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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 37 records · Page 2Linked to original sources
PubMed1998

Eye findings in 8 children and a spontaneously aborted fetus with RSH/Smith-Lemli-Opitz syndrome.

We evaluate the ophthalmologic findings in 8 children with RSH/Smith-Lemli-Opitz syndrome (SLOS) and document abnormal concentrations of cholesterol and cholesterol precursors in the ocular tissues in a case of SLOS. The most common ophthalmologic finding was blepharoptosis, which was found in 6 of 8 patients, with the severity ranging from mild to moderate. None of the patients in the present study demonstrated cataracts; none had amblyopia from blepharoptosis. One patient had a right hypertropia with overaction of the inferior oblique muscle. This patient also had optic atrophy and a second patient had bilateral optic nerve hypoplasia. The importance of these findings to the visual function remains to be defined. Sterol analysis from ocular tissues of an aborted fetus with SLOS showed increased 7- and 8-dehydrocholesterol and a low cholesterol concentration in the retinal pigment epithelium, lens, cornea, and sclera. Routine ophthalmologic examination is indicated in SLOS because of the high incidence of abnormalities, most likely due to the abnormal synthesis of cholesterol and cholesterol precursors in the ocular tissues of these patients, as evidenced by sterol analysis of the ocular tissues in a case of SLOS.

Child, Preschool↗
PubMed1998

Premenopausal black women have more risk factors for coronary heart disease than white women.

Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 +/- 9.2 vs 29.0 +/- 9.4 kg/m2, p = 0.021), and higher systolic (124 +/- 17 vs 115 +/- 14 mm Hg, p <0.0001) and diastolic (79 +/- 14 vs 75 +/- 11 mm Hg, p = 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 +/- 31.3 mg/dl) than in the white women (19.2 +/- 23.7 mg/dl, p <0.0001). The plasma total homocysteine level was also higher in the black women (8.80 +/- 3.38 vs 7.81 +/- 2.58 micromol/L, p = 0.013). The black women, however, had lower plasma triglyceride levels (0.91 +/- 0.46 vs 1.22 +/- 0.60 mmol/L, p <0.0001), and a trend toward higher high-density lipoprotein (HDL) cholesterol levels (1.37 +/- 0.34 vs 1.29 +/- 0.31 mmol/L, p = 0.064) than the white women. Plasma total and low-density lipoprotein (LDL) cholesterol levels were similar, despite a greater consumption of saturated fat and cholesterol by the black women. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, premenopausal black women had a higher mean body mass index, blood pressure, lipoprotein(a), and plasma total homocysteine level, and a greater consumption of saturated fat and cholesterol than white women. These differences in coronary risk factors may place the black women in our study at increased risk for CHD compared with the white women.

Adolescent↗
PubMed1998

Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol Delta7-reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol Delta7-reductase. We cloned cDNA encoding a human sterol Delta7-reductase (DHCR7) on the basis of its homology with the sterol Delta7-reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta7-reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol Delta7-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS.

Alleles↗
PubMed1998

Acute effects of dietary fatty acids on the fatty acids of human milk.

Although it is known that the fatty acid profile of human milk is altered by diet, the rapidity with which this occurs has not been addressed. We hypothesized that after absorption the fatty acids of a given meal would be transferred rapidly from the chylomicrons of the blood into human milk. Fourteen lactating women drank six test formulas, each containing a different fat: menhaden oil, herring oil, safflower oil, canola oil, coconut oil, or cocoa butter. The subjects collected a midfeeding milk sample before consuming the breakfast test formula and additional samples at 6, 10, 14, and 24 h and then once daily for 4-7 d. Fatty acids of special interest included eicosapentaenoic and docosahexaenoic acids from menhaden oil, cetoleic acid from herring oil, linoleic acid from safflower oil, linolenic acid from canola oil, lauric acid from coconut oil, and palmitic and stearic acids from cocoa butter. Each of these fatty acids increased significantly in human milk within 6 h of consumption of the test formulas (P < 0.001). Maximum increases occurred 10 h after safflower oil; 14 h after cocoa utter, coconut oil, canola oil, and menhaden oil (eicosapentaenoic acid); and 24 h after herring oil and menhaden oil (docosahexaenoic acid). All of these fatty acids remained significantly elevated in milk (P < 0.05) for 10-24 h, except for docosahexaenoic acid, which remained significantly elevated for 2 d, and eicosapentaenoic acid, which remained elevated for 3 d. These data support the hypothesis that there is a rapid transfer of dietary fatty acids from chylomicrons into human milk.

Adult↗
PubMed1998

Uneven distribution of desmosterol and docosahexaenoic acid in the heads and tails of monkey sperm.

Previously we demonstrated high concentrations of desmosterol and docosahexaenoic acid (DHA, 22:6 n-3) in monkey testes and sperm. Desmosterol, a cholesterol precursor, is not present elsewhere in the body. High concentrations of DHA are found elsewhere only in the retina and brain. To examine the distribution of these compounds in the heads and tails of sperm, we separated them and determined their sterol, fatty acid, and phospholipid molecular species composition. Desmosterol predominated in tails (134.4 vs. 1.7 microg/10(9) cells in heads). The cholesterol content was also greater in the tails (66.2 vs. 30.3 microg/10(9) cells in heads). Sperm tails had more polyunsaturated fatty acids than the heads (34.1 vs. 12.1% of total fatty acids) which resulted mainly from the higher contents of DHA (19.6 vs. 1.1%) and arachidonic acid (20:4 n-6) (6.4 vs. 1.6%) in the tails. These differences in fatty acid composition occurred mainly in phospholipids: phosphatidyl choline and phosphatidyl ethanolamine for n-3 fatty acids and phosphatidyl serine and cardiolipin for n-6 fatty acids. Fifteen phospholipid molecular species were identified. Sperm tails had more molecular species containing unsaturated fatty acids than the heads. Our results reveal the large differences in membrane lipid composition between the heads and tails of sperm. Most (99%) of the desmosterol and DHA in sperm is located in the tail. These differences may be responsible for the different functions of these two components of sperm. The large number of double bonds in DHA, six, and in desmosterol, two, may contribute to the membrane fluidity necessary for the motility of the sperm tails.

Animals↗
PubMed1997

Are fish oils beneficial in the prevention and treatment of coronary artery disease?

The n-3 fatty acids of fish and fish oil have great potential for the prevention and treatment of patients with coronary artery disease. Unlike many of the pharmaceutical agents used in patients with coronary artery disease that have just a single mechanism of action, the eicosapentaenoic and docosahexaenoic acids of fish oil have multifaceted actions. One of their most important effects is the prevention of arrhythmias, with documentation derived from experiments in cultured myocytes, experiments in animals, epidemiologic correlations, and clinical trials. Especially important is the ability of these n-3 fatty acids to inhibit ventricular fibrillation and consequent cardiac arrest. Eicosapentaenoic acid has several antithrombotic actions, particularly in inhibiting the synthesis of thromboxane A2, the prostaglandin that causes platelet aggregation and vasoconstriction. Fish oil retards the growth of the atherosclerotic plaque by inhibiting both cellular growth factors and the migration of monocytes. The n-3 fatty acids promote the synthesis of the beneficial nitric oxide in the endothelium. Experiments in humans indicate a profound hypolipidemic effect of fish oil, especially lowering of plasma triacylglycerol. Both very-low-density lipoprotein production and apolipoprotein B synthesis are inhibited by fish oil. Finally, fish oil has a mild blood pressure-lowering effect in both normal and mildly hypertensive individuals. These composite effects suggest a prominent therapeutic role for fish oil in the prevention and treatment of coronary artery disease.

Animals↗
PubMed1997

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Anthropometry↗
PubMed1997

Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels.

The factors responsible for the variability in plasma leptin levels observed among individuals with similar body compositions remain unclear. To examine the impact of dietary variables, we compared the changes in leptin levels induced by fasting and dietary fat restriction with the expected decrease following a significant loss in adipose mass. A 21.4 +/- 3.7% weight loss led to a 76.3 +/- 8.1% decrease in mean plasma leptin level (25.2 +/- 9.3 to 6.1 +/- 3.4 ng/mL, P = 0.0001) in a group of 9 obese males. Despite a weight loss of only 2.6 +/- 0.8%, mean plasma leptin levels fell by 61.9 +/- 25.2% (8.5 +/- 4.5 to 2.4 +/- 0.5 ng/mL, P < 0.01) in 7 nonobese females subjected to 3 days of fasting. Leptin levels in fasted subjects returned to baseline within 12 h of refeeding. Individual high- and low-fat meals given to 19 subjects after an overnight fast had no effect on plasma leptin levels. Reduction in dietary fat content from 37-10% of total calories for 7 weeks was also without effect on plasma leptin levels in these subjects. We conclude that plasma leptin levels primarily reflect total adipose mass, rather than meal consumption or dietary energy source, but that the reduction in leptin levels with ongoing fasting is disproportionate to the reduction in adipose mass. The ability of fasting to deactivate this presumed physiological satiety system may have been advantageous in environments characterized by rapid changes in food availability.

Adult↗
PubMed1997

Biochemical markers for puberty in the monkey testis: desmosterol and docosahexaenoic acid.

We previously reported that the sperm of rhesus monkeys and humans uniquely contain large amounts of desmosterol not found in other tissues and have a high concentration of the highly polyunsaturated n-3 fatty acid, docosahexaenoic acid (22:6 n-3). However, the lipid composition of the testis, from which sperm originate, is unknown. During puberty, the testis undergoes remarkable morphological changes as testosterone levels rise and sperm production begins. We hypothesized that testicular maturation might also involve dramatic changes in lipid composition. Accordingly, we characterized the sterol and fatty acid composition of the testis of rhesus monkeys throughout the lifespan, from birth to old age. Although the cholesterol content in the testis remained relatively unchanged throughout life, the desmosterol content first decreased from 59 microg/g in infants to 6 microg/g in prepubertal monkeys, increased to 83 microg/g during puberty, and reached a plateau of 248 microg/g in the young adult, where it remained into old age. The polyunsaturated fatty acid composition of the testis also changed markedly. Docosahexaenoic acid (22:6 n-3) increased from 5.1% of total fatty acids in infants and juveniles to 18.1% in postpubertal young adults. Although some n-6 fatty acids, arachidonic (20:4 n-6) and linoleic (18:2 n-6), decreased from 16.0% and 10.0% in prepubertal juveniles, respectively, to 7.1% and 3.3% in young adults; dihomogamma-linolenic acid (20:3 n-6), the precursor of 1 series PGs, increased greatly from 1.8% to 10.3%. Similar changes occurred in both membrane and storage lipids (phospholipids and triglycerides), respectively. After puberty, the testicular fatty acid pattern remained stable into old age. Our data demonstrated that puberty is accompanied by substantial changes in the lipid composition of the primate testis. These changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids may have important roles in sexual maturation.

Aging↗
PubMed1997

Sperm abnormalities in retinitis pigmentosa.

PURPOSE: To determine the fatty acid composition of erythrocytes and sperm, along with the functional characteristics of sperm, in patients with retinitis pigmentosa. Sperm and retinal cells share important homologies. Both are rich in the highly polyunsaturated fatty acid, docosahexaenoic acid (DHA, 22:6[n-3]), and both contain a structural component called the axoneme. Low concentrations of DHA in the retina of monkeys are known to cause visual impairment. Because blood levels of DHA in retinitis pigmentosa patients are less than normal, reduced DHA in the retina might contribute to the visual impairment characteristic of this disease. This study was conducted on the hypothesis that the sperm of retinitis pigmentosa patients might be abnormal and that these abnormalities might infer similar lipid and structural abnormalities of the retina. METHODS: The lipid composition of erythrocytes and sperm (fatty acids and sterols) and sperm function were analyzed in 26 patients with retinitis pigmentosa and in 8 healthy men. RESULTS: The sperm of patients with retinitis pigmentosa had a much lower DHA concentration, a lower desmosterol-to-cholesterol ratio, reduced motility, abnormal structure, and lower sperm counts compared with that in normal subjects. Usher's II patients exhibited the most pronounced reductions of DHA in sperm. Sperm DHA concentration was positively correlated to sperm motility, to sperm count, and to the desmosterol-to-cholesterol ratio. Lower erythrocyte DHA was also observed in retinitis pigmentosa patients. CONCLUSIONS: These results indicate that the sperm of patients with retinitis pigmentosa, particularly those with Usher's II, have an abnormal lipid composition that is associated with reduced motility. The possibility exists that these patients might have similar abnormalities in the DHA biochemistry of the retina. Sperm biochemistry and function may be a marker for this disease. A clinical trial of DHA in retinitis pigmentosa is suggested for future study.

Biomarkers↗
PubMed1997

Abnormal phospholipid molecular species of erythrocytes in sickle cell anemia.

As the lipid composition of cell membranes has significant effects upon cellular function, we hypothesized that the membranes of sickle cells might have a distorted lipid composition. Accordingly, we analyzed the molecular species of the choline and ethanolamine glycerophospholipids, the fatty acid composition of the total phospholipids and of the five major individual phospholipids of erythrocytes from 8 patients with sickle cell anemia and from 14 normal subjects. Of the 31 molecular species identified for each subclass of the glycerophospholipids, 12 were found to be distinctly abnormal. Sickle cells contained more molecular species with saturated and monounsaturated fatty acid at the sn-2 position and fewer molecular species with polyunsaturated fatty acids at the sn-2 position. The values ranged from 20 to 60% above or below normal values. In diacyl choline glycerophospholipids (outer membrane leaflet), sickle erythrocytes contained lower amounts of the 16:0-18:2 species and higher 16:0-18:1 and 16:0-16:0 species. In diacyl ethanolamine glycerophospholipid (inner membrane leaflet), sickle erythrocytes had lower amounts of 18:0-22:6; 16:0-22:4; 18:0-18:2; 18:1-18:2; and 18:1-20:3. In phosphatidylcholine and phosphatidylethanolamine, sickle erythrocytes contained less linoleic acid, less docosahexaenoic acid (30-40%) and more oleic and palmitic acids (20-30%) compared to normal erythrocytes. These same differences were seen also in the total phospholipids. Our data demonstrated distinct abnormalities of the phospholipid molecular species composition in the membrane lipids of sickle erythrocytes. These defects might have a role in one or more known metabolic abnormalities of sickle cell disease including cation imbalance, dehydration, disturbed membrane phospholipid asymmetry, and hypercoagulability. Furthermore, detailed information of the phospholipid molecular species composition of normal erythrocytes was provided.

Anemia, Sickle Cell↗
PubMed1996

Increased docosahexaenoic acid levels in human newborn infants by administration of sardines and fish oil during pregnancy.

In rhesus monkeys, maternal n-3 fatty acid deficiency during pregnancy produces infant monkeys deficient in n-3 fatty acids at birth. These results stimulated current experiments to find out if n-3 fatty acids from fish in the diets of pregnant women would influence the concentration of docosahexaenoic acid (DHA, 22:6 n-3) in the newborn human infant. Fifteen healthy pregnant women were enrolled to receive a 9-wk dietary supplementation of n-3 fatty acids from the 26th to the 35th wk of pregnancy. Sixteen pregnant women were not supplemented and served as controls. n-3 Fatty acid supplementation consisted of sardines and additional fish oil, which provided a total of 2.6 g of n-3 fatty acids per day (d) for the 9-wk period of supplementation. This included 1.01 g DHA. The end point of this study was the blood concentrations of DHA in the newborn infant. DHA in maternal red blood cells increased from 4.6% of total fatty acids to 7.15% at the end of the supplement period and at the time of delivery decreased (as expected) to 5.97% of total fatty acids. Maternal plasma showed a similar change from 2.12 to 3.51% of total fatty acids and then decreased to 2.35%. Levels of DHA in plasma and red blood cells of unsupplemented mothers did not change during the same time period. Levels of DHA in blood of newborn infants differed greatly in infants born from n-3-supplemented mothers compared with control infants. In red blood cells, DHA was 7.92% of total fatty acids compared with 5.86% (control infants). Plasma values showed a similar difference: 5.05% vs. 3.47% (controls). In n-3-supplemented infants, DHA concentrations were 35.2% higher than in control infants in red blood cells and 45.5% higher in plasma. These data indicate the importance of maternal dietary n-3 fatty acids and, in particular, maternal dietary DHA in promoting higher concentrations of DHA in the blood of the newborn infant.

Animals↗