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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 73 records · Page 4Linked to original sources
PubMed1993

Human cholesterol synthesis measurement using deuterated water. Theoretical and procedural considerations.

Human cholesterogenesis is measurable as the rate of incorporation of deuterium derived from deuterium oxide (D2O) within the body water pool into plasma or erythrocyte cholesterol pools. Oral D2O equilibrates across body water, thus enabling extracellular sampling of pools (such as urine) to serve as accurate indicators of intracellular deuterium enrichments at the point of synthesis. Required doses of D2O fall below the threshold associated with negative side effects. Deuterium/carbon incorporation ratios into cholesterol during biosynthesis have been established that are applicable in humans. Models using unconstrained and constrained curve fitting permit improved flexibility in interpretation of deuterium-uptake kinetics. However, sample-size restrictions presently limit the ability of the technique to examine the kinetics within individual lipoprotein species. Correction of enrichment data for proton exchange during combustion and reduction phases of sample preparation is an additional important procedural concern. In summary, the deuterated-water procedure is a useful tool in studies of human cholesterol synthesis that offers the advantages of short measurement interval, relative noninvasiveness, and provision of a direct index of synthesis in comparison with other available techniques.

Animals↗
PubMed1993

Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates.

BACKGROUND: Because of discrepant claims regarding the relative biological effects of n-3 fatty acids (n-3FAs), we have concurrently measured the effects of dietary n-3FAs on blood and vascular lipid composition, hemostatic function, blood thrombotic responses, vascular thrombus formation, and vascular lesion formation in baboons. METHODS AND RESULTS: Dietary n-3FAs displaced n-6FAs in plasma, platelets, blood vessels, and corresponding urinary eicosanoid metabolites (p < 0.01 in all cases) within weeks after initiation of a semipurified diet containing 1 g/kg per day n-3FA-ethyl ester concentrate (composed of two thirds eicosapentanoic acid and one third docosahexanoic acid). Coincidentally, platelet hemostatic function became minimally impaired (template bleeding times prolonged from 4.3 +/- 0.5 minutes to 7.6 +/- 1.3 minutes, p = 0.039); concentrations of collagen producing half-maximal platelet aggregation increased (from 6.4 +/- 2.1 to 8.5 +/- 2.5 micrograms/mL, p = 0.045); and tissue factor expression by endotoxin-stimulated blood monocytes fell (from 6.5 +/- 1.2 to 1.7 +/- 0.14 mU/10(6) cells, p < 0.005). Dietary n-3FAs decreased deposition of platelets onto thrombogenic segments of Dacron vascular graft incorporated into chronic exteriorized femoral arteriovenous (AV) shunts, a thrombotic process resistant to the effects of both aspirin and heparin (111In-labeled platelet deposition decreased from 14.1 +/- 1.4 x 10(9) platelets/5-cm segment at 40-60 minutes with occlusion to 7.5 +/- 0.8 x 10(9) platelets/5-cm segment without occlusion; p < 0.001). Platelet deposition onto segments of endarterectomized homologous normal aorta in the AV shunts of n-3FA-treated animals was similarly reduced (from 4.4 +/- 0.9 to 1.8 +/- 0.4 x 10(9) platelets; p < 0.01). Dietary n-3FAs interrupted vascular thrombus formation at sites of surgical carotid endarterectomy (platelet deposition, 1.5 +/- 0.4 versus 4.4 +/- 1.0 x 10(9) platelets in untreated controls; p < 0.001). Moreover, endarterectomized aortic segments (EASs) from n-3FA-treated donors exhibited little capacity to induce thrombus formation when tested in the AV shunts of control recipient animals (0.24 +/- 0.10 versus 4.4 +/- 0.90 x 10(9) platelets). However, in the converse crossover experiments, EASs from control animals actively accumulated platelets when studied in the AV shunts of n-3FA-treated animals (1.8 +/- 0.4 x 10(9) platelets; p < 0.01 versus n-3FA-treated EASs in shunts of normal animals). Dietary n-3FAs also abolished vascular lesion formation at sites of carotid endarterectomy 6 weeks after surgery (cross-sectional area of neointima 0.048 +/- 0.031 mm2 compared with 0.428 +/- 0.104 mm2 in control arteries; p = 0.010). CONCLUSIONS: In nonhuman primates, dietary n-3FAs in high doses eliminate both vascular thrombus formation and vascular lesion formation after mechanical vascular injury while largely sparing hemostatic function and modestly reducing blood thrombotic responses. These effects are attributed to selective n-3FA-dependent alterations in cellular membrane functions.

Animals↗
PubMed1993

Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.

BACKGROUND: For decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in the diets besides cholesterol and saturated fat. METHODS AND RESULTS: CHD death rates for men aged 55 to 64 years were derived from the World Health Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture Organization of the United Nations database. Forty countries at various levels of economic development and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol and saturated fat (Cholesterol-Saturated Fat Index [CSI]). The CSI was significantly and positively related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates. Countries with high CSIs had a wide range of CHD death rates. France, Finland, and other Western industrialized countries had similar CSIs. After adjusting for cholesterol and saturated fat, milk and many components of milk (butterfat, milk protein, calcium from milk, and riboflavin) and total calcium remained positively related to CHD mortality for all 40 countries. There were differences in the consumption of these foods and nutrients in France and Finland. Milk and butterfat (fat from milk, cream, cheese, and butter) consumption was higher in Finland than in France. The consumption of plant foods, recently shown to be protective against CHD (vegetables and vegetable oils containing monounsaturated and polyunsaturated fatty acids), was greater in France than in Finland. CONCLUSIONS: Over the years, France and Finland, with similar intakes of cholesterol and saturated fat, consistently have had very different CHD mortality rates. This paradox may be explained as follows. Given a high intake of cholesterol and saturated fat, the country in which people also consume more plant foods, including small amounts of liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of CHD mortality. On the other hand, milk and butterfat were associated with increased CHD mortality, possibly through their effects on thrombosis as well as on atherosclerosis.

Cholesterol, Dietary↗
PubMed1993

Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid.

Spermatozoa represent a tissue readily accessible for study after various exogenous perturbations. To characterize the lipid composition of monkey sperm and to establish a baseline from which dietary or pharmaceutical influences may then be evaluated, we collected semen samples from five rhesus monkeys by electroejaculation and analyzed the sperm for sterols, fatty acid composition, and the molecular species of the ethanolamine glycerophospholipids. Two sterols were identified: cholesterol, 41%, and desmosterol, 59% of total sterols. Desmosterol was found only in the free form. Cholesterol existed in three different forms: free, 60%; esterified, 20%; and sulfated, 20%. Docosahexaenoic acid (22:6, DHA) was almost the only n-3 fatty acid in sperm phospholipids, 24% of the total fatty acids. DHA was present mainly in phosphatidylcholine and phosphatidylethanolamine. Oleic and palmitic acids were the predominant monounsaturated and saturated fatty acids. The ethanolamine glycerophospholipids were separated into three subclasses: diacyl 49%, alkenylacyl 43%, and alkylacyl 8%. Thirteen molecular species were identified and quantified. The sn-1 position of these molecular species contained exclusively 16:0, 18:0, or 18:1. The sn-2 position contained n-3, n-6, and n-9, as well as saturated fatty acids. The molecular species having n-3 fatty acids in the sn-2 position contributed 43, 73, and 100% of the total in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. The presence of the unusual sterol, desmosterol, a cholesterol precursor not found in measurable quantities in any other tissue suggests an important functional and structural role for desmosterol in spermatozoa. The other unique lipids, cholesterol sulfate and the n-3 docosahexaenoic acid, may also have a significant role in the function of spermatozoa.

Animals↗
PubMed1992

Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study.

OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.

Adult↗
PubMed1992

Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks.

Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet-induced lowering of high levels of 22:6(n-3).

Analysis of Variance↗
PubMed1992

Postnatal deficiency of omega-3 fatty acids in monkeys: fluid intake and urine concentration.

Previous studies demonstrated increased fluid intake in rhesus monkeys exposed to combined prenatal and long-term postnatal (PRE+POST) dietary deficiency of omega-3 fatty acids. Here we determined the effect of dietary deficiency in omega-3 fatty acids occurring only prenatally (PRE) or only postnatally (POST). Water intake over 24 hours, water intake in 15-minute tests, and excretion of combined urine and feces over 24 hours were all about twice as great in POST as in PRE monkeys. Neither group preferred or avoided salt solutions compared to water in two-bottle tests. Serum electrolytes, total protein, and glucose were within the normal range, and both groups concentrated urine when deprived of water. Levels of all omega-3 fatty acids in red blood cells were greatly depressed in POST monkeys, while levels of omega-6 fatty acids were elevated or unchanged. These results confirm the effects of PRE+POST deficiency on fluid intake and demonstrate that postnatal deficiency by itself is sufficient for the effects.

Aging↗
PubMed1992

The Diet Habit Survey: a new method of dietary assessment that relates to plasma cholesterol changes.

The Diet Habit Survey was designed to identify eating habits and measure dietary changes made over time by 442 adults in the Family Heart Study, a coronary heart disease prevention project. Reliability was determined by test-retest analysis. Validity was assessed by comparison with 24-hour dietary recalls and by comparing changes in diet with changes in plasma cholesterol levels. At baseline, 89% of the subjects were classified as eating the current American diet (37% fat), 10% reported eating Diet 1 (30% fat), and 1% reported eating Diet 2 (25% fat). After 5 years of dietary intervention, the population's eating habits had shifted; 48% reported eating the current American diet, 37% reported Diet 1, 14% reported Diet 2, and 1% reported Diet 3 (20% fat). Significant plasma cholesterol lowering was associated with changes in Diet Habit Survey scores reflecting lower cholesterol and saturated fat and higher complex carbohydrate intakes. This questionnaire is an inexpensive, reliable, and valid instrument for rapid assessment of eating habits and diet composition and, thus, is an important new tool for dietetics researchers and practitioners.

Adult↗
PubMed1991

Changes in lipid and lipoprotein levels and body weight in Tarahumara Indians after consumption of an affluent diet.

BACKGROUND: Major new public health problems occur in developing countries as they become more affluent and change their traditional dietary patterns. To study this phenomenon in microcosm, we substituted an "affluent" diet for the traditional diet of a group of Tarahumara Indians, a Mexican people known to consume a low-fat, high-fiber diet and to have a very low incidence of risk factors for coronary heart disease. METHODS: Thirteen Tarahumara Indians (five women and eight men [including one adolescent]) consumed their traditional diet (2700 kcal per day) for one week, and were then fed a diet typical of affluent societies, which contained excessive calories (4100 kcal per day), total fat, saturated fat, and cholesterol, for five weeks. RESULTS: After five weeks of consuming the affluent diet, the subjects' mean (+/- SE) plasma cholesterol level increased by 31 percent, from 121 +/- 5 to 159 +/- 6 mg per deciliter (3.13 +/- 0.13 to 4.11 +/- 0.16 mmol per liter, P less than 0.001). The increase in the plasma cholesterol level was primarily in the low-density lipoprotein (LDL) fraction, which rose 39 percent, from 72 +/- 3 to 100 +/- 4 mg per deciliter (1.86 +/- 0.08 to 2.59 +/- 0.10 mmol per liter, P less than 0.001). High-density lipoprotein (HDL) cholesterol, usually low in this population, increased by 31 percent, from 32 +/- 2 to 42 +/- 3 mg per deciliter (0.83 +/- 0.05 to 1.09 +/- 0.08 mmol per liter). Consequently, the ratio of LDL to HDL levels changed little (2.25 with the base-line diet and 2.38 with the affluent diet). Plasma triglyceride levels increased by 18 percent, from 91 +/- 8 to 108 +/- 11 mg per deciliter (1.03 +/- 0.09 to 1.22 +/- 0.12 mmol per liter, P less than 0.05), with a significant increase in the very-low-density lipoprotein triglyceride fraction. All the subjects gained weight, with a mean increase of 3.8 kg (7 percent). CONCLUSIONS: When Tarahumara Indians from a population with virtually no coronary risk factors consumed for a short time a hypercaloric diet typical of a more affluent society, they had dramatic increases in plasma lipid and lipoprotein levels and body weight. If sustained, such changes might increase their risk of coronary heart disease.

Adolescent↗
PubMed1991

Increased intake of water and NaCl solutions in omega-3 fatty acid deficient monkeys.

We previously reported that long-term omega-3 fatty acid deficiency is associated with increased water intake in rhesus monkeys. To determine whether the increase was specific to water, intakes of salt solutions were measured in 15-minute single-bottle tests. Deficient monkeys drank at least twice as much of all NaCl concentrations as controls. Overall intake decreased as salt concentration increased. In 2-bottle preference tests, deficient monkeys again drank more total fluid but neither preferred nor avoided normal saline compared to controls. When deprived of water, deficient monkeys concentrated urine as well as controls, demonstrating that the increased intake was not a result of renal failure or diabetes insipidus. Omega-3 fatty acids have roles both in neural membrane function and in metabolism of prostaglandins and other eicosanoids. Omega-3 fatty acid deficiency may affect drinking through changes in one or both of these functions.

Animals↗
PubMed1991

Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans.

Five normolipemic subjects received three test meals containing 28 g n-3 (omega-3) fatty acids provided as 1) triglycerides, 2) ethyl esters, and 3) ethyl esters + 12 g olive oil. The control meal contained olive oil. When equivalent amounts of fat were given, the increase in chylomicron and plasma triglycerides was similar; n-3 fatty acid contents were also similar after n-3 fatty acid intake as ethyl esters or triglycerides. Ethyl esters alone were well absorbed and produced similar n-3 fatty acid responses in plasma triglycerides and chylomicrons. At 24 h after the n-3 fatty acid-containing meals, the fatty acid plasma concentration of these acids was similar. This study showed that n-3 fatty acids in fish oil given as ethyl esters or triglycerides were equally well absorbed. Eicosapentaenoic and docosahexaenoic acids were also equally absorbed.

Absorption↗
PubMed1991

High levels of the (n-6) fatty acid 4,7,10,13,16-docosapentaenoate in the retinas of rabbits are reduced by feeding dietary fish oil from birth to adult life.

High levels of 4,7,10,13,16-docosapentaenoic acid [22:5(n-6)], a fatty acid usually associated with (n-3) fatty acid deficiency, have been reported in the retina of young rabbits. We studied the fatty acid composition of the rabbit retina throughout development, from birth to adult life. We also attempted to modify the fatty acid composition of the retina by the feeding of fish oil, high in docosahexaenoic acid [22:6(n-3), DHA]. Female rabbits were fed either a control or 2% fish oil diet through pregnancy and the nursing period. Weaned rabbits received the mothers' diet. In the retinas of control rabbits, 22:5(n-6) represented 3.7% of total fatty acids at birth, reached 15.1% at 9 wk and declined to 5.6% in adult rabbits. However, 22:6(n-3) increased steadily from birth onwards, from 3.8% of total fatty acids at birth to 19.6% in adults. Dietary fish oil increased the trace concentrations of long-chain (n-3) fatty acids in the milk to 10% of total fatty acids, reduced retinal 22:5(n-6) to less than or equal to 0.5% at all ages, and increased DHA to approximately 30% by 9 wk. Retinal phosphatidylethanolamine was even more sensitive to the impact of the fish oil diet, with DHA levels in newborn rabbits rising from 10% (control diet) to 43% of total fatty acids. These results demonstrated that 22:5(n-6) in the normal rabbit retina remains elevated (compared with other species) at all ages even as retinal DHA increases. The great increase of DHA in newborns whose mothers were fed fish oil suggests placental transfer of DHA and incorporation into retinal lipids.

Animals↗
PubMed1991

Sex differences in high density lipoprotein cholesterol among low-level alcohol consumers.

The purpose of this study was to examine high density lipoprotein cholesterol (HDL-C) levels in a sample of community-living women and men who consumed 1 drink of alcohol/day or less. Self-reports of alcohol consumption and clinical assessments of plasma lipid and lipoprotein levels were obtained twice, at 12 months apart. Among men, consumption of 1 drink/day or less was unrelated to levels in HDL-C. In contrast, among women alcohol consumption throughout this relatively low consumption range was positively associated with HDL-C levels. These findings indicate that the association of alcohol and higher levels of HDL-C may occur at lower intakes of alcohol in women than in men.

Adult↗
PubMed1991

The incorporation of n-3 and n-6 essential fatty acids into the chick embryo from egg yolks having vastly different fatty acid compositions.

The effect of egg yolk fatty acid composition on essential fatty acid utilization by the developing chick embryo was studied by feeding laying hens a fat-free diet supplemented with oils containing widely divergent contents of the essential n-6 and n-3 fatty acids. A control hen was fed a commercial feed for laying hens. The diets contained 20 to 4370 mg/100 g n-3 fatty acids and 360 to 8020 mg/100 g n-6 fatty acids. Fertile eggs were collected in pairs: one was incubated and the other served as an unincubated control. The fatty acid content of the unincubated egg and the newly hatched chick from each pair was compared. Some 50% of the total fatty acids in the egg yolk were incorporated into the tissues of the newly hatched chick. Regardless of diet, more yolk n-6 fatty acids were incorporated into the chick compared to saturated or monounsaturated fatty acids. The percentage of incorporation especially increased from the eggs containing relatively low amounts of n-6 fatty acid. The percentage of incorporation of n-3 fatty acids was similar to that of saturated and monounsaturated fatty acids when n-3 fatty acids were plentiful in the egg yolk, but increased significantly when n-3 fatty acids were low in the eggs. There was a generally linear relationship between essential fatty acids in the egg and in the chick, although levels of docosahexaenoic acid [DHA; 22:6(n-3)] in the brain did not respond proportionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Lymphadenopathy associated with severe hypertriglyceridemia.

The clinical recognition of diffuse lymphadenopathy generates a variety of important differential diagnostic considerations. We describe a woman with severe hypertriglyceridemia (type V hyperlipidemia) associated with diffuse lymphadenopathy. This association has not been described previously and should be included in the differential diagnosis of diffuse lymphadenopathy.

Female↗