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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 19 recordsLinked to original sources
PubMed2001

Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to dietary sterol intake.

BACKGROUND: Sterols in feces reflect sterols in the diet. In previous analyses of the fecal steroids in 1000-2000-y-old Native American coprolites found in the dry caves of Nevada, we showed that the sterol nucleus was stable. The coprolites provided useful dietary information. OBJECTIVE: In the present study, we analyzed the fecal steroids of an Eskimo mummy buried and frozen >500 y ago in Greenland. We compared these analyses with our findings in the coprolites from Nevada and in present-day stool samples from Tarahumara Indians of Mexico and Americans consuming low- and high-cholesterol diets. DESIGN: The fecal material from the Eskimo mummy was subjected to saponification, extraction, and digitonin precipitation. The sterols and bile acids were further analyzed by thin-layer chromatography and gas-liquid chromatography. RESULTS: The fecal steroids of the Greenland Eskimo mummy were remarkably similar to those of present-day stool samples. However, unlike in the stool of modern humans, a portion of the neutral steroids in the coprolite had been converted to sterol epimers. Instead of deoxycholic acid, 3alpha,6beta,12alpha-trihydroxycholanic acid was one of the major fecal bile acids. The plant sterol output in the coprolite was only 0.4% of the output of Americans consuming 250-400 mg plant sterols/d. The ratio of bile acid to cholesterol in the coprolite was similar to that in stool from Tarahumara Indians consuming a low-cholesterol diet. CONCLUSION: The sterol nucleus is stable when frozen. The analysis of coprolite showed that the young Eskimo woman had consumed a diet very low in plant sterols and moderate to low in cholesterol content.

Bile Acids and Salts↗
PubMed2001

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

OBJECTIVES: A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. METHODS: Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. RESULTS: Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants </=1250 g. When Spanish-speaking infants and twins were excluded from the analyses, the MacArthur Communicative Development Inventory revealed that control infants (LS means +/- SE, 94.1 +/- 2.9) had lower vocabulary comprehension at 14 months' CA than AA+DHA (fish/fungal) infants (100.6 +/- 2.9) or AA+DHA (egg-TG/fish) infants (102.2 +/- 2.8). There were no consistent differences in weight, length, head circumference, or anthropometric gains. CONCLUSION: These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.

Apgar Score↗
PubMed2001

Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids.

The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain episodes and ex vivo blood tests of thrombosis have been evaluated in patients with sickle cell disease (SCD) utilizing a double-blind, olive oil-controlled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as menhaden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA), and 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary olive oil (n = 5) experienced 7.1 pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression of platelet membrane P-selectin (CD62p; p <0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmin (PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2, D-dimer, and PAP (p <0.05, compared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that dietary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothrombotic activity in sickle cell disease.

Adult↗
PubMed2000

Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping.

We report the clinical and molecular data of 16 patients with RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) with varying phenotypic severity, for which we have identified mutations in both alleles. RSH/SLOS is an autosomal recessive malformation syndrome caused by mutations in the gene encoding the sterol Delta(7)-reductase. This protein catalyzes the reduction of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis via the Kandutsch-Russell pathway. In addition to previously reported mutations (T93M, L109P, G147D, W151X, T154M, R242C, A247V, T289I, IVS8-1G-->C, Y408H, and E448K), we have identified six previously undescribed mutations (321G-->C, W177R, R242H, Y318N, L341P, and C444Y). We also report rapid polymerase chain reaction (PCR)-based assays developed to detect four of the recurring mutations (T93M, W151X, V326L, and R404C) and six other RSH/SLOS mutations (321G-->C, L109P, T154M, T289I, Y318N, and L341P). The purpose of this article is to correlate detailed clinical information with molecular data in order to improve our understanding of the genotype-phenotype correlation of RSH/SLOS and to report the development of PCR-based assays that will allow more rapid mutation analysis.

Alleles↗
PubMed2000

Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition comprising multiple malformations, mental retardation, and growth failure, results from reduced activity of the final enzyme in cholesterol biosynthesis, 7-dehydrocholesterol Delta(7)-reductase (DHCR7). Reduced plasma and tissue cholesterol concentrations and accumulation of cholesterol precursors including 7-dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities. While it is still unclear what role these potentially toxic precursors have in the pathogenesis of this disorder, the accumulation of 7-DHC in the brain has been associated with impaired learning in rats and oxidized 7-DHC has been shown to induce growth retardation in cultured rat embryos. We hypothesized that supplemental dietary cholesterol would increase plasma cholesterol levels and suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS. After baseline sterol levels were obtained, patients were provided supplemental cholesterol as egg yolk. Plasma sterols were analyzed by capillary-column gas chromatography over time in four children with SLOS. When evaluated at 4-8 weeks after the initiation of cholesterol supplementation, there was a marked increase in mean plasma cholesterol, from 53 mg/dl to 82 mg/dl. While the percent of total sterols as 7-DHC decreased from 15% to 10%, there was no change in total plasma 7-DHC levels. However, when evaluated 35-90 weeks after the institution of cholesterol supplementation, mean plasma 7-DHC decreased, from 11.3 mg/dl to 3.5 mg/dl (-67%, P < 0.05), along with an increase in mean plasma cholesterol from 53 mg/dl to 114 mg/dl (+116%, P < 0.05). These results support the hypothesis that over time dietary cholesterol supplementation from egg yolk increases the plasma cholesterol levels and decreases levels of 7-DHC which may be toxic. These data have important therapeutic implications in the management of SLOS.

Cholesterol↗
PubMed2000

Importance of n-3 fatty acids in health and disease.

In the past 2 decades, views about dietary n-3 fatty acids have moved from speculation about their functions to solid evidence that they are not only essential nutrients but also may favorably modulate many diseases. Docosahexaenoic acid (22:6n-3), which is a vital component of the phospholipids of cellular membranes, especially in the brain and retina, is necessary for their proper functioning. n-3 Fatty acids favorably affect atherosclerosis, coronary heart disease, inflammatory disease, and perhaps even behavioral disorders. The 38 articles in this supplement document the importance of n-3 fatty acids in both health and disease.

Cardiovascular Diseases↗
PubMed2000

Cheek cell phospholipids in human infants: a marker of docosahexaenoic and arachidonic acids in the diet, plasma, and red blood cells.

BACKGROUND: Assessment of essential fatty acid status requires collection of blood or adipose tissue samples. However, these invasive techniques cannot always be used in studies involving infants, young children, or subjects from whom it is difficult to obtain blood. A body tissue that is easy to access is the buccal mucosa (cheek cells). OBJECTIVE: The objective was to investigate the degree to which fatty acids of cheek cells reflect the fatty acid content of plasma, red blood cells, and the diet. DESIGN: Thirty-one infants aged 12 mo were enrolled. Five infants were fed human milk and 26 infants received formulas that provided a wide range of arachidonic acid and docosahexaenoic acid (DHA) intakes. Cheek cells were collected on a small piece of gauze by gently swabbing the inside of the cheek 3 times. Lipids were extracted from the gauze and the phospholipid fatty acid content of the cheek cells was determined. RESULTS: Cheek cell DHA and arachidonic acid in phospholipids were significantly correlated with DHA and arachidonic acid in plasma [r = 0.61 (P < 0.001) and r = 0.37 (P <0.05), respectively], red blood cells [r = 0.58 (P < 0.001) and r = 0.37 (P < 0.05), respectively], and the diet [r = 0.65 (P < 0.001) and r = 0. 51 (P < 0.01), respectively]. CONCLUSIONS: Given these correlations and the ease and noninvasive nature of this technique, cheek cell fatty acids may serve as a marker of the essential fatty acid content, especially of DHA and arachidonic acid, in plasma, red blood cells, and the diet.

Analysis of Variance↗
PubMed2000

Plasma lipid and lipoprotein responsiveness to dietary fat and cholesterol in premenopausal African American and white women.

BACKGROUND: Premenopausal African American women have a 2-3 times greater incidence of coronary heart disease (CHD) than do white women. The plasma lipid responsiveness to dietary fat, which may be associated with CHD, has not been adequately studied in premenopausal African American or white women. OBJECTIVE: The objective of our study was to compare the effect of diet on fasting plasma lipids and lipoproteins and postprandial lipemia in premenopausal African American and white women. DESIGN: Thirteen African American and 9 white healthy premenopausal women were fed a low-fat, high-fiber diet and a high-fat, low-fiber diet for 4 wk each in a randomized crossover design. Fasting plasma lipid and lipoprotein concentrations and the 24-h plasma triacylglycerol response to a standard fatty test meal were measured at the end of each dietary period. RESULTS: Plasma total and LDL-cholesterol concentrations were higher after the high-fat, low-fiber diet in both white and African American women (P < 0.0001). The 24-h area under the plasma triacylglycerol curve after the test meal was lower after the low-fat diet than after the high-fat diet (P < 0.04). CONCLUSIONS: African American and white women had lower fasting plasma total and LDL-cholesterol concentrations and less postprandial lipemia after the low-fat than the high-fat diet. Diets low in total and saturated fat and cholesterol and high in fiber may reduce the risk of CHD by lowering fasting plasma total and LDL-cholesterol concentrations and by reducing the lipemic response to fatty meals.

Adolescent↗
PubMed2000

Premenopausal black women are uniquely at risk for coronary heart disease compared to white women.

Premenopausal black women have a two to threefold greater rate of coronary heart disease than premenopausal white women. This study was designed to provide greater insight into the reasons for this difference which is currently unclear. Coronary heart disease risk factors were compared in 100 black and 100 white, healthy premenopausal women, ages 18-45 years, and of relatively advantaged socioeconomic status. Compared to 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 mmol/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 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 cholesterol levels were similar. Black women consumed more saturated fat and cholesterol. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, compared to white women, black women had a higher mean body mass index, higher blood pressures, higher lipoprotein(a) and plasma total homocysteine levels, and greater consumption of saturated fat and cholesterol. The differences in coronary risk factors between these two premenopausal groups may explain the higher incidence of coronary heart disease in black women. (c) 2000 by CHF, Inc.

Journal Article↗
PubMed2000

Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol Delta(7)-reductase activity in chorionic villi.

Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition with multiple malformations, mental retardation, and growth failure, results from markedly reduced activity of the final enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol Delta(7)-reductase (DHCR7). We diagnosed SLOS in a fetus following intrauterine demise at 32 weeks' gestation. Chorionic villus (CV) sampling had been performed at 30 weeks because oligohydramnios and atrioventricular septal defect were noted on fetal ultrasound. On fetal post-mortem examination, a midline U-shaped soft palate cleft, micrognathia, postaxial polydactyly of the fingers with single transverse palmar creases bilaterally, and cutaneous syndactyly of toes two-three bilaterally suggested SLOS. We hypothesized that SLOS could be confirmed by analysis of tissue sterols despite extensive autolysis, and by measurement of enzyme activity in CV cells. Measurement of DHCR7 activity in CV cells was undertaken using ergosterol as a substrate. CV cells were unable to convert any ergosterol to brassicasterol after a 72 h incubation period while control CV cells reduced 12.6-71.8% of ergosterol to brassciasterol in a 72 h period. SLOS was confirmed by measurement of elevated 7-dehydrocholesterol (7-DHC) in the CV cells. Measurements of sterols were made in multiple fetal tissues. All tissues analysed showed elevated 7-DHC with markedly increased 7-DHC/cholesterol ratios.

Adult↗
PubMed2000

Sterol balance in the Smith-Lemli-Opitz syndrome. Reduction in whole body cholesterol synthesis and normal bile acid production.

The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol Delta(7)-reductase. This enzyme converts 7-dehydrocholesterol (7-DHC) to cholesterol in the last step in cholesterol biosynthesis. The pathology of this condition may result from two different factors: the deficiency of cholesterol itself and/or the accumulation of precursor sterols such as 7-DHC. Although cholesterol synthesis is defective in cultured SLOS cells, to date there has been no evidence of decreased whole body cholesterol synthesis in SLOS and only incomplete information on the synthesis of 7-DHC and bile acids. In this first report of the sterol balance in SLOS, we measured the synthesis of cholesterol, other sterols, and bile acids in eight SLOS subjects and six normal children. The diets were very low in cholesterol content and precisely controlled. Cholesterol synthesis in SLOS subjects was significantly reduced when compared with control subjects (8.6 vs. 19.6 mg/kg per day, respectively, P < 0.002). Cholesterol precursors 7-DHC, 8-DHC, and 19-nor-cholestatrienol were synthesized in SLOS subjects (7-DHC synthesis was 1.66 +/- 1.15 mg/kg per day), but not in control subjects. Total sterol synthesis was also reduced in SLOS subjects (12 vs. 20 mg/kg per day, P < 0.022). Bile acid synthesis in SLOS subjects (3.5 mg/kg per day) did not differ significantly from control subjects (4.6 mg/kg per day) and was within the range reported previously in normals. Normal primary and secondary bile acids were identified. This study provides direct evidence that whole body cholesterol synthesis is reduced in patients with SLOS and that the synthesis of 7-DHC and other cholesterol precursors is profoundly increased. It is also the first reported measure of daily bile acid synthesis in SLOS and provides evidence that bile acid supplementation is not likely to be necessary for treatment. These sterol balance studies provide basic information about the biochemical defect in SLOS and strengthen the rationale for the use of dietary cholesterol in its treatment.

Adolescent↗
PubMed1999

Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.

BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.

Adolescent↗