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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 37 records · Page 2Linked to original sources
PubMed2002

Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1.

The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible for the burning sensation elicited by capsaicin. A similar sensation is reported by patients with esophagitis when they consume alcoholic beverages or are administered alcohol by injection as a medical treatment. We report here that ethanol activates primary sensory neurons, resulting in neuropeptide release or plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat and lowered the threshold for heat activation of VR1 from approximately 42 degrees C to approximately 34 degrees C. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds.

Animals↗
PubMed2002

The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART).

OBJECTIVE: To assess the long-term effect of dietary advice on diet and mortality after a randomised trial of men with a recent history of myocardial infarction. DESIGN: Questionnaire survey and mortality follow-up after a trial of dietary advice. SETTING: Twenty-one hospitals in south Wales and south-west England. SUBJECTS: Former participants in the Diet and Reinfarction Trial. MAIN OUTCOME MEASURES: Current fish intake and cereal fibre intake. All-cause mortality, stroke mortality and coronary mortality. RESULTS: By February 2000, after 21147 person years of follow-up, 1083 (53%) of the men had died. Completed questionnaires were obtained from 879 (85%) of the 1030 men alive at the beginning of 1999. Relative increases in fish and fibre intake were still present at 10 y but were much smaller. The early reduction in all-cause mortality observed in those given fish advice (unadjusted hazard 0.70 (95% CI 0.54, 0.92)) was followed by an increased risk over the next 3 y (unadjusted hazard 1.31 (95% CI 1.01, 1.70). Fat and fibre advice had no clear effect on coronary or all-cause mortality. The risk of stroke death was increased in the fat advice group-the overall unadjusted hazard was 2.03 (95% CI 1.14, 3.63). CONCLUSIONS: In this follow-up of a trial of intensive dietary advice following myocardial infarction we did not observe any substantial long-term survival benefit. Further trials of fish and fibre advice are feasible and necessary to clarify the role of these foods in coronary disease.

Animals↗
PubMed2002

Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: results of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Alverine citrate has been used in the treatment of irritable bowel syndrome for many years. AIMS: To compare the efficacy and safety of a new formulation of alverine citrate, a 120-mg capsule, with placebo given three times daily for 12 weeks. METHODS: One hundred and seven patients with irritable bowel syndrome were entered into this three-centre, double-blind, randomized, placebo-controlled, parallel group trial. The primary end-point was relief of abdominal pain indicated by improvement in the scores for severity and frequency. Secondary efficacy variables included scores for other clinical symptoms and for overall well-being. RESULTS: The severity and frequency of abdominal pain improved in 66% and 68% of patients treated with alverine citrate vs. 58% and 69% of the placebo group, but these differences were not significant. The mean percentage reduction in the scores for abdominal pain from baseline to the final assessment, although greater in the alverine citrate group (43.7%) compared with the placebo group (33.3%), was not statistically significant. CONCLUSIONS: Alverine citrate is no better than placebo at relieving the symptoms of irritable bowel syndrome. Future trials should be designed to take into account the high and persistent placebo response seen in this condition.

Abdomen↗
PubMed2001

Mode locking in a periodically forced integrate-and-fire-or-burst neuron model.

The minimal "integrate-and-fire-or-burst" (IFB) neuron model reproduces the salient features of experimentally observed thalamocortical relay neuron response properties, including the temporal tuning of both tonic spiking (i.e., conventional action potentials) and post-inhibitory rebound bursting mediated by the low-threshold Ca2+ current, I(T). In previous work focusing on experimental and IFB model responses to sinusoidal current injection, large regions of stimulus parameter space were observed for which the response was entrained to periodic applied current, resulting in repetitive burst, tonic, or mixed (i.e., burst followed by tonic) responses. Here we present an exact analysis of such mode-locking in the integrate-and-fire-or-burst model under the influence of arbitrary periodic forcing that includes sinusoidally driven responses as one case. In this analysis, the instabilities of mode-locked states are identified as both smooth bifurcations of an associated firing time map and nonsmooth bifurcations of the underlying discontinuous flow. The explicit construction of borders in parameter space that define the instabilities of mode-locked zones is used to build up the Arnol'd tongue structure for the model. The zones for mode-locking are shown to be in excellent agreement with numerical simulations and are used to explore the observed stimulus dependence of burst versus tonic response of the IFB neuron model.

Action Potentials↗
PubMed2001

Phase changes in T(3)R(3)(f) human insulin: temperature or pressure induced?

The structure of T(3)R(3) hexameric human insulin has been determined at 100 K from two different crystals at 1.2 and 1.3 A resolution and refined to residuals of 0.169 and 0.176, respectively. Owing to a phase change, the c axis is double its room-temperature value and the asymmetric unit contains two independent TR(f) insulin dimers. Compared with the orientation in the room-temperature structure, one dimer undergoes a rotation about the c axis of -5 degrees, while the second is rotated +4 degrees. A superposition of the backbone atoms of the two independent dimers shows that the C(alpha) atoms of five residues within the R(f)-state monomers are displaced by more than 1.0 A; smaller displacements are observed for the T-state monomers. Four zinc ions lie on the crystallographic threefold axis and each forms bonds to three symmetry-related HisB10 N(varepsilon2) atoms from the T- and R(f)-state trimers. While three of the zinc ions are tetrahedrally coordinated with a chloride ion completing the coordination sphere, mixed tetrahedral/octahedral coordination is observed for one of the T-state zinc ions. The three symmetry-related "phenolic binding sites" in one hexamer contain water molecules and a glycerol molecule, but the same sites in the second hexamer are occupied by a zinc ion coordinated to an alternate conformation of HisB10, a symmetry-related HisB5 and two chloride ions. Two additional and partially occupied zinc ion sites are observed at the interface between the two independent dimers. One zinc ion is coordinated by a T-state HisB5 of one dimer, an R-state HisB5 of the second dimer and two water molecules; the second zinc ion is coordinated by an alternate side-chain conformation of the T-state HisB5 and three water molecules. The carboxyl group of one GluB13 side chain, which exists in two discrete conformations, appears to be protonated, because short contacts exist to a second carboxyl group or to a carbonyl O atom.

Crystallization↗
PubMed2001

Income inequality, the psychosocial environment, and health: comparisons of wealthy nations.

BACKGROUND: The theory that income inequality and characteristics of the psychosocial environment (indexed by such things as social capital and sense of control over life's circumstances) are key determinants of health and could account for health differences between countries has become influential in health inequalities research and for population health policy. METHODS: We examined cross-sectional associations between income inequality and low birthweight, life expectancy, self-rated health, and age-specific and cause-specific mortality among countries providing data in wave III (around 1989-92) of the Luxembourg Income Study. We also used data from the 1990-91 wave of the World Values Survey (WVS). We obtained life expectancy, mortality, and low birthweight data from the WHO Statistical Information System. FINDINGS: Among the countries studied, higher income inequality was strongly associated with greater infant mortality (r=0.69, p=0.004 for women; r=0.74, p=0.002 for men). Associations between income inequality and mortality declined with age at death, and then reversed among those aged 65 years and older. Income inequality was inconsistently associated with specific causes of death and was not associated with coronary heart disease (CHD), breast or prostate cancer, cirrhosis, or diabetes mortality. Countries that had greater trade union membership and political representation by women had better child mortality profiles. Differences between countries in levels of social capital showed generally weak and somewhat inconsistent associations with cause-specific and age-specific mortality. INTERPRETATION: Income inequality and characteristics of the psychosocial environment like trust, control, and organisational membership do not seem to be key factors in understanding health differences between these wealthy countries. The associations that do exist are largely limited to child health outcomes and cirrhosis. Explanations for between-country differences in health will require an appreciation of the complex interactions of history, culture, politics, economics, and the status of women and ethnic minorities.

Birth Weight↗
PubMed2001

Quantitative detection of aromatic compounds in single aerosol particle mass spectrometry.

Most laser-based aerosol mass spectrometers rely on a single ultraviolet laser to both ablate and ionize the aerosol particle. This technique produces complex and fragmented mass spectra, especially for organic compounds. The approach presented here achieves a more robust and quantitative analysis using a CO2 laser to evaporate the aerosol particle and a vacuum ultraviolet laser to ionize the vapor plume. Vacuum ultraviolet laser ionization produces little fragmentation in the mass spectra, making the identification of an aerosol particle's constituents more straightforward. An analysis of simple, three-component mixtures of aniline, benzyl alcohol, and m-nitrotoluene shows that the technique also provides a quantitative analysis for all the components of the mixture. Furthermore, the detection of predominantly parent ion signal from anthracene particles demonstrates the utility of the technique in the analysis of lower vapor pressure, solid-phase aerosols. Finally, we discuss the potential and limitations of this technique in analyzing organic atmospheric aerosols.

Journal Article↗
PubMed2001

Changes in blood pressure among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys.

OBJECTIVES: To examine the changes in blood pressure over time in a cohort of young adults attending university between 1948 and 1968. DESIGN: Cross sectional study. SETTING: Glasgow University. PARTICIPANTS: 12 414 students aged 16-25 years-9248 men (mean age 19.9 years) and 3164 women (19.2 years)-who participated in health screening on entering university between 1948 and 1968. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure. RESULTS: In male students mean systolic blood pressure adjusted for age decreased from 134.5 (95% confidence interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to 126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from 80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) mm Hg. For female students the corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to 121.4) mm Hg and from 79.7 (78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg. Adjustment for potential confounding factors made little difference to these findings. The proportion of students with hypertension declined substantially in both sexes. CONCLUSIONS: Substantial declines in systolic and diastolic blood pressure over time were occurring up to 50 years ago in young adults who were not taking antihypertensive medication. Since blood pressure tracks into adult life, the results of the cross sectional comparisons suggest that factors acting in early life may be important in determining population risk of cardiovascular disease. Changes in such factors may have made important contributions to the decline in rates of cardiovascular diseases, particularly stroke, seen in developed countries during the past century.

Adolescent↗
PubMed2001

Dietary fat intake and prevention of cardiovascular disease: systematic review.

OBJECTIVE: To assess the effect of reduction or modification of dietary fat intake on total and cardiovascular mortality and cardiovascular morbidity. DESIGN: Systematic review. DATA SOURCES: Cochrane Library, Medline, Embase, CAB abstracts, SIGLE, CVRCT registry, and biographies were searched; trials known to experts were included. INCLUDED STUDIES: Randomised controlled trials stating intention to reduce or modify fat or cholesterol intake in healthy adult participants over at least six months. Inclusion decisions, validity, and data extraction were duplicated. Meta-analysis (random effects methodology), meta-regression, and funnel plots were performed. RESULTS: 27 studies (30 902 person years of observation) were included. Alteration of dietary fat intake had small effects on total mortality (rate ratio 0.98; 95% confidence interval 0.86 to 1.12). Cardiovascular mortality was reduced by 9% (0.91; 0.77 to 1.07) and cardiovascular events by 16% (0.84; 0.72 to 0.99), which was attenuated (0.86; 0.72 to 1.03) in a sensitivity analysis that excluded a trial using oily fish. Trials with at least two years' follow up provided stronger evidence of protection from cardiovascular events (0.76; 0.65 to 0.90). CONCLUSIONS: There is a small but potentially important reduction in cardiovascular risk with reduction or modification of dietary fat intake, seen particularly in trials of longer duration.

Cardiovascular Diseases↗
PubMed2001

Employment status and health after privatisation in white collar civil servants: prospective cohort study.

OBJECTIVES: To determine whether employment status after job loss due to privatisation influences health and use of health services and whether financial strain, psychosocial measures, or health related behaviours can explain any findings. DESIGN: Data collected before and 18 months after privatisation. SETTING: One department of the civil service that was sold to the private sector. PARTICIPANTS: 666 employees during baseline screening in the department to be privatised. MAIN OUTCOME MEASURES: Health and health service outcomes associated with insecure re-employment, permanent exit from paid employment, and unemployment after privatisation compared with outcomes associated with secure re-employment. RESULTS: Insecure re-employment and unemployment were associated with relative increases in minor psychiatric morbidity (mean difference 1.56 (95% confidence intervals interval 1.0 to 2.2) and 1.25 (0.6 to 2.0) respectively) and having four or more consultations with a general practitioner in the past year (odds ratio 2.04 (1.1 to 3.8) and 2.39 (1.2 to 4.7) respectively). Health outcomes for respondents permanently out of paid employment closely resembled those in secure re-employment, except for a substantial relative increase in longstanding illness (2.25; 1.1 to 4.4). Financial strain and change in psychosocial measures and health related behaviours accounted for little of the observed associations. Adjustment for change in minor psychiatric morbidity attenuated the association between insecure re-employment or unemployment and general practitioner consultations by 26% and 27%, respectively. CONCLUSIONS: Insecure re-employment and unemployment after privatisation result in increases in minor psychiatric morbidity and consultations with a general practitioner, which are possibly due to the increased minor psychiatric morbidity.

Adult↗
PubMed2001

Inhibition of bacterial RNA polymerase by the cyanobacterial metabolites 12-epi-hapalindole E isonitrile and calothrixin A.

The alkaloid 12-epi-hapalindole E isonitrile, from a cyanobacterial Fischerella species, and the indolophenanthridine calothrixin A, from Calothrix, inhibited Escherichia coli RNA polymerase competitively with respect to ATP, and non-competitively with respect to UTP. The inhibition was dependent on the order of addition of the inhibitors. The K(I) values, with ATP as the variable substrate, were 1.3+/-0.2 mM and 0.23+/-0.11 mM, respectively. Based on comparisons with the sensitivity of whole cells to these inhibitors, it is concluded that other targets in addition to RNA polymerase may also be implicated in their action.

Cyanobacteria↗
PubMed2001

Identification and characterization of the gene encoding human cytoplasmic polyadenylation element binding protein.

The maturation of human oocytes occurs in the absence of gene transcription. In model organisms, such as Drosophila, Xenopus, and the mouse, oocyte maturation and early pattern formation is mediated through the regulated translation of maternally derived mRNAs. The maturation-dependent stimulation of maternal mRNA translation is correlated with increases in poly(A) tail length, controlled through a process termed cytoplasmic polyadenylation. However, this mechanism of mRNA translational control has not been characterized in humans. In this study we report the cloning of a human cytoplasmic polyadenylation element binding (hCPEB) protein with sequence-specific RNA binding activity. Our data demonstrate that alternative splicing generates hCPEB mRNAs that encode proteins with a conserved C-terminal RNA binding domain but with different N-terminal regulatory domains. The hCPEB mRNA is expressed in the brain and heart as well as in immature oocytes, consistent with the hypothesis that cytoplasmic polyadenylation may regulate the translation of human mRNAs in both oocytes and somatic cells.

Adult↗