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Biomedical subjects

N E Miller

Publications and source records attributed to N E Miller.

At least 163 records · Page 9Linked to original sources
PubMed1981

A micro-method for the rapid ultracentrifugal separation of human plasma high density lipoprotein subfractions, HDL2 and HDL3.

Currently available ultracentrifugal procedures for separating the two major density subfractions of HDL (HDL2 and HDL3) are time-consuming and expensive, and require relatively large volumes of plasma. In order to overcome these problems, a rapid and simple procedure, requiring only 0.5 ml plasma, has been developed. After precipitation of apoprotein B-containing lipoproteins with heparin and MnCl2, 120 microliters of the supernatant is adjusted to a density of 1.125 g/ml with aqueous NaCl-NaBr, and centrifuged for 3.5 h at 160000 x g in an air-driven bench-top ultracentrifuge (Beckman Airfuge). The HDL2 is then removed in a tube-slicer, constructed to permit six Airfuge tubes to be sliced simultaneously, and the cholesterol content assayed by a cholesterol oxidase procedure. The method provides an alternative to the recently described heparin/MnCl2/dextran sulphate double-precipitation procedure, with the advantage of permitting quantitative recovery of intact HDL2.

Humans↗
PubMed1981

Relation of angiographically defined coronary artery disease to plasma lipoprotein subfractions and apolipoproteins.

The relation of coronary artery disease to plasma lipoproteins was examined in 104 men aged 35-65 years undergoing coronary angiography for suspected myocardial ischaemia. A score reflecting the number, degree, and length of stenoses in seven major coronary arteries was assigned to each angiogram. Lipid concentrations in lipoprotein subfractions were measured after preparative ultracentrifugation; plasma apolipoprotein concentrations were measured by electroimmunoassay. Men with high coronary scores tended to have lower plasma high-density lipoprotein (HDL) cholesterol concentrations and higher low-density lipoprotein (density 1.019-1.063 g/ml) cholesterol concentrations than subjects of similar age with low coronary scores (p approximately equal to 0.1). The strongest relation, however, was with the cholesterol concentration in the HDL2 subfraction (density 1.063-1.125 g/ml) of HDL, which averaged 44% lower in the severely affected patients (p less than 0.005). No associations were found between the coronary score and HDL3 cholesterol, the cholesterol content of lipoproteins of density less than 1.019 g/ml, plasma triglyceride, or the concentrations of apolipoproteins AI, AII, and E. The high coronary scores associated with low HDL2 concentrations reflected an increase in the number of both partial and complete stenoses distributed throughout the coronary tree. In contrast the sizes of the lesions and the proportion producing complete occlusion were unrelated to HDL2.

Adult↗
PubMed1981

Associations between sex hormones, thyroid hormones and lipoproteins.

1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and alcohol intake, and significant negative correlations between HDL cholesterol and both serum thyroxine and obesity. These associations persist when examined by multiple linear regression, indicating their independence. 2. Significant positive correlations are also shown between plasma triglyceride levels and both obesity and serum thyrotropic hormone (TSH) levels. 3. There are no evident relationships between serum oestrone or oestradiol and either HDL cholesterol or triglyceride levels, nor between any of the hormones and either total or low-density-lipoprotein (LDL) cholesterol. 4. Because of the potential importance in relation to coronary heart disease prevention, further studies are needed to try and understand the mechanisms of the associations between HDL cholesterol and obesity, alcohol intake and thyroid and sex hormone levels.

Alcohol Drinking↗
PubMed1981

Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man. Studies of low density lipoprotein receptor activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in blood mononuclear cells.

The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL(2) subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased. THESE EFFECTS ON PLASMA LIPOPROTEINS WERE ACCOMPANIED BY THREE CHANGES IN FRESHLY ISOLATED BLOOD MONONUCLEAR CELLS: (a) an increase in cell cholesterol content (mean change, +17%; P < 0.01); (b) suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (-32%; P < 0.001); and (c) reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of (125)I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade (125)I-LDL after derepression by preincubation for 72 h in lipoprotein-deficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to down-regulate cholesterol synthesis.

Adult↗
PubMed1981

Splanchnic metabolism of plasma apolipoprotein B: studies of artery-hepatic vein differences of mass and radiolabel in fasted human subjects.

The metabolism of apoprotein B-containing plasma lipoproteins by human splanchnic tissues has been studied in 29 men undergoing coronary angiography. Before catheterization autologous radio-iodinated lipoproteins were infused into a peripheral vein: 10 subjects received (125)I-labeled Sf 12-60 lipoproteins; 12 received (125)I-labeled Sf 12-60 plus (131)I-labeled Sf 100-400 lipoproteins; and 7 received (125)I-labeled Sf 12-60 plus (131)I-labeled Sf 0-12 lipoproteins. Paired arterial and hepatic vein blood samples were subsequently collected for replicate measurements of apoprotein B (apo B) mass, radioactivity and specific activity in each lipoprotein class. Splanchnic plasma flow was measured with indocyanine green. All studies were conducted after a 14-h overnight fast. Newly synthesized apo B was shown to be secreted by splanchnic tissues as a component of Sf 100-400 lipoproteins, with no detectable uptake of apo B from this class. Sf 12-60 apo B was extracted by the splanchnic bed, with no detectable secretion. After continuous intravenous infusion of (125)I-labeled Sf 12-60 for five or more hours, 41-67% (mean 55%) of extracted Sf 12-60 apo B radioactivity reappeared in hepatic vein Sf 0-12 apo B. There was no detectable splanchnic catabolism of Sf 0-12 apo B. The rates of Sf 100-400 apo B secretion, calculated as the product of artery-hepatic vein concentration difference and splanchnic plasma flow, were greater than the previously reported rates of very low density lipoprotein apo B turnover in fed subjects obtained by kinetic analysis of plasma specific radioactivity decay curves, suggesting that there may be a diurnal variation in hepatic apo B synthesis. They also exceeded the splanchnic extraction rates of Sf 12-60 apo B, suggesting there was some extrasplanchnic catabolism of the apo B of Sf > 60 lipoproteins.

Adult↗
PubMed1980

Acute effects of the pattern of fat ingestion on plasma high density lipoprotein components in man.

Since Apoprotein A-I (apo A-I) is partially synthesized in the intestine and is secreted into plasma via chylomicrons, we have tested the effects of the daily distribution of fat intake on the concentration and composition of plasma high density lipoprotein (HDL). Ten normal subjects ingested 136 g fat either as a single load (SL) at 0 h or in 6 divided doses from 0 to 10 h (DL). Serial blood samples were obtained over a 24-h period. Studies were performed 7 days apart using a double crossover design and paired comparisons. HDL apo A-I increased during DL (+11% at 9 h, P < 0.01) but was not significantly altered after SL. The HDL Apo A-II concentration did not change. HDL cholesterol decreased significantly (-4 to -7%) during postprandial lipaemia in both phases of the study. Apo A-I and A-II were detected in lipoproteins of d < 1.006 during alimentary lipaemia but not in fasting plasma. These results indicate that HDL apo A-I increases when fat intake is distributed throughout the day (DL), perhaps due to intestinal production of particles with a higher protein/lipid ratio during DL than after a large bolus of oral lipid (SL). Alimentary lipaemia is associated with acute alterations in HDL components including a transient reduction in HDL cholesterol and an increase in the apo A-I/A-II ratio during DL.

Adolescent↗
PubMed1980

Plasma high-density lipoprotein metabolism in subjects with primary hypertriglyceridaemia: altered metabolism of apoproteins AI and AII.

1. The metabolism of the major proteins of plasma high-density lipoprotein (HDL), apoproteins AI and AII, have been studied in 10 normotriglyceridaemic subjects and in 11 hypertriglyceridaemic subjects (plasma triglyceride 4.5--25 mmol/l) by kinetic analysis of the plasma specific radioactivity versus time curves of the apoproteins after intravenous injection of autologous 125I-labelled high-density lipoprotein. 2. The specific radioactivity versus time curves of both apoproteins (followed for 14 days) were bi-exponential in all subjects. 3. The plasma apoprotein AI and AII concentrations were significantly lower in the hypertriglyceridaemic subjects than in the normotriglyceridaemic subjects. Kinetic analysis showed that this was associated with a lower rate of synthesis of apoprotein AI (P < 0.01) and a higher fractional catabolic rate of apoprotein AII (P < 0.01) in the hypertriglyceridaemic group. 4. There were no significant differences between the two groups in the synthetic rate of apoprotein AII, the fractional catabolic rate of apoprotein AI or the intravascular/extravascular distributions of the apoproteins. 5. Thus hypertriglyceridaemia appears to be frequently associated with divergent abnormalities of the metabolism of the major high density lipoprotein apoproteins.

Adult↗
PubMed1980

Prevention of coronary heart disease: the role of high density lipoproteins.

There is now strong evidence that the risk of developing clinical coronary heart disease (CHD) in apparently healthy middle-aged men is inversely related to the plasma high density lipoprotein (HDL) cholesterol concentration. This reflects an underlying relationship between HDL cholesterol concentration and the severity of coronary atherosclerosis. This new information represents a significant development in atherosclerosis research. In the author's opinion, however, it is not yet justifiable, or indeed possible, to utilize this knowledge in CHD prevention programmes for 3 reasons. Firstly, there is still little prospective information on HDL and CHD in women, in younger subjects and in patients with existing clinical disease. Secondly, although there are at least 2 working hypotheses, a causal relationship between HDL metabolism and atherogenesis has not yet been established. Thirdly, there is still a relative paucity of information on the environmental determinants of HDL concentration and metabolism. Thus, premature attempts at intervention in an uncontrolled manner, and particularly the use of drugs for an HDL-raising effect, might only confuse the issue. While further research is being undertaken, attention should continue to be directed towards other reversible coronary risk factors (including hypercholesterolaemia, hypertension, and cigarette smoking) in CHD prevention programmes.

Adult↗
PubMed1980

A chronic arterial catheter and low compliance system for recording blood pressure and heart rate from the rat.

A procedure for cannula construction, surgical implantation, and utilization is presented for recording arterial blood pressure and heart rate from the renal artery of unanesthetized mobile rats. The method involves unilateral nephrectomy, but the animals recover quickly and remain in excellent health. The cannula requies minimal maintenance; it has been used in cardiovascular experiments to make multiple periodic arterial blood pressure recordings. Patency for 2 mo or longer is common.

Animals↗
PubMed1979

Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension.

The hypothesis was tested that an acute rise of blood pressure may reduce reactivity to noxious stimuli through a baroreceptor-mediated reduction of cerebral arousal. When blood pressure was raised by an infusion of phenylephrine, rats showed less running to terminate or avoid noxious stimuli than during saline infusions. This effect was not seen in rats with denervated baroreceptors. The results suggest that a rise of blood pressure could have motivational consequences significant for human hypertension.

Animals↗
PubMed1979

Effects of microtubule-disruptive and membrane-stabilizing agents on low density lipoprotein metabolism by cultured human fibroblasts.

The cellular mechanisms involved in the uptake and metabolism of low density lipoprotein (LDL) by cultured normal human fibroblasts have been investigated with the aid of drugs known to disrupt cytoplasmic microtubules or to inhibit membrane fusion. Two drugs which disrupt microtubules by differing mechanisms, colchicine and vinblastine, each reduced the high affinity surface binding of 125I-labelled LDL by fibroblasts. Associated reductions of the endocytosis and degradation of the lipoprotein could be attributed almost entirely to this effect. In contrast, lumicolchicine, an analogue of colchicine without microtubule-disruptive activity, had little or no effect on 125I-labelled LDL metabolism. Each of two groups of membrane-stabilizing agents, the phenothiazines and the tertiary amine local anaesthetics, directly inhibited both the internalization of 125I-labelled LDL following high affinity binding to cell surface receptors and the catabolism of the lipoprotein subsequent to endocytosis, supporting previous morphological evidence for the importance of membrane fusion in these processes.

Biological Transport↗