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P Vaughan

Publications and source records attributed to P Vaughan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Creutzfeldt-Jakob disease latest unknown in struggle to restore faith in blood supply.

There was considerable medical interest in a recent Toronto conference on prion disease--and in Creutzfeldt-Jakob disease (CJD) in particular--because of the recent tainted-beef controversy in Britain. Although there is no proven link between a newly recognized variant form of CJD and "mad cow disease," and no evidence that CJD can be spread through the blood supply, the theoretical risk has scientists scrambling to understand how the disease is spread and policymakers struggling with the thorny issue of whether to notify persons who have received blood or blood products that may place them at risk. Until the mysteries of prion diseases and their transmission are unravelled, Dr. Peter Vaughan reports, physicians and their patients will have to live with uncertainty.

Adolescent↗
PubMed1995

Mortality study of construction workers in the UK.

BACKGROUND: Construction is one of the most dangerous industries in the world. However, there has been little literature on occupational epidemiology in this field. A study of the mortality experience over a 13-year period among construction workers in the UK was carried out. METHOD: This was based on 15,007 death certificates of members of the Building and Civil Engineering Holiday and Benefit Scheme, who had died during 1975 to 1987 aged 20-64 years. Proportional mortality ratio (PMR) and mortality odds ratio techniques were used. RESULTS: Significantly elevated PMR were found for deaths from all cancers, including cancer of the lung and stomach, and for accidental deaths. Associations were demonstrated between several job categories and an increased risk of cancer mortality. Occupational exposures to hazardous substances may have contributed to the elevated cancer mortality, although the study findings should be interpreted with caution. Inadequate supervision of safety procedures, together with a high proportion of young and inexperienced workers, may be associated with the high number of accidental deaths. CONCLUSIONS: The results support the hypothesis that working in the construction industry is associated with a high risk for accidental death and probably also for malignant diseases including lung, mesothelium and stomach cancers. Further epidemiological studies among construction workers are needed to support policies aimed at improving occupational health, including the prevention of accidents.

Accidents, Occupational↗
PubMed1993

Induction of the adaptive response of Escherichia coli to alkylation damage by the environmental mutagen, methyl chloride.

Methyl chloride (MeCl) is an abundant environmental mutagen and carcinogen and may be one of several environmental alkylating agents against which the protection of an adaptive response is required in microorganisms. Both MeCl and methyl iodide (MeI), at micromolar concentrations, induced the adaptive response to alkylation damage in Escherichia coli. This response is regulated by the Ada protein which is converted into a transcriptional activator by self-methylation on repair of methylphosphotriesters in methylated DNA. However, using high amounts of Ada protein, activation of Ada occurred in vitro following direct protein methylation by both MeI (in agreement with previously published data) and MeCl. Activation was enhanced when methyl halide treatments were performed in the presence of DNA. An unadapted E. coli cell contains only 2 to 4 molecules of Ada protein, and presents an extremely small target of 2 to 4 specific cysteine residues per cell for activation of Ada by direct protein methylation in vivo. Thus, it is proposed that induction of the adaptive response in vivo initially occurs via efficient repair by the Ada protein of a low number of methylphosphotriesters in DNA. When the cellular Ada protein level has substantially increased, a greater probability of direct methylation and activation of Ada at cysteine-69 by MeCl may sustain and further increase induction of the adaptive response.

Adaptation, Physiological↗
PubMed1991

Kinetic analysis of chloride conductance in frog skeletal muscle at pH 5.

At pH 5 the steady-state chloride chord conductance in frog skeletal muscle rises to an asymptotic maximum at very negative voltages and approaches an asymptotic minimum at positive voltages. When a two-pulse test paradigm is used, the conductance computed from steady-state currents during the first (conditioning) voltage step are not duplicated by the conductance at the onset of a second (test) step. If the test step is to a more negative voltage than the conditioning step the steady-state conductance is overestimated; if it is to a less negative voltage the conductance is underestimated. In some fibres the initial currents accompanying steps from the resting potential are inwardly rectified. From this it was inferred that chloride channel conductance is voltage dependent: in those fibres in which no such initial inward rectification was observed it was inferred that at rest the voltage-dependent chloride channels are all closed. Time-dependent ("gated") changes of conductance could be reasonably described by a first-order process, but the relaxations were not simple exponentials. Simulation of the experimental set-up predicted the type of deviation from exponentiality seen experimentally, although the observed deviations were often more pronounced than those predicted.

Animals↗
PubMed1991

Substitute anions and the chloride conductance of frog muscle: effects of chlorate and bromate on steady-state values and kinetics.

Voltage-clamp experiments have been used to study the effects of external nitrate, chlorate and bromate on the chloride conductance of sarcolemma of Xenopus laevis. Nitrate reduces inward current (chloride efflux), but less potently than does thiocyanate [Vaughan (1987) Pflügers Arch 410:153-158] and does not affect conductance kinetics. As its concentration is increased the blocking effect of nitrate saturates; at a nitrate mole fraction of 0.6 the anion conductance is reduced to about 50% and further increases in nitrate concentration are without significant effect. Nitrate's influences are not voltage-dependent. Chlorate is a much less potent blocker than is nitrate, and its effects are voltage-dependent. With small hyperpolarizations, currents are sometimes seen to be larger than the control, but the degree of block (or the conversion of augmentation to reduction) increases with the size of the voltage step. Anomalous mole-fraction effects are observed in the range 0.4-0.6 mol/mol, in that in some cells the reduction of conductance is noticeably greater in the lower than in the higher concentration of the replacement ion. In the presence of chlorate, relaxation rates are significantly increased, and this influence is not anomalously dependent on the mole fraction. Similar effects are observed in bromate. The effect on kinetics is not pH-dependent. The main series of experiments was conducted at pH 5, but the same influence on kinetics was observed at pH 9. Using point voltage-clamp experiments, chlorate and thiocyanate were both seen to lower the contraction threshold voltage, but thiocyanate has no influence on conductance kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Environmental mutagens that induce the adaptive response to alkylating agents in Escherichia coli.

Many microorganisms exhibit an adaptive response to mutagenic alkylation damage. In Escherichia coli the response is regulated by the inducible Ada protein. A sensitive immunoassay employing two anti-Ada monoclonal antibodies has been developed here to monitor low levels of induction of the Ada protein. This protein was detected in non-induced E. coli which contained an average of two molecules of Ada per cell. The occurrence of the adaptive response in bacteria signals the existence of an ecological niche in which cells are exposed to direct-acting methylating compounds, but the structure and identity of these agents are unknown. Using the immunoassay to search for possible candidates, a number of methylating agents and precursors of such agents have been investigated. Carbamyl phosphate and methylamine yield N-methylurea, which reacts subsequently with nitrite to generate the strong inducer N-methyl-N-nitrosourea. The antibiotic streptozotocin also is a potent inducer of the adaptive response. Moreover, the abundant environmental mutagen methyl chloride acts as an inducer.

Adaptation, Physiological↗
PubMed1991

A weak adaptive response to alkylation damage in Salmonella typhimurium.

An efficient adaptive response to alkylation damage was observed in several enterobacterial species, including Klebsiella aerogenes, Shigella sonnei, Shigella boydii, Escherichia alkalescens, Escherichia hermanii, and Escherichia fergusonii. Increased O6-methylguanine-DNA and methylphosphotriester-DNA methyltransferase activities correlated with the induction of a 39-kDa protein recognized by monoclonal antibodies raised against the Escherichia coli Ada protein. Induced methyltransferase activities were similarly observed in Aerobacter aerogenes and Citrobacter intermedius, although no antigenically cross-reacting material was present. Weak induction of a 39-kDa protein immunologically related to the E. coli Ada protein occurred in Salmonella typhimurium. This protein encoded by the cloned S. typhimurium ada gene was shown to be an active methyltransferase which repaired O6-methylguanine and methylphosphotriesters in DNA as efficiently as did the E. coli Ada protein. However, the mehtyltransferase activity of the weakly induced 39-kDa protein in S. typhimurium was not detected, apparently because it was self-methylated and thus inactivated during the adaptive N-methyl-N-nitro-N-nitrosoguanidine pretreatment. In contrast, the E. coli ada gene on a low-copy-number plasmid was efficiently induced in S. typhimurium, and high methyltransferase activities were observed. We concluded that the inefficient induction of the adaptive response in S. typhimurium results from weak transcriptional activation of its ada gene by the self-methylated protein.

Alkylation↗
PubMed1991

Rules of engagement: key factors in the successful management of interagency projects.

In recent years the implementation of community care policies in relation to the mentally ill has led to increasing collaboration between the caring agencies. Unfortunately early experience has shown that joint projects employing multidisciplinary mental health teams are difficult and time consuming to manage. Phillip Vaughan comments on some of the difficulties encountered by such teams and offers suggestions for their remedy.

Administrative Personnel↗
PubMed1990

Adult respiratory distress syndrome. A complication of shock.

ARDS is a complex type of respiratory failure that usually is a complication of a catastrophic critical illness, such as shock. Mortality is high, especially in patients with septic shock and multisystem failure. Mortality often is related to complications of refractory hypoxemia. Identifying patients at risk for developing ARDS and early recognition of ARDS are important so that treatment can be initiated to prevent the potentially lethal consequences of refractory hypoxemia. The nurse has an important role in collaborating with the physician and respiratory therapist to support the patient's oxygenation, ventilation, and tissue oxygen delivery system. The nurse is responsible for performing highly sophisticated assessment of clinical and hemodynamic parameters to evaluate the effectiveness of therapy. A key role of the nurse is anticipating, recognizing, and reporting to the physician complications of hypoxemia and complications of therapy that can lead to sepsis, airway trauma, or failure of other organ systems.

Humans↗
PubMed1989

A reappraisal of frog muscle chloride conductance-voltage relations at pH9.

Voltage clamp experiments in muscle show that the steady state chloride conductance at pH 9 remains rather independent of [Cl-]o, for [Cl-]o in the range 165-265 mM. The steady state conductance-voltage relation has a maximum near Vrest -20 mV. The initial-conductance-voltage relation obtained when the voltage is stepped away from a constant conditioning value (e.g. the resting potential) approaches an asymptotic maximum for hyperpolarizing steps and a minimum for depolarizing steps. The conductance declines with time if the test voltage is more negative than the resting potential, but remains constant if it is more positive. When the conditioning voltage is varied and the test kept constant the initial conductance at the step is also seen to be sigmoidal, if the test step is hyperpolarizing: for large negative conditioning steps the conductance at the test potential approaches the same asymptotic value as does the steady state relation, independent of the test voltage. At positive conditioning voltages it approaches a maximum asymptote which is dependent on the test voltage. When the test step is positive-going the initial conductance at the step is weakly dependent on the conditioning voltage and for large negative conditioning potentials is larger than predicted from the steady state relation. In summary, during hyperpolarizing voltage steps the chloride conductance seems to decline due to a "gating" phenomenon, but openstate conductance seems to be voltage-dependent, and at membrane potentials more positive than the resting it rapidly (within the settling time of the clamp) assumes a value almost independent of any preceding (conditioning) voltage.

Animals↗
PubMed1982

The influence of voltage conditioning on chloride currents in amphibian muscle membrane: the sigmoid conductance-voltage relation extended into the outward current region.

Sartorius muscle fibres of Xenopus laevis were depolarized in solutions of high K+ content and then voltage clamped in solutions in which K+ was replaced by Rb+ and(or) tetraethylammonium ion (TEA+) at pH 9. A three-microelectrode clamp system was used in which the bath was held at virtual ground using an operational amplifier in a current meter configuration. The holding potential was set at zero membrane current potential (resting potential), close to -25 mV. A two-pulse paradigm was used to test the effects of conditioning the membrane at voltages away from the resting potential on initial currents at positive test potentials. In the absence of TEA+ rapidly rising outward currents were generated at positive test potentials, following hyperpolarizing conditioning. These currents inactivated in time and obscured predicted chloride currents. When TEA+ was added to the solution (60 mequiv./L) the currents at positive potentials rose more slowly and declined either very slowly or not at all. Projection of these current waveforms, by curve fitting, to the instant of potential change gave a sigmoid dependence of test current on conditioning voltage that was predicted from earlier results. Predictably there is a test voltage at which the initial current is independent of conditioning potential: from the data it appears that this is not necessarily the resting potential, but the cause of the shift is not clear. The results also indicated that there is a component of outward current that is very small, apparently carried by cations ("delayed rectifier current"), that does not inactivate, even at potentials more positive than the resting potential.

Animals↗