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G A Ferns

Publications and source records attributed to G A Ferns.

63 records · Page 4Linked to original sources

DNA polymorphic haplotypes on the short arm of chromosome 11 and the inheritance of type I diabetes mellitus.

The linked polymorphic loci 5' to the insulin gene and 3' to the c-Harvey-ras-1 (c-Ha-ras) gene, both localised to the short arm of chromosome 11, have been studied in 14 type I diabetic pedigrees. The use of a cloned gene probe corresponding to the polymorphic locus adjacent to the insulin gene, in combination with the restriction endonuclease PvuII, has permitted an improvement in the resolution of sizes of insert at this locus. An MspI restriction fragment length polymorphism at the c-Ha-ras proto-oncogene locus (4 cM upstream from the insulin gene) was used to identify parental insulin gene related alleles unambiguously, and subsequently a pedigree analysis was performed to determine whether subclasses of inserts at this locus track with insulin dependent diabetes. Segregation analysis demonstrated no linkage between the polymorphic loci 5' to the insulin gene, nor 3' to the c-Ha-ras, and type I diabetes. However, a similar analysis confirmed an association between the HLA locus chromosome 6 and insulin dependent diabetes.

Adolescent↗

HDL-cholesterol subfractions in healthy males: relation to serum triglyceride levels and age.

The relationship between plasma HDL-cholesterol subfractions (HDL2 and HDL3), measured using a differential precipitation method, and serum triglycerides, was studied in 402 healthy Caucasian males attending a health screening centre in London. Mean values for HDL2 and HDL3 were 0.42 +/- 0.24 mmol/L and 0.81 +/- 0.15 mmol/L respectively. HDL2 was found to show a stronger negative correlation with serum triglyceride and a stronger positive correlation with total HDL than HDL3. HDL2 also showed a stronger correlation with age than either total HDL or HDL3. Mean levels of HDL2 were 20% higher in subjects over 55 years of age compared with those who were less than 55 years of age. Reference values of HDL2 and HDL3 are presented for different age ranges.

Adult↗

Genetic polymorphisms of apolipoprotein C-III and insulin in survivors of myocardial infarction.

Genetic polymorphisms of apolipoprotein C-III (apo C-III) and insulin were studied in 48 Caucasian post-myocardial infarction patients. 10 patients (21%) had an uncommon allelic variant of the apo A-I/C-III gene cluster (on the long arm of chromosome 11); in 47 control subjects this variant was present in only 2 and in none of those who were normotriglyceridaemic. Distribution of genotypes between post-infarct and normotriglyceridaemic control groups was significantly different and the difference persisted when the normotriglyceridaemic subgroups of these patients were compared. In contrast, there was no difference in distribution of alleles at the highly polymorphic locus on the short arm of chromosome 11 adjacent to the insulin gene.

Adult↗

The measurement of high density lipoprotein subfractions in patients with primary gout using a simple precipitation method.

We have evaluated a simple dextran sulphate precipitation method for measuring high density lipoprotein cholesterol (HDL) subfractions and have used this method to measure plasma HDL2 and HDL3 in a group of 28 patients with primary gout. These patients were found to have significantly lower levels of plasma HDL and HDL2 than a group of healthy controls, matched for age and sex and of similar body mass index (BMI); no significant difference in mean levels of the HDL3 subfraction was found however. We have confirmed the high prevalence of hypertriglyceridaemia in subjects with gout compared to controls and the mean serum triglyceride levels were significantly higher (P less than 0.01) in the gout group than in controls. We have also shown that subjects with high serum triglyceride levels tend to have low plasma HDL2 concentrations, a finding which is consistent with an inverse relationship between these two parameters. These lipid abnormalities may partly explain the high prevalence of premature atherosclerosis in patients with primary gout.

Chemical Precipitation↗

RT-PCR study on the effects of minimally modified low-density lipoproteins and probucol treatment on gene expressions of interleukin-1 and platelet-derived growth factor B-chain in human peripheral blood mononuclear cells.

Oxidatively modified low-density lipoprotein has been identified in early atherosclerotic lesions and may play an important role in atherogenesis. Minimally modified low-density lipoprotein (MM-LDL) derived by prolonged storage under sterile conditions results in mild oxidation and is recognised by the LDL receptor rather than the scavenger receptor. Therefore, it may be closer to the real pathophysiological circumstances in the initial state of atherosclerosis. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique, the present study demonstrates that MM-LDL is capable of inducing gene expression of both interleukin-1 alpha (IL-1 alpha) and interleuking-1 beta (IL-1 beta) in human peripheral blood mononuclear cells in a dose-dependent manner. Concomitant treatment of the cells with the anti-oxidant probucol results in an inhibitory effect in steady-state levels of both IL-1 alpha and IL-1 beta mRNA and the effects were also shown in a dose-dependent fashion. We also found an inhibitory effect of MM-LDL on gene expression of platelet-derived growth factor B chain (PDGF-B) mRNA levels by mononuclear cells. Hence MM-LDL is biologically active and may contribute to the early stages of atherogenesis by stimulating the inflammatory cytokine IL-1 and the efficacy of probucol in inhibiting the progression of atherosclerosis may be due, both to its inhibition of IL-1 expression by intimal macrophages, and its prevention of LDL oxidation.

Adult↗

High density lipoprotein subfractions and coronary risk factors in normal men.

Plasma levels of total high density lipoprotein cholesterol (HDL) and its subfractions (HDL2 and HDL3) were measured in 366 healthy Caucasian males; these values were related to a number of coronary risk factors. On univariate statistical analysis, total HDL was negatively correlated with cigarette consumption, body mass index, and serum triglycerides, and positively associated with level of physical activity and alcohol consumption. HDL2 showed an inverse relationship with cigarette consumption, body mass index, triglycerides, and systolic blood pressure and a positive relationship with age. HDL3 was negatively correlated with cigarette smoking, body mass index, and triglycerides and positively associated with exercise level and alcohol consumption. Total HDL and HDL2 were inversely related to coronary risk rating, but HDL3 showed no significant correlation. Many of these relationships became nonsignificant after allowing for the effects of other variables. In particular, none of the HDL measurements correlated significantly with risk score after allowing for the effect of triglycerides. There is insufficient evidence at present to recommend the inclusion of HDL subfractions as routine screening tests for heart disease.

Adult↗

Detection of minor myocardial injury after successful percutaneous transluminal coronary angioplasty with or without stenting.

Cardiac troponins are sensitive and specific markers for the detection of minor myocardial injury. However, they have been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels after apparently successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare their results with serum creatine kinase (CK) and its isoform, creatine kinase-MB (CKMB). CTnI and cTnT levels were compared with those of CK or CKMB in 50 consecutive patients with stable angina undergoing visually successful PTCA with stenting (n = 35) or without stenting (n = 15). Cardiac TnI, cTnT, CK and CKMB levels were measured before and 6, 24, and 48 hours after the procedures was performed. None of the patients had abnormal cTnI or cTnT levels, CK activity, or CKMB levels before the procedures. Moreover, no patient showed electrocardiographic evidence of myocardial infarction. 13 patients (26%) had abnormal peak values of one or more markers at 24 hours after coronary intervention. Troponin I was elevated in 10/35 patients after coronary stenting (29%) and in 2/15 patients after PTCA (13%) (P = 0.327). Troponin T was elevated in 6 patients (17%) and CKMB activity was elevated in 3 patients (9%) of the coronary stenting group. CTnI was more significant than CKMB (P = 0.023) in detecting minor myocardial injury. When compared with cTnI and CKMB, cTnT did not reach significance (P = 0.129 and 0.489, respectively). 5 out of the 13 patients with abnormal markers (38%) developed side branch occlusion after stenting. In conclusion, cTnI was a very sensitive marker in detecting minor myocardial injury after coronary angioplasty with or without stenting. The frequency of increased serum levels of cardiac troponins was higher in patients undergoing stent implantation than in those treated with angioplasty alone but did not reach significance. Side branch occlusion may have accounted for some, but not all, periprocedural minor myocardial injury in the stent group.

Adult↗

Changes in serum concentrations of markers of myocardial injury following treadmill exercise testing in patients with suspected ischaemic heart disease.

BACKGROUND: The treadmill exercise test (TEST) is frequently used in patients with suspected ischaemic heart disease to establish a diagnosis and estimate future risk. However, its predictive value is poor. We aimed to investigate whether measurement of biochemical markers of myocardial injury could improve the diagnostic value of the procedure. MATERIAL AND METHODS: Twenty-four subjects with suspected acute coronary syndrome underwent a treadmill exercise stress test. Of these 13 had had a previous myocardial infarction and two had a past history of coronary artery bypass grafting. Nine subjects were found to be positive for coronary ischaemia during the treadmill test. Serum cardiac markers (total creatine kinase [CK], CK-MB, Troponin I and Troponin T) were measured pre-TEST, and 0, 1, 2, 4, 8 and 24 hours following the treadmill test. RESULTS: Total CK remained within the reference range for all subjects and showed no significant rise. However, mean serum concentrations of CK-MB were significantly higher than pre-test values at 2 hours (p < 0.03) following treadmill exercise testing in subjects who had a positive exercise stress test, but not in those with a negative test. In the subjects with a positive stress test, CK-MB levels returned to pre-Test value by 24 hours. Levels of neither serum troponin I, nor troponin T altered significantly at any point. CONCLUSION: The measurement of CK-MB, but not cardiac troponins may add to the diagnostic utility of the TEST.

Angina Pectoris↗