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Biomedical subjects

R McPherson

Publications and source records attributed to R McPherson.

At least 19 recordsLinked to original sources
PubMed2006

Safety of Triamcinolone acetonide (TA)-assisted pars plana vitrectomy in macular hole surgery.

AIM: To evaluate whether Triamcinolone acetonide (TA)-assisted pars plana vitrectomy for visualisation of posterior hyaloid during macular hole surgery has any adverse effects on macular hole closure rate and intraocular pressure (IOP). METHODS: Case series comparing outcomes and adverse effects in patients who had surgery for macular holes with ILM peel, with and without the use of TA-assisted vitrectomy. RESULTS: During the study period, 29 patients had vitrectomy for macular holes. In 18 patients (group 1), TA was used intraoperatively to facilitate visualisation of the posterior hyaloid and in 11 patients (group 2) no TA was used. There was no statistically significant difference in the macular hole closure rates and the improvement in visual acuity between the two groups. No long-term increase in IOP was recorded in any of the 29 patients. The total anatomical success rate in both groups was 85.6% and the average improvement in visual acuity in both groups was two Snellen lines. CONCLUSIONS: TA is safe and there is no contraindication for its use as an intraoperative aid to facilitate vitreous visualisation in macular hole surgery.

Aged↗
PubMed2001

The bioaccumulation of cadmium by the Blue Swimmer Crab Portunus pelagicus L.

The Blue Swimmer Crab (Portunus pelagicus) accumulates only cadmium in the hepatopancreas after being presented elevated levels of the metals Cd, Cu, Zn, As, Fe and Al via a food source, the mussel Trychomya hirsuta. Over 8 weeks, crabs were fed a controlled diet to determine the accumulation of metals. Significant (P = 0.05) Cd accumulation was detected after 4 weeks of feeding. Food mussels were sourced from either 'contaminated' or 'uncontaminated' sites. Mussels from uncontaminated sites had an average Cd level of 0.07 microg/g wet weight and contaminated mussels had an average of 5.2 microg/g wet weight. The usefulness of presenting metals in this way to assess potential bioaccumulators is further considered against other presentation methods.

Animals↗
PubMed2001

The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes.

The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, alpha(2)-macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL(2) or HDL(3) subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, alpha(2)-macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RAP, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.

Adipocytes↗
PubMed2001

Endocytosis is enhanced in Tangier fibroblasts: possible role of ATP-binding cassette protein A1 in endosomal vesicular transport.

A human genetic disorder, Tangier disease, has been linked recently to mutations in ATP-binding cassette protein A1 (ABCA1). In addition to its function in apoprotein A-I-mediated lipid removal, ABCA1 was also shown to be a phosphatidylserine (PS) translocase that facilitates PS exofacial flipping. This PS translocation is crucial for the plasma membrane to produce protrusions enabling the engulfment of apoptotic cells. In this report, we show that ABCA1 also plays a role in endocytosis. Receptor-mediated endocytosis, probed by both transferrin and low density lipoprotein, is up-regulated by more than 50% in homozygous Tangier fibroblasts in comparison with controls. Fluid-phase uptake is increased similarly. We also demonstrate that bulk membrane flow, including lipid endocytosis and exocytosis, is accelerated greatly in Tangier cells. Moreover, endocytosis is similarly enhanced in normal fibroblasts when ABCA1 function is inhibited by glyburide, whereas glyburide has no effect on endocytosis in Tangier cells. In addition, we demonstrate a decreased annexin V binding in Tangier fibroblasts as compared with controls, supporting the notion that PS transmembrane distribution is indeed defective in the presence of ABCA1 mutations. Furthermore, adding a PS analog to the exofacial leaflet of the plasma membrane normalizes endocytosis in Tangier cells. Taken together, these data demonstrate that ABCA1 plays an important role in endocytosis. We speculate that this is related to the PS translocase function of ABCA1. A loss of functional ABCA1, as in the case of Tangier cells, enhances membrane inward bending and facilitates endocytosis.

ATP Binding Cassette Transporter 1↗
PubMed2001

Cerivastatin versus branded pravastatin in the treatment of primary hypercholesterolemia in primary care practice in Canada: a one-year, open-label, randomized, comparative study of efficacy, safety, and cost-effectiveness.

BACKGROUND: Potential cost differences between statins are driven primarily by drug costs, differential lowering effects on low-density lipoprotein cholesterol (LDL-C) levels, and adverse drug interactions and reactions. OBJECTIVE: The purpose of this study was to compare the efficacy, safety, and direct treatment costs of cerivastatin and branded pravastatin in adult patients with primary hypercholesterolemia over a 1-year period. METHODS: This was a multicenter (48 sites), randomized, open-label, parallel-group, optional dose-titration study conducted in Canada. Patients aged 18 to 75 years with documented primary hypercholesterolemia (mean LDL-C > or = 160 mg/dL [> or = 4.5 mmol/L] and at least 1 fasting triglyceride measurement < or = 400 mg/dL [< or = 4.5 mmol/L]) that did not respond adequately to dietary intervention were enrolled. Patients who were on a diet at study entry were instructed to continue that diet for the duration of the study. Patients not following a diet were also entered into the study provided they had received previous dietary counseling and were unwilling or unable to comply with this dietary advice. Before randomization, treating physicians were required to record a target lipid level for each patient and then instructed to randomize patients to treatment with any dose and any titration schedule of cerivastatin or branded pravastatin according to their normal practice. Physicians were not required to titrate the study drug dose if the patient did not achieve the predefined target goal. Lipid analyses were conducted at baseline/randomization and at months 3, 6, 9, and 12. All samples drawn for lipid analyses were collected after a fast of > or = 10 hours. A cost-minimization approach was used to compare the direct treatment costs between cerivastatin and branded pravastatin. Since the analysis was from the perspective of the third-party payer (Ministries of Health), only costs attributed to the third-party payer were included. RESULTS: A total of 417 patients were randomized to once-daily treatment with cerivastatin 0.1 mg to 0.4 mg (n = 209) or branded pravastatin 10 mg to 40 mg (n = 208); 39 (9.4%) of patients discontinued prematurely, 19 (4.6%) because of an adverse event. The incidence of adverse events was similar for cerivastatin (73.6%) and branded pravastatin (74.9%). The majority of adverse events were mild or moderate and included headache, nausea, pain, and dizziness. Both cerivastatin and pravastatin were effective in lowering LDL-C to target levels (mean reduction 29.8% and 27.5%, respectively, P = 0.35). An LDL-C decrease of > or = 20% from baseline to end point was achieved in 74.2% of cerivastatin patients and 74.0% of pravastatin patients. The annualized direct hyperlipidemia treatment cost was 19% higher in the branded pravastatin group compared with the cerivastatin group. A sensitivity analysis designed to examine the impact of generic pricing on the cost-minimization analysis indicated that the cost difference between cerivastatin and generic pravastatin was not significant. CONCLUSIONS: Both cerivastatin and branded pravastatin were well tolerated and effective in lowering LDL-C by > or = 20% versus baseline. A cost savings in favor of cerivastatin was a reflection of the lower drug acquisition cost of cerivastatin compared with branded pravastatin.

Adolescent↗
PubMed2001

Adaptive hypersensitivity to estradiol: potential mechanism for secondary hormonal responses in breast cancer patients.

Women with hormone dependent breast cancer initially respond to hormone deprivation therapy with tamoxifen or oophorectomy for 12-18 months but later relapse. Upon secondary therapy with aromatase inhibitors, patients often experience further tumor regression. The mechanisms responsible for secondary responses are unknown. We postulated that hormone deprivation induces hypersensitivity to estradiol. Evidence of this phenomenon was provided in a model system involving MCF-7 cells grown in vitro and in xenografts. To determine if the ER transcriptional process is involved in hypersensitivity, we examined the effect of estradiol on ER reporter activity, PgR, PS2, and c-myc as markers and found no alterations in hypersensitive cells. Next, we examined whether MAP kinase may be upregulated in the hypersensitive cells as a reflection of increased growth factor secretion or action. Basal MAP kinase activity was increased both in vitro and in vivo in hypersensitive cells. Proof of principle studies indicated that an increase in MAP kinase activity induced by TGFalpha administration caused a two- to three-fold shift to the left in estradiol dose response curves in wild type cells. Blockade of MAP kinase with PD98059 returned the shifted curve back to baseline. These data suggested that MAP kinase overexpression could induce hypersensitivity. To determine why MAP kinase was increased, we excluded constitutive receptor activity and growth factor secretion by the demonstration that the pure anti-estrogen, ICI 182780, could inhibit MAP kinase activation. We also excluded hypersensitivity to estradiol induced growth factor secretion, and thus MAP kinase activation, since estradiol stimulated MAP kinase at 24, 48, and 72 h at the same concentrations in hypersensitive as in wild type cells. Surprisingly, a series of experiments suggested that MAP kinase increased in hypersensitive cells as a result of estrogen activation via a non-genomic pathway. We examined the classical signal pathway in which SHC is phosphorylated and binds to SOS and GRB-2 to activate Ras, Raf, and MAP kinase. With 5-20 min of exposure, estradiol caused binding of SHC to the estrogen receptor, phosphorylation of SHC, binding of GRB-2 to SOS, and activation of MAP kinase. All of these affects could be blocked by ICI 182780. Taken together, these observations suggest that the cell membrane ER pathway may be responsible for upregulation of MAP kinase and hypersensitivity in cells adapted to estradiol deprivation.

Adaptation, Physiological↗
PubMed2001

UCP3 and its putative function: consistencies and controversies.

The physiological function of uncoupling protein 3 (UCP3) is as yet unknown. Based on its 57% homology to UCP1 whose physiologic function is uncoupling and thermogenesis, UCP3 was attributed with the function of mitochondrial uncoupling through proton-leak reactions. UCP3 is expressed selectively in muscle, a tissue in which it has been estimated that proton leak accounts for approx. 50% of resting energy metabolism. Genetic linkage, association and variant studies suggest a role for UCP3 in obesity and/or diabetes. Studies of the heterologous expression of UCP3 in yeast provide support for the idea that UCP3 can uncouple mitochondrial oxidative phosphorylation, but the physiological relevance of these results is questionable. In vitro studies of mitochondria from Ucp3(-/-) mice provide support, but there are no changes in resting metabolic rate (RMR) of mice. In vivo studies demonstrate increased ATP synthesis, but estimates of substrate oxidation rate indicate no change. Mice that greatly overexpress Ucp3 in muscle have increased RMR. Inconsistent with the function of uncoupling are the observations that fasting results in increased expression of UCP3, but no change in muscle proton leak. Moreover, fasting decreases energy expenditure in muscle. Expression patterns for Ucp3 and lipid-metabolism genes support a physiological role in fatty acid oxidation. Overall, findings support a role for Ucp3 in fatty acid metabolism that may have implications for obesity and/or Type II diabetes.

Animals↗
PubMed2001

Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH).

BACKGROUND: Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. METHODS AND RESULTS: We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C <or=100 mg/dL (2.6 mmol/L) with 10 mg and 60% reached this target with up to 20 mg of atorvastatin. With maximal titration to the LDL-C target, up to and including 80 mg atorvastatin, 87% of women without CVD and 80% of women with established CVD achieved LDL-C targets. The presence of mixed dyslipidemia with obesity did not affect the frequency of achieving LDL-C targets. CONCLUSION: Atorvastatin is very effective in achieving National Cholesterol Education Program Adult Treatment Panel II target concentrations for LDL-C in the majority of women with established CVD or CVD risk factors.

Adult↗
PubMed2001

Attachment styles in older European American and African American adults.

OBJECTIVES: Differential attachment styles have been linked to differential emotion regulation and ability to cope with stress in samples of young adults. There are few data on attachment styles in older adults despite the fact that attachment relationships are said to play a significant role in psychological well-being throughout the life span. The goal of the study was to examine attachment patterns in older adults. METHODS: Participants were 800 community-dwelling older European Americans and African Americans (M = 74 years) living in a large urban community. Attachment measures included the family and friend intimacy subscales from the Network Analysis Profile and the Relationship Scales Questionnaire. RESULTS: In contrast to findings with younger individuals, where the majority of respondents have been found to be secure (i.e., comfortable with closeness and dependency), the majority of the present sample were found to be dismissing/avoidant (i.e., uncomfortable with closeness, compulsively self-reliant). European Americans scored higher than African Americans on attachment security, whereas African Americans scored higher than European Americans on dismissing attachment. However, the assessment of relatedness based on the Network Analysis Profile, where respondents named their closest kin, indicated that African Americans had higher scores than European Americans, though their networks were smaller. DISCUSSION: Age and ethnicity differences appear to reflect cohort effects related to the impact of economic hardship on families earlier this century and racial prejudice. The high rates of dismissing attachment and low rates of secure attachment in this large urban population suggest that these individuals may be at risk for social isolation and poor health as they become older and more frail.

Adaptation, Psychological↗
PubMed2000

Lipid screening to prevent coronary artery disease: a quantitative evaluation of evolving guidelines.

BACKGROUND: There is strong evidence to support the treatment of abnormal blood lipid levels among people with cardiovascular disease. Primary prevention is problematic because many individuals with lipid abnormalities may never actually develop cardiovascular disease. We evaluated the 1998 Canadian lipid guidelines to determine whether they accurately identify high-risk adults for primary prevention. METHODS: Using data from the Lipid Research Clinics and receiver operating characteristic (ROC) curves, we compared the diagnostic performance of the 1998 lipid guidelines when risk factors for coronary artery disease (CAD) were counted versus calculating risk using Framingham risk equations. We also compared the diagnostic accuracy of the 1998 guidelines with guidelines previously published by the National Cholesterol Education Program in the United States and the 1988 Canadian Consensus Conference on Cholesterol and then used Canadian Heart Health Survey data to forecast lipid screening and treatment rates for the Canadian population. RESULTS: The Framingham risk equations were more accurate than counting risk factors for predicting CAD risk (areas under the ROC curves, 0.83 [standard deviation (SD) 0.02] v. 0.77 [SD 0.03], p < 0.05). Risk counting was a particularly poor method for predicting risk for women. The 1998 Canadian guidelines identified high-risk individuals more accurately than the earlier guidelines, but the increased accuracy was largely due to a lower false-positive rate or a higher true-negative rate (i.e., increased test specificity). Using the 1998 lipid guidelines we estimate that 5.9 million Canadians currently free of cardiovascular disease would be eligible for lipid screening and 322,705 (5.5%) would require therapy. INTERPRETATION: Calculating risk using risk equations is a more accurate method to identify people at high risk for CAD than counting the number of risk factors present, especially for women, and the 1998 Canadian lipid screening guidelines are significantly better at identifying high-risk patients than the 1988 guidelines. Many of our findings were incorporated into the new 2000 guidelines.

Adult↗
PubMed2000

High-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins mediated by cholesteryl ester transfer protein in the fasting and postprandial periods are not altered in type 1 diabetes mellitus.

Background: Diabetes mellitus is associated with atherosclerosis that has, in part, been ascribed to abnormalities in the reverse cholesterol transport system. Methods: We determined, in the fasting and post-alimentary periods, rates of HDL cholesterol esterification and transfer to apoB-containing lipoproteins, cholesteryl ester transfer protein (CETP) concentration, and apoB lipoprotein size in 10 type 1 diabetics and 10 well-matched controls. Autologous HDL was labeled with [14C]cholesterol and incubated at 37 degrees C during a period of 30 min for measurement of the cholesterol esterification rate (CER), as well as for 24 h for measurement of the endogenous HDL [14C]cholesteryl ester ([14C]CE) transfer rate to apoB-containing lipoproteins after 2- and 4-h incubations with the subject's own plasma. Exogenous cholesteryl ester transfer activity (CETA) was estimated by incubation of the participant's plasma (CETP source) with [14C]CE-HDL and VLDL from a pool of plasma donors. ApoB lipoprotein size was determined using non-denaturing polyacrylamide gradient gel electrophoresis of whole plasma. Results: Contrary to previous studies, we showed that even not well-controlled type 1 diabetics did not differ from lipid-matched, non-diabetic subjects in HDL-[14C]cholesterol esterification rate, transfer rates, or CETP concentration. CETP concentration correlates with the exogenous method of [14C]CE transfer and with the endogenous method only when the latter is corrected for plasma triacylglycerol (TG) concentration. In addition, during the postprandial phase, diabetic patients' VLDL are smaller and IDL size increases less than in controls. Conclusion: In type 1 diabetes mellitus, CETA is not altered when the plasma levels of donor and/or acceptor lipoproteins are within the normal range.

Journal Article↗
PubMed2000

Coronary artery disease and women: applying the guidelines for risk factor management.

Coronary artery disease (CAD) is the leading cause of death for women. In large part because of increased age at presentation and a greater frequency of concomitant morbidities, women who develop CAD have a poorer prognosis than do men. Although the long term outcome of revascularization procedures is good, the associated procedural morbidity and mortality in women is high. More emphasis should be placed on the primary and secondary prevention of CAD in women. Although women respond well to risk factor modification, including lipid-lowering therapies, recent data indicate that their awareness of risk factors and prevention strategies is poor. Physician risk factor assessment and adherence to current guideline recommendations are essential in preventing the development or progression of CAD in women.

Coronary Disease↗
PubMed2000

Is hormone replacement therapy cardioprotective? Decision-making after the heart and estrogen/progestin replacement study.

Coronary artery disease (CAD) is the major cause of death in women. Postmenopausal status is associated with a twofold increase of risk for cardiovascular events, in part because of detrimental changes in plasma lipoproteins and endothelial function. Hormone replacement therapy (HRT) has beneficial effects on plasma lipids, flow-mediated vasodilation and fibrinolysis that could be expected to have positive effects on the incidence of cardiovascular events in many postmenopausal women. However, oral HRT also has procoagulant effects and clearly increases the risk of venous thromboembolism. The prothrombotic effects of oral estrogen are not a major concern for the majority of healthy women and major studies including the Framingham Heart Study and the Nurses' Health Study showed that HRT use is associated with protection from cardiovascular disease. In contrast, the Heart and Estrogen/progestin Replacement Study (HERS) failed to show a beneficial effect of oral HRT on cardiovascular events in older women with advanced CAD. In such women, the acute prothrombotic effects of oral estrogen may outweigh the long-term antiatherosclerotic effects of HRT. Until the results of other randomized controlled studies are complete, advice regarding HRT should be based on anticipated benefits on CAD risk factors versus the overall risk of both venous and arterial thrombosis.

Cholesterol↗
PubMed2000

Evaluation of a second set of lateral lasers for easier patient positioning in radiotherapy.

On modern linear accelerators patient set-up is often awkward due to the height of the isocentre. A second set of lateral lasers was mounted approximately 20 cm below the isocentre allowing patient positioning at an ergonomical height. A small randomised study involving 16 heavy patients treated for pelvic malignancies demonstrated that using the lower lasers for patient set-up is not only likely to reduce strain on staff but also speed up the set-up process.

Aged↗
PubMed1999

Transplantation of cryopreserved osteochondral Dowel allografts for repair of focal articular defects in an ovine model.

The purpose of this study was to test whether successful cryopreservation of osteochondral tissue is possible and whether, with the appropriate surgical procedure, it can be used for the successful repair of focal articular defects within joints. Fresh (nonfrozen) and snap-frozen (plunged in liquid nitrogen and thawed in a water bath at 37 degrees C, repeated three times) autografts were used as positive and negative controls, respectively. Snap-frozen, frozen (fresh tissue placed in a freezer at -80 degrees C), and cryopreserved (immersed in 10% dimethyl sulfoxide for 30 minutes and then frozen at 1 degrees C/min to -80 degrees C) allografts were transplanted into the knees of adult sheep. Outcomes were evaluated 3, 6, and 12 months after transplantation. The morphological, histological, biochemical, and biomechanical behaviors and characteristics of the graft cartilage, the host cartilage adjacent to the grafts, and the opposing tibial cartilage were assessed. Freezing protocols that yielded poor chondrocyte recovery after thawing (frozen and snap-frozen) resulted in poor overall graft outcome. The cryopreservation protocol, however, resulted in intermediate recovery (50%) of chondrocytes and in intermediate overall graft outcome compared with fresh autografts. The membrane integrity of the allograft chondrocytes immediately following cryopreservation was identified as the most reliable predictor of long-term outcome of the graft. Further improvements in cryopreservation technique may lead to an effective method of banking osteochondral tissue for successful transplantation for the repair of focal defects and larger joint reconstructions.

Animals↗
PubMed1999

Diet and waist-to-hip ratio: important predictors of lipoprotein levels in sedentary and active young men with no evidence of cardiovascular disease.

OBJECTIVE: Healthy, young men were studied to determine the relationship of energy and nutrient intake and physical activity to concentrations of plasma lipoprotein and cholesteryl ester transfer protein. DESIGN: A cross-sectional study compared active and sedentary male subjects (17 to 35 years old) with no personal or family history of coronary heart disease. Participants kept 20-day food and activity journals. Individual intakes of energy, protein, carbohydrate, fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, dietary fiber, and alcohol were evaluated. Measurements of blood lipids (total cholesterol and triglycerides, high- and low-density lipoprotein cholesterol); apolipoproteins; cholesteryl ester transfer protein; anthropometric variables (body mass index, waist-to-hip ratio, percentage of body fat); and aerobic capacity were taken during fall and spring data collection periods. SUBJECT SELECTION: Subjects were selected on the basis of normal blood lipid levels, absence of underlying disease, and willingness to comply with their current level of physical activity for the duration of the study. Minimal sample size for statistical power was 12 men per group: 12 of 15 subjects who exercised and 13 of 15 subjects who were sedentary completed all phases of the study. STATISTICAL ANALYSES: Statistical analyses consisted of 2-way analysis of variance (activity level and season). Pearson product moment correlations and multiple regression analyses were conducted to assess whether energy and nutrient intakes, physical activity status, and/or anthropometric variables predicted plasma concentrations of lipids and apolipoproteins. RESULTS: Lower waist-to-hip ratio, and not specifically activity level, was associated with higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of low-density lipoprotein cholesterol (LDL-C). Dietary intake of saturated and monounsaturated fats and alcohol predicted changes in some apolipoprotein and lipoprotein levels. APPLICATIONS: Use of waist-to-hip ratio in the primary prevention of coronary heart disease is a simple and cost-effective measure to predict development of abnormal lipoprotein profiles in young men. Specific dietary recommendations include adoption of a heart-healthy diet with emphasis on monounsaturated fatty acids (10% to 12% of energy or one third of total fat intake) and the suggestion that small amounts of alcohol (< 3 drinks per week) may, indeed, be beneficial. Because alcohol and waist-to-hip ratio were both important predictors of LDL-C level, even in active young men, the consumption of low levels of alcohol may be beneficial only if waist-to-hip ratio is maintained within the healthful range by achieving an appropriate balance of physical activity and macronutrient intake.

Adolescent↗
PubMed1999

Cholesteryl ester transfer protein gene expression during differentiation of human preadipocytes to adipocytes in primary culture.

The expression pattern of the CETP gene in relationship to that of LPL, adipsin, PPARgamma, C/EBPalpha, ADD1/SREBPI and actin was examined by RT-PCR during differentiation of human fibroblastic preadipocytes to adipocytes in primary culture. Preadipocytes were isolated from subcutaneous fat obtained from healthy female subjects undergoing mammary reduction procedures, and induced to differentiate in culture. Morphologically, adipogenesis was confirmed by the accumulation of lipid droplets in cells. We show that the gene encoding CETP is expressed in preadipocytes and is present throughout differentiation as compared to LPL and adipsin which were detected in the majority of samples by day 2 or 3 of adipogenesis. The transcription factors, PPARgamma, ADD1/SREBP1 and C/EBPalpha were expressed by day 2, concomitant with the appearance of LPL and adipsin but subsequent to the appearance of CETP. CETP mRNA was not detectable in human skin fibroblasts. These studies demonstrate that CETP. expression is induced at an early stage of commitment to the adipocyte lineage and may be activated by transcription factor(s), which are not members of the PPAR, ADD1/SREBP1 or C/EBP families.

Actins↗