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Biomedical subjects

M R Thomas

Publications and source records attributed to M R Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Respiratory function of very prematurely born infants at follow up: influence of sex.

OBJECTIVE: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. DESIGN: Prospective follow up study. SETTING: Tertiary neonatal intensive care units PATIENTS: Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study. INTERVENTIONS: Lung function measurements at a corrected age of 1 year. MAIN OUTCOME MEASURES: Airways resistance (Raw) and functional residual capacity (FRC(pleth)) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRC(pleth), and FRC measured by a helium gas dilution technique (FRC(He)). RESULTS: The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRC(pleth) were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRC(pleth) and sGaw were 15% and 26% respectively and remained significant. CONCLUSION: Lung function at follow up of prematurely born infants is influenced by sex.

Airway Resistance↗
PubMed2006

Somatic chimerism, genetic inheritance, and mapping of the fleshless berry (flb) mutation in grapevine (Vitis vinifera L.).

The fleshless berry (flb) mutation of grapevine (Vitis vinifera L. 'Ugni Blanc') impairs the differentiation and division of inner mesocarp cells responsible for flesh in grapevine berries. In order to study the inheritance of the mutation and to map the flb locus, 5 segregating populations were created. Progeny plants were classified as mutant or wild type by scoring for the presence of an ovary phenotype associated with the Flb- phenotype at anthesis. Phenotypic segregation revealed the involvement of a single dominant allele that was heterozygous in the original mutant. Through bulk segregant analysis, microsatellite (simple sequence repeat (SSR)) markers linked to the mutation were identified, and the flb locus was assigned to linkage group 18. The locus position was then refined by analyzing individual progeny and the segregation of SSR markers in the target region with the closest marker 5.6 cM distant from the flb locus. All progeny with the Flb- ovary phenotype differed from the original fleshless berry mutant in that no berries formed after anthesis. Our data suggest that the original mutant plant was a chimera with the mutated allele present in only 1 cell layer (L2 layer) of the ovary and berry.

Alleles↗
PubMed2006

Diagnostic and therapeutic difficulties in type 2A von Willebrand disease: resolution.

A patient with type 2A von Willebrand disease and a long history of gastrointestinal (GI) bleeding is presented, in whom no abnormality was found on sequencing the von Willebrand factor gene at the DNA level. Subsequent RNA analysis revealed him to be heterozygous for a T-C substitution at nucleotide 4,883, a mutation previously described and associated with type 2A von Willebrand disease. This illustrates the value of a dual DNA/ RNA approach to genetic investigations of highly polymorphic genes. GI bleeding from angiodysplasia is a feature of von Willebrand disease, particularly type 2A. Proactive management with definitive diagnosis of angiodysplasia and ablative treatment where feasible is recommended to stop bleeding symptoms and minimize exposure to blood products.

Angiodysplasia↗
PubMed2005

Plethysmograph and interrupter resistance measurements in prematurely born young children.

BACKGROUND: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age. OBJECTIVE: To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children. DESIGN: Prospective study. SETTING: Infant and Paediatric Lung Function Laboratories. PATIENTS: Thirty children with a median gestational age of 25-29 weeks and median postnatal age of 13 months. INTERVENTIONS AND MAIN OUTCOME MEASURES: The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep. RESULTS: Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p = 0.006). Limits of agreement for the mean difference between Rint and Raw were -1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement -0.28 to 1.44 kPa/l/s). CONCLUSION: The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.

Airway Obstruction↗
PubMed2005

Epidemiological implications of the contact network structure for cattle farms and the 20-80 rule.

The network of movements of cattle between farm holdings is an important determinant of the potential rates and patterns of spread of infectious diseases. Because cattle movements are uni-directional, the network is unusual in that the risks of acquiring infection (by importing cattle) and of passing infection on (by exporting cattle) can be clearly distinguished, and there turns out to be no statistically significant correlation between the two. This means that the high observed degree of heterogeneity in numbers of contacts does not result in an increase in the basic reproduction number, R0, in contrast to findings from studies of other contact networks. Despite this, it is still the case that just 20% of holdings contribute at least 80% of the value of R0.

Agriculture↗
PubMed2005

Genetic and physical mapping of the grapevine powdery mildew resistance gene, Run1, using a bacterial artificial chromosome library.

Resistance to grapevine powdery mildew is controlled by Run1, a single dominant gene present in the wild grapevine species, Muscadinia rotundifolia, but absent from the cultivated species, Vitis vinifera. Run1 has been introgressed into V. vinifera using a pseudo-backcross strategy, and genetic markers have previously been identified that are linked to the resistance locus. Here we describe the construction of comprehensive genetic and physical maps spanning the resistance locus that will enable future positional cloning of the resistance gene. Physical mapping was performed using a bacterial artificial chromosome (BAC) library constructed using genomic DNA extracted from a resistant V. vinifera individual carrying Run1 within an introgression. BAC contig assembly has enabled 20 new genetic markers to be identified that are closely linked to Run1, and the position of the resistance locus has been refined, locating the gene between the simple sequence repeat (SSR) marker, VMC4f3.1, and the BAC end sequence-derived marker, CB292.294. This region contains two multigene families of resistance gene analogues (RGA). A comparison of physical and genetic mapping data indicates that recombination is severely repressed in the vicinity of Run1, possibly due to divergent sequence contained within the introgressed fragment from M. rotundifolia that carries the Run1 gene.

Ascomycota↗
PubMed2005

Prognostic role of cardiac troponin I after percutaneous coronary intervention in stable coronary disease.

OBJECTIVE: To assess the role of cardiac troponin I (cTnI) in predicting outcome after percutaneous coronary intervention (PCI). METHODS AND RESULTS: cTnI was measured immediately before and at 6, 14, and 24 hours after PCI in 316 consecutive patients with stable symptoms and native coronary artery disease. The study end point was the occurrence of major adverse cardiac events (MACE) at 30 days and at 18 months after PCI: death, Q wave myocardial infarction (MI), or repeat revascularisation in hospital. Postprocedural cTnI increased in 31% of patients. The cumulative MACE rate at 18 months was 25% (17.7% due to repeat PCI procedures). There was a significant association between postprocedural cTnI increase and death, Q wave MI, or both (odds ratio (OR) 3.28, 95% confidence interval (CI) 1.7 to 6.4, p = 0.01). Post-PCI cTnI increase had a positive predictive value (PPV) for adverse events at 18 months of 0.47 and a negative predictive value (NPV) of 0.96 (OR 18.9, 95% CI 9.7 to 37, p < 0.0001). The presence of both a postprocedural cTnI rise and a procedural angiographic complication gave a PPV for adverse events of 0.69 and an NPV of 0.92 (OR 22.6, 95% CI 2.6 to 68.6, p = 0.0005). CONCLUSIONS: cTnI increased post-procedurally in one third of this stable patient population undergoing elective PCI and was independently and significantly predictive of an increased risk of adverse events at 18 months, predominantly in the form of repeat PCI.

Aged↗
PubMed2004

Occurrence and risks associated with chlormequat residues in a range of foodstuffs in the UK.

Trends in the usage pattern of chlormequat (a plant growth regulator) on cereal crops in the UK over the past 6 years are presented. The figures have been supplemented by monitoring of chlormequat residues in food commodities through the UK surveillance programme, and for cereals, the carry-through into a number of processed cereal-based foods has been followed. A downward trend of chlormequat residue levels in pears sampled between 1997 and 2002 was observed. This decline reflects changes that were introduced in European and national regulations and which have proven to be extremely effective in reducing both the frequency of detection and levels of chlormequat residues. Both acute and chronic risk assessments were undertaken based on aggregate dietary exposure data. Even when the highest residues observed were used in the calculations, the assessments showed that both the short- and long-term intakes for all consumer groups would be unlikely to cause adverse health effects and were therefore not of any cause for concern.

Chlormequat↗
PubMed2003

Crop management and agronomic context of the Farm Scale Evaluations of genetically modified herbicide-tolerant crops.

The Farm Scale Evaluations of genetically modified herbicide-tolerant crops (GMHT) were conducted in the UK from 2000 to 2002 on beet (sugar and fodder), spring oilseed rape and forage maize. The management of the crops studied is described and compared with current conventional commercial practice. The distribution of field sites adequately represented the areas currently growing these crops, and the sample contained sites operated at a range of management intensities, including low intensity. Herbicide inputs were audited, and the active ingredients used and the rates and the timings of applications compared well with current practice for both GMHT and conventional crops. Inputs on sugar beet were lower than, and inputs on spring oilseed rape and forage maize were consistent with, national averages. Regression analysis of herbicide-application strategies and weed emergence showed that inputs applied by farmers increased with weed densities in beet and forage maize. GMHT crops generally received only one herbicide active ingredient per crop, later and fewer herbicide sprays and less active ingredient (for beet and maize) than the conventional treatments. The audit of inputs found no evidence of bias.

Agriculture↗
PubMed2002

Coronary artery perforation during percutaneous intervention: incidence and outcome.

OBJECTIVE: To examine the clinical outcome of percutaneous coronary intervention where the procedure was complicated by vessel perforation. SETTING: Tertiary referral centre. METHODS: The procedural records of 6245 patients undergoing coronary intervention were reviewed. In 52 patients (0.8%) the procedure was complicated by vessel perforation, ranging from wire exit to free flow of contrast into the pericardial space. The majority of lesions treated were complex (37% type B, 59% type C) and 9 of 52 (17%) were chronic occlusions. Ten patients (19%) received abciximab. Four underwent rotational atherectomy (8%). RESULTS: In 28 of 52 patients (54%) the perforation was benign and managed conservatively without the development of haemodynamically significant sequelae. In 24 of 52 (46%) a significant pericardial effusion ensued requiring drainage. Of these 24 procedures 6 had involved the treatment of a chronic occlusion (25%). Eight of the 24 patients were referred for emergency bypass surgery (33%), 3 of whom died. Of the remaining 16 not referred for surgery, 3 died. Of the 10 procedures complicated by vessel perforation where abciximab had been administered, 9 (90%) led to pericardial tamponade. Latterly 2 vessel perforations were successfully treated by the deployment of a covered stent. CONCLUSIONS: Coronary artery perforation with sequelae during intervention is rare--26 of 6245 (0.4%). This complication was seen in the treatment of chronic occlusions, which are therefore not risk-free procedures. The development of pericardial tamponade carries a high mortality. While prompt surgical intervention may be life saving, expertise in the use of covered stents may provide a valuable rescue option for this serious complication. Caution should be exercised where coronary perforation occurs and abciximab has been used.

Abciximab↗
PubMed2001

FTIR and resonance Raman studies of nitric oxide binding to H93G cavity mutants of myoglobin.

Nitric oxide (NO) binds to the myoglobin (Mb) cavity mutant, H93G, forming either a five- or six-coordinate Fe-NO complex. The H93G mutation eliminates the covalent attachment between the protein and the proximal ligand, allowing NO to bind H93G possibly from the proximal side of the heme rather than the typical diatomic binding pocket on the distal side. The question of whether NO binds on the distal or proximal side was addressed by FTIR spectroscopy of the N-O vibrational frequency nuN(-O) for a set of Mb mutants that perturb the electrostatic environment of the heme pocket. Vibrational spectra of five- and six-coordinate MbNO complexes indicate that nu(N-O) shifts (by as much as 26 cm(-1)) to higher energies for the distal mutants H64V and H64V/H93G relative to the energies of wild-type and H93G MbNO, while nu(N-O) is not affected by the proximal side mutation S92A/H93G. This result suggests that NO binds on the distal side of heme in the five- and six-coordinate MbNO complexes of H93G. Additionally, values of the Fe-NO vibrational frequency nu(Fe-NO) as measured by resonance Raman spectroscopy are reported for the distal and proximal double mutants of H93G. These results suggest that nu(Fe-NO) is not very sensitive to mutations that perturb the electrostatic environment of the heme pocket, leading to the observation that nu(N-O) and nu(Fe-NO) are not quantitatively correlated for the MbNO complexes presented here. Furthermore, nu(N-O) and nu(Fe-NO) do not correlate well with equilibrium constants for imidazole binding to the five-coordinate MbNO complexes of the H93G double mutants. The data presented here do not appear to support the presence of pi-back-bonding or an inverse trans effect of NO binding in Mb mutants that alter the electrostatic environment of the heme pocket.

Animals↗
PubMed2001

19F NMR of trifluoroacetyl-labeled cysteine mutants of myoglobin: structural probes of nitric oxide bound to the H93G cavity mutant.

Nitric oxide (NO) binds to the myoglobin (Mb) cavity mutant, H93G, forming either a 5- or 6-coordinate Fe--NO heme complex. The H93G mutation replaces the proximal histidine of Mb with glycine, allowing exogenous ligands to occupy the proximal binding site. In the absence of the covalently attached proximal ligand, NO could bind to H93G from the proximal side of the heme rather than the typical diatomic binding pocket on the distal side when the 5-coordinate complex forms. The question of whether NO binds on the distal or proximal side was addressed by (19)F NMR. Site-directed mutagenesis was used to introduce unique cysteine residues at the protein surface on either the distal (S58C) or proximal (L149C) side, approximately equidistant from and perpendicular to the heme plane of both wild-type and H93G Mb. The cysteine thiols were alkylated with 3-bromo-1,1,1-trifluoroacetone to attach a trifluoroacetyl group at the mutation site. (19)F NMR spectra of 5-coordinate, NO bound S58C/H93G and L149C/H93G double mutants depict peaks with line widths of 100 and 23 Hz, respectively. As fluorine peaks broaden with increasing proximity to paramagnetic centers, such as 5-coordinate Fe--NO, the (19)F NMR data are consistent with NO binding in the distal heme pocket of H93G, even in the absence of a sixth axial ligand. Additionally, (19)F NMR spectra are reported for deoxy, oxy, CO, met CN, and met H(2)O forms of the labeled cysteine mutants. These results demonstrate that the fluorine probes are sensitive to subtle conformational changes in the protein structure due to ligation and oxidation state changes of the heme iron in Mb.

Animals↗
PubMed2001

A photolysis-triggered heme ligand switch in H93G myoglobin.

Resonance Raman spectroscopy and step-scan Fourier transform infrared (FTIR) spectroscopy have been used to identify the ligation state of ferrous heme iron for the H93G proximal cavity mutant of myoglobin in the absence of exogenous ligand on the proximal side. Preparation of the H93G mutant of myoglobin has been previously reported for a variety of axial ligands to the heme iron (e.g., substituted pyridines and imidazoles) [DePillis, G., Decatur, S. M., Barrick, D., and Boxer, S. G. (1994) J. Am. Chem. Soc. 116, 6981-6982]. The present study examines the ligation states of heme in preparations of the H93G myoglobin with no exogenous ligand. In the deoxy form of H93G, resonance Raman spectroscopic evidence shows water to be the axial (fifth) ligand to the deoxy heme iron. Analysis of the infrared C-O and Raman Fe-C stretching frequencies for the CO adduct indicates that it is six-coordinate with a histidine trans ligand. Following photolysis of CO, a time-dependent change in ligation is evident in both step-scan FTIR and saturation resonance Raman spectra, leading to the conclusion that a conformationally driven ligand switch exists in the H93G protein. In the absence of exogenous nitrogenous ligands, the CO trans effect stabilizes endogenous histidine ligation, while conformational strain favors the dissociation of histidine following photolysis of CO. The replacement of histidine by water in the five-coordinate complex is estimated to occur in < 5 micros. The results demonstrate that the H93G myoglobin cavity mutant has potential utility as a model system for studying the conformational energetics of ligand switching in heme proteins such as those observed in nitrite reductase, guanylyl cyclase, and possibly cytochrome c oxidase.

Animals↗