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Biomedical subjects

G Inglis

Publications and source records attributed to G Inglis.

At least 19 recordsLinked to original sources
PubMed2005

Polymorphisms of the renin-angiotensin system and the severity of fibrosis in chronic hepatitis C virus infection.

SUMMARY: Patients with chronic hepatitis C virus (HCV) infection vary in their rates of fibrosis progression. The renin-angiotensin system (RAS) regulates fibrosis. Polymorphisms in the genes of the RAS may contribute to the outcome of renal and cardiovascular disease. We studied four RAS gene polymorphisms in 195 patients with chronic HCV infection. Patients were grouped by Ishak stage of fibrosis on liver biopsy: group 1 (fibrosis score 0 or 1; n = 97), group 2 (fibrosis score 2 or 3; n = 73) and group 3 (fibrosis score 4-6; n = 25). Polymorphisms of the angiotensinogen (AGT) gene (M235T and AT-6), the angiotensin I converting enzyme gene and the type 1 angiotensin II receptor gene were assayed. There was no difference in the distribution of these polymorphisms of the RAS between the fibrosis groups. There did not appear to be any increased prevalence of fibrosis if two or even three of the polymorphisms associated with increased RAS effect were present. On multivariate analysis factors significantly associated with fibrosis were necroinflammatory activity (P < 0.001) and age (P < 0.001). No association was identified between these four RAS polymorphisms and fibrosis in chronic HCV infection.

Adult↗
PubMed2003

The determination of carotid intima medial thickness in adults--a population-based twin study.

INTRODUCTION: Although cardiovascular events are known to cluster in families it is unclear the extent to which atherosclerosis per se is genetically determined. The aim of this study was to assess the heritability of carotid intima media thickness (IMT) measurements, a surrogate marker of early atherosclerosis, using a population-based twin study methodology. METHODS: B-mode carotid artery ultrasound images were acquired on 264 twin subjects (142 monozygotic (MZ); mean age 54.3 years and 122 dizygotic (DZ); mean age 51.7 years). An estimate of genetic determination, heritability, was calculated for the IMT parameters before and after correction for confounding variables. RESULTS: An increased carotid IMT was associated with known cardiovascular risk factors (total cholesterol r=0.24, P<0.001 and systolic blood pressure r=0.42, P<0.001) and with a history of coronary events (0.79+/-0.12 vs. 0.72+/-0.14, P=0.01). Carotid IMT measurements demonstrated a familial influence (intra-class correlation of 0.54 for MZ vs. 0.39 for DZ) but no specific genetic determination (heritability estimate 0.31, P=0.15). CONCLUSION: Within a normal population carotid IMT is under a familial, but not genetic influence. The mechanism of genetic control over cardiovascular events may not be mediated through atherosclerotic load as measured by IMT.

Adult↗
PubMed2003

The genetic determination of left ventricular mass in healthy adults.

AIMS: The extent to which left ventricular (LV) mass, an independent cardiovascular risk factor, is determined by genetic factors is unclear. The aim of this study was to assess the heritability of LV mass and its association with three potential candidate genes. METHODS: A population-based adult twin study model was utilized. Echocardiographic assessment of LV mass was performed in 110 twin pairs (mean age 55.9+/-10.9 years). An estimate of genetic determination, heritability, was calculated for the main echocardiographic parameters. The cohort were genotyped for the G-protein beta-3, aldosterone synthase, and beta-1 adrenoceptor genes. RESULTS: The intra-class correlation coefficients for LV mass were 0.69 for monozygotic (r-MZ) twins and 0.32 for dizygotic (r-DZ) twins, P=0.008 (heritability estimate of 0.69). This pattern persisted following correction for known confounding factors. Within-pair differences in the monozygotic, discordant and concordant dizygotic twins showed no differences for the three genes with respect to left ventricular wall thickness or mass. There was a non-significant trend towards a relationship between LV mass and the beta-1 adrenoceptor genotype. CONCLUSION: Within a normal population left ventricular mass has a significant genetic determination. Further investigation of potential candidate genes is required.

Cohort Studies↗
PubMed1999

Selection and characterization of feather-degrading bacteria from canola meal compost.

Canola meal that contains a high level of protein (40% crude protein) was used as compost material for the isolation of feather-degrading bacteria. After 7 and 14 days, bacteria were isolated from compost amended and unamended with soil. Eighty bacterial isolates from canola meal compost were then grown on milk-agar and isolates that produced proteolytic enzymes were identified by the formation of clear haloes around the colonies. A feather medium was chosen for a secondary selection of feather-degrading isolates. Of the eight isolates that hydrolyzed milk protein, five isolates hydrolyzed feathers. Their keratinolytic activities were subsequently confirmed by an assay using azo-keratin as substrate. Seven of the eight bacteria that hydrolyzed milk protein were Bacillus spp, and all five isolates that hydrolyzed feathers were strains of Bacillus licheniformis. Protease inhibition studies indicated that serine proteases are the predominant proteolytic enzymes produced by these feather-degrading isolates.

Journal Article↗
PubMed1998

Manipulation for cervical spinal dislocation under general anaesthesia: serial review for 4 years.

Manipulation under anaesthesia is an important method to reduce cervical spinal dislocations in the acute stage. Causes of failure have not been clearly identified and neurological complications can be the major concern. All cervical dislocations have been traditionally treated by manipulation under anaesthesia in the Christchurch Spinal Injuries Unit as the primary treatment. We reviewed all 31 patients treated from 1991-1995, with detailed documentation of neurological progression and final outcome. Three patterns were identified: bilateral dislocation, unifacet dislocation and fracture dislocation. Most of the dislocations (74%) were successfully reduced by manipulation alone with minimum complications. The remaining 26% patients required open reduction. The predominant causes of failure of reduction by manipulation were co-existing fractures. The success rate of reduction by manipulation was 90% for pure bifacet and unifacet dislocations, but was only 22% for the fracture dislocations. The study concluded that manipulation under anaesthesia is a safe and effective procedure for pure cervical spinal dislocations. Fractures related to the dislocation should be identified early and open reduction be considered.

Adolescent↗
PubMed1996

Corticosteroids in essential hypertension: multiple candidate loci and phenotypic variation.

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11 beta-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11 beta-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5' regulatory regions from 11 beta-hydroxylase and 3' coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11 beta-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.

Adrenal Cortex Hormones↗
PubMed1994

Monoclonal antibodies to high-incidence Kell epitopes: characterization and application in automated screening of donor samples.

Monoclonal antibodies, LM313/706 and LM357/828, recognize high-frequency epitopes which are absent on red cells of Ko phenotype. Both antibodies have proved suitable for automated screening of blood donor samples, with 5 ml of each culture supernatant sufficient to screen 3,000 donor samples. In a screen of 45,545 samples, LM313/706 revealed 11 samples (1:3686) of Kp(a+b-) phenotype. Thirty-seven samples of K+k- phenotype were identified in 15,235 samples screened with LM357/828 antibody (0.24%). The epitope recognized by LM313/706 was inactivated by 2 mM DTT suggesting a possible association with the Jsa/Jsb antigen structure. The expression of the k-like epitope detected by LM357/828 antibody was found to be influenced by pH change.

Antibodies, Monoclonal↗
PubMed1993

Peripheral neuropathy associated with monoclonal IgM anti-Pr2 cold agglutinins.

A patient with a chronic, large fibre sensory neuropathy had an immunoglobulin M lambda monoclonal paraprotein reactive at titres in excess of 1/10(5) with NeuNAc(alpha 2-8)NeuNAc(alpha 2-3)Gal configured disialosyl groups present on the gangliosides GD1b, GT1b, GQ1b, and GD3. The paraprotein showed weaker reactivity with GD1a, GM3, and LM1 but no reactivity with GM2, GM1, or asialo-GM1. In addition, the paraprotein had cold agglutinating activity with anti-Pr2 specificity, Pr2 being an antigenic determinant on membrane glycoproteins or glycolipids in erythrocytes or both. A large fibre sensory neuropathy with monoclonal anti-disialosyl antibodies is an increasingly recognised form of paraproteinaemic neuropathy.

Agglutinins↗
PubMed1989

The role of dopamine in the control of corticosteroid secretion and metabolism.

The relation between aldosterone and its trophins is altered by electrolyte status and in some hypertensive conditions in man by a mechanism or mechanisms not understood. Dopamine has been suggested as the agent for the altered sensitivity of plasma aldosterone to angiotensin II based on the results of studies with dopamine itself, both in vivo and in vitro, and with pharmacological agonists and antagonists. The evidence derived from these studies is presented and discussed. Questionable specificity of the agents used makes interpretation difficult. Similarly, dopamine infusion rates used in man and animals have resulted in plasma concentrations far in excess of those found normally and these pharmacological concentrations have been shown to alter both the clearance rate of exogenous angiotensin II, and the pattern of steroid response to ACTH. Direct study of adrenal tissue has provided more promising results. The adrenal cortex possesses specific dopamine receptors and dopamine has been shown to modify aldosterone biosynthesis in vitro. Moreover, dopamine is present in adrenocortical tissue in concentrations in the range calculated to operate the receptors. However, there is, as yet, no evidence that dopamine concentrations change in a physiological meaningful way, for example, during changes in sodium status.

Adrenal Cortex↗
PubMed1989

Effects of the renin inhibitor H77 on angiotensin II, arterial pressure and cardiac function in conscious dogs: comparison with captopril.

The renin inhibitor H77 and the angiotensin I converting enzyme (ACE) inhibitor captopril were compared in separate experiments with infusion of 5% dextrose as a control for the effects on plasma angiotensin II (Ang II) concentration, arterial pressure and cardiac function, measured by Swan-Ganz catheter, in conscious dogs. The effects of a high dose of H77 (10 mg/kg per h) were similar to those of high-dose captopril (6 mg/kg per h). Both reduced plasma Ang II concentration, systemic vascular resistance and arterial pressure; both increased the heart rate; both increased cardiac output but the change was significant only with captopril; neither affected stroke volume, pulmonary artery pressure or pulmonary vascular resistance; both reduced left and right atrial pressures. The similar pattern of effects for the two inhibitors suggests that the mechanism by which they act is the same--reduction in Ang II--and that the cardiovascular effects of H77 are not a specific action of the peptide that is unrelated to the reduction in plasma Ang II concentrations.

Angiotensin II↗
PubMed1988

Low dose infusions of 26- and 28-amino acid human atrial natriuretic peptides in normal man.

To investigate the effects of a small rise in the plasma atrial natriuretic peptide (ANP) concentration, 6 normal subjects received 2-h low dose (2 pmol/kg.min) infusions of both 28 [human alpha hANP-(99-126)]- and 26 [human ANP-(101-126)]-amino acid peptides in a placebo-controlled study. Both peptides induced more than 2-fold increases in urinary sodium, calcium, and magnesium excretion. Effective renal plasma flow was slightly reduced, glomerular filtration rate did not change, and renal filtration fraction increased during the ANP infusions. Plasma renin, angiotensin II, and aldosterone concentrations fell by about 50%. Arterial blood pressure and plasma catecholamines did not change. Hematocrit and serum albumin concentrations rose significantly. ANP effects on urinary electrolytes and the renin-angiotensin-aldosterone system were sustained for over an hour after completion of the ANP infusions. The two peptides did not differ in their effects. These results are consistent with a physiological role for plasma ANP in the regulation of extracellular fluid volume and demonstrate that minor N-terminal truncation of alpha hANP has little effect on its biological activity.

Adult↗
PubMed1987

Clinical and biochemical effects of the renin inhibitor H142 in humans.

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Adult↗
PubMed1987

Serological characterisation of a mouse monoclonal anti-P-like antibody.

An IgM mouse monoclonal antibody, LM 147/328, raised against an Escherichia coli immunogen, was found to possess anti-P-like specificity. It is proposed that this antibody recognises an epitope on a Gal beta 1-3GalNAc disaccharide structure (GalNAc = N-acetyl-D-galactosamine). The haemagglutinating activity of this antibody was consistently strong with adult erythrocytes, but gave significantly weak reactions with about 7% of cord erythrocyte samples.

Animals↗
PubMed1987

Dopamine affects angiotensin II-induced steroidogenesis by altering clearance of the peptide in man.

Infusion of dopamine is reported to reduce the response of aldosterone to infused angiotensin II in sodium-deplete but not sodium-replete man. Six normal male subjects were infused with angiotensin II in graded doses (2, 4 and 8 ng/kg per min) with or without dopamine (1.0 microgram/kg per min) during both dietary sodium repletion and depletion. The responses of both aldosterone and 18-hydroxycorticosterone to infusion of angiotensin II appeared to be reduced by dopamine in sodium-deplete, but not sodium-replete, subjects. However, when the relationships between plasma concentrations of angiotensin II and corticosteroid were examined it was evident that plasma concentrations of angiotensin II were lower when dopamine was infused concurrently with the peptide (P less than 0.05). In a second study, six sodium-deplete males were infused with angiotensin II at a constant rate (6 ng/kg per min) while dopamine (or placebo) was given in graded doses (0.5, 1 and 5 micrograms/kg per min). Renal plasma flow was estimated from total body clearance of para-aminohippuric acid. Overall, angiotensin II concentrations were lower during dopamine infusion compared with those during infusion of placebo (63.2 +/- 9.7 (S.E.M.) vs 92.3 +/- 6.4 pmol/l; P less than 0.01) and this was associated with a 40% increase in effective renal plasma flow (627 +/- 68 vs 451 +/- 15 ml/min; P less than 0.05); there again appeared to be a reduced aldosterone response during combined angiotensin II/dopamine infusion compared with that during infusion of angiotensin II alone (1003 +/- 404 vs 1225 +/- 146 pmol/l; 0.05 less than P less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxycorticosterone↗