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Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 73 records · Page 4Linked to original sources

Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET)

OBJECTIVE: The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result. METHODS: Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination. RESULTS: Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters. CONCLUSION: Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Adult↗

Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET)

OBJECTIVE: The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result. METHODS: Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination. RESULTS: Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters. CONCLUSION: Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Cardiovascular Diseases↗

Family history of early cardiovascular disease in children with moderate to severe hypercholesterolemia: relationship to lipoprotein (a) and low-density lipoprotein cholesterol levels.

Lipoprotein (a) (Lp(a)) is an established cardiovascular risk factor in adults. We sought to evaluate whether raised Lp(a) levels were predictive of a family history of early cardiovascular disease (CVD) in children already at increased risk for premature atherosclerosis because of elevated low-density lipoprotein (LDL) cholesterol levels. Lp(a) and serum lipid levels were measured in 69 children and offspring with established moderate to severe hypercholesterolemia (serum cholesterol > 170 mg/dL) who were aged 10.7 +/- 4.3 years (range 1.5 to 21 years) and had been referred to a pediatric lipid center. The children represented families with a positive (n = 27) or negative (n = 42) history for premature CVD (<55 years of age in parent or grandparent). In all children, Lp(a) levels ranged from 1 to 140 mg/dL, with a median of 29 mg/dL. Mean total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels were 234 mg/dL, 166 mg/dL, and 45 mg/dL, respectively. There was no difference in median Lp(a) levels between the children with a positive family history and those with a negative family history (29.9 mg/dL vs 29.0 mg/dL, respectively). In contrast, children with a positive family history showed significantly higher LDL cholesterol levels (186 +/- 61 mg/dL vs 153 +/- 52 mg/dL, P = .02). Thus, in this group of hypercholesterolemic children, LDL cholesterol but not Lp(a) levels were associated with a family history of premature CVD. Further studies are needed to identify additional specific risk factors associated with the development of CVD in this population.

Adolescent↗

Imperforate hymen and ruptured hematosalpinx: a case report with a review of the literature.

The imperforate hymen is a common genital disorder, but a ruptured hematosalpinx is a fairly rare complication. This article presents one case with an imperforate hymen as well as a bilateral hematosalpinx, with unilateral ruptured hematosalpinx, giving a picture of acute abdomen. The pathology, diagnosis, treatment, and complications of these rare cases are discussed. The most important factor for the clinician to remember is the history; a simple inspection provides the diagnostic clue.

Adolescent↗

Plasma endothelin-1 and total insulin exposure in diabetes mellitus.

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate >300 microg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P=0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r=0.5018, P<0.0001), with stimulated plasma C-peptide (r=0.5379, P<0.0001), and with total daily insulin dose (r=0.2219, P=0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.

Adult↗

Factors associated with adolescent use of doping agents: anabolic-androgenic steroids.

AIMS: The purpose was to assess the importance of risk factors such as socio-demographics, sports activities, tobacco use, alcohol consumption, use of certain psychotropic substances and violence in the use of doping agents in adolescents. DESIGN: Cross-sectional survey using anonymous closed response questionnaire. SETTING: Eight senior high schools in Uppsala, Sweden. PARTICIPANTS: A total of 2742 senior high school students; 1592 were in their first year (aged 16-17 years) and 1150 in their third (aged 18-19 years). FINDINGS: Multiple logistic regression analyses revealed that strength training, tobacco use, heavy alcohol consumption, truancy at least once a week and living alone were significantly independently associated in the use of doping agents. Further, the study showed that use of cannabis oil, LSD, amphetamine and opioids were related specifically to anabolic-androgenic steroid use. CONCLUSIONS: Use of doping agents probably involves more than a desire to enhance appearance or sports performance and appears to have much in common with use of alcohol, tobacco and psychotropic drugs.

Adolescent↗

Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters.

BACKGROUND: Compartmental models with constant parameters are commonly used in kinetic analysis of low-density lipoproteins (LDLs). Recent studies in animals have demonstrated the existence of circadian rhythms (CRs) in cholesterol synthesis and LDL catabolism. In this study, we investigated the possible existence of a CR in the fractional catabolic rate (FCR) of LDL apoB in man. MATERIALS AND METHODS: Radioactivity data from 45 turnover studies using 125I-labelled LDL apoB were analysed. In a preliminary analysis the pattern of radioactivity decay was investigated. Kinetic analysis was performed by using one- and two-compartment models with constant parameters (steady-state, SS, analysis). Parameters were estimated by the use of the whole data set, which included frequent sampling during the first day of the turnover study, or the once-a-day data, taken at 08.00 h. The selection of once-a-day data allowed elimination of the impact of a CR on parameter evaluation. Furthermore, non-steady-state (NSS) analysis was performed in which the FCR of LDL apoB was calculated as a function of time. In one additional subject, the FCR of LDL apoB was calculated separately for the day and the night using the urine-to-plasma (U/P) radioactivity ratio. RESULTS: The presence of a CR in LDL apoB catabolism, with higher FCR values during the day than during the morning, was demonstrated by the NSS analysis and confirmed by LDL apoB calculation from the U/P ratio. The SS analysis with the whole and the once-a-day data sets resulted in similar average FCR of apoB values (0.329 +/- 0.076 and 0.321 +/- 0.071 respectively) when the two-compartment model was used. Thus, a CR appeared to have little impact on the average FCR of apoB estimation. However, frequent sampling used in the hope of improving parameter estimation accuracy actually resulted in deterioration of the intercompartmental parameter estimators. CONCLUSION: The fractional catabolic rate of LDL apoB exhibited a circadian rhythm with higher FCR values during the day than during the morning. The presence of a CR had, however, a limited impact on the overall FCR of apoB values.

Apolipoproteins B↗

Insulin-mediated vasodilation and glucose uptake are independently related to fasting serum nonesterified fatty acids in elderly men.

OBJECTIVES: To investigate candidate predictors for insulin sensitivity in healthy elderly males, with special reference to the influence of insulin-mediated skeletal muscle blood flow and serum nonesterified fatty acids (NEFA). SUBJECTS: From the participants in a health survey of 70-year-old males, focusing on cardiovascular risk factors, a subgroup of 46 men was sampled. Only men who declared themselves healthy and without medication were included. INTERVENTIONS: Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Leg blood flow was measured before and during the clamp, using the Doppler ultrasound technique. RESULTS: Hyperinsulinaemia [steady-state plasma insulin 105(15) mU L-1] increased leg blood flow by 10% (P < 0.004). When tested in bivariate analysis incremental leg blood flow was only significantly related to the serum NEFA concentration (r = - 0.38, P < 0.01) amongst a number of measured variables. Insulin-mediated glucose disposal was related to body mass index (BMI) (r = -0.49, P = 0. 0006), waist/hip ratio (r = - 0.31, P = 0.036), NEFA (r = - 0.50, P = 0.0004) and heart rate (r = - 0.34, P = 0.02). In multivariate analysis only BMI and NEFA remained significantly related to whole-body glucose uptake. CONCLUSIONS: The study demonstrates that in elderly men BMI and fasting serum NEFA but not insulin-induced vasodilation are related to insulin sensitivity. High fasting levels of NEFA relate to both impaired insulin-mediated vasodilation and impaired glucose disposal, respectively. These two insulin actions were not interrelated, however, a finding which may indicate dissociated mechanisms.

Aged↗

Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.

BACKGROUND: Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. METHODS: One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. RESULTS: Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. CONCLUSION: These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.

Absorptiometry, Photon↗

Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus.

BACKGROUND: The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR. METHODS: We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter. RESULTS: Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control. CONCLUSIONS: Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.

Adult↗

Elevated plasma levels of neuropeptide Y in female fibromyalgia patients.

Neuropeptide Y(NPY) co-exists with norepinephrine in the sympathetic nervous system, and NPY may represent the sympathetic-neuronal output. Fibromyalgia syndrome (FMS) patients have perturbations in the hypothalmic-pituitary-adrenal (HPA) axis and in the sympathetic stress axis as well. As opioid peptides, monoamines and sex steroids are integrated in the regulation of stress, it is interesting to further explore the role of NPY in FMS patients, as they show many symptoms that are related to perturbations of those systems.In this study, plasma NPY levels were assessed in subgroups of FMS patients: cyclic (regular menstrual cycles), non-cyclic (post-menopausal), depressed and non-depressed patients. In order to examine whether pain and other symptoms seen in FMS patients are correlated to the NPY levels, the patients were also registering 15 different symptoms daily during 28 days. Sex and age-matched healthy controls were recruited for comparisons. Non-parametric tests were used for the statistical analyses.The results showed that the NPY levels were significantly elevated in the patients compared to the controls. In the luteal phase of the cyclic patients, the levels of the peptide were higher than in the corresponding controls. For the non-cyclic patients, there was a positive correlation between physical symptoms and NPY levels, however, pain per se did not reach the significant level of correlation. The non-depressed patients had the same levels of NPY as the depressed FMS patients, who also had a positive correlation between anxiety and NPY levels.These results suggest that FMS patients have an altered activity in the NPY system, most likely due to prolonged and/or repeated stress, and that the hormonal state and time of the menstrual cycle also may be of importance in the complex pathophysiologic mechanism behind the development of FMS. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

Constraint and material properties of the subregions of the scapholunate interosseous ligament.

The material and constraint properties of the dorsal, proximal, and palmar regions of the scapholunate ligament were studied using isolated bone-ligament-bone preparations from 24 adult intact cadaver wrists. Determinations of constraint to differential rotation and translation as well as failure strength were made using a servohydraulic testing machine incorporating an additional rotatory actuator. The dorsal region of the scapholunate ligament offered the greatest constraint to differential translation, while both the dorsal and palmar regions demonstrated statistically significant combined constraints to differential rotation between the scaphoid and lunate. The greatest yield strength was found in the dorsal region (260.3 N +/- 118.1 N), followed by the palmar region (117.9 N +/- 21.3 N) and the proximal region (62.7 N +/- 32.2 N).

Adult↗

HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects.

BACKGROUND: Little information is available about HDL subpopulations during dietary changes. OBJECTIVE: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations. DESIGN: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat,15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat). RESULTS: HDL(2)-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 +/- 0.21, 0.53 +/- 0.19, and 0.48 +/- 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL(3) cholesterol decreased (P < 0.01) less: 0.76 +/- 0.13, 0.73 +/- 0.12, and 0.72 +/- 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL(2b) subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL(3a, 3b), and (3c) subpopulations (P < 0.01). HDL(2)-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = -0.46, -0.37, and -0.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL(2b), whereas HDL(3a, 3b), and (3c) correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL(2) and HDL(2b) cholesterol. CONCLUSIONS: A reduction in dietary total and saturated fat decreased both large (HDL(2) and HDL(2b)) and small, dense HDL subpopulations, although decreases in HDL(2) and HDL(2b) were most pronounced.

Adult↗

Heme oxygenase inhibitors transiently increase serum ferritin concentrations without altering other acute-phase reactants in man.

Sn protoporphyrin (SnPP) and Sn mesoporphyrin (SnMP), potent inhibitors of heme oxygenase (HO), significantly suppress bilirubin production, lower serum and biliary bilirubin levels and increase biliary heme output in animals and man. In this study, 20 healthy volunteers, 7 patients with primary biliary cirrhosis and 4 patients with idiopathic hemochromatosis were treated with SnPP and 4 healthy volunteers with SnMP. In all cases, serum ferritin levels increased substantially but transiently after administration of these HO inhibitors. Values returned to baseline within a few days. Infusion of hematin in 4 healthy volunteers did not significantly affect ferritin levels. No increases occurred in 7 other acute-phase reactants. The observation that these HO inhibitors transiently increase serum ferritin levels implies a link between ferritin, iron metabolism and HO activity which may be usefully explored in disorders of iron metabolism.

Acute-Phase Proteins↗

Peripheral atherosclerosis and serum lipoprotein(a) in diabetes.

OBJECTIVE: Serum lipoprotein(a) [Lp(a)] is strongly associated with atherosclerosis in nondiabetic individuals. To see if atherosclerosis is also associated with serum Lp(a) in both IDDM and NIDDM, we determined the correlation between the toe systolic blood pressure index (TSPI) and serum Lp(a) in tightly controlled diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS: Cross-sectional study of 57 IDDM and 35 NIDDM patients. All patients had been under strict glycemic control for at least 6 months. The main outcome measure was TSPI of both lower extremities. In addition, we measured serum Lp(a) and other serum lipids, serum uric acid, total plasma homocysteine, plasma C-peptide, HbA1c, albumin excretion rate, glomerular filtration rate, BMI, abdominal fat distribution, left ventricular hypertrophy, probabilities for cardiovascular disease (CVD), and routine clinical parameters. RESULTS: TSPI was closely and independently related to serum Lp(a) in IDDM patients: R2 = 0.2999, partial P = 0.0005, and in NIDDM patients: R2 = 0.7326, partial P = 0.0030. TSPI was associated with symptoms of CVD. Median serum Lp(a) concentration was normal in IDDM (45 mg/l [range 10-870]) and NIDDM (72 mg/l [11-803]) patients. CONCLUSIONS: Systemic atherosclerosis measured as the degree of peripheral occlusive arterial disease is strongly associated with serum Lp(a) in both IDDM and NIDDM patients. Serum Lp(a), however, is normal in both types of diabetic patients. Thus, it is indicated that serum Lp(a) should be measured in diabetic patients when assessing their risk profile for atherosclerosis.

Arteriosclerosis↗

Isolation of adipophilin and butyrophilin from bovine milk and characterization of a cDNA encoding adipophilin.

The milk fat globule membrane-associated proteins adipophilin (alias adipocyte differentiation-related protein) and butyrophilin were purified from bovine milk by reverse-phase chromatography. The nucleotide sequence of bovine adipophilin was obtained via peptide mapping and sequencing of a mammary gland cDNA clone, which comprises 1841 nucleotides and has an open reading frame of 450 amino acids. By peptide mapping, 19% of the amino acid sequence was confirmed. The obtained amino acid sequence has 87 and 80% identical residues with human and mouse adipophilin, respectively. Alignment with the proteins perilipin and TIP47 revealed two highly conserved segments, which may assemble into amphipathic alpha-helices.

Amino Acid Sequence↗

A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E.

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at -317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE varepsilon2 was 0. 98, without significant ethnic difference. In contrast, the frequency of H2 with apoE epsilon4 was 0.85 in European-Americans but only 0.55 in African-Americans (P < 0.001). The frequency of H2 with apoE epsilon3 was 0.02 in European-Americans and 0.08 in African-Americans (P < 0.001). African-American apoE epsilon3/epsilon3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes (P = 0.03) along with 18% higher HDL-cholesterol levels (P = 0.02). ApoB levels were 21% lower (P = 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatoma-cell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations.

Alleles↗

Re-evaluation of the ferrous oxidation in xylenol orange assay for the measurement of plasma lipid hydroperoxides.

The ferrous oxidation in xylenol orange version 2 (FOX2) assay coupled with triphenylphosphine has recently been employed for the measurement of total plasma hydroperoxides (ROOHs). In this study, we have evaluated sample handling and the effect of storage conditions on ROOH levels in human plasma (n = 32). Mean level of ROOHs in fresh plasma was 8.35 +/- 3.09 mumol/l (range 4.03-19.5 mumol/l). Addition of butylated hydroxytoluene (BHT) immediately after sample collection had no effect on the concentration of ROOHs. Storage of samples at -70 degrees C for 6 weeks was associated with a variable degree of loss of detectable ROOHs. A mean ROOH level of 6.00 +/- 2.23 mumol/l (range 2.88-13.5 mumol/l) was recorded after 6 weeks of storage at -70 degrees C. There was no difference in the mean level of ROOHs between samples stored for 6 and 60 weeks at -70 degrees C. Inclusion of BHT had no effect on the stability of plasma ROOHs during prolonged storage. Intra-assay coefficients of variation were < 12%, with the lowest variation in fresh samples (7.6%). In conclusion, these results suggest that the FOX2 assay should be a useful tool for measurement of ROOHs in fresh plasma samples but not in stored samples.

Adult↗