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Biomedical subjects

N E Miller

Publications and source records attributed to N E Miller.

At least 127 records · Page 7Linked to original sources
PubMed1984

Inhibition of cholesterol synthesis reduces low-density-lipoprotein apoprotein B production without decreasing very-low-density-lipoprotein apoprotein B synthesis in rabbits.

The kinetics of the apoprotein B (apo B) of very-low-density (VLDL; d less than 1.006) and low-density (LDL; d 1.019-1.063) lipoproteins were studied in six rabbits by using radioiodinated homologous lipoproteins, before and during oral administration of mevinolin (5 mg/kg per day), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), to explore the mechanism by which the drug reduces LDL synthesis. Before treatment LDL-apo B production greatly exceeded VLDL-apo B production in all animals, indicating that a large proportion of plasma LDL was derived from a VLDL-independent pathway. Five animals responded to mevinolin with a fall in plasma cholesterol (mean change - 53%; P less than 0.01). This was associated with a 66% decrease in LDL-apo B synthesis (P less than 0.05). In contrast, VLDL-apo B synthesis was unaffected by mevinolin. Furthermore, in all but one animal the decrement in LDL-apo B synthesis was greater than the rate of VLDL-apo B synthesis before treatment, demonstrating that mevinolin had reduced the VLDL-independent production of LDL.

Animals↗
PubMed1984

A multifactorial diet in the management of hyperlipidaemia.

To augment the effectiveness of conventional lipid-lowering treatment, a diet has been evolved combining modified fat content with an increase in vegetable-derived fibre and protein. This was evaluated in 37 hyperlipidaemic and normal ambulant subjects in whom plasma lipid and lipoprotein responses were measured for 4.7-11 months. Mean reductions in plasma cholesterol, triglyceride and low density lipoprotein cholesterol levels were 22, 24 and 25% respectively; there was no significant change in the cholesterol concentrations in high density lipoprotein or in its HDL2 subclass. The effectiveness of the diet in reducing hyperlipidaemia, its influence in optimizing the distribution of cholesterol between plasma lipoprotein classes, and its nutrient composition suggest that it is an advance on existing lipid-lowering dietary patterns.

Adult↗
PubMed1984

Studies of lipoprotein metabolism in a patient with fish-eye disease.

In the rare familial disorder fish-eye disease, hypertriglyceridaemia is associated with elevated levels of very-low-density lipoprotein (VLDL) and enrichment of low-density lipoprotein (LDL) with triglyceride. The kinetic basis of the dyslipoproteinaemia was investigated by studying the metabolism of the apolipoprotein-B moeity of VLDL, intermediate-density lipoprotein (IDL) and LDL in a 68-year-old woman with this condition. The major kinetic abnormality was a pronounced reduction in the rate of fractional conversion of VLDL-B to IDL-B and of IDL-B to LDL-B, suggesting that the dyslipoproteinaemia represents accumulation in plasma of partly degraded products of VLDL metabolism. This kinetic disorder has features in common with type-III hyperlipoproteinaemia. In studies in vitro no defect in the enzyme, activator or substrate components of the lipoprotein lipase or hepatic lipase systems was observed.

Aged↗
PubMed1984

Paraplegic energy expenditure during negotiation of architectural barriers.

Long-leg braces are often used by persons with paraplegia to negotiate architectural barriers, and thereby increase their wheelchair mobility. Such barriers include ramps, stairways, and narrow corridors requiring multiple turns. This study was designed to measure the energy expenditure during such activities for two long-leg orthoses: standard braces without a dorsiflexion stop and Scott-Craig braces. Energy expenditure was measured in eight subjects by indirect spirometry using Douglas bag collection and Haldane analysis. Data obtained were used to calculate oxygen consumption per minute, volume of oxygen per turn, step, or meter, and calories per minute during each activity. Using Scott-Craig braces on one day and standard braces on another day, each subject negotiated five 90 degrees turns and two 180 degree turns, ten 15.24 cm steps, both up and down, and an 11.9 m ramp inclined 12 degrees, both up and down. Milliliters of oxygen consumed per kilogram of body weight per turn, step, or meter were recorded for Scott-Craig braces, standard braces, and normal walking. All of these activities required a high expenditure of energy. No significant difference was apparent between the standard and the Scott-Craig braces for any activity.

Adult↗
PubMed1984

Energy expenditure of paraplegic patients standing and walking with two knee-ankle-foot orthoses.

To determine which kind of knee-ankle-foot orthosis (KAFO) is more efficient, we measured energy expenditure in standing, walking with a walker, and walking with crutches by eight subjects using the Scott-Craig KAFO and a single-stopped long-leg KAFO. All subjects had complete motor paralysis below the level of their lesion and had been fully trained to use KAFOs. Every subject used both types of KAFO, and energy expenditure--per minute and per meter traveled--was measured by oxygen consumption. No significant difference in energy expenditure appeared during standing. During ambulation, however, mean energy expenditure was less with the Scott-Craig KAFO than with the single-stopped type: 31% less kcal/m with a walker and 25% less kcal/min with crutches. These results suggest that the Scott-Craig KAFO is more energy-efficient than the single-stopped long-leg KAFO.

Adult↗
PubMed1983

Stress-induced suppression of immunity in adrenalectomized rats.

Stress-induced suppression of lymphocyte stimulation by phytohemagglutinin was demonstrated in Isolated lymphocytes and in cultures of whole blood from adrenalectomized rats. The results demonstrate that corticosteroid independent mechanisms participate in the suppression of lymphocyte function by stressors. Stress-induced lymphopenia, however, was found to be adrenal dependent, indicating that the modulation of immunity by stress is complex and multidetermined.

Adrenalectomy↗
PubMed1983

Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial.

The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication. 24 patients were randomly assigned to treatment and usual-care groups, the former receiving dietary advice and cholestyramine, nicotinic acid, or clofibrate depending on their lipoprotein phenotype. Biplanar arteriography was performed when the study began and after a mean period of 19 months. Angiograms were assessed visually, with blinding, and by computerised image analysis. Therapy reduced mean plasma total cholesterol by 25%, mean low density lipoprotein (LDL) cholesterol by 28%, and mean plasma triglycerides by 45%. Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group. The mean increase in plaque area (mm2/segment/year) in the treatment group was only one third of that in the usual-care group. The mean increase in edge irregularity index (a measure of the severity of disease) in the treatment group was only 40% of that in the usual care group. Twice as many arterial segments showed improvement in the treatment group. In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration. This study, the first randomised controlled trial of its type, provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis.

Angiography↗
PubMed1983

Hypocholesterolaemia and non-cardiovascular disease: metabolic studies on subjects with low plasma cholesterol concentrations.

Some epidemiological studies have suggested an inverse relation between serum cholesterol concentration and mortality from cancer. Two hypotheses that might explain such a relation were investigated. To assay potentially deleterious effects of hypocholesterolaemia on cell membranes the lipid content and fluidity of blood mononuclear cells were measured in healthy male volunteers with a wide range of serum cholesterol concentration (3.2-10.0 mmol/l (124-387 mg/100 ml)). Fluidity, unesterified cholesterol content, and the ratio of cholesterol to phospholipid were unrelated to serum cholesterol and to low density lipoprotein cholesterol concentrations. Similar measurements were made on fibroblasts and mononuclear cells incubated with a range of concentrations of low density lipoprotein; fluidity was altered only at extremely low concentrations, suggesting that changes in cell membranes are unlikely to occur at serum cholesterol concentrations attainable by dietary or drug treatment of hyperlipidaemia. In the same population direct relations were confirmed between low density lipoprotein concentration and plasma concentrations of retinol and beta carotene. This is compatible with the suggestion that an association between low cholesterol concentration and cancer may be secondary to a relation between low retinoid concentrations and cancer.

Adult↗
PubMed1983

Coronary heart disease in 'low risk' men.

An attempt was made to explore the reasons why men develop coronary heart disease (CHD) despite being at low risk on the basis of established risk factors. A case control study was designed to take place after the end of a longitudinal study in which both low- and high-risk men who had developed CHD over the course of 5-6 years were compared with controls who had remained CHD-free, matched for initial risk characteristics. Low-risk men who had developed CHD had significantly lower levels of high density lipoprotein (HDL) cholesterol than their controls. This difference was not seen when high-risk men were compared with their controls. Apart from a suggestion that low risk cases had lower levels of free thyroxine (seen mainly when less severe categories of CHD were examined) there were no other significant differences between cases and controls (either low- or high-risk) in the other measured variables, which included levels of total testosterone and oestradiol in plasma, packed cell volume and heart rate. It is concluded that low levels of HDL cholesterol may partly explain why men who are otherwise at low risk develop CHD. This study design may be useful to test other hypotheses, particularly where it has not been possible to make the appropriate measurements at the start of a longitudinal study.

Adult↗
PubMed1983

Lack of correlation between the maximum low-density lipoprotein (LDL) receptor activity of blood lymphocytes and plasma LDL concentration in normal men.

1. Measurements were made of the maximal low-density lipoprotein (LDL) receptor activities of blood lymphocytes from 81 healthy men with a wide range of plasma LDL cholesterol concentrations (1.45-7.55 mmol/l). 2. Receptor activity was quantified by measuring the degradation of 125I-labelled LDL (10 micrograms of protein/ml) to trichloroacetic acid-soluble material during a 6 h incubation, after derepression of the lymphocytes for 72 h in lipoprotein-deficient medium. 3. No significant correlation existed between LDL receptor activity in vitro and plasma LDL cholesterol concentration in vivo (r = -0.08).

Adult↗
PubMed1983

Modes of action of lipid-lowering diets in man: studies of apolipoprotein B kinetics in relation to fat consumption and dietary fatty acid composition.

The mechanisms by which dietary fat influences fasting plasma lipid concentrations have been investigated in hyperlipidaemic subjects. The synthetic and fractional catabolic (FCR) rates of the apoprotein B (apo B) of very-low density (VLDL) and low-density (LDL) lipoproteins were measured using radioiodinated autologous lipoproteins. Reductions of LDL concentration in eight subjects during low-fat (25% of energy) diets were largely explained by diminished synthesis (-20%, P less than 0.02), and possibly also by an increased FCR (+15%, P = 0.05) of LDL, compared with observations made during a high-fat (45% of energy) diet of similar fatty acid composition. VLDL apo B synthesis and FCR were not significantly altered. When a diet rich in polyunsaturated fatty acids was exchanged for one high in saturated fatty acids (fat providing 45% of energy on both occasions) in four subjects, the synthetic rates of both VLDL apo B (-31%, P less than 0.02) and LDL apo B (-23%, P less than 0.10) were reduced while their FCRs were unchanged.

Adult↗
PubMed1983

Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin.

A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.

Alcohol Drinking↗
PubMed1983

Familial chylomicronemia due to a circulating inhibitor of lipoprotein lipase activity.

A mother and her son who have lipoprotein phenotype I are described. They differed from subjects with lipoprotein lipase deficiency in that lipoprotein lipase was present in adipose tissue respectively at 30- and 2-fold the levels seen in normal subjects, and from subjects with apoprotein C-II deficiency in that apoprotein C-II was present in their plasma. They appeared to have an inhibitor to lipoprotein lipase activity in their whole plasma that inhibited that activity eluted from adipose tissue with heparin and that activity present in postheparin plasma of normals. The inhibitor was non-dialyzable, heat-stable, sensitive to repeated freezing and thawing, and appeared to be present in the non-lipoprotein fraction of plasma. The presence of chylomicronemia and the plasma inhibitor in the mother and her son, and possibly in her father and grandson, argues against this being inherited as an autosomal recessive abnormality, as are lipoprotein lipase deficiency and apoprotein C-II deficiency.

Adipose Tissue↗