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Biomedical subjects

S Humphries

Publications and source records attributed to S Humphries.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modelling territorial behaviour of animals in variable environments.

We present an individual-based model describing the distribution and resource gain of territorial individuals in situations where the rank order of territory quality changes over time. The model integrates both competitive (territory-holding ability) asymmetries and a memory function. A balance of effects resulted in a peak in movement rates, but not resource gain, for individuals of intermediate ability. Furthermore, when the system was reduced to a linear array of territories (as commonly used in empirical studies) the model generated quite different predictions because of the severe limitation in movement that the linear array imposes. We suggest that the model can be used to generate testable predictions for territorial species such as salmonids, and that future empirical work should take into account the consequences of reductions in movement imposed by a linear array of territories. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Patch choice and risk: relative competitive ability is context dependent.

The relative abilities of individual cichlids, Tilapia zillii to obtain food under scramble competition was highly repeatable between trials using a single input source, regardless of whether the input was constant or variable. However, when given a choice between two patches differing only in their temporal variability in input about an identical mean, an individual's rank based on intake in one patch was uncorrelated with either its intake in the other patch or its intake in the single-patch trials. In the two-patch trials, certain individuals both spent more time in food patches and visited patches more often than others, and overall the fish spent more time in the constant rate patch than the variable patch, leading to more items being consumed from the constant rate patch. We discuss possible causes and consequences of this dependence of relative competitive ability on the context of the foraging situation. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Low dietary magnesium is associated with insulin resistance in a sample of young, nondiabetic Black Americans.

In both humans and experimental animals, dietary induced magnesium deficiency is correlated with insulin resistance. The purpose of this study was to determine whether dietary magnesium intake is associated with insulin sensitivity or blood pressure in a sample of nondiabetic, young adult black Americans. We also examined dietary calcium, potassium, and sodium intake. The study was conducted on a sample (n = 179) of young adults aged 30 +/- 3.4 years who had been followed longitudinally. Nutrient intake was assessed by obtaining a 24-h recall interview of dietary intake. Intake data were entered in a nutrient analysis program (Nutritionist III), which quantitated micronutrients, macronutrients, and minerals. We classified the sample into insulin-sensitive (IS) and insulin-resistant (IR) groups, according to insulin-stimulated glucose use (M) measured during insulin clamp. M correlated positively with magnesium intake in mg/kg of fat-free mass (r = 0.15, P < .05 overall; in men, r = 0.25, P < .02). There was a significant negative correlation of total dietary magnesium intake with the sum of insulin levels measured during an oral glucose tolerance test (OGTT) (r = -0.13, P < .05). When corrected for body fat, in men there was also a significant correlation of dietary magnesium intake, measured in mg/kg of fat-free mass, with the sum of insulin concentrations on the OGTT (r = -0.22, P < .05). When cases were categorically classified as IS versus IR, magnesium intake in mg/kg of fat-free mass was lower in IR (2.97 +/- 1.4) than in IS (3.68 +/- 2.2; P = .022). These results suggest a possible role for dietary magnesium in insulin resistance.

Adult↗
PubMed1999

Cholesteryl ester transfer protein gene effect on CETP activity and plasma high-density lipoprotein in European populations. The EARS Group.

BACKGROUND: Variation at the cholesteryl ester transfer protein (CETP) gene locus has been implicated in determining the levels and activity of CETP, apoAI and high-density lipoprotein (HDL) plasma concentration and the risk of developing coronary artery disease. STUDY DESIGN: The effects of two common polymorphisms of CETP, TaqIB in intron 1 and isoleucine 405 to valine (I405-->V) in exon 14, were examined in a sample of 822 men age 18-28 years from 11 countries in Europe who had participated in a study (the European Atherosclerosis Research Study II) of the offspring of myocardial infarction sufferers before the age of 55 years and age-matched control subjects. RESULTS: The frequency of the rare TaqIB allele (B2) and the rare V405 allele was 0.44 and 0.28 respectively and was the same in different regions of Europe. There was a moderate linkage disequilibrium between the two polymorphisms in all the regions (D' = +0.31, P < 0.001), explained by the preferential association between the two common alleles, B1 and I405. There was a statistically significant association of the rare alleles for both the polymorphisms with lower activity of CETP (P < 0.001), 11.2% lower for the TaqIB and 7.0% lower for the I405-->V polymorphism. The TaqIB polymorphism explained 9.1% (P < 0.001) and I405-->V explained 3.7% (P < 0.001) of the variance in CETP activity, and in combination these genotypes explained 12.0% of the variance (P < 0.001). Overall, subjects whose fathers had had an early coronary heart disease had 2.4% higher plasma CETP activity than those without such family history, which became statistically significant when adjusted for the effect of the genotypes (P = 0.015), but the significance disappeared after adjustment for the effect of lipids. There was a statistically significant effect of the TaqIB polymorphism on both plasma HDL cholesterol and apoAI level (P < 0.001), with those homozygous for the rare B2 allele having the highest level. Those individuals homozygous for the rare V405 allele had the highest HDL and apoAI levels, although these effects only reached statistical significance for HDL (P < 0.03). CONCLUSION: These results suggest that the TaqIB and I405-->V polymorphisms represent two independent functional variations in the CETP gene that may affect the activity of CETP and thus plasma levels of HDL.

Adolescent↗
PubMed1999

Human angiotensin I-converting enzyme gene and endurance performance.

Human physical performance is strongly influenced by genetic factors. A variation in the structure of the human angiotensin I-converting enzyme (ACE) gene has been reported in which the insertion (I) variant is associated with lower ACE levels than the deletion (D) gene. We have previously reported that the I variant was associated with improved endurance performance in high-altitude mountaineers and British Army recruits. We now examine this genotype distribution in 91 British Olympic-standard runners (79 Caucasians). DNA was extracted from the buccal cells contained in 10 ml of saline mouthwash donated by the subjects, and the I and D variants of the ACE gene were identified by PCR amplification of the polymorphic region. There was an increasing frequency of the I allele with distance run [0.35, 0.53, and 0.62 for </=200 m (n = 20), 400-3,000 m (n = 37), and >/=5,000 m (n = 34), respectively; P = 0.009 for linear trend]. Among 404 Olympic-standard athletes from 19 other mixed sporting disciplines (in which endurance performance was not necessarily a key factor), the I allele did not differ significantly from that found in control subjects: 0.50 vs. 0.49 (P = 0.526). These results support a positive association of the I allele with elite endurance performance.

Alleles↗
PubMed1998

The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.

During active disease, patients with systemic-onset juvenile chronic arthritis (S-JCA) demonstrate a rise and fall in serum interleukin-6 (IL-6) that parallels the classic quotidian fever. To investigate the possibility that this cytokine profile results from a difference in the control of IL-6 expression, we examined the 5' flanking region of the IL-6 gene for polymorphisms. A G/C polymorphism was detected at position -174. In a group of 383 healthy men and women from a general practice in North London, the frequency of the C allele was 0.403 (95% confidence interval 0.37-0.44). In comparison, 92 patients with S-JCA had a different overall genotype frequency, especially those with onset of disease at < 5 yr of age. This was mainly due to the statistically significant lower frequency of the CC genotype in this subgroup. When comparing constructs of the 5' flanking region (-550-+61 bp) in a luciferase reporter vector transiently transfected into HeLa cells, the -174C construct showed 0.624+/-0.15-fold lower expression than the -174G construct. After stimulation with LPS or IL-1, expression from the -174C construct did not significantly change after 24 h, whereas expression from the -174G construct increased by 2.35+/-0.10- and 3.60+/-0.26-fold, respectively, compared with the unstimulated level. Plasma levels of IL-6 were also measured in 102 of the healthy subjects, and the C allele was found to be associated with significantly lower levels of plasma IL-6. These results suggest that there is a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. The reduced frequency of the potentially protective CC genotype in young S-JCA patients may contribute to its pathogenesis. Similarly the individual's IL-6 genotype may be highly relevant in other conditions where IL-6 has been implicated, such as atherosclerosis.

Adolescent↗
PubMed1998

C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. EARS group.

A common polymorphism has been described in the methylenetetrahydrofolate reductase (MTHFR) gene, substituting an alanine (A) for a valine (V), where the V allele results in a thermolabile enzyme with reduced activity. This polymorphism is easily detectable by PCR amplification and digestion with HinfI restriction enzyme. We describe the use of the MADGE high throughput genotyping system for rapid typing of this polymorphism. Seven hundred and eighty five individuals participating in the European Atherosclerosis Research Study II (EARS II), aged 22-25 from 14 universities in 12 countries across Europe were genotyped for this polymorphism. The frequency of the V allele was 0.32 overall (95% CI; 0.30-0.35), but was significantly lower in the Baltic countries (0.23; 95% CI; 0.19-0.28) compared with the other regions of Europe (0.37; 95% CI; 0.32-0.38) (P < 0.001). Individuals homozygous for the V allele had statistically significant (P < 0.001) higher plasma homocysteine (16.5 micromol/l) compared with those heterozygous for an A allele (10.4 micromol/l) or homozygous for an A allele (10.0 micromol/l). This effect was seen in all countries and regions of Europe. Mean plasma homocysteine levels were significantly higher in the South compared to the Baltic, UK and Middle regions (P = 0.001), but this difference was not explained by the difference in the frequency of the V allele in the samples. This polymorphism explained 12.3% of the total sample variance in plasma homocysteine, other measured factors (smoking, alcohol consumption, systolic blood pressure, physical activity) explained 0.7%. This study demonstrates the large and consistent impact of the thermolabile MTHFR variant on plasma homocysteine levels in different European populations, and shows a regional difference in the levels of homocysteine that must be explained by other genetic or environmental factors.

Adolescent↗
PubMed1998

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo.

Tamoxifen (tam) is used extensively for treatment of patients with breast cancer and is being evaluated for chemoprevention in healthy women. It has, however, been reported to increase the risk of endometrial cancer in post-menopausal women, probably by an oestrogenic effect on the endometrium. It also causes endometrial cysts and polyps. The aims of this study were to identify the incidence of endometrial thickening, polyps and cysts by transvaginal ultrasound (TVUS) screening of a population of post-menopausal healthy women in the Royal Marsden tamoxifen chemoprevention trial and to evaluate the possible benefit from the use of intermittent norethisterone (NE) in women with persistent changes. Since 1990, we have undertaken regular TVUS, using an endovaginal B mode probe, of the 463 post-menopausal women in the trial randomized to tam (20 mg day(-1)) or placebo (plac), without breaking the randomization code. Endometrial thickening (ET) was defined as > or = 8 mm at the widest point across the myometrial cavity in the longitudinal plane, including any stromal changes. Cystic changes were defined as more than one hypoechogenic area > 1 mm. Polyps were identified using saline hydrosonography. Oral NE (2.5 mg day(-1)) was used for 21 days out of 28 for three consecutive cycles by women with persistent endometrium > or = 8 mm, including cystic and polypoid changes. TVUS was repeated after the three courses to evaluate any change caused by NE and endometrial biopsies, including hysteroscopy, was performed on those women with persistent abnormalities. A persistent ET > or = 8 mm was identified in 56 (24%) of the 235 women on tamoxifen compared with only 5 (2%) of 228 women on placebo (P <0.0005). Stromal changes, including cysts, were detected in 36 (15%) and polyps in 26 (11%) of the women on tamoxifen compared with only two (< 1%) of the women on placebo (P << 0.0005). After 3 months of cyclical norethisterone, 39 of 47 women (83%) on tamoxifen had persistent ultrasound changes. However, 45 (96%) had a progesterone withdrawal bleed. Hysteroscopy was performed in 39 women on tamoxifen (28 endometrial biopsy, 15 polypectomy), five of whom had histological evidence of a proliferative endometrium and a further three had an atypical hyperplastic endometrium (one of whom had a focus of invasive carcinoma). The cysts and polyps which were detected in women on tam could not be reversed by NE and were presumably stromal and not of malignant risk. However, 96% of the women had withdrawal NE bleeding, indicating an oestrogenically primed endometrium which could be a mechanism for an increased risk of endometrial cancer. Further studies are required to ascertain whether a progestin would protect against this risk. As in other studies, these results indicate that any increased risk of endometrial cancer caused by tamoxifen is low, and that TVUS screening is probably not justified for asymptomatic women on tamoxifen.

Aged↗
PubMed1998

Matrix metalloproteinases: implication in vascular matrix remodelling during atherogenesis.

1. The matrix metalloproteinases are a family of at least 16 zinc-dependent endopeptidases possessing catalytic activity against extracellular matrix components. Some members of this family have been implicated in vascular matrix remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally occurring variant has been identified in the promoter of the stromelysin gene with one allele having a run of five adenosines (5A) and the other having six adenosines (6A). Functional analyses have shown that the 6A allele has a lower promoter activity than the 5A allele, which is probably attributable to preferential binding of a putative transcriptional repressor protein. 3. In patients with coronary artery disease, the 6A allele has been found to be associated with progression of atherosclerosis assessed by sequential quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be over-expressed in certain locations in atherosclerotic plaques, which might contribute to local destruction of connective tissue and thus plaque rupture. In the majority of lesional areas, however, matrix synthesis is likely to outstrip matrix degradation, because matrix accumulation is a major feature of most atheromas. This imbalance favouring matrix deposition is likely to be exacerbated in individuals with the 6A6A genotype in whom stromelysin expression is lower due to the weaker stromelysin promoter.

Alleles↗
PubMed1998

The effects of imagery and sensory detection distractors on different measures of pain: how does distraction work?

OBJECTIVES: Two experiments compared the effects of different distraction tasks on pain. Based on multiple-resource theory, Expt 1 predicted that the more a distractor shares processing resources with pain perception the greater the interference between the two. Experiment 2 tested whether the emotional content of the distractor would differentially effect measures that are supposedly reflective of the affective component of pain. DESIGN: Both experiments used repeated measures designs, with counterbalanced distraction conditions. METHODS: In Expt 1 20 participants indicated their pain threshold. No instructions, or one of three distraction conditions were presented across four blocks of potassium iontophoresis. The distractors were: thermal and light detection, and neutral imagining. In Expt 2 30 participants had three blocks of pain threshold, pain tolerance, and pain rating trials. For threshold, tolerance, and rating trials, one block was without distraction, a second block was completed during light detection, and a third block while imagining an enjoyable holiday. RESULTS: In Expt 1 all the distractors increased pain threshold. The two detection tasks were similarly effective, and more so than the imagination task. Performance on the two detection tasks was impaired by painful stimulation similarly for both tasks. In Expt 2 the visual detection distractor increased pain threshold and tolerance and reduced pain ratings while pleasant imagery only increased pain threshold. CONCLUSIONS: These results indicate that a task that requires attention to external cues has more impact on pain than either a positive or neutral imagination task. However, it is not clear that the specific resources used by the distraction tasks moderated pain differentially as predicted by multiple-resource theory.

Adult↗
PubMed1997

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.

BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the ACE gene is associated with higher ACE levels than its presence (insertion allele [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then individuals of DD genotype might show a greater hypertrophic response than those of II genotype. We tested this hypothesis by studying exercise-induced LV hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions and mass (n=140), electrocardiographically determined LV mass and frequency of LV hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels (n=49) were compared at the start and end of a 10-week physical training period in male Caucasian military recruits. Septal and posterior wall thicknesses increased with training, and LV mass increased by 18% (all P<.0001). Response magnitude was strongly associated with ACE genotype: mean LV mass altered by +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence of electrocardiographically defined LVH rose significantly only among those of DD genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II, respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is strongly associated with the ACE I/D polymorphism.

Adult↗
PubMed1997

The angiotensin-converting enzyme gene and the angiotensin II type I receptor gene as candidate genes for microalbuminuria. A study in nondiabetic and non-insulin-dependent diabetic subjects.

Familial clustering of microalbuminuria with cardiovascular disease suggests a possible common genetic antecedent. We have tested the hypothesis that the angiotensin-converting enzyme (ACE) DD genotype and the angiotensin II type I receptor (AT1R) gene C allele represent the common link between microalbuminuria and coronary heart disease. The frequency of polymorphisms of the ACE and AT1R genes were investigated in 509 nondiabetic white subjects and in 86 non-insulin-dependent diabetic white patients. There was no significant difference in albumin excretion rate between the genotypes in nondiabetic subjects on either a daytime or an overnight sample or in diabetic subjects expressed as a normalized albumin concentration on an untimed morning urine collection. We have found no evidence for an association between polymorphism of the ACE or AT1R genes and microalbuminuria in two groups of subjects without insulin-dependent diabetes.

Adult↗
PubMed1997

A variation in the apolipoprotein C-III gene is associated with an increased number of circulating VLDL and IDL particles in familial combined hyperlipidemia.

Detailed plasma lipoprotein analyses were conducted on 16 familial combined hyperlipidemic (FCHL) probands, all their available family members (n = 106) together with 12 normolipidemic control families (n = 68), and the results were assessed in relation to a C1100-T polymorphism in exon 3 of the apoC-III gene. The frequency of the T1100 genotype (CT+TT) was significantly elevated in the probands relative to control subjects (0.64 vs. 0.36; P < 0.01) and was associated with elevated concentrations of plasma triglyceride (P < 0.02) and apoC-III (P < 0.03), VLDL cholesterol (P < 0.005), VLDL triglyceride (P < 0.009), IDL cholesterol (P < 0.01). and IDL triglyceride (P < 0.007). The T1100 genotype was also associated with elevations in VLDL-apoB (P < 0.005) and IDL-apoB (P < 0.04) indicating a relationship between this variation and an increased number of triglyceride-rich particles. These findings were confined to the hyperlipidemic members of the FCHL families and showed a strong genotype-status interaction (P < 0.001). It is considerable clinical relevance that the apoC-III gene may be acting as a modifier gene that is only expressed in the presence of other factors (e.g., increased VLDL flux, low LPL activity) and therefore may predispose those members of FCHL families carrying the T1100 allele to express the FCHL phenotype.

Adolescent↗
PubMed1997

The usefulness of three biallelic restriction fragment length polymorphisms versus a polymorphic dinucleotide tandem repeat polymorphism at the low-density-lipoprotein receptor gene locus for diagnosis of familial hypercholesterolemia.

Indirect molecular diagnosis of familial hypercholesterolemia is possible based on genetic linkage analysis of DNA polymorphisms at the low-density-lipoprotein receptor gene locus in family studies. The use of biallelic restriction fragment length polymorphisms, however, is restricted by their low degree of heterogeneity, and therefore several of these markers have to be combined. To overcome these restrictions we examined the value and applicability of an (AT)n tandem repeat polymorphism at the 3' untranslated region of the gene, alone and in combination with three biallelic restriction fragment length polymorphisms in 35 independent healthy subjects and in familial hypercholesterolemia families with 23 parents and 52 children. For each family one of the parents had the clinical diagnosis of familial hypercholesterolemia. The probands were genotyped using the TaqI, HincII and NcoI restriction fragment length polymorphism and the (AT)n tandem repeat polymorphism of the gene. The heterozygosity index (0.60) and the polymorphism information content (PIC value) (0.53) of the ATn repeat polymorphism were higher compared to each single biallelic restriction fragment length polymorphism (heterozygosity index 0.26-0.54; PIC value 0.24-0.36). The combined PIC value of all three biallelic restriction fragment length polymorphisms (0.79) was comparable to the combination of the HincII and the ATn polymorphism (0.74). Using these two markers, a definitive molecular diagnosis could be made in 36 children from 15 parents compared to just 12 parents and their children using the three biallelic restriction fragment length polymorphisms. We conclude that the ATn tandem repeat polymorphisms is useful for indirect molecular diagnosis of familial hypercholesterolemia in affected families.

Chromosome Mapping↗
PubMed1996

Factor VII Arg/Gln353 polymorphism determines factor VII coagulant activity in patients with myocardial infarction (MI) and control subjects in Belfast and in France but is not a strong indicator of MI risk in the ECTIM study.

This paper describes the relationship of factor VII coagulant activity (FVIIc), FVII Arg/Gln353 genotype and risk of myocardial infarction (MI) in the ECTIM (Etude Cas Témoin sur l'Infarctus du Myocarde) study, a multi-centre case-control study on MI. FVIIc was significantly higher in controls from all four centres: Belfast, Lille, Strasbourg and Toulouse, perhaps because elevated FVIIc may predispose to fatal rather than non-fatal MI. Major influences on FVIIc were FVII Arg/Gln353 genotype, triglyceride and cholesterol levels. There was no significant effect of genotype on MI risk however there was a non-significant trend towards increased MI risk in FVII Arg353 homozygotes. Confirming previous observations, FVIIc was highest in FVII Arg353 homozygotes, intermediate in heterozygotes and lowest in FVII Gln353 homozygotes (except Toulouse cases) these differences being highly statistically significant (except Strasbourg cases P = 0.1). In Belfast, consistent with previous findings, there was significant interaction between FVII Arg/Gln353 genotype and triglyceride level in determining FVIIc, whilst this was absent in the French centres. In conclusion, FVII Arg/Gln353 genotype strongly determines FVIIc although neither factor has a strong impact on MI risk in the ECTIM study.

Adult↗