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Biomedical subjects

R McPherson

Publications and source records attributed to R McPherson.

At least 37 records · Page 2Linked to original sources

Controversies in primary prevention among hyperlipidemic patients.

Data from a number of population-based primary prevention trials clearly indicate that reducing total serum cholesterol levels leads to a reduced risk of coronary artery disease and death. Similarly, for patients with coronary artery disease, reducing total serum cholesterol levels proved to be an effective secondary prevention strategy, leading to a reduced risk of coronary events and death. Targeting high risk patients is a particularly important component of primary prevention. The overall benefit of treatment is significantly reduced when cholesterol-lowering strategies are initiated later in life. To assist in both primary and secondary prevention strategies, an outline of guidelines developed by a Health Canada working group for the management of hyperlipidemia have recently been published.

Anticholesteremic Agents↗

Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1.

Cholesteryl ester transfer protein (CETP) is expressed in human adipocytes, where it acts to promote selective uptake of HDL-CE (Benoist, F., M. McDonnell, P. Lau, R. Milne, and R. McPherson. 1997. J. Biol. Chem. 272: 23572;-23577). In contrast to other major sterol-responsive genes such as 3-hydroxy-3-methylglutaryl coenzyme A reductase CETP expression is up-regulated rather than down-regulated in response to cholesterol. To define elements involved in cholesterol-mediated up-regulation of CETP gene expression, deletion derivatives of the CETP promoter were cloned into a luciferase reporter construct and transfected into the human liposarcoma cell line SW872, cultured in the presence or absence of lipoproteins. A fragment associated with a positive cholesterol response was identified between nucleotides -361 and -138 (relative to the initiation site of transcription) of the promoter. This region contains a tandem repeat of a sequence known to mediate sterol dependent regulation of the hamster HMG-CoA reductase gene. We have putatively denoted this region, the cholesterol response element (CRE). Using gel mobility shift assays we demonstrate that both YY1 and SREBP-1 interact with the CRE of CETP. Furthermore, in transient co-transfection experiments, both YY1 and SREBP-1a were found to trans-activate, in a dose-dependent manner, the luciferase activity of constructs harboring the CRE. We also demonstrate that SREBP-2, is able to trans-activate a luciferase construct harboring the CRE although much less effectively as compared to SREBP-1. Finally, functional analysis of the CRE confirms its regulatory role in modulating CETP gene expression through its interaction with YY1 and SREBP-1a.

Animals↗

Comparative effects of simvastatin and cholestyramine on plasma lipoproteins and CETP in humans.

Cholesteryl ester transfer protein (CETP) mediates neutral lipid transport in plasma, resulting in a net transfer of cholesteryl ester from high density lipoprotein to very low density lipoprotein. CETP gene expression is regulated by cholesterol, and plasma CETP level increases in patients with hyperlipidemia and with cholesterol feeding. Simvastatin, unlike cholestyramine, reduces hydroxymethylglutaryl coenzyme A reductase activity and may decrease a cellular pool of cholesterol, which is regulatory for CETP gene expression. The effects of simvastatin and cholestyramine on plasma lipids and CETP in 24 male and 19 female patients with primary hypercholesterolemia were compared. Following a four-week placebo period, patients were randomly assigned to receive either simvastatin or cholestyramine. Medication was increased in a stepwise fashion (from 10 to 40 mg for simvastatin and from 8 to 24 g for cholestyramine) as required at six-week intervals to maintain a low density lipoprotein cholesterol (LDL-C) level below 3.4 mmol/L. At the end of the 18-week study, the mean dose of simvastatin was 28.6 mg/day and of cholestyramine 19.3 g/day. Simvastatin was more effective than cholestyramine in lowering LDL-C (-36.8% versus -27. 2%; P=0.031) and triglycerides (-8.5% versus +12.5%; P=0.045). Plasma CETP level decreased by 14.8% following treatment with simvastatin (P=0.003) but did not change following cholestyramine treatment. This study demonstrates that, compared with cholestyramine, simvastatin results in more favourable improvements in the plasma lipoprotein profile and also lowers plasma levels of CETP.

Adolescent↗

Preferential expression of cholesteryl ester transfer protein mRNA by stromal-vascular cells of human adipose tissue.

Cholesteryl ester transfer protein (CETP) mRNA is more abundantly expressed in small mature adipocytes as compared to large, lipid-rich adipocytes [Radeau et al., J. Lipid Res. 36 (1995) 2552-2561]. In the present study, the stromal vascular fraction (SVF) of human adipose tissue was isolated and the presence of very small fat cells in this fraction confirmed by electron microscopy and by demonstrating the presence of mRNA for adipsin and for CCAAT enhancer binding protein alpha (C/EBPalpha), a marker of adipocyte differentiation. sn-Glycerol 3-phosphate dehydrogenase (GPDH) activity was present in the SVF but not in the preadipocyte fraction. Northern blot analysis of human adipose tissue demonstrated that CETP mRNA expression was significantly greater (+96%, P<0.03) in stromal-vascular cells (SVC) as compared to mature fat cells. By comparison, lipoprotein lipase mRNA expression was lower (-75%, P<0.03) in SVC while apolipoprotein E mRNA expression was not significantly different in SVC as compared to isolated adipocytes. By RT-PCR analysis, we demonstrated that CETP mRNA was expressed by human pre-adipocytes at levels less than those of SVC and adipocytes. The absence of monocytes/macrophages in SVC was confirmed by the absence of FcgammaRIII (CD16) mRNA in these fractions. These data demonstrate that CETP mRNA is most highly expressed in the immature fat cells of human adipose tissue, consistent with other experiments from this laboratory demonstrating that CETP plays an important local role in adipocyte cholesterol accumulation.

Adipocytes↗

Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia.

To assess the long-term efficacy and use of fenofibrate together with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") in the treatment of elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol, we conducted a study that compared a before- and after-case series. The study involved 80 patients with a diagnosis of combined hyperlipidemia and existing coronary artery disease (81% of patients) or outpatients with > or = 3 risk factors for coronary artery disease who had been receiving treatment at a tertiary care center. Fasting biochemical measures were obtained at baseline during monotherapy with a statin consisting of pravastatin 20 mg once daily or simvastatin 10 mg once daily (39 patients) or fenofibrate 300 mg once daily (41 patients), and during a 2-year period of combination therapy. This combination therapy comprised fenofibrate 300 mg once daily or micronized fenofibrate 200 mg once daily taken together with pravastatin 20 mg once daily (63 patients) or simvastatin 10 mg once daily (17 patients). The main outcome measures were: (1) absolute and percent change in total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol; (2) percentage of patients with alanine aminotransferase > or = 2x the upper limits of normal on any occasion; (3) percentage of patients with creatinine kinase > or = 3 times the upper limits of normal on any occasion; (4) absolute changes in alanine aminotransferase and creatinine phosphokinase; and (5) months on combination therapy. Patients receiving combination therapy had a mean total cholesterol (+/- standard error of the mean [SEM]) that was significantly decreased by 26+/-1%, triglycerides by 41+/-3%, and LDL cholesterol by 28+/-2%, and mean HDL cholesterol that was significantly increased by 22+/-6%. These changes correspond to mean absolute changes of total cholesterol: -75+/-5 mg/dL; triglycerides: -94+/-13 mg/dL; LDL cholesterol: -52+/-5 mg/dL; and HDL cholesterol: 5+/-1 mg/dL. During combination treatment, alanine aminotransferase increased by 2+/-2 U/liter (not significant) and creatinine phosphokinase decreased by 4+/-13 U/liter (not significant). During treatment, 8 patients (10%) had transitory isolated elevations in alanine aminotransferase levels > or = 2 times the upper limits of normal and 2 patients (2.5%) had an isolated and transitory elevation of creatinine kinase (> or = 3x but < 6x upper limits of normal) without associated muscle symptoms. Patient-years on combination therapy equaled 220.6 (average 2.06 years per patient). The results demonstrated that combination treatment with fenofibrate and low-dose simvastatin or pravastatin is generally safe and effective for the treatment of combined hyperlipidemia in patients with normal hepatic and renal function.

Cholesterol, HDL↗

The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group.

BACKGROUND: The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis. METHODS: The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP. The presence of this DNA variation was referred to as B1, and its absence as B2. All patients participated in a cholesterol-lowering trial designed to induce the regression of coronary atherosclerosis and were randomly assigned to treatment with either pravastatin or placebo for two years. RESULTS: The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations (mean [+/-SD], 2.29+/-0.62 microg per milliliter for the B1B1 genotype vs. 1.76+/-0.51 microg per milliliter for the B2B2 genotype) and lower HDL cholesterol concentrations (34+/-8 vs. 39+/-10 mg per deciliter). In addition, we observed a significant dose-dependent association between this marker and the progression of coronary atherosclerosis in the placebo group (decrease in mean luminal diameter: 0.14+/-0.21 mm for the B1B1 genotype, 0.10+/-0.20 mm for the B1B2 genotype, and 0.05+/-0.22 mm for the B2B2 genotype). This association was abolished by pravastatin. Pravastatin therapy slowed the progression of coronary atherosclerosis in B1B1 carriers but not in B2B2 carriers (representing 16 percent of the patients taking pravastatin). CONCLUSIONS: There is a significant relation between variation at the CETP gene locus and the progression of coronary atherosclerosis that is independent of plasma HDL cholesterol levels and the activities of lipolytic plasma enzymes. This common DNA variant appears to predict whether men with coronary artery disease will benefit from treatment with pravastatin to delay the progression of coronary atherosclerosis.

Anticholesteremic Agents↗

Relationship of adipose tissue cholesteryl ester transfer protein (CETP) mRNA to plasma concentrations of CETP in man.

Adipose tissue is an important site of cholesteryl ester transfer protein (CETP) synthesis and CETP plays a local role in adipocyte cholesteryl ester accumulation from high density lipoproteins (HDL). Human adipose tissue maintained in organ culture secretes CETP, but it is not known to what extent adipose tissue CETP contributes to the plasma pool of CETP in man. Aging is associated with changes in adipose tissue composition and function, including impaired adipocyte triglyceride lipolysis. We determined pericardiac adipose tissue CETP mRNA levels and plasma concentrations of CETP and lipoproteins in middle-aged and elderly subjects (47-78 years) with stable coronary heart disease (CHD) undergoing elective coronary artery bypass grafting (CABG). Plasma concentrations of CETP were highly correlated with adipose tissue CETP mRNA abundance (r = 0.85, P < 0.002, n = 13), suggesting that adipose tissue may contribute to the plasma pool of CETP. There was an inverse correlation between age and plasma CETP concentrations in this population (r = -0.70, P <0.008, n = 13). CETP mRNA levels in pericardial adipose tissue were also negatively associated with age (r = -0.70, P < 0.035, n = 10). These relationships were independent of plasma lipids, lipoproteins and body mass index. However, adipose tissue CETP mRNA concentrations levels were related to adipocyte size. CETP mRNA abundance in pericardial adipose tissue was negatively correlated with mean adipocyte size, estimated as adipose tissue triglyceride/mg protein (r = -0.76, P < 0.02, n = 9), in accord with previous studies from this laboratory demonstrating that CETP gene expression is greatest in small lipid-poor adipocytes. A negative relationship between age and adipose tissue CETP mRNA abundance (r = -0.63, P < 0.05, n = 10) was confirmed in a separate population of healthy female subjects, aged 18-63 years, from whom subcutaneous adipose tissue was obtained at the time of reduction mammoplasty. The decrease in plasma concentrations of CETP with age may be explained in part by changes in adipose tissue CETP gene expression.

Adipocytes↗

A decision aid for women considering hormone therapy after menopause: decision support framework and evaluation.

Although postmenopausal women are advised to consider their values when deliberating about potential benefits and risks of hormone therapy (HRT), feasible, effective methods of decision support in primary care have yet to be established. Using an explicit decision support framework, we developed a self-administered HRT decision aid and evaluated it in a before/after study of 94 women from six family practices. An audiotape guided women through an illustrated booklet including: detailed information about HRT benefits and risks tailored to a woman's clinical risk, and a values clarification exercise to promote informed decision making consistent with personal values. After using the decision aid participants: had better general knowledge and more realistic personal expectations of HRT benefits and risks; and, felt more certain, informed, clear about values, and supported in decision making. Women's values elicited in the clarification exercise were 84% accurate in discriminating between decisions. Women with polarized preferences at baseline did not change their minds, but were better informed. Changes in preferences occurred in the uncertain group, with equal numbers accepting or declining HRT. Most participants found the decision aid comprehensible, acceptable in length and pace, and balanced. Decision aids are useful in preparing women for decision making about this complex, personal issue.

Aged↗

Sequence characteristics of natural populations of tomato spotted wilt tospovirus infecting flue-cured tobacco in Georgia.

Using primers from conserved regions, the nucleocapsid (Nc) gene sequences of naturally occurring tomato spotted wilt tospovirus (TSWV) isolates from flue-cured tobacco (Nicotiana tabacum) grown in several Georgia counties were amplified by immunocapture-reverse transcription-polymerase chain reaction. The resulting amplicons were cloned and sequenced. Sequence analyses showed a high degree of sequence conservation among the Nc genes of the tobacco isolates, and those reported from other parts of the world. However, distinct differences that were unique to these tobacco isolates as well as the previously studied peanut, tomato and pepper isolates from Georgia were present. The Georgia isolates formed a distinct cluster that was clearly resolved from the rest of the TSWV isolates based on sequence phylograms.

Base Sequence↗

Rationale for and outline of the recommendations of the Working Group on Hypercholesterolemia and Other Dyslipidemias: interim report. Dyslipidemia Working Group of Health Canada.

A panel consisting of lipidologists, epidemiologists, cardiologists, internists, general practitioners, and public health and government representatives used the evidence-based approach to examine the rationale for a draft of recommendations for medical management of lipid disorders. The proposed recommendations deal with assessment of cardiovascular risk based on history, physical examination and laboratory findings; assessment of the fasting lipid profile; diagnosis and treatment of secondary risk factors; calculation of the 10-year risk of a cardiac event; initiation of lifestyle modifications in patients in whom low density lipoprotein cholesterol (LDL-C), total:high density lipoprotein cholesterol (HDL-C) ratio or triglycerides exceeds target values based on a patient's risk category; follow-up; treatment with drugs; and choices of drugs. In contrast to previous recommendations, there are new, considerably lower, cholesterol level targets for secondary prevention, with a less important emphasis on total cholesterol value than on LDL-C or total:HDL-C ratio and triglyceride levels, and an emphasis on determining the likelihood of a cardiac event by evaluating all relevant risk factors and sharpening the focus on nondrug treatment, which should result in treating a greater percentage of at-risk patients.

Anticholesteremic Agents↗

Mechanical integrity of subchondral bone in osteochondral autografts and allografts.

OBJECTIVE: To assess the influence of osteochondral graft preservation techniques on post-transplant biomechanics of graft and host subchondral bone in the knee joint. DESIGN: An experimental animal model (sheep), specifically the weight-bearing articular surface of the medial femoral condyle of the knee joints. INTERVENTION: Each sheep received, in the ipsilateral knee, an allograft that was (a) frozen without dimethyl sulfoxide (DMSO), (b) snap-frozen in liquid nitrogen or (c) frozen with DMSO. The contralateral knee received an autograft that was (a) snap-frozen, (b) treated with DMSO or (c) left untreated (fresh). MAIN OUTCOME MEASURES: Mechanical and material properties of bone, including maximal compression stress, modulus of elasticity and bone cores (from the graft centre and surrounding host bone). RESULTS: No significant differences were found in the mechanical properties of the subchondral bone under the graft, but there were significant changes in surrounding bone. Bone surrounding the grafts that were snap-frozen or frozen without DMSO was significantly stronger than the normal control bone. However, bone surrounding fresh autografts and cryoprotected allografts was not significantly different from normal control bone. CONCLUSIONS; The changes in the mechanical behaviour of the host bone may be associated with graft cell viability. The great stiffness of the subchondral host bone may have consequences for long-term graft integrity and for the development of degenerative osteoarthritis.

Animals↗

Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue.

We have determined the role of cholesteryl ester transfer protein (CETP) in selective uptake of high density lipoprotein (HDL)-derived cholesteryl esters (CE) by human adipose tissue, using organ culture or collagenase-digested adipocytes. Incubation of the fresh tissue fragments with HDL containing [3H]CE or 125I-apoprotein (apo) A-I resulted in significant uptake of HDL-CE-derived label. Addition of recombinant CETP (rCETP) increased CE uptake in a dose-response fashion. In contrast, little association of 125I-apoA-I with adipose tissue was noted, and addition of rCETP did not alter apoA-I uptake or degradation. Incubation of adipose tissue with TP2, an anti-CETP monoclonal antibody, which inhibits neutral lipid transfer, markedly reduced selective uptake of HDL-CE. Studies using human adipocytes isolated by collagenase digestion also demonstrated selective uptake of HDL-CE and enhancement of this process by rCETP. To confirm that the association of HDL-CE-derived radioactivity with adipose tissue was not due to neutral lipid exchange between adipocytes and HDL, we measured changes in HDL composition following incubation of HDL and rCETP with isolated adipocytes. A decrease in HDL-CE concentration in the medium was observed, an effect which was markedly attenuated when incubations were carried out in the presence of monoclonal antibody TP2. Furthermore, the decrease in HDL-CE was accompanied by an increase in HDL free cholesterol, likely representing efflux of adipocyte cholesterol to HDL. There were no significant changes in phospholipid, apoA-I, or apoA-II in the medium following incubation with adipocytes. These data demonstrate a novel and important role for CETP in selective uptake of HDL-cholesteryl esters by human adipocytes and suggest that this pathway may be of quantitative physiological significance in HDL remodeling and adipocyte cholesterol accumulation.

Adipocytes↗

Activity of plasma membrane-recruited Raf-1 is regulated by Ras via the Raf zinc finger.

Ras recruits Raf to the plasma membrane for activation by a combination of tyrosine phosphorylation and other as yet undefined mechanism(s). We show here that the Raf zinc finger is not required for plasma membrane recruitment of Raf by Ras but is essential for full activation of Raf at the plasma membrane. Membrane targeting cannot compensate for the absence of the zinc finger. One facet of the zinc finger activation defect is revealed using a constitutively activated Raf mutant. Targeting Raf Y340D,Y341D to the plasma membrane increments activity, but full activation requires coexpression with activated Ras. This sensitivity to regulation by Ras at the plasma membrane is abrogated by mutations in the Raf zinc finger but is unaffected by mutation of the minimal Ras binding domain. These data show for the first time that Ras has two separate roles in Raf activation: recruitment of Raf to the plasma membrane through an interaction with the minimal Ras binding domain and activation of membrane-localized Raf via a mechanism that requires the Raf zinc finger.

Animals↗

Plasma kinetics of cholesteryl ester transfer protein in the rabbit. Effects of dietary cholesterol.

The plasma kinetics of recombinant human cholesteryl ester transfer protein (rCETP) were studied in six rabbits before and after cholesterol feeding (0.5% wt/wt). The rCETP, labeled with the use of the Bolton Hunter reagent, was shown to retain neutral lipid transfer activity. After intravenous infusion, labeled rCETP associated with rabbit lipoproteins to an extent similar to endogenous rabbit CETP (62% to 64% HDL associated). The plasma kinetics of CETP, modeled with the use of SAAM-II, conformed to a two-pool model, likely representing free and loosely HDL-associated CETP (fast pool) and a tightly apo (apolipoprotein) AI-associated (slow pool) CETP. The plasma residency time (chow diet) of the fast pool averaged 7.1 hours and of the slow pool, 76.3 hours. The production rate (PR) into and the fractional catabolic rate (FCR) of the fast pool were 20 and 10 times the PR and FCR, respectively, of the slow pool. In response to cholesterol feeding, CETP PR, FCR, and plasma mass increased by 416%, 60%, and 230%, respectively. There was a strong correlation (r = .95, P = .003) between the increase in rabbit plasma CETP and the modeled increase in CETP PR in response to cholesterol feeding, suggesting that labeled human rCETP is a satisfactory tracer for rabbit plasma CETP. CETP is catabolized by distinct pools, likely corresponding to an apo AI-associated (slow) pool and a free and/or loosely HDL-associated (fast) pool. Factors that alter the affinity of CETP for HDL would be predicted to result in altered CETP catabolism. The effect of dietary cholesterol on plasma CETP mass can be explained largely by the effects on CETP synthesis, consistent with the observed effects of cholesterol on tissue mRNA levels.

Animals↗

Effect of 360His mutation in apolipoprotein A-IV on plasma HDL-cholesterol response to dietary fat.

In order to determine whether genetic variability of apolipoprotein (apo) A-IV is responsible for the improvement in lipid profile when dietary saturated fats are replaced by carbohydrates or monounsaturated fats, 41 healthy male subjects were studied: 33 were homozygous for the 360Gln allele and 8 were heterozygote carriers of the 360His allele. These were administered three consecutive 4-week diets. The first was a diet rich in saturated fat (SAT diet, with 38% fat, 20% saturated. This was followed by a low fat diet (NCEP-I, with < 30% fat, < 10% saturated). The final diet was rich in monounsaturated fat (MUFA diet, with 38% fat, 22% monounsaturated). There was no difference in plasma lipid and apolipoprotein levels of both groups of individuals after consuming the SAT diet. Switching from this diet to the NCEP-I diet, carriers of the 360His allele presented a greater decrease in high density lipoprotein-cholesterol (HDL-C) (-10 vs. -1 mg/dL, P < 0.004) and apoA-I levels (-19 vs. -8 mg/dL, P < 0.037). Similarly, replacement of carbohydrates by monounsaturated fats produced a greater increase in HDL-C (9 vs. 1 mg/dL, P < 0.003) and apoA-I levels (9 vs. 2 mg/dL, P < 0.036) in carriers of the 360His mutation. Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities and apoA-IV levels were also measured. However, no genotype-related differences were observed for these parameters. Our results suggest that variability in HDL-C and apoA-I response to diet is, at least partially, determined by the 360His mutation of apoA-IV.

Adult↗

Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls.

Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester transfer from the HDL-containing plasma fraction to lipoproteins of lighter densities (apo B-containing LP) and plasma cholesteryl ester transfer protein concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n = 11) and normal controls (n = 10) both in the fasting state and 4 h after a standard milk-shake test meal (50g of fat/m of body surface). The percent of [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL containing preparation incubated for 30 min and the [3H]cholesteryl ester transfer was measured upon precipitation of apo B-containing lipoproteins with dextran sulphate/MgCl2 following a 2 h period of plasma incubation with [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma triglyceride concentration and to a similar extent in diabetics and in normal controls. Both a HDL-[3H]cholesteryl ester synthesis and transfer rates were equally stimulated in diabetics and in controls. When data were expressed by the concentration of plasma triglycerides, cholesteryl ester formation and transfer rates were similar in the alimentary and fasting periods, and when expressed per apo B concentration, cholesteryl ester transfer rates rose during the alimentary period in both diabetics and controls indicating that there was a net gain of cholesteryl ester per apo B lipoprotein. Plasma CETP mass, and neutral lipid transfer activity were similar in diabetics and normal controls demonstrating that the reverse transport of cholesterol through the apo B lipoprotein pathway is not altered in normotriglyceridemic Type II diabetics.

Apolipoproteins B↗

Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states.

Hypercholesterolemic women (n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides. When transfer data were related to the plasma concentration of apo B, the gain of cholesteryl ester by the triglyceride-containing particles (VLDL + LDL) also increased in the postprandial period to a similar extent for both diets. Cholesteryl ester transfer protein (CETP) concentration measured by radioimmunoassay was similar during both experimental diets, although greater in the postprandial period for the PUFA diet. The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester (CE) was the plasma triglyceride concentration, that is, the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles (VLDL + LDL). In contrast, the fatty acid composition of these particles had less effect on CETP-mediated CE transfer.

Adult↗

Visual recovery under glare conditions following laser capsulotomy.

The purpose of this study was to look at the changes in Snellen visual acuity and contrast sensitivity under standard and glare conditions before and after Nd:YAG laser capsulotomy. Contrast sensitivity was measured with a Pelli-Robson chart; a Brightness Acuity Tester was used as a glare source. Seventeen pseudophakic patients with no other ocular disease underwent a capsulotomy. Under standard conditions, 7 showed an improvement in visual acuity and 15 showed an improvement in contrast sensitivity. Under glare conditions, 10 patients showed an improvement in visual acuity and all 17 showed an improvement in contrast sensitivity. The improvement in average contrast sensitivity was greater under glare (0.330) than under standard conditions (0.210; p = 0.01). Contrast sensitivity measurement, particularly under glare conditions, provides additional information in the assessment of pseudophakes with opaque posterior capsules.

Aged↗