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Biomedical subjects

R G Reed

Publications and source records attributed to R G Reed.

At least 19 recordsLinked to original sources
PubMed2001

Fluorescence-based, nonradioactive method for efficient detection of the pentanucleotide repeat (TTTTA)(n) polymorphism in the apolipoprotein(a) gene.

BACKGROUND: The apolipoprotein(a) [apo(a)] gene is a major predictor of plasma lipoprotein(a) concentrations, an independent risk factor for cardiovascular disease. The apo(a) gene contains a pentanucleotide repeat (PNR) polymorphism, 1.4 kb upstream from the apo(a) gene reading frame. This polymorphism has been suggested to be important in control of apo(a) gene expression. METHODS: We developed a fluorescence-based, nonradioactive procedure to detect the PNR polymorphism. After amplification of the polymorphism by PCR, the respective PCR products were separated by denaturing polyacrylamide gel electrophoresis and detected using a 3'-end fluorescently labeled oligonucleotide as a probe. We used the method to characterize the PNR polymorphism pattern in 313 individuals, 195 Caucasians and 118 African Americans. The new method efficiently separated DNAs corresponding to the different PNR repeats. RESULTS: Among both ethnic groups, alleles containing eight PNRs were most common. Smaller PNRs were more common among African Americans, and larger PNRs were more common among Caucasians. CONCLUSIONS: We developed a nonradioactive technique that separates the PNR polymorphism in the apo(a) gene and can be used in other studies involving closely sized polymorphisms.

Apolipoproteins A↗
PubMed2000

Variation of lipids and lipoproteins in premenopausal women compared with men and postmenopausal women. DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) Investigators.

Numerous studies have reported cyclic fluctuations in lipids and lipoproteins as a function of the phase of the menstrual cycle. However, the reported patterns are quite variable and have led to an unclear picture of the influence of the menstrual cycle on the variability of lipids, and hence of the role of the menstrual cycle phase in the interpretation of serum lipids for premenopausal women. As part of the DELTA Study (Dietary Effects on Lipoproteins and Thrombogenic Activity), we evaluated the cyclic variation of circulating lipids and lipoproteins in 39 premenopausal women and compared intraindividual variances in these women, 18 postmenopausal women, and 46 men under conditions of tight dietary control. Cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, apolipoproteins A-1 (apo A-1) and B-100 (apo B-100), and lipoprotein (a) [Lp(a)] all demonstrated cycling in the premenopausal women. However, the observed cycling accounts for only a small fraction of the total biologic variability of lipids in premenopausal women. The magnitude of total intraindividual variability based on coefficient of variation (CV) for these lipids in premenopausal women (CV, 4% to 8.1%) was similar to that found for men (CV, 4.3% to 9.1%) and for postmenopausal women (CV, 3.7% to 6.7%). These results suggest that protocols for screening and monitoring of serum lipids in premenopausal women need not differ from those used for men or postmenopausal women.

Adult↗
PubMed2000

Race-related differences among patients with left ventricular dysfunction: observations from a biracial angiographic cohort. Harlem-Bassett LP(A) Investigators.

BACKGROUND: This study was designed to describe race-related differences in left ventricular function among a consecutive series of patients undergoing cardiac catheterization and to identify racial differences in coexistent medical and social conditions that are associated with the development of heart failure (HF). METHODS AND RESULTS: This was a prospective cohort study conducted at 2 university-affiliated teaching hospitals. We used the database of the Harlem-Bassett Lp(a) Study. We included all black (N = 143) or white (N = 313) patients from the main study database for whom complete survey, laboratory, coronary angiographic, and ventriculographic data were available. "Left ventricular dysfunction" was arbitrarily defined as an ejection fraction < or =0.40 or prior pharmacologic treatment for HF. We found that blacks were younger, had a higher proportion of women, and had fewer years of formal education than their white counterparts. Coronary artery disease was less common among blacks, although this group had a higher prevalence of hypertension, diabetes, cigarette smoking, illicit drug use, and alcohol consumption. Black patients had a higher prevalence of previous treatment for HF, larger left ventricular volumes, and lower ejection fractions than white patients. Blacks with left ventricular dysfunction were more likely to have had a previous myocardial infarction or a history of hypertension compared with those without left ventricular dysfunction. CONCLUSIONS: Regarding left ventricular dysfunction and HF, we conclude that blacks seem to have a much higher burden of disease than whites. Our observations support prior evidence that hypertension is linked to race-related differences in the epidemiology of HF. The interaction between race and access to quality care for HF remains an important area for future investigation.

Adult↗
PubMed2000

Plasma sphingomyelin level as a risk factor for coronary artery disease.

Only a fraction of the clinical complications of atherosclerosis are explained by known risk factors. Animal studies have shown that plasma sphingomyelin (SM) levels are closely related to the development of atherosclerosis. SM carried into the arterial wall on atherogenic lipoproteins may be locally hydrolyzed by sphingomyelinase, promoting lipoprotein aggregation and macrophage foam cell formation. A novel, high-throughput, enzymatic method to measure plasma SM levels has been developed. Plasma SM levels were related to the presence of coronary artery disease (CAD) in a biethnic angiographic case-control study (279 cases and 277 controls). Plasma SM levels were higher in CAD patients than in control subjects (60+/-29 versus 49+/-21 mg/dL, respectively; P:<0. 0001). Moreover, the ratio of SM to SM+phosphatidylcholine (PC) was also significantly higher in cases than in controls (0.33+/-0.13 versus 0.29+/-0.10, respectively; P:<0.0001). Similar relationships were observed in African Americans and whites. Plasma SM levels showed a significant correlation with remnant cholesterol levels (r=0.51, P:<0.0001). By use of multivariate logistic regression analysis, plasma SM levels and the SM/(SM+PC) ratio were found to have independent predictive value for CAD after adjusting for other risk factors, including remnants. The odds ratio (OR) for CAD was significantly higher for the third and fourth quartiles of plasma SM levels (OR 2.81 [95% CI 1.66 to 4.80] and OR 2.33 [95% CI 1.38 to 3. 92], respectively) as well as the SM/(SM+PC) ratio (OR 1.95 [95% CI 1.10 to 3.45] and OR 2.33 [95% CI 1.34 to 4.05], respectively). The findings indicate that human plasma SM levels are positively and independently related to CAD. Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase.

Case-Control Studies↗
PubMed2000

High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men.

Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).

Black or African American↗
PubMed2000

Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms.

STUDY OBJECTIVES: Improvement in coronary artery endothelial function has been demonstrated after cholesterol lowering in hypercholesterolemic patients with significant atherosclerosis. However, to our knowledge, no previous study has shown improvement in resistance artery function in subjects with normal coronary arteries after cholesterol lowering. The purpose of our study was to investigate the effect of cholesterol lowering with pravastatin on coronary resistance artery endothelial function in the setting of angiographically normal coronary arteries. METHODS: Invasive testing of coronary endothelial and vasomotor function was performed at baseline and after 6 months of pravastatin treatment in six patients with normal coronary arteriograms. RESULTS: After 6 months of pravastatin treatment, low-density lipoprotein cholesterol level dropped from 157+/-11 to 117+/-8 mg/dL (p = 0.02) and percent increase in coronary blood flow after acetylcholine improved from 97+/-13% to 160+/-16% (p = 0.01). There was a trend (p = 0.17) toward enhanced epicardial dilation in response to acetylcholine after pravastatin treatment when compared with the baseline study. CONCLUSIONS: Our study demonstrates significant improvement in coronary resistance artery endothelial function after 6 months of cholesterol lowering with pravastatin in six subjects presenting with chest pain who were found to have normal coronary arteriograms. A trend toward improved epicardial vasomotion was also observed.

Adult↗
PubMed1997

Fatty acid carbon isotope ratios in humans on controlled diets.

Carbon stable isotope ratios for six serum fatty acids (FA) are reported for human subjects on controlled fat diets to determine the range of natural isotope abundance and to demonstrate the leveling effect of a well-controlled diet. Twenty-nine subjects were randomly assigned to one of three controlled diets containing high, medium, or low fat. Diets were consumed for 8 wk. Serum samples were collected at baseline (0), 5, 6, 7, and 8 wk. FA were extracted and methylated. Isotope ratios were analyzed by high-precision gas chromatography combustion-isotope ratio mass spectrometry. At baseline, mean delta 13C for 16:0b, 16:1a, 18:0a, 18:1c,18:2n-6d and 20:4n-6bc were -24.1, -21.7, -21.6, -25.6, -29.6, and -25.0/1000, respectively, with an average standard deviation of 1.9/1000. Most delta 13C decreased during the diet period and appeared to have stabilized by week 5 at -25.3, -21.9, -22.3, -26.5, -30.1, and -24.5/1000, respectively. Between-subjected variability decreased from 1.74 to 1.20/1000 on the controlled diets. Measurement variability was 0.53/1000. The within-subject variability during weeks 5-8 was 0.57/1000 (range of 0.32-0.84/1000), showing a minimum biological fluctuation on controlled diets. There was no diet group effect on delta 13C of serum FA. Except for 18:2, the delta 13C of experimental diets was lower than that of serum FA, consistent with observations in animals. These data show that carbon isotope ratios stabilize in response to controlled diets within 5 wk, reflecting the isotope ratio of their dietary source, and establish isotope ratio fluctuations for endogenous compounds for future studies.

Adult↗
PubMed1995

Role of a central laboratory in implementing national cholesterol education panel guidelines in rural practices: model system for managed care.

We describe the use of a central laboratory to identify patients who may be candidates for a hypercholesterolemia treatment program and to direct their referral into this program. The laboratory, providing service for 16 medical practices in a rural area of upstate New York, served as the entry point to the treatment program for those patients with serum cholesterol > or = 5.18 mmol/L. This treatment program, designed to follow the National Cholesterol Education Program Adult Treatment Panel Guidelines, was provided by the lipid referral center staff, including a registered dietitian and a lipid specialist. After introduction of this program, 52% of eligible patients received nutritional counseling for hypercholesterolemia, compared with only 29% in usual care settings. This program represents an enhanced role for laboratories in the implementation of treatment protocols typical of those adopted by managed care networks.

Counseling↗
PubMed1991

Locations of the three primary binding sites for long-chain fatty acids on bovine serum albumin.

Binding of 13C-enriched oleic acid to bovine serum albumin and to three large proteolytic fragments of albumin--two complementary fragments corresponding to the two halves of albumin and one fragment corresponding to the carboxyl-terminal domain--yielded unique patterns of NMR resonances (chemical shifts and relative intensities) that were used to identify the locations of binding of the first 5 mol of oleic acid to the multidomain albumin molecule. The first 3 mol of oleic acid added to intact albumin generated three distinct NMR resonances as a result of simultaneous binding of oleic acid to three heterogeneous sites (primary sites). Two of these resonances were seen upon addition of 1 or 2 mol of oleic acid to fragments representing either the carboxyl-terminal half (residues 307-582) or the carboxyl-terminal domain (residues 377-582); the third resonance was seen upon addition of 1 mol of oleic acid to the fragment representing the amino-terminal half (residues 1-306). The resonance patterns for the fourth and fifth moles of oleic acid added to albumin (secondary sites) could not be duplicated by addition of more oleic acid to individual fragments. These resonance patterns were generated, however, when the two complementary fragments were mixed in equimolar proportions to form an albumin-like complex with a reconstituted middle domain. Thus, two primary fatty acid binding sites are assigned to the carboxyl-terminal domain, one primary site is assigned to the amino-terminal half, and the secondary sites are assigned to the middle domain. This distribution suggests albumin to be a less symmetrical binding molecule than theoretical models predict. This work also demonstrates the power of NMR for the study of microenvironments of individual fatty acid binding sites in specific domains.

Binding Sites↗
PubMed1991

The prognostic value of immunoperoxidase staining with monoclonal antibodies NCRC-11 and 3E1.2 in breast cancer.

The variation in survival of women with clinically similar breast cancers may lead to difficulty in clinical management so it is important to recognise factors which indicate the prognosis. Immunoperoxidase staining patterns of primary breast tumours using monoclonal antibody NCRC-11 have been shown to relate to overall survival (Ellis et al., 1985) but the results have not been reproducible in other centres. In this study paraffin sections of 483 primary breast cancers were stained with NCRC-11 and 3E1.2 using an immunoperoxidase system. The tumour staining patterns were compared with overall survival using life tables and tested for relative prognostic significance by Cox's multivariate analysis. NCRC-11 related to survival in all 483 cases (chi 2 5.8, P = 0.02) but both antibodies achieved maximum prognostic significance in lymph node negative patients (chi 2 9.4, P less than 0.002 and chi 2 10.7, P less than 0.001) in whom no other factor was more significant. Immunoperoxidase staining patterns produced by monoclonal antibodies NCRC-11 and 3E1.2 are important prognostic factors in breast cancer.

Antibodies, Monoclonal↗
PubMed1990

Spurious cell surface receptors: inadequate correction for saturable, nonspecific binding mimics receptor binding.

Methods commonly used for the characterization of receptors on cell surfaces may be subject to adsorption artifacts that mimic the action of receptors even when no receptors are present. Traditional techniques such as incubation in the presence of an unrelated protein to minimize adsorption or extensive washing to eliminate nonspecific binding may be inadequate to ensure that the observed binding is due to a cell membrane--ligand interaction. In this paper three serum proteins, albumin, transferrin, and immunoglobulin G, are shown to exhibit behavior suggestive of receptor-mediated binding even in the absence of cells. Two types of control studies are suggested to establish that observed binding is attributable to interaction with cells.

Adsorption↗
PubMed1989

The albumin receptor effect may be due to a surface-induced conformational change in albumin.

To determine whether equilibrium binding between albumin and hepatocytes involves a cell surface receptor for albumin, we incubated freshly isolated rat hepatocytes with 125I-albumin and determined the amount of albumin associated with the cells as a function of the total albumin concentration. The resulting two-phase binding curve showed the rat albumin-hepatocyte interaction to consist of a saturable binding interaction with a dissociation constant of 1.1 microM and 2 X 10(6) sites/cell in addition to a weak, nonsaturable binding interaction. However, the saturable binding of albumin to hepatocytes did not appear to result from the presence of an albumin receptor on the cell surface; the interaction was the same for different species of albumin, for chemically modified albumins, and for fragments of albumin representing mutually exclusive domains of the molecule. The saturable binding was, instead, found to involve a subpopulation of albumin with an enhanced affinity for the cell surface. We show that this subpopulation of albumin is generated upon contact with either solid surfaces or cell surfaces and can be transferred from one surface to another. We propose that the two-phase Scatchard binding curve and the "albumin receptor effect" reflect two populations of albumin that bind to the cell surface with different affinities rather than one population of albumin that binds to two classes of binding sites.

Animals↗
PubMed1988

Ligand-binding properties of albumin Parklands: Asp365----His.

An albumin variant, isolated from the plasma of a patient with bisalbuminemia, was compared with albumin A from the same patient for binding of long-chain fatty acids and bilirubin. No differences in binding of [14C]palmitate, cis-parinaric acid or bilirubin could be detected for the variant form. These results suggest that the region adjacent to residue 365 is unlikely to be part of a major binding site for any of these ligands.

Bilirubin↗
PubMed1988

Non-resolving jaundice: bilirubin covalently attached to serum albumin circulates with the same metabolic half-life as albumin.

In hepatobiliary disease and biliary obstruction, bilirubin often becomes covalently bound to albumin circulating in serum, producing a nondissociable complex. To determine how long this complexed bilirubin remains in the circulation, we compared the metabolic clearance of bilirubin-albumin complexes with the clearances of free bilirubin and unmodified albumin. Radiolabeled bilirubin, albumin, and covalent bilirubin-albumin were injected into the circulation of Sprague-Dawley rats and serial samples of plasma were analyzed for the injected compounds. The half-life of bilirubin was 6.2 min. The half-life of bilirubin covalently bound to rat serum albumin was 1.9 to 2.1 days, identical to that of unmodified rat albumin. We conclude that bilirubin covalently attached to albumin is maintained in the circulation with the long half-life of albumin rather than the short half-life of bilirubin. Because albumin in humans has a half-life of 19 days, covalent attachment of bilirubin to human albumin could result in persistence of hyperbilirubinemia long after the resolution of disease.

Animals↗