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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 127 records · Page 7Linked to original sources

Familial apolipoprotein A-I and C-III deficiency, variant II.

The biochemical, clinical, and genetic features were examined in the proband (homozygote) and heterozygotes (n = 17) affected with familial apolipoprotein A-I and C-III deficiency, variant II (previously described as apolipoprotein A-I absence). The proband was a 45-year-old white female with mild corneal opacification and significant three-vessel coronary artery disease (CAD), who died shortly after bypass surgery. Autopsy findings included significant atherosclerosis in the coronary and pulmonary arteries and the abdominal aorta as well as extracellular stromal lipid deposition in the cornea. No reticuloendothelial lipid deposits in the liver, bone marrow, or spleen were noted (unlike Tangier disease). Laboratory features included marked high density lipoprotein (HDL) deficiency and undetectable plasma apolipoproteins (apo) A-I and C-III. The percentage of plasma cholesterol in the unesterified form was normal at 30%. The activity and mass of lecithin:cholesterol acyltransferase (LCAT) were 42% and 36% of normal, respectively, and the cholesterol esterification rate was 43% of normal. Deficiencies of plasma vitamin E and essential fatty acid (linoleic, C18:2) were also noted. Evaluation of plasma lipoproteins and apolipoproteins in 37 kindred members revealed 17 heterozygotes with HDL cholesterol values below the 10th percentile of normal. Of these, all had apoA-I levels more than one standard deviation below the normal mean, and 37.5% had a similar decrease in apoC-III values. Mean (+/- SD) plasma HDL cholesterol, apoA-I, and apoC-III values (mg/dl) in heterozygotes were 54.0%, 62.4%, and 79.2% of normal, respectively. No evidence of CAD was observed in 10 heterozygotes 40 years of age or less; however, CAD was detected in 3 of 7 heterozygotes over 40 years of age, one of whom died at age 56 years of complications of myocardial infarction and stroke. The inheritance pattern in this kindred was autosomal codominant. ApoA-I isolated from a heterozygote had an isoelectric focusing pattern and amino acid composition similar to normal. Utilizing DNA isolated from two obligate heterozygotes, no abnormalities in the apoA-I or apoC-III genes were detected by Southern blot analysis utilizing specific probes following restriction enzyme digestion. The data indicate that familial apolipoprotein A-I and C-III deficiency, variant II, is similar to variant I (described by Norum et al. 1982. N. Engl. J. Med. 306: 1513-1519), but differs at the clinical level (lack of xanthomas), the biochemical level (lack of detectable apoA-I, lower apoA-II level), and at the gene level.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Dietary omega-3 fatty acids prevent carbohydrate-induced hypertriglyceridemia.

Dietary fish oils rich in omega-3 fatty acids are remarkably hypotriglyceridemic in both normal and hypertriglyceridemic subjects. This present study was designed to examine the hypothesis that dietary fish oils could prevent the usual sharp increase in plasma triglyceride and very low-density lipoprotein (VLDL) levels that occur physiologically after the induction by a high-carbohydrate diet. Seven healthy volunteers consumed three experimental liquid formula diets: the baseline diet (45% fat, 10% protein, 45% carbohydrate) and two high-carbohydrate diets (15% fat, 10% protein, 75% carbohydrate), one as a control diet and the other containing fish oil. The baseline and control dietary fats were a mixture of peanut oil and cocoa butter, whereas the fish oil diet contained high levels of omega-3 fatty acids. The plasma triglyceride levels rose from 105 mg/dL during baseline diet to 194 mg/dL during the high-CHO control diet (P less than 0.005). VLDL triglyceride levels increased from 69 to 156 mg/dL (P less than 0.005) and VLDL cholesterol from 18 to 34 mg/dL (P less than 0.005). When fish oil was substituted for the control fats, plasma triglyceride levels fell from 194 to 75 mg/dL (P less than 0.005), VLDL triglyceride and cholesterol levels were reduced from 156 to 34 mg/dL (P less than 0.005) and from 34 to 12 mg/dL (P less than 0.005), respectively. These effects were noted by two to three days after beginning the fish oil diet. Thus, dietary omega-3 fatty acids from fish oil rapidly and markedly reduced VLDL triglyceride levels even in the face of a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Knowledge of and attitudes toward coronary heart disease and nutrition in Oregon families.

In an effort to examine knowledge about heart disease and nutrition and attitudes toward dietary change, 754 women and 125 men were interviewed. The majority of respondents recognized the association between coronary heart disease and various risk factors, including dietary cholesterol. Although they acknowledged the value of dietary change in reducing risk, the majority denied that the food they now eat increases their risk for heart disease, which suggests a lack of perception about possible benefits to be derived from dietary change. The importance of addressing perceived barriers to change is discussed.

Adult↗

Type A behavior, attentional style, and symptom reporting among adult men and women.

Type A behavior and its components (measured on the JAS) were examined in relation to attentional style and symptom reporting in 294 healthy adult men and women. The results showed that for both men and women the JAS Type A, Job Involvement, and Hard Driving factors were all associated with self-reported attentional effectiveness as measured by the Nideffer Test of Attentional and Interpersonal Style. However, a fourth JAS factor, Speed and Impatience, was associated with Nideffer measures of cognitive overload. For both men and women, the Type A, Speed and Impatience, and Hard Driving factors were all positively associated with the number of medical and psychological symptoms reported on the Cornell Medical Index. In addition, acute psychological distress (Hopkins SCL-90R) was associated with Type A behavior for men and with Speed and Impatience for both sexes. Attention differences did not account for the observed positive relationships between Type A factors and symptom reporting with one exception; attentional overload (internal) appeared to partially explain the relationships between symptom reporting and Speed and Impatience in women. In summary, Type As described themselves as having a broader attentional focus and reported more naturally occurring physical and psychological symptoms than did Type Bs.

Adult↗

Will dietary omega-3 fatty acids change the composition of human milk?

The most abundant long-chain polyunsaturated fatty acid in brain and retinal lipids is docosahexaenoic acid (DHA, C22:6 omega 3). It becomes incorporated into nerve tissues mostly in utero and during the 1st yr of life. DHA is derived in humans either performed in the diet or by hepatic synthesis from dietary linolenic acid (C18:3 omega 3). Since human milk contains DHA, this study was designed to see if increased dietary DHA would be reflected in a higher DHA content in human milk. Eight lactating women were given supplements of a fish oil concentrate rich in omega-3 fatty acids, including DHA (11% of fatty acids). Six women took 5 g/day of fish oil for 28 days; five women consumed 10 g/day for 14 days; and one woman consumed 47 g/day for 8 days. Each intake level of fish oil produced significant dose-dependent increases in the DHA content of milk and plasma. Base-line DHA levels in milk were 0.1 +/- 0.06% of total fatty acids. Five g/day of fish oil raised the levels to 0.5 +/- 0.1% (p less than 0.001); 10 g/day raised DHA levels to 0.8 +/- 0.1% (p less than 0.001); and 47 g/day produced DHA levels of 4.8%. The results of this study indicated that relatively low intakes of dietary DHA significantly elevated milk DHA content. This would clearly elevate the infant's DHA intake and might have implications for brain and retinal development.

Adult↗

Hypercholesterolemia associated with alpha-1 antitrypsin deficiency and hepatitis: lipoprotein and apoprotein determinations, sterol balance and treatment.

Lipid metabolism was investigated in a 4-year-old boy with alpha-1 antitrypsin deficiency (ZZ phenotype) and liver disease. Plasma cholesterol and triglyceride levels were 604 mg/dl and 336 mg/dl respectively. Both parents had normal plasma lipids. Lipoprotein X was present at a concentration of 855 mg/dl and levels of apoproteins A-I, A-II, B and C-III were elevated. The plasma free fatty acid pattern was normal. Plasma cholesterol esterification was greatly depressed. Cholesterol absorption on two occasions was reduced about 13% compared with adult controls. Neutral and total steroid excretion was normal with increased excretion of bile acids. A low-cholesterol, low-fat diet reduced plasma cholesterol to 374 mg/dl and triglyceride to 236 mg/dl in two months. Cholesterol and lipoprotein X concentrations were elevated far out of proportion to the severity of the liver disease (total bilirubin 3.7 mg/dl, SGOT 280 IU/L). This suggests that lipoprotein metabolism in patients with this disorder is unusual and may differ from the derangements seen in other forms of liver disease.

Apolipoproteins↗

The effects of familial relationships, age, body weight, and diet on blood pressure and the 24 hour urinary excretion of sodium, potassium, and creatinine in men, women, and children of randomly selected families.

Two hundred thirty-three randomly selected families provided a population for studying the effects of familial relationships, age, diet, body weight, and urinary electrolyte excretion on blood pressure. There was a strong familial component for urinary sodium, potassium, and creatinine excretion and for systolic blood pressure. In individuals, age, heart rate, and body weight were independently related to blood pressure. In women, urinary sodium and potassium levels were related to diastolic blood pressure. These individual relationships persisted when age was accounted for but were no longer significant after adjusting for both age and body weight, suggesting that heavier people eat more food, which in our culture means greater sodium intake. In fact, our randomly selected families were eating as much sodium (130 to 170 meq/day) and as little potassium (50 to 70 meq/day) as consumed by Americans several decades ago. Furthermore, this study again documented the rise in blood pressure with age, which may represent the effect of environmental influences on blood pressure over time. The familial aggregation of urinary sodium, potassium, and creatinine excretion, along with the well-established familial aggregation of body weight, emphasizes the importance of the entire family in the treatment and prevention of hypertension.

Adolescent↗

Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys.

Linolenic acid (18:3 omega 3) is a dietary precursor of docosahexaenoic acid (22:6 omega 3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary omega-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets low in omega-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from birth. A control group of mothers and infants received similar diets but supplying ample linolenic acid. In the plasma phospholipids of deficient infants, linolenic acid was generally undetectable and 22:6 omega 3 levels became progressively depleted, falling from 42% of control values at birth to 21% at 4 wk, 9% at 8 wk, and 6% at 12 wk of age. In the other plasma lipid classes, 22:6 omega 3 was undetectable by 12 wk. The visual acuity of the deprived infants, as measured by the preferential looking method, was reduced by one-fourth at 4 wk (P less than 0.05) and by one-half at 8 and 12 wk (P less than 0.0005) compared with control infants. These results suggest that omega-3 fatty acids may be an essential nutrient, and that 22:6 omega 3 may have a specific function in the photoreceptor membranes of the retina.

Aging↗

Suppression by diets rich in fish oil of very low density lipoprotein production in man.

The highly polyunsaturated fatty acids in fish oils lower the plasma triglyceride concentration. We have studied the effect of a diet rich in fish oil on the rate of production of the triglyceride-transporting very low density lipoprotein (VLDL). Seven subjects, five normal and two with hypertriglyceridemia received up to 30% of daily energy needs from a fish oil preparation that was rich in eicosapentaenoic acid and docosahexaenoic acid, omega-3 fatty acids with five and six double bonds, respectively. Compared with a diet similarly enriched with safflower oil (in which the predominant fatty acid is the omega-6 linoleic acid, with two double bonds), the fish oil diet lowered VLDL lipids and B apoprotein concentrations profoundly. High density lipoprotein lipids and A1 apoprotein were also lowered, but the effect on low density lipoprotein (LDL) concentration was inconsistent. The daily production or flux of VLDL apoprotein B, calculated from reinjected autologous 125I-labeled lipoprotein, was substantially less in six subjects studied after 3 wk of fish oil, compared with after safflower oil. This effect on flux was more consistent than that on the irreversible fractional removal rate, which was increased in the four normolipidemic but inconsistent in the hypertriglyceridemic subjects. This suggests that fish oil reduced primarily the production of VLDL. The daily production of VLDL triglyceride, calculated from the kinetics of the triglyceride specific radioactivity-time curves after [3H]glycerol was injected, also showed very substantial reductions in five subjects studied. The marked suppression in VLDL apoprotein B and VLDL triglyceride formation was found not to be due to diminished plasma total free fatty acid or plasma eicosapentaenoic flux, calculated during constant infusions of [14C]eicosapentaenoic acid and [3H]oleic acid in four subjects. In two subjects there was presumptive evidence for substantial independent influx of LDL during the fish oil diet, based on the precursor-product relationship between the intermediate density lipoprotein and LDL apoprotein B specific radioactivity-time curves.

Adult↗

Sterol composition of normal human bile. Effects of feeding shellfish (marine) sterols.

To examine the sterol composition of normal human bile and the effects of dietary components from certain shellfish upon bile composition, we fed 7 subjects diets rich in shellfish for 2 wk following a typical American diet. The total cholesterol, bile acid, and phospholipid, and the individual sterols and bile acids of the bile samples during each dietary period were measured. In the bile of 7 subjects consuming the typical American diet, nine different neutral sterols, in addition to cholesterol, were identified. Similar patterns of these sterols have been found in human gallstones and in plasma after shellfish feeding. The five shellfish sterols (22-dehydrocholesterol, 24-methylene cholesterol, brassicasterol, isofucosterol, and a C-26 sterol) increased from 0.3% to a total of 5.2% (p less than 0.001) of total sterols. A comparison of the ratios of various shellfish sterols to cholesterol in plasma and in bile suggested selectively greater excretion of shellfish sterols relative to cholesterol. Our data demonstrated that human bile contains a mixture of sterols and that its sterol composition can be readily altered by dietary changes. The lithogenicity of the bile based on the ratio of cholesterol, bile acids, and phospholipids, and the bile acid composition was not affected by the presence of shellfish sterols. However, since some of these sterols occur in human gallstones, their lithogenic capacity cannot be ruled out.

Adult↗

Plasma lipid and lipoprotein profiles of cigarette smokers from randomly selected families: enhancement of hyperlipidemia and depression of high-density lipoprotein.

Cigarette smoking is an important risk factor for coronary heart disease. However, its mechanisms of action remain to be fully explored. The hypothesis of the present study is that 1 mechanism whereby cigarette smoking enhances coronary disease might result from its effects upon the plasma lipids. Accordingly, we measured the plasma lipids and lipoproteins in cigarette smokers, exsmokers and nonsmokers from 233 randomly selected American families. Cigarette smokers (male and female) had significantly lower high-density lipoprotein levels and higher very low density lipoprotein and plasma triglyceride levels than the exsmokers and nonsmokers. The plasma levels of lipids and lipoproteins were related to the number of cigarettes smoked per day. Heavier cigarette smokers (greater than 25 cigarettes/day) had significantly lower high-density lipoprotein levels and significantly higher very low density lipoprotein total cholesterol and plasma triglyceride levels than those who smoked less than 25 cigarettes/day, nonsmokers and exsmokers. The lipid and lipoprotein values of those who smoked less than 15 cigarettes/day were similar to those of exsmokers and nonsmokers. Inasmuch as exsmokers had levels of plasma lipids and lipoproteins similar to those of nonsmokers, these findings add another health-enhancing benefit to the cessation of smoking.

Adolescent↗

Normocholesterolemic tendon xanthomatosis with overproduction of apolipoprotein B.

This report describes a 46-yr-old man with normocholesterolemic tendon xanthomatosis. He had severe bilateral xanthomas of Achilles tendons and small lesions on patellar tendons; biopsy of the latter revealed a fibroxanthoma of high cholesterol content. He did not have clinical evidence of atherosclerotic disease. The patient's total cholesterol (TC) and triglycerides (TG) were 245 and 258 mg/dl, respectively. LDL-TC was 168 mg/dl and HDL-TC was 32 mg/dl. VLDL consisted mainly of small particles (SfO 20-100) which were unusually rich in apolipoproteins B and E (and low in apo Cs). Plasma LDL-apo B was not increased (85-120 mg/dl), but VLDL-apo B was distinctly elevated (58 mg/dl). The synthesis rate of apoLDL (29.9 mg/kg/d) was increased markedly compared to a matched control (13.9 mg/kg/d) and to a patient with familial hypercholestrolemia (15.9 mg/kg/d). The concentration of apoLDL in our patient was not increased; this was because of an associated high FCR (0.484 day-1). His HDL was relatively low in TC but high in TG, which caused an increase in HDL2b. The patient's xanthomata may have been the result of an overproduction of apo B possibly combined with a defect in HDL metabolism.

Apolipoproteins↗

The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: salmon oil versus vegetable oils.

The lower plasma lipid levels and lower incidence of atherosclerotic diseases in Greenland Eskimos suggested that the unusual fatty acids present in their diet of seal and fish may be anti-atherogenic. These fatty acids are eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids and are of the omega-3 fatty acid family. We have compared a salmon oil diet containing high levels of these unique fatty acids to a control diet high in saturated fat and to a vegetable oil diet high in linoleic acid (C18:2). All diets contained 40% of the total calories as fat and 500 mg of cholesterol; they differed only in fatty acid composition. In 4 wk the salmon oil diet reduced plasma cholesterol levels from 188 to 162 mg/dl (p less than 0.001) and triglyceride levels from 77 to 48 mg/dl (p less than 0.005). LDL and VLDL cholesterol levels changed from 128 to 108 and 13 to 8 mg/dl (p less than 0.005), respectively. HDL cholesterol levels did not change. The vegetable oil diet caused similar decreases in cholesterol levels but did not lower triglyceride levels. The omega-3 fatty acids comprised up to 30% of the total fatty acids in each plasma lipid class after the salmon diet. Fish oils contain fatty acids which may be metabolically unique and potentially useful in the control of both hypercholesterolemia and hypertriglyceridemia.

Adult↗

Effects of saturated, monounsaturated, and omega-6 polyunsaturated fatty acids on plasma lipids, lipoproteins, and apoproteins in humans.

The effects of dietary fats on plasma cholesterol, serum lipoproteins, and apoproteins (Apo), A-1, B, and CIII were studied. Twelve men consumed three different cholesterol-free formula diets in which polyunsaturated and saturated fats were partially substituted (20% of calories) for monoenoic fats with a constant of 40% of calories from fat. Total cholesterol and low-density lipoprotein cholesterol dropped from base-line values of 166 and 103 to 133 and 81 mg/dl (sat), 127 and 71 mg/dl (mono), and 123 and 65 mg/dl (poly), respectively. High-density lipoprotein cholesterol changed very little from base-line values of 46 to 40 mg/dl (sat), 45 mg/dl (poly), and 43 mg/dl (mono). The plasma concentrations of ApoB declined from base-line values of 80.3 mg/dl to 54.6 mg (mono), 51.8 mg (poly), and 59.6 mg (sat) while Apo CIII and Apo AI did not show any changes. This study demonstrates that: 1) changes in dietary fat affect serum lipids, lipoproteins, and apoproteins even when consumed on a cholesterol-free diet, and 2) omega-6 polyunsaturated fat lowers low-density lipoprotein cholesterol, total cholesterol, and ApoB to a greater extent than monounsaturated or saturated fat, 3) consumption of a cholesterol-free formula diet results in significant decreases in the concentrations of total and low-density lipoprotein cholesterol in plasma when compared to values obtained on a mixed food home diet containing approximately 300 mg cholesterol/day.

Adult↗