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Biomedical subjects

M Upton

Publications and source records attributed to M Upton.

At least 19 recordsLinked to original sources
PubMed2006

Rapid cost-effective subtyping of meticillin-resistant Staphylococcus aureus by denaturing HPLC.

The importance of meticillin-resistant Staphylococcus aureus (MRSA) in hospital-acquired infection is widely acknowledged. The UK government has stated that MRSA bloodstream infection rates will have to be halved by 2008. Such radical improvements will require advances on several fronts. Screening for MRSA in high-risk patients on arrival at hospital allows isolation of carriers and reduces transmission to staff and other patients. Concurrent subtyping of MRSA could also inform outbreak investigations and long-term epidemiological studies. The variability within the staphylococcal protein A, or spaA, gene-repeat region can be used as a marker of short- and long-term genetic variation. A novel application is described of denaturing HPLC (DHPLC) for rapid, inexpensive characterization of spaA gene amplification products, without the need for DNA sequence determination. The method allowed rapid and precise sizing of spaA gene-repeat regions from 99 S. aureus strains and was combined with heteroduplex analysis, using reference PCR products, to indicate the spa type of the test isolate. The method allowed subtyping of strains in less than 5 h from receipt of a primary isolation plate. When applied to an outbreak that occurred during this study, the authors were able to demonstrate relatedness of the isolates more than 5 days before results were received from a reference laboratory. If combined with direct amplification from swabs, DHPLC analysis of spaA gene variation could prove extremely valuable in outbreak investigation and MRSA surveillance.

Chromatography, High Pressure Liquid↗
PubMed2006

The natural history of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the USA, and it remains one of the few diseases that continues to increase its numbers. The development and progression of COPD can vary dramatically between individuals. A low level of lung function remains the cornerstone of COPD diagnosis and is a key predictor of prognosis. Lung function, however, is not the only factor in determining morbidity and mortality related to COPD, with factors such as body mass index, exercise capability and comorbid disease being important predictors of poor outcomes. Exacerbations of COPD are additional important indicators of both quality of life and outcomes in COPD patients. Definitions of exacerbations can vary, ranging from an increase in symptoms to COPD-related hospitalisations and death. COPD exacerbations are more common in patients with lower levels of lung function and may lead to more rapid declines in lung function. Better understanding of the natural history of COPD may lead to better definitions of specific COPD phenotypes, better interventions and improved outcomes.

Cardiovascular Diseases↗
PubMed2006

Investment in preventing and preparing for biological emergencies and disasters: social and economic costs of disasters versus costs of surveillance and response preparedness.

Biological emergencies such as the appearance of an exotic transboundary or emerging disease can become disasters. The question that faces Veterinary Services in developing countries is how to balance resources dedicated to active insurance measures, such as border control, surveillance, working with the governments of developing countries, and investing in improving veterinary knowledge and tools, with passive measures, such as contingency funds and vaccine banks. There is strong evidence that the animal health situation in developed countries has improved and is relatively stable. In addition, through trade with other countries, developing countries are becoming part of the international animal health system, the status of which is improving, though with occasional setbacks. However, despite these improvements, the risk of a possible biological disaster still remains, and has increased in recent times because of the threat of bioterrorism. This paper suggests that a model that combines decision tree analysis with epidemiology is required to identify critical points in food chains that should be strengthened to reduce the risk of emergencies and prevent emergencies from becoming disasters.

Animal Welfare↗
PubMed2001

Intra- and interspecies signaling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides.

Streptococcus salivarius 20P3 produces a 22-amino-acid residue lantibiotic, designated salivaricin A (SalA), that inhibits the growth of a range of streptococci, including all strains of Streptococcus pyogenes. Lantibiotic production is associated with the sal genetic locus comprising salA, the lantibiotic structural gene; salBCTX genes encoding peptide modification and export machinery proteins; and salYKR genes encoding a putative immunity protein and two-component sensor-regulator system. Insertional inactivation of salB in S. salivarius 20P3 resulted in abrogation of SalA peptide production, of immunity to SalA, and of salA transcription. Addition of exogenous SalA peptide to salB mutant cultures induced dose-dependent expression of salA mRNA (0.2 kb), demonstrating that SalA production was normally autoregulated. Inactivation of salR encoding the response regulator of the SalKR two-component system led to reduced production of, and immunity to, SalA. The sal genetic locus was also present in S. pyogenes SF370 (M type 1), but because of a deletion across the salBCT genes, the corresponding lantibiotic peptide, designated SalA1, was not produced. However, in S. pyogenes T11 (M type 4) the sal locus gene complement was apparently complete, and active SalA1 peptide was synthesized. Exogenously added SalA1 peptide from S. pyogenes T11 induced salA1 transcription in S. pyogenes SF370 and in an isogenic S. pyogenes T11 salB mutant and salA transcription in S. salivarius 20P3 salB. Thus, SalA and SalA1 are examples of streptococcal lantibiotics whose production is autoregulated. These peptides act as intra- and interspecies signaling molecules, modulating lantibiotic production and possibly influencing streptococcal population ecology in the oral cavity.

Amino Acid Sequence↗
PubMed2000

Combined molecular ecological and confocal laser scanning microscopic analysis of peat bog methanogen populations.

Confocal laser scanning microscopy, using fluorescently labelled oligonucleotide probes targeting the 16S rRNA of different physiological groups of methanogens, was used to identify which methanogenic genera were present and to describe their in situ spatial locations in samples taken at different depths from blanket peat bog cores. Total bacterial DNA was also extracted and purified from the samples and used as template for amplification of 16S rRNA and regions of methyl CoM reductase-encoding genes using the polymerase chain reaction, as well as for oligonucleotide hybridisation experiments. These techniques, used in concert, demonstrated that methanogens of several physiological groups were present in highest numbers in the mid regions of 25 cm deep peat cores. Some discrepancies were apparent in the findings of the microscopic and molecular methods, though these may be partially accounted for by the different sensitivities of the techniques employed. The combined approaches used in this study gave an insight into the diversity and distribution of methanogens in peat environments not possible using molecular ecological methods alone.

DNA, Archaeal↗
PubMed2000

How accurately do adult sons and daughters report and perceive parental deaths from coronary disease ?

OBJECTIVES: To describe how adult sons and daughters report and perceive parental deaths from heart disease DESIGN: Two generation family study. SETTING: West of Scotland. SUBJECTS: 1040 sons and 1298 daughters aged 30-59 from 1477 families, whose fathers and mothers were aged 45-64 in 1972-76 and have been followed up for mortality over 20 years. OUTCOME: Perception of a "family weakness" attributable to heart disease. RESULTS: 26% of sons and daughters had a parent who had died of coronary heart disease (CHD). The proportion was higher in older offspring (+18% per 10 year age difference) and in manual compared with non-manual groups (+37%). Eighty nine per cent of parental deaths from CHD were correctly reported by offspring. Only 23% of sons and 34% of daughters with at least one parent who had died of CHD considered that they had a family weakness attributable to heart disease. Perceptions of a family weakness were higher when one or both parents had died of CHD, when parental deaths occurred at a younger age, in daughters compared with sons and in offspring in non-manual compared with manual occupations. CONCLUSIONS: Only a minority of sons and daughters with experience of a parent having died from CHD perceive this in terms of a family weakness attributable to heart disease. Although men in manual occupations are most likely to develop CHD, they are least likely to interpret a parental death from CHD in terms of a family weakness. Health professionals giving advice to patients on their familial risks need to be aware of the difference between clinical definitions and lay perceptions of a family history of heart disease.

Adult↗
PubMed2000

Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality.

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting in--or being associated with--shorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers.

Body Height↗
PubMed1999

Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions.

Quantitative information on the cell-to-cell distribution of all possible mitochondrial DNA (mtDNA) mutations in young and aged tissues is needed to assess the relevance of these mutations to the aging process. In the present study, we used PCR amplification of full-length mitochondrial genomes from single cells to scan human cardiomyocytes for all possible large deletions in mtDNA. Analysis of more than 350 individual cells that were derived from three middle-aged and four centenarian donors demonstrates that while most of the cells contain no deletions, in certain cardiomyocytes a significant portion of the mtDNA molecules carried one particular deletion. Different affected cells contained different deletions. Although similar numbers of cells were screened for each donor, these deletion-rich cells were found only in the hearts of old donors, where they occurred at a frequency of up to one in seven cells. These initial observations demonstrate the efficiency of the method and indicate that mitochondrial mutations have the potential to play an important role in human myocardial aging.

Aged↗
PubMed1999

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment.

Androgen Antagonists↗
PubMed1999

Financial analysis of East Coast fever control strategies in traditionally managed Sanga cattle in Central Province of Zambia.

Five different East Coast fever (ECF)-control strategies (involving ECF immunisation by the infection-and-treatment method) were tested in groups of traditionally managed Sanga cattle in the Central Province of Zambia over a period of 2.5 years. Two groups were under intensive tick control (weekly spraying with acaricide)--one group immunised and the other non-immunised. Two groups were under no tick control--one group immunised and the other non-immunised. The fifth group was under seasonal tick control (18 sprays/year) and was immunised against ECF. The input and output data were used to construct discounted cash flows for each group. The seasonally sprayed and immunised group gave the highest net present value, and the non-immunised group with no tick control, the lowest. A break-even analysis showed that the immunisation costs could rise to US$25.9 per animal before profitability was affected. For herds under intensive tick control, immunisation was of no financial benefit. The results demonstrate the value of immunisation, and indicate the importance of its combination with seasonal tick-control measures.

Animals↗
PubMed1999

Molecular Ecological Analysis of Methanogens and Methanotrophs in Blanket Bog Peat.

Abstract Methane production and methane oxidation potential were measured in a 30 cm peat core from the Moorhouse Nature Reserve, UK. The distribution of known groups of methanogens and methane oxidizing bacteria throughout this peat core was assessed. Using 16S rRNA gene retrieval and functional gene probing with genes encoding key proteins in methane oxidation and methanogenesis, several major groups of microorganisms were detected. Methane production and oxidation was detected in all depths of the peat core. PCR amplification and oligonucleotide probing experiments using DNA isolated from all sections of the peat core detected methanotrophs from the groups Methylosinus and Methylococcus and methanogens from the groups Methanosarcinaceae, Methanococcaceae, and Methanobacteriaceae. 16S rDNA sequences amplified with the Methylosinus-specific primer were shown to have a high degree of identity with 16S rDNA sequences previously detected in acidic environments. However, no methanogen sequences were detected by the probes available in this study in the sections of the peat core (above 7 cm) where the majority of methanogenesis occurred, either because of low methanogen numbers or because of the presence of novel methanogen sequences.http://link.springer-ny.com/link/service/journals/00248/bibs/38n3p225.html</hea

Journal Article↗
PubMed1999

Novel nitrated derivatives of 5,8-diazabenzo[c]phenanthrene and 9,14-diazadibenz[a,e]acephenanthrylene: new classes of potent mutagenic compounds.

We report the synthesis of 4-nitro-5,8-diazabenzo[c]phenanthrene (4-NDBP) and 11-nitro-9,14-diazadibenz[a,e]acephenanthrylene (11-NDDA) and the remarkable mutagenic activity of the latter. These two compounds and their non-nitrated parents, 5, 8-diazabenzo[c]phenanthrene (DBP) and 9,14-diazadibenz[a, e]acephenanthrylene (DDA), were screened in Ames plate incorporation assays against Escherichia coli WP2uvrA and Salmonella typhimurium TA98 both in the presence and absence of S9 liver fraction from Aroclor 1254-induced rats. None of the four compounds were cytotoxic up to the limits of their solubility and none showed mutagenic activity in E.coli WP2uvrA, which suggested that any such activity they may have had was not mediated via a base substitution mechanism. DBP and DDA also displayed a lack of activity in TA98 up to their precipitating doses (560 and 33.5 microg/plate, respectively). The two nitrated compounds, however, were genotoxic. 4-NDBP was active at a dose of 500 ng/plate, in the absence of S9, producing 80.0 +/- 28.0 prototrophic organisms (equivalent to 44 revertants/nmol) and at 0.5 ng/plate, in the presence of S9, giving 147 +/- 6.6 revertants (equivalent to 81 000/nmol) and allowed the description of this tetracycle as a potent mutagen. Much more striking was the activity of 11-NDDA: in the absence of S9 a dose of 8.0 ng produced 2000 revertants/nmol and, remarkably, in the presence of S9 80 pg produced the equivalent of 643 000 revertants/nmol. This makes the hexacyclic 11-NDDA the most potent mutagen to date, in the Ames procedures described here.

Coumarins↗
PubMed1999

The economic implications of greater global trade in livestock and livestock products.

The Uruguay Round of the General Agreement on Tariffs and Trade (GATT) established the World Trade Organization to supervise the reduction of barriers to, and liberalisation of, world trade. The application of sanitary and phytosanitary measures will be standardised to avoid use for protectionist purposes by countries or regional trade blocks. Harmonisation of animal disease control measures within regional blocks is essential if benefits to freer trade are to occur, but this harmonisation must be balanced against potential disease risks and costs associated with disease outbreaks. World trade in livestock products is concentrated among developed countries, although developing countries are responsible for approximately a third of poultry meat imports and exports. Despite liberalisation, the share of global trade by developing countries is unlikely to increase greatly in the short term. The benefits of trade and of freer trade are emphasised. Examples are given of the impacts of trade barriers on developing countries and of the harmonisation of European Union animal health standards. Economic implications for the future of greater global trade are assessed.

Africa, Western↗
PubMed1998

Novel 5,8-diazabenzo[c]phenanthrenes: synthesis and mutagenicity.

The polycyclic aromatic hydrocarbons have been recognized as carcinogens and mutagens since the early part of this century. More recently their aza and polyaza derivatives have been shown to have the same biological activity. A major source of these compounds is the combustion of fresh or metamorphosed plant materials; this contributes to the environmental burden of, and exposure to, these carcinogens. We report the synthesis and characterization of a series of novel 5,8-diazabenzo[c]phenanthrenes which are isosteric with the known epidermal carcinogen benzo[c]phenanthrene but have not yet been reported as components of soot or diesel particulate matter. The synthesis of the compounds exploits a versatile, double Friedlander reaction between the appropriately substituted 2,2'-diaminobenzophenone and beta-diketones, with yields of purified product ranging from 30-90%. The nucleophilic substitution of these diazabenzophenanthrenes with ethanolamine is also described. This strategy will enable further elaboration of these heterocyclic nuclei at a later date. Mutagenicity testing of these agents was performed using spot tests and in Ames plate-incorporation assays using Escherichia coli WP2 and WP2uvrA as test organisms. The plate-incorporation assays were performed in the presence or absence of metabolic enzymes contained in the S9 liver fraction from Aroclor 1254-induced rats, to investigate whether bioactivation of the diazabenzophenanthrenes contributed to their toxicity. No differences between these two protocols were observed, with neither test showing reversion to prototrophic behaviour. Furthermore, the compounds were not toxic to the test organism. These initial results suggest that these compounds are not mutagenic in the Ames tests employed.

Animals↗
PubMed1997

Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study.

OBJECTIVE: To investigate the association between birth weight of offspring and mortality among fathers and mothers in the west of Scotland. DESIGN: Prospective observational study. PARTICIPANTS: 794 married couples in Renfrew district of the west of Scotland. MAIN OUTCOME MEASURES: Mortality from all causes and from cardiovascular disease over 15 year follow up. RESULTS: Women who had heavier babies were taller, had higher body mass index and better lung function, and were less likely to be smokers than mothers of lighter babies. Fathers of heavier babies were taller and less likely to be smokers than fathers of lighter babies. Mortality was inversely related to offspring's birth weight for both mothers (relative rate for a 1 kg lower birth weight 1.82 (95% confidence interval 1.23 to 2.70)) and fathers (relative rate 1.35 (1.03 to 1.79)). For mortality from cardiovascular disease, inverse associations were seen for mothers (2.00 (1.18 to 3.33)) and fathers (1.52 (1.03 to 2.17)). Adjustment for blood pressure, plasma cholesterol, body mass index, height, social class, area based deprivation category, smoking, lung function, angina, bronchitis, and electrocardiographic evidence of ischaemia had little effect on these risk estimates, although levels of statistical significance were reduced. CONCLUSIONS: Birth weight of offspring was related inversely to mortality, from all causes and cardiovascular disease, in this cohort. The strength of this association was greater than would have been expected by the degree of concordance of birth weights across generations, but an extensive range of potential confounding factors could not account for the association. Mortality is therefore influenced by a factor related to birth weight that is transmissible across generations.

Birth Weight↗