxide potentiates response of trigeminal neurones to dural or facial stimulation in the rat.

Infusing glyceryl trinitrate as a donor molecule, we have used electrophysiological and c-fos immunostaining techniques to study the effects of nitric oxide on neurones in the nucleus trigeminalis caudalis. Following infusion of glyceryl trinitrate, responses of neurones to electrical stimulation of periorbital cutaneous afferents were potentiated and threshold for activation of neurones by stimulation of dural afferents was reduced. Expression of c-fos was unchanged by glyceryl trinitrate compared to saline controls. Intradermal injection of capsaicin in the periorbital area increased c-fos expression in nucleus trigeminalis caudalis; this was significantly potentiated by glyceryl trinitrate. These results suggest that, in the anaesthetized rat, glyceryl trinitrate alone may not acutely activate the trigeminovascular system to a significant degree at doses that cause headache and later trigger migraine headache in migraineurs. Nevertheless, it is susceptible to exogenous nitric oxide in that activation of trigeminal neurones through cutaneous or dural pathways is potentiated. This may in some measure underlie the pathogenesis of migraine headache.

Afferent Pathways↗
PubMed2000

Artefacts in organic acid analysis: occurrence and origin of partially trimethylsilylated 3-hydroxy-3-methyl carboxylic acids.

Previous reports of patients with 3-hydroxy-3-methylglutaric aciduria have described the occurrence of di-trimethylsilyl (TMS) and tri-TMS derivatives of 3-hydroxy-3-methylglutaric acid on analysis using gas chromatography and mass spectrometry, leading to difficulty in quantification and ambiguity in diagnosis. We have extracted organic acids from the urine of patients with 3-hydroxy-3-methylglutaric aciduria using a variety of procedures. Solvent extraction combined with hydrochloric acid/sodium chloride resulted in production of both di-TMS and tri-TMS derivatives of 3-hydroxy-3-methylglutaric acid and also mono-TMS and di-TMS derivatives of 3-hydroxyisovaleric acid. The effects were not abolished by heating. Use of sulphate-based reagents minimised artefact formation and use of DEAE-Sephadex anion exchange extraction resulted in single fully trimethylsilylated derivatives. Artefact formation during use of chloride-based reagents was abolished by pyridine added prior to trimethylsilylation. Chloride ions form adducts with hydroxyl groups in these 3-hydroxy-3-methyl carboxylic acids that prevent complete trimethylsilylation. Chloride-based reagents should be avoided in the solvent extraction of organic acids from physiological fluids or, if used, pre-treatment of the dried extract with pyridine is essential to avoid partial trimethylsilylation of 3-hydroxy-3-methyl carboxylic acids.

Artifacts↗
PubMed2000

Identification of four novel interleukin-13 gene polymorphisms.

The development of allergic asthma is thought to involve environmental and inherited genetic components and has pathophysiological features reflecting in part the activity of T cell cytokines. Interleukin-13, a product primarily of activated lymphocytes, is considered to be a critical effector molecule in allergic airway response and has been found to be overexpressed in the airways of patients with asthma. The IL-13 gene is located on chromosome 5q31, one of the major loci to be linked to asthma susceptibility, and amongst a cluster of genes which dominate the immunopathology of allergic disease. Recently, an IL-13 promoter polymorphism was found to be associated with allergic asthma. In the present study we report the identification of four novel biallelic polymorphisms in the IL-13 gene, two intronic and two exonic, one of which results in a basic to hydrophilic amino acid change. We characterised the frequencies of these four biallelic polymorphisms and the frequencies of the haplotypes, resulting from the combination of these four biallelic polymorphisms, in a population of 196 UK Caucasoid healthy individuals.

Alleles↗
PubMed2000

Sensitization to oilseed rape is not due to cross-reactivity with grass pollen.

BACKGROUND: Oilseed rape is an important crop grown in the UK which can cause specific immunological sensitization with clinical symptoms in a relatively small number of the general population. Individuals with immunoglobulin (Ig) E-mediated allergy to oilseed rape have also been found to be sensitized to other pollen allergens, most frequently being grass pollen. Cross-reactivity between common grass and oilseed rape would have important implications, especially as their flowering period coincides. OBJECTIVE: We have investigated whether the cosensitization found in individuals sensitized to both oilseed rape and grass pollen is due to cross-reactivity. METHODS: Cross-reactivity between oilseed rape and grass pollen was determined using RAST, RAST inhibition, Western blotting and inhibition studies with Western blotting. RESULTS: Competitive RAST inhibition studies between pollen of oilseed rape and grass failed to show any cross-reactivity between the pollen types. Self-inhibition with oilseed rape resulted in 90% inhibition, whereas there was less than 10% inhibition with grass pollen. Western blotting revealed allergens of similar molecular weight in both oilseed rape and grass pollen. Despite allergens of similar molecular weights being present in both pollen types, inhibition immunoblot studies confirmed that the allergens in the two allergens were immunologically distinct. CONCLUSION: The allergens of oilseed rape and grass pollen, although similar in molecular weights, are immunologically distinct and there is no evidence of cross-reactivity between them. Individuals allergic to grass pollen will not necessarily develop a specific nasal or airway response to inhaled oilseed rape pollens.

Adult↗
PubMed2000

A defined sequence within the 3' UTR of the areA transcript is sufficient to mediate nitrogen metabolite signalling via accelerated deadenylation.

Nitrogen metabolism in Aspergillus nidulans is regulated by AREA, a member of the GATA family of transcription factors. One mechanism that modulates AREA activity involves the rapid degradation of the areA transcript when sufficient NH4+ or Gln are available. This signalling mechanism has been shown to require a region of 218 nucleotides within the 3' untranslated region of areA mRNA. We demonstrate that this region functions independently in a heterologous transcript and acts to accelerate degradation of the poly(A) tail, which in turn leads to rapid transcript degradation in response to the addition of NH4+ or Gln to the growth medium. areA transcript degradation is inhibited by cycloheximide, but this is not a general consequence of translational inhibition. We believe that this is the first reported example in which specific physiological signals, acting through a defined sequence within a transcript, have been shown to promote accelerated poly(A) degradation, which in turn triggers transcript degradation.

3' Untranslated Regions↗
PubMed2000

Abnormal substance P release from the spinal cord following injury to primary sensory neurons.

The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. Normally, SP is uniquely contained in a subpopulation of small-calibre axons (Adelta- and C-fibres) within primary afferent nerve. However, it has been shown that after nerve transection, besides being downregulated in small axons, SP is expressed de novo in large myelinated Abeta-fibres. In this study we investigated whether, following peripheral nerve injury, SP was released de novo from the spinal cord after selective activation of Abeta-fibres. Spinal cords with dorsal roots attached were isolated in vitro from rats 2 weeks following distal sciatic axotomy or proximal spinal nerve lesion (SNL). The ipsilateral dorsal roots were electrically stimulated for two consecutive periods at low- or high-threshold fibre strength, spinal cord superfusates were collected and SP content was determined by radioimmunoassay. SNL, but not axotomized or control rat cords, released significant amounts of SP after selective activation of Abeta-fibres. Not only do these data support the idea that Abeta myelinated fibres contribute to neuropathic pain by releasing SP, they also illustrate the importance of the proximity of the lesion to the cell body.

Afferent Pathways↗