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Biomedical subjects

Martin Tobin

Publications and source records attributed to Martin Tobin.

7 recordsLinked to original sources
PubMed2007

Leukotriene B4 production in healthy subjects carrying variants of the arachidonate 5-lipoxygenase-activating protein gene associated with a risk of myocardial infarction.

Leukotrienes are implicated in the pathogenesis of coronary artery disease. Recently two haplotypes (HapA and HapB) in the gene encoding ALOX5AP (arachidonate 5-lipoxygenase-activating protein), the main regulator of 5-lipoxygenase, have been associated with a doubling of the risk of myocardial infarction. Studies have also shown that treatment with a leukotriene inhibitor reduces biomarkers of coronary risk in patients carrying HapA, raising the possibility of developing genotype-specific therapy. In the present study, we examined whether carriage of HapA or HapB is associated with increased LTB(4) (leukotriene B(4)) production in healthy subjects. Age- and gender-matched healthy HapA carriers (n=21), HapB carriers (n=20) and non-A/non-B carriers (n=18), with no reported history of cardiovascular disease, were recruited following DNA screening of 1268 subjects from a population-based study. Blood neutrophils were isolated, and LTB(4) production was measured in response to stimulation with 1 mumol/l of the calcium ionophore A23187. There was no difference in the mean level for LTB(4) production in the three groups (non-A/non-B, 24.9+/-8.3 ng/10(6) cells; HapA, 22.2+/-11.9 ng/10(6) cells; HapB, 19.8+/-4.8 ng/10(6); P=0.14). The findings indicate that if either the HapA or the HapB haplotype of ALOX5AP indeed increases cardiovascular risk, then the mechanism is not simply due to a systematically observable effect of the haplotype on LTB(4) production in response to stimulation. The results suggest that knowledge of a patient's haplotype may not provide useful information on the probable clinical response to ALOX5AP inhibitors.

5-Lipoxygenase-Activating Proteins↗
PubMed2006

Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

Aged↗
PubMed2003

Genome-wide linkage analysis of longitudinal phenotypes using sigma2A random effects (SSARs) fitted by Gibbs sampling.

The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time) were estimated to account for approximately 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma2A) were estimated to account for approximately 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.

Adult↗
PubMed2003

Longitudinal data analysis in pedigree studies.

Longitudinal family studies provide a valuable resource for investigating genetic and environmental factors that influence long-term averages and changes over time in a complex trait. This paper summarizes 13 contributions to Genetic Analysis Workshop 13, which include a wide range of methods for genetic analysis of longitudinal data in families. The methods can be grouped into two basic approaches: 1) two-step modeling, in which repeated observations are first reduced to one summary statistic per subject (e.g., a mean or slope), after which this statistic is used in a standard genetic analysis, or 2) joint modeling, in which genetic and longitudinal model parameters are estimated simultaneously in a single analysis. In applications to Framingham Heart Study data, contributors collectively reported evidence for genes that affected trait mean on chromosomes 1, 2, 3, 5, 8, 9, 10, 13, and 17, but most did not find genes affecting slope. Applications to simulated data suggested that even for a gene that only affected slope, use of a mean-type statistic could provide greater power than a slope-type statistic for detecting that gene. We report on the results of a small experiment that sheds some light on this apparently paradoxical finding, and indicate how one might form a more powerful test for finding a slope-affecting gene. Several areas for future research are discussed.

Cardiovascular Diseases↗
PubMed2002

Teaching and learning about human sexuality in undergraduate medical education.

BACKGROUND: Effective management of the doctor's role in relation to human sexuality requires sensitivity and tact, an ability to put patients at ease, use of appropriate language, and therapeutic, non-discriminatory attitudes. However, previous research suggests that medical students and doctors may hold negative attitudes towards homosexuality and some forms of sexual behaviour. Some educational programmes have started to help students develop communication skills for sexual health consultations, but little work has addressed the broader issue of attitudes and values which may underlie behaviour. It is vital that medical students begin early the process of reflection and recognition of how their attitudes and values might influence their care of patients. In this paper we report on a course designed to initiate this process at Leicester-Warwick Medical School (LWMS). COURSE DESCRIPTION: The course utilizes techniques of desensitization, problem-solving and reflection to enable the students to achieve the learning outcomes, which are primarily oriented towards reflection and self-development. It uses a variety of teaching and learning strategies, combining peer learning with self-directed learning, and small-group learning with whole class learning. COURSE EVALUATION: We report observations and a before-and-after questionnaire study of students' views and attitudes. This evaluation suggests that the course is successful in reducing students' anxieties about human sexuality and improving their confidence in developing appropriate skills. CONCLUSIONS: The LWMS course is one model which might be used to begin the process of encouraging medical students to develop ways of appropriately managing their responsibilities in relation to human sexuality.

Attitude to Health↗