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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 199 records · Page 11Linked to original sources
PubMed1976

The effect of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids of normotensive man.

Eight normotensive white middle-aged men were given low, moderate, and high salt diets with constant potassium intakes each for periods of at least 4 weeks. There was a tendency for body weight, serum sodium, exchangeable sodium, and inulin space to increase. Indirect blood pressure measurements revealed no change in blood pressure, either supine or upright measurements, during the 3 study intervals. Inulin clearance (and presumably glomerular filtration rate) rose with increase in dietary salt. Urinary potassium excretion rose progressively as salt intake increased. Total body potassium tended to decrease with increase in dietary salt. There was no changes in the excretion of calcium, magnesium, phosphorus, nor were there changes in the blood level of potassium. There was no change in total body water. The serum cholesterol and triglyceride levels were not appreciably affected by the different dietary sodium intakes. Plasma renin activity and urinary aldosterone excretion rose progressively with the two levels of sodium restriction. These studies indicate that normal man is able to compensate for large differences in sodium intake with minor metabolic changes. These changes do not necessarily lead to hypertension over a one-month period. Nevertheless, many hemodynamic and hormonal compensatory mechanisms come into play. It is evident that hypertension might result should the sodium load not be excreted, the circulating volume become too great for the excretory capacity, or if neural or endocrine adjustments be inadequate.

Adult↗
PubMed1976

Turnover of xanthoma cholesterol in hyperlipoproteinemia patients.

The turnover of xanthoma cholesterol was measured in 9 hyperlipidemic and one normocholesterolemic patients. Sequential biopsies of the xanthomas were obtained 13 to 364 days after the administration of isotopic cholesterol and were then analyzed for cholesterol specific activity. A total of 34 xanthomas of 3 different types - 10 tendon xanthomas, 3 tuberous xanthomas, and 21 xanthelasmas - comprised the material for analysis. The cholesterol specific activity ratio of tendron xanthomas to that of the plasma varied from 11 per cent at 21 days to a maximum of 543 per cent at 122 days after the intravenous administration of isotopic cholesterol. This ratio declined to 426 per cent at 182 days and was still 131 per cent at 364 days. Similarly, the cholesterol specific activity of xanthelasmas increased gradually. In most instances, the xanthelasma cholesterol attained isotopic equilibration with plasma cholesterol by about 50 days but varied from patient to patient (minimum time, 46 days and maximum time, 91 days). The cholesterol content of xanthomas ranged from 10.7 to 197.0 mg per gram of dry weight of the tissue. Sixty-one to 87 per cent of the total xanthoma cholesterol was esterified. No other sterols were identified in these xanthomas. Thus, the cholesterol of 3 types of xanthoma readily attained isotopic equilibration with the plasma cholesterol which suggested total exchangeability of cholesterol between plasma and xanthomas. The uptake of cholesterol by the xanthomas from plasma was rapid considering the large mass of cholesterol in the lesions. The turnover of xanthoma cholesterol was intermediate between that of the rapidly exchangeable pool and of the slowly exchangeable pool of body cholesterol. Comparison of these results with those obtained in human advanced atheroma suggest that the turnover of xanthoma cholesterol and atheroma cholesterol are quite different.

Adult↗
PubMed1976

Abnormalities of cholesterol turnover in hypercholesterolemic (type II) patients.

Cholesterol turnover was measured in 5 normal subjects and 14 familial hypercholesterolemic (Type II) patients. All patients were fed eucaloric cholesterol-free or very low cholesterol formula or mixed-food diets. They were given single doses of cholesterol-1,2-3H and cholesterol-4-14C simultaneously, one isotope intravenously (IV), and the other orally. Plasma cholesterol specific radioactivity decay curves for 3H and 14C isotopes in each patient conformed to the short-term (10 to 12 weeks) kinetics of the two-pool model. In type II patients, the total mass of cholesterol in pool A was significantly larger by about 17 Gm. (by the IV method) and 27 Gm. (by the oral method) as compared with normal subjects. The increase in size of pool A in Type II patients occurred equally in plasma and tissues comprising pool A (probably liver and intestine). The rate constant for the excretion of cholesterol from pool A was significantly reduced in the Type II patients. The rate constant for the transfer of cholesterol from pool A to pool B was also reduced in the Type II patients. Furthermore, the metabolic clearance fraction was decreased by 50 per cent as compared with normal subjects. In normal subjects and in Type II patients, the size of pool A was significantly larger by about 5 Gm. and 15 Gm., respectively, by the oral method as compared with the IV method. This difference in the size of pool A probably reflects differences in isotopic equilibration with the intestinal mucosal cholesterol pool. All other parameters of cholesterol turnover by the IV method as compared with the oral method were similar. Our results suggest that the expanded rapidly exchangeable pool of cholesterol (pool A) is due to a defect in cholesterol transport and excretion in familial hypercholesterolemia (Type II). The decreased rate of removal of cholesterol from the plasma and/or catabolism in tissues could be one important cause of familial hypercholesterolemia in man.

Administration, Oral↗
PubMed1975

Coronary heart disease risk factors in school children: the Muscatine study.

The frequency of coronary risk factors was documented in 4,829 school children in Muscatine, Iowa, over a 14-month period of time. Serum cholesterol levels were similar for children at all ages; the mean serum cholesterol level was 182 mg/dl (SD lus or minus 29). Twenty four percent had levels larger than or equal to 200 mg/dl, 9% were larger than or equal to 220 mg/dl, 3 % were larger than or equal to 240 mg/dl, and 1% were larger than or equal to 260 mg/dl. Casual levels of serum triglyceride increased with age: the mean level was 71 mg/dl (SD plus or minus 36) at age 6 years and 108 mg/dl (SD plus or minus 45) at age 18 years. Only 15% of the children had serum triglyceride levels of 140 mg/dl or more. Blood pressure increased strikingly with age. No child between 6 and 9 years of age had blood pressures larger than or equal to 140 mm Hg systolic or larger than or equal to 90 mm Hg diastolic. In the age group 14 to 18 years, 8.9% had systolic blood pressures larger than or equal to 140 mm Hg, 12.2% had diastolic blood pressures larger than or equal to 90 mm Hg, and in 4.4% both pressures were at or above these levels. Obesity also increased through the school years. At ages 6 to 9 years, 20% had weights relative to those of the group as a whole of larger than or equal to 110%, and 5% were larger than or equal to 130%; in the 14 to 18 years age group, 25% had relative weights of larger than or equal to 110%, and 8% were larger than or equal to 130%. These data indicate that a considerable number of school-age children have risk factors which in adults are predictive of coronary heart disease.

Adolescent↗
PubMed1975

Incorporation of the dietary trans fatty acid (C18:1) into the serum lipids, the serum lipoproteins and adipose tissue.

Two diets, identical except for differences in trans and cis fatty acids, were fed to rabbits in order to evaluate the effects of dietary trans fatty acids on the fatty acid composition of serum lipids, lipoproteins and adipose tissue. The animals were first starved to deplete adipose tissue stores and then were red a diet containing 15% of the calories as C18:1 trans fatty acid (elaidic acid). A second group received a diet containing an equivalent amount of C18:1 cis fatty acid (oleic acid). A third group of animals, the control group, was fed only the baseline low fat rabbit chow. Dietary trans fatty acid was incorporated into all serum lipid and lipoprotein fractions and into the adipose tissue. In the serum the triglycerides contained the greatest amount of trans fatty acid followed by the phospholipids with cholesterol esters containing the least. The trans fatty acids of the phospholipids and cholesterol esters were distributed equally among the lipoprotein fractions, but the triglycerides of high density lipoproteins contained less trans fatty acids than did the triglycerides of other lipoproteins. Adipose tissue developed a high content of C18:1 trans fatty acid (21.7%), apparently at the expense of C18:1 cis fatty acid. In addition to the incorporation of C18:1 trans fatty acid, the content of other fatty acids, including C18:2 and the total of C18:1 cis and trans, was influenced by the substitution of dietary trans for cis fatty acids. The serum phospholipids of the trans-fed rabbits contained more C18:2 than the phospholipids of the cis-fed rabbits. The serum cholesterol esters of the trans-fed rabbits contained more C18:2 and a smaller total of C18:1 (cis puls trans) than the cholesterol esters of the cis-fed rabbits. These differences indicated that C18:1 trans fatty acid was not necessarily the metabolic equivalent of 18:1 cis fatty acid. These results suggested that dietary trans fatty acids which are contained in hydrogenated margarines, shortenings and oils of the human diet are readily incorporated into the lipids of the body including membranous structures such as lipoproteins.

Adipose Tissue↗
PubMed1975

Hypercholesterolemia of total starvation: its mechanism via tissue mobilization of cholesterol.

After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero.

Adipose Tissue↗
PubMed1975

Effects of high and low sodium intake on arterial pressure and forearm vasular resistance in borderline hypertension. A preliminary report.

The purpose of this study was to evaluate effects of high and low sodium intake on arterial pressure and forearm vascular resistance in subjects with borderline hypertension and to compare responses to sodium excess in these subjects with responses in a recent study in normotensive subjects. Six subjects with borderline hypertension were studied after ten days of high (410 mEq/24hr) and low (10mEq/24hr) sodium intake. Potassium intake was constant. In five of six subjects, high sodium intake decreased forearm blood flow and increased forearm vascular resistance and arterial pressure. During low and high sodium intake forearm blood flow averaged 7.8 plus or minus 1.2 (SE) and 5.9 plus or minus 0.8 ml/min x 100 ml, respectively; forearm vascular resistance averaged 13.5 plus or minus 2.2 and 19.1 plus or minus 3.0 units, respectively; and mean arterial pressure averaged 89 plus or minus 3 and 98 plus or minus 2 mm Hg, respectively. High sodium intake augmented forearm vasoconstrictor responses to lower body negative pressure, a stimulus to neurogenic vasoconstriction. The results contrast with our earlier results in normotensive subjects in whom sodium excess produced forearm vasodilatation and failed to increase arterial pressure significantly. Decreases in renin and aldosterone with high sodium intake were similar in the two groups. The results suggest that excessive sodium intake in subjects with borderline hypertension produces abnormal increases in forearm vascular resistance, neurogenic vasoconstriction, and arterial pressure. The reasons for the contrast between the borderline hypertensives and normotensives are unknown, but they do not seem to be related to the renin-angiotensin-aldosterone system.

Adult↗
PubMed1975

The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally.

The hypothesis that clinical and biochemical essential fatty acid deficiency (EFA) might occur from the feeding of eucaloric, fat-free diets was tested in two experiments in healthy men. In Study I, eight men were given fat-free, eucaloric diets containing 80% of calories as glucose and 20% as amino acid hydrolysates by a constant drip over a 24-h period. The diets were fed in succession for periods of 2 wk each, either through a superior vena cava catheter or via a nasogastric tube. EFA deficiency was detected by decreases in linoleic acid and by the appearance of 5, 8, 11-eicosatrienoic acid in lipid fractions of plasma. Linoleic acid decreased significantly during 2 wk of the fat-free diet given intravenously from 48.8 to 9.8% (percent of total fatty acids) in cholesterol esters, from 21.2 to 3.2% in phospholipids, from 9.6 to 2.0% in free fatty acids, and from 14.1 to 2.6% in triglycerides. Eicosatrienoic acid, normally undetectable, appeared 0.6% in cholesterol esters, 2.5% in phospholipids, 0.2% in free fatty acids, and 2.3% in triglycerides. EFA deficiency occurred similarly during the nasogastric feeding. In Study II a subject received the same diet continuously by the nasogastric route for 10 days followed by a 24-h fast. He was then given the fat-free diet intermittently in three meals per day for 3 days. Finally, he was repleted with a diet containing 2.6% linoleic acid. By the 3rd day of the continuous nasogastric feeding, linoleic acid had fallen significantly and eicosatrienoic acid had appeared in plasma lipid fractions as in Study I. These findings were accentuated by day 10. Adipose tissue fatty acid composition did not change. Free fatty acid outflow from adipose tissue was presumably suppressed during the 10 days of continuous feeding. With increased free fatty acid outflow during fasting and intermittent feeding, linoleic acid rose and eicosatrienoic acid decreased. After 13 days of repletion with dietary linoleic acid, the EFA deficiency readily develops when fat-free diets containing glucose are given intravenously or orally as constant 24-h infusions. These diets are similar to the hyperalimentation formulas now being used clinically.

Adipose Tissue↗
PubMed1975

The transport of triglyceride in the high-density lipoproteins of human plasma.

The metabolism of the small pool of triglyceride in human high-density lipoproteins (HDL) has been studied. In 28 postabsorptive and unmedicated subjects the previously reported reciprocal relationships between the concentration of very low-density lipoprotein (VLDL) lipids and HDL cholesterol was confirmed. It was also found that the HDL triglyceride correlated positively and significantly with the concentration of VLDL triglyceride, and there was a significant negative correlation between the concentrations of triglyceride and cholesterol in HDL. Five normal and 3 hypertriglyceridemic subjects were given 5,000 units of heparin intravenously. Not only was there a pronounced reduction in VLDL triglyceride, but there was a 60 to 80 per cent reduction in HDL triglyceride; the low-density lipoprotein (LDL) triglyceride was unchanged. To test a possible precursor-product relationship between the triglyceride pools in VLDL and HDL, 5 subjects were given an intravenous pulse injection of (14-C)-palmitic acid. The specific activity-time curves of triglyceride in VLDL and HDL did not conform to a typical precursor-product relationship; rather the HDL curve reached its peak well before it crossed the VLDL curve, quite compatible with an origin of HDL triglyceride which was independent of VLDL. However, when the lipoproteins of density smaller than 1.006 (VLDL and chylomicrons) were labeled in the intestine after an oral tracer dose of (3-H)-palmitic acid in 2 subjects, the relationship of the triglyceride labeling in HDL to that in d smaller than 1.006 lipoproteins was very similar to the relationship observed after the intravenous dose. Although an independent intestinal origin of HDL triglyceride could not be excluded, this result did suggest that the labeling of triglyceride in d smaller than 1.006 lipoproteins and in HDL was related and was consistent with a transfer from the larger lipoproteins to the HDL. In three subjects given a constant intravenous infusion of (3-H)-palmitic acid, the specific activity of triglyceride in VLDL became constant after 3 to 4 hours; it also became constant in the HDL after about 4 hours but at a level of only 40 to 70 per cent of the VLDL level. It appeared that 30 to 60 per cent of the HDL triglyceride was either derived from an unlabeled source or else turned over too slowly to become labeled to any extent during the infusions. Whatever the explanation, the same phenomenon would be likely to influence the level of the peak specific activity of HDL triglyceride after the pulse intravenous injections of label. It is possible that the specific activity of the "labeled" fraction of HDL triglyceride may have reached its peak at the point at which it crossed the VLDL curve, which would be consistent with a precursor-product relationship between VLDL and one fraction of the HDL triglyceride. It has been concluded that HDL triglyceride is heterogeneous and includes at least one pool, possibly transferred from VLDL, which is relatively rapidly turning over.

Adult↗
PubMed1974

Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters.

Although the usual diet may contain 150-250 mg of plant sterols, chiefly beta-sitosterol, only trace amounts of these sterols have heretofore been found in human or animal blood and tissues. We now report elevated plant sterol levels in the blood and tissues of two sisters with extensive tendon xanthomas but normal plasma cholesterol levels. Besides beta-sitosterolemia and xanthomatosis, no other physical, mental, or biochemical abnormalities were detected.Repeatedly, the plasmas of the two sisters have contained 27.1 and 17.7 mg/100 ml of beta-sitosterol, 9.7 and 8.2 mg/100 ml of campesterol, and 0.5 and 0.5 mg/100 ml of stigmasterol, respectively. These plant sterols constituted 15.6 and 11.3% of the total plasma sterols. Some 60% of the plasma beta-sitosterol and campesterol was esterified; the measurable stigmasterol was entirely unesterified. The transport of the plasma beta-sitosterol and campesterol was largely in low density lipoproteins (76 and 83%, respectively). High density lipoproteins carried the remainder. Plant sterols were barely detectable in the very low density lipoprotein fraction. Only trace amounts of stigmasterol could be detected in the low density and high density lipoprotein fractions. The plant sterol content of the red blood cells averaged 12-13 mg/100 ml packed cells or about 13% of the total sterols. Two tendon xanthoma biopsies with the usual high concentration of cholesterol had 36.7 and 4.0 mg of plant sterols/g dry wt, of which 25.7 and 2.9 mg were beta-sitosterol, entirely in the free form. Plant sterols were also found in adipose tissue (0.2 mg/g wet wt) and in skin surface lipids (3.2 mg/g of lipid). The intestinal absorption of beta-sitosterol in both the patients, measured by two techniques, indicated greatly increased absorption of this sterol (about 24 and 28% in the patients L. H. and R. H., respectively, normal absorption being <5%). We suggest that increased absorption of beta-sitosterol must be considered as one cause of this disease. The reason for the extensive xanthomatosis in these two patients remains unknown. Perhaps in some way plant sterols initiated the development of xanthomas with otherwise normal plasma cholesterol levels. Clinical atherosclerosis has not yet occurred. The occurrence of beta-sitosterolemia in these two sisters with un-affected parents suggests an inherited recessive trait.

Adipose Tissue↗
PubMed1974

The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly related to the amount of cholesterol in the test meal, and absorption was not affected by background diets high or low in cholesterol content.

Adult↗
PubMed1974

The turnover of cholesterol in human atherosclerotic arteries.

The equilibration of cholesterol between plasma and atherosclerotic arteries was studied in 13 patients with obstructive atherosclerosis 2-96 days after the intravenous and/or oral administration of isotopic cholesterol. Arterial specimens were obtained in 12 patients during surgery for arterial reconstruction and in a 13th patient at autopsy. Equilibration was calculated as the specific radioactivity of cholesterol in the arterial tissue relative to that in the plasma (percent).In specimens obtained 2-4 days after pulse labeling, the specific activity of cholesterol in atheroma ranged from 0.3 to 4.5% of that in the plasma. By 17-27 days, the relative specific activity ranged from 6 to 20% in different arteries. In contrast, cholesterol of skeletal muscle had a relative specific activity of 96% by 22 days. By 61-96 days, atheroma cholesterol in the abdominal aorta, common iliac, and femoral arteries had equilibrated to 55, 30, and 26%, respectively. In the patient who died at 96 days, the cholesterol in the coronary arteries had a mean equilibration of 66%, similar to the values for the abdominal (66%) and thoracic (57%) aortas. The route of administration of the isotope did not influence the equilibration. Within the atheromatous plaque, the superficial layers equilibrated better than the deeper layers (75% vs. 22%). The free cholesterol in the atheroma equilibrated to a significantly higher extent than did esterified cholesterol (59% vs. 38%). There was a fourfold higher specific activity of cholesterol in the media than in the corresponding intima (916 vs. 230 dpm/mg). The estimated minimal influx rates of plasma cholesterol into the atheromatous intima ranged from 0.065 to 0.274 mg of cholesterol/g dry tissue per day for different arteries. The approximated turnover times of atheroma cholesterol ranged from 442 days for the abdominal aorta and the coronary arteries to 580 days for the common iliac and 821 and 934 days, respectively, for the femoral and the carotid arteries. These data indicate a definite, though slow, exchange of cholesterol between the plasma and severely atherosclerotic human arteries. Within the atheroma, there are multiple pools of cholesterol, each turning over differently and more slowly than the cholesterol of most other tissues, such as the skeletal muscle. The estimates of influx rate and turnover time of atheroma cholesterol suggest the possibility that this cholesterol is mobilizable, an indication of potential regression of atheromatous lesions in man.

Adult↗