Search PubMed⌕ Search

Biomedical subjects

B A Kottke

Publications and source records attributed to B A Kottke.

At least 37 records · Page 2Linked to original sources
PubMed1993

Quantification of human plasma apolipoproteins C-I, C-II, and C-III by radioimmunoassays.

We have developed radioimmunoassays for the quantification of apolipoproteins (apo) C-I, C-II, and C-III in human plasma. The apo C proteins were isolated from very low-density lipoproteins of patients with hypertriglyceridemia, fractionated on a Sephacryl column, and purified by diethylaminoethyl cellulose anion-exchange chromatography followed by reverse-phase fast protein liquid chromatography. The assays were sensitive, specific, and reproducible, and the standards demonstrated parallel immunoreactivity with plasma samples. Patients with hypertriglyceridemia (triglyceride level more than 2,200 mg/liter)--14 patients with diabetes and 12 with type V hyperlipoproteinemia--were compared with age- and sex-matched control subjects. In comparison with the control groups, levels of apoproteins C-I, C-II, and C-III were significantly increased in both disease groups, but the ratios of the C peptides to triglycerides were significantly lower, an indication of a relative deficiency of C apoproteins in hypertriglyceridemic states. Independent radioimmunoassays for each of the C apolipoproteins would help to study their individual roles in triglyceride-rich lipoprotein metabolism.

Adult↗
PubMed1993

Differential health benefits of weight loss in upper-body and lower-body obese women.

Upper-body obesity (UB Ob) is more strongly associated with adverse health consequences; however, few obesity-treatment studies have examined outcome according to body-fat distribution. To examine whether diet and formal- or informal-exercise instruction causes differential changes in health and lipid profiles, ten LB Ob and nine UB Ob premenopausal women received dietary intervention (2.1 MJ-deficit/d for 16 wk) and were randomly assigned to either formal- or informal-exercise instruction. Weight loss was similar between groups (approximately 8 kg), and no change occurred in lean body mass or basal metabolic rate. Baseline cholesterol and triglycerides were greater (P < 0.01) in UB Ob than LB Ob women and decreased more (P < 0.01) in response to treatment in UB Ob women. Formal exercise instruction increased high-density-lipoprotein cholesterol (P < 0.05) especially in UB Ob women. Future studies on treatment of obesity should include consideration of regional fat distribution.

Adipose Tissue↗
PubMed1993

Lipoprotein compositional changes in the fasting and postprandial state on a high-carbohydrate low-fat and a high-fat diet in subjects with noninsulin-dependent diabetes mellitus.

Our aims were 1) to examine the effects of a high-carbohydrate low-fat diet on fasting and postprandial plasma lipids, apolipoproteins (apo), and lipoprotein composition in noninsulin-dependent diabetes mellitus, and 2) to determine whether postprandial shift of apo between triglyceride-rich lipoproteins (TRLP) and high density lipoproteins (HDL) is affected by diet. A cross-over study, of 4 weeks duration, of a high-carbohydrate (60% carbohydrate, 20% fat) and a high-fat (40% carbohydrate, 40% fat) diet was performed in seven subjects with noninsulin-dependent diabetes mellitus. TRLP, low density lipoproteins (LDL), and HDL were separated by fast protein liquid chromatography. The high-carbohydrate diet resulted in a decrease of fasting total, HDL, and LDL cholesterol and a trend toward an increase in plasma triglycerides. The apo composition of fasting TRLP and HDL was similar on both diets. TRLP apo CII, CIII, and E increased whereas HDL apo CII, CIII, and E decreased postprandially on both diets. In contrast, TRLP apo CI increased, and HDL apo CI decreased only after the high-carbohydrate diet. We conclude that 1) a high carbohydrate diet results in a decrease in total, LDL, and HDL cholesterol and a trend toward an increase in plasma triglycerides; 2) fasting TRLP and HDL apo composition was similar on a high-carbohydrate or a high-fat diet; and 3) on both diets, apo CII, CIII, and E transfer from HDL to TRLP postprandially. However, only the high-carbohydrate diet induced postprandial transfer of apo CI from HDL to TRLP. This may explain in part the changes in lipoproteins observed with this diet.

Aged↗
PubMed1993

Insulinemia in children at low and high risk of NIDDM.

OBJECTIVE: Fasting hyperinsulinemia in the presence of normoglycemia usually indicates insulin resistance and is characteristic of populations at high risk for developing NIDDM. Hyperinsulinemia predicts the development of impaired glucose tolerance and NIDDM in Pima Indians, a population with a high incidence of NIDDM. Insulin concentrations in population-based samples of children who have different risks of developing NIDDM later in life have not been reported previously. RESEARCH DESIGN AND METHODS: We compared fasting insulin concentrations in two populations of nondiabetic children, 6-19 yr of age: Pima Indians from southern Arizona and Caucasians from Minnesota. RESULTS: Insulin concentration varied with age, sex, glucose concentration, and relative weight. Mean fasting insulin concentration was 140.3 pM in Pima Indian males, 94.4 pM in Caucasian males, 171.5 pM in Pima Indian females, and 107.1 pM in Caucasian females. For each sex, the mean fasting insulin concentration, controlled for age, glucose, and relative weight, was significantly higher in the Pima Indians than in the Caucasians (P < 0.001). CONCLUSIONS: From a young age, Pima Indian children have higher fasting insulin concentrations than Caucasian children. As hyperinsulinemia predicts subsequent NIDDM, these data suggest that the susceptibility to NIDDM is manifest at a young age as fasting hyperinsulinemia.

Adolescent↗
PubMed1992

Estimation of the frequency of isoform-genotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms.

Estimates of the impact of apolipoprotein E (apo E) alleles coding for the three common isoforms on plasma lipid levels assume genetic homogeneity among the genotype classes. To test this assumption, we have determined the apo E genotype at the two common polymorphic sites (amino acids 112 and 158) by DNA amplification and hybridisation with allele-specific oligoprobes, in 195 unrelated Caucasian participants of the Rochester Family Heart Study previously classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant samples were initially detected. Repeat typing of these samples by both methods resolved nine discrepancies and analysis of additional blood samples from the remaining five individuals eliminated a further four discrepancies. The only truly discordant allele was found in a female subject who had an E3 isoform with the common E2 (Cys112, Cys158) genotype. Transmission of this allele from the mother was demonstrated. From these results, we estimate the frequency of discrepancies between isoforms and common genotypes to be 0.25% in this population. Allele misclassification was caused by poor amplification of the DNA in six samples and superimposition of glycosylated and nonglycosylated apo E isoforms on isoelectric focusing gels in five samples. We conclude that the assumption of genetic homogeneity among genotype classes is valid and that misclassification due to technical difficulties is more frequent than true discordancies.

Adult↗
PubMed1992

Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk?

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.

Adult↗
PubMed1992

Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E-rich very low density lipoprotein fraction.

To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.

Adult↗
PubMed1992

Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol.

In a retrospective analysis, 63 participants in a cardiac rehabilitation-preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time-release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty-four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol, HDL↗
PubMed1992

Apolipoprotein B quantified by particle-concentration fluorescence immunoassay.

We have developed a particle-concentration fluorescence immunoassay (PCFIA) for estimating apolipoprotein (apo) B concentrations in plasma. A two-step antigen-detection system with a polyclonal antibody to apo B bound to carboxyl-polystyrene particles binds the antigen, and a fluorescein-labeled monoclonal antibody detects the bound apo B. Narrow-cut low-density lipoproteins (d = 1.03-1.05 kg/L) were used as the primary standard. The assay compares well with the enzyme-linked immunosorbent assay. The PCFIA gives parallel responses with low-density lipoprotein, very-low-density lipoproteins, and plasma samples, and can be fully automated and completed in 3 h. In a pilot study of patients with diabetes, coronary artery disease (CAD), or both, we found statistically significant differences in apo B concentrations for patients with both CAD and diabetes compared with those for patients with diabetes alone or for control subjects (P < 0.01).

Apolipoproteins B↗
PubMed1992

The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants.

The influence of the apolipoprotein E (Apo E) polymorphism and gender on the regression relationships between each of nine plasma lipid and apolipoprotein traits (total cholesterol; ln triglycerides; high-density-lipoprotein cholesterol; apolipoproteins AI, AII, B, and CII; ln CIII; and ln E) and four concomitants (age, weight, waist-to-hip ratio, and smoking) was studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Analyses are presented separately for females and males. Each lipid and apolipoprotein trait exhibited at least one Apo E genotype-specific regression relationship with the concomitants investigated in this study. In most cases the heterogeneity of regression was associated with differences between the epsilon 32 and epsilon 33 genotype. This study documents that the influence of Apo E genotype on average levels of plasma lipids and apolipoproteins varies among subdivisions of the population defined by age, body size, and smoking status.

Adult↗
PubMed1991

Effect of coconut oil on plasma apo A-I levels in WHHL and NZW rabbits.

Age-matched Watanabe (WHHL) and New Zealand White (NZW) rabbits were fed a coconut oil-enriched diet (14%, w/w) for 2 weeks. Lipid and apolipoprotein (apo) A-I levels in plasma and lipoprotein fractions were monitored. Within 3 days after the start of the coconut oil diet, plasma apo A-I and high-density lipoprotein (HDL)-apo A-I levels increased 3-fold in the WHHL rabbits. A smaller but significant increase (63%) in apo A-I and HDL-apo A-I levels was also observed in the NZW rabbits. HDL cholesterol levels also increased from 16 +/- 3 mg/dl during a regular diet to 46 +/- 16 mg/dl (288%) during the coconut oil diet in the WHHL rabbits and from 37 +/- 7 mg/dl to 69 +/- 19 mg/dl (186%), respectively, in the NZW rabbits. Apo A-I and HDL cholesterol levels fell sharply to the original levels soon after switching back to a regular diet (within 3 days for WHHL rabbits and within 5 days for NZW rabbits). The fractional catabolic rate calculated from 125I-HDL kinetic studies indicated that the turnover rate for HDL was significantly slower in WHHL rabbits fed the coconut oil diet than the control diet (0.018 +/- 0.004 h-1 vs. 0.027 +/- 0.007 h-1, P less than 0.01). No changes were found in the NZW rabbits fed either diet. Trilaurin, the main component of the coconut oil (46.9%) supplemented diet (6.5%, w/w), was also used in this study. The effect of trilaurin on plasma apo A-I and HDL-cholesterol levels is discussed.

Animals↗
PubMed1991

Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels.

The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension.

Adult↗
PubMed1991

ApoA-I secretion by rabbit intestinal mucosa cell cultures.

Lipid and apolipoprotein (apo) A-I concentrations in different density fractions of New Zealand White (NZW) and Watanabe (WHHL) rabbit plasma were studied. Aside from the low plasma apoA-I and high density lipoprotein (HDL) cholesterol levels in WHHL rabbits, the distribution of apoA-I was also different between the two rabbits. ApoA-I was concentrated in both the HDL2 and HDL3 fractions of NZW rabbits but was found primarily in the HDL3 fraction of WHHL rabbits. ApoA-I secretion in these two rabbits was further studied in vitro by using intestinal and hepatocyte cell cultures. ApoA-I secretion was highest from cultures of the duodenum and the proximal end of the jejunum; whereas, cell cultures of the distal end of the small intestine secreted very little apoA-I into the medium. Intestinal cell cultures from WHHL rabbits secreted less, but significant amounts of, apoA-I compared to that of NZW rabbits. ApoA-I was most concentrated in the density range of 1.12-1.21 (HDL3) fraction in medium containing 10% fetal calf serum (FCS). Serum-free medium promoted apoA-I secretion by intestinal cell cultures that was mostly found in the d greater than 1.21 (lipoprotein-deficient) fraction. Hepatocytes isolated from the same rabbits by collagenase perfusion secreted little apoA-I, and it was found only in the d greater than 1.21 fraction. The addition of oleic acid into the culture medium with 10% FCS decreased the secretion of total apoA-I and HDL by intestinal cell cultures and increased the secretion of very low density lipoprotein (VLDL) and intermediate density lipoproteins (IDL).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension.

The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension.

Adult↗
PubMed1991

Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin.

Hepatitis developed in five patients who were taking low dosages (3 g/day or less) of time-release niacin. In four of the five patients, clinical symptoms of hepatitis developed after the medication had been taken for a relatively short time (2 days to 7 weeks). This manifestation of hepatotoxicity seems to differ from that previously reported in association with use of crystalline niacin, which occurred with high dosage and prolonged usage of the medication. In view of the recent increased frequency of prescribing niacin for the treatment of hyperlipidemia, physicians should be aware of the potential for hepatotoxicity with even low-dose and short-term use of time-release niacin.

Adult↗
PubMed1991

Lipoprotein analysis in the evaluation of chest pain in the emergency department.

Apolipoproteins were measured in a prospective blinded fashion in blood specimens from patients with chest pain in the emergency department. A definitive diagnosis for the chest pain (non-cardiac-related in 32% and angina or myocardial infarction in 68%) was available in 136 of the 162 patients originally enrolled in the study. Logistic regression and multivariate analysis failed to show any usefulness of apolipoprotein determinations in distinguishing patients with cardiac ischemia from those without it. The clinician's initial impression of the chest pain, the electrocardiogram, a history of previous angina, myocardial infarction, or peripheral atherosclerosis, and male sex were strongly associated with the final diagnosis. We conclude that, although apolipoprotein analysis has proved useful in epidemiologic studies, the most reliable indicators of ischemic pain remain the medical history, the electrocardiogram, and the clinician's overall initial impression.

Aged↗
PubMed1991

Levels of lipids, lipoproteins, and apolipoproteins in a defined population.

As part of a large cross-sectional investigation--the Rochester Family Heart Study--plasma levels of lipids, lipoproteins, and apolipoproteins were measured in a sample from the general population of male and female subjects who ranged in age from 5 to 90 years. Polyclonal radioimmunoassays developed at the Mayo Clinic were used for measurement of apolipoproteins A-I, A-II, C-II, C-III, and E, whereas a monoclonal enzyme-linked immunosorbent assay was used for apolipoprotein B. On the basis of 984 subjects who reported that they were fasting, were not pregnant, had never smoked, and were taking no medications thought to influence lipid levels, we determined age- and gender-specific percentiles for plasma levels of cholesterol, triglycerides, high-density lipoprotein cholesterol, and six apolipoproteins. These percentiles will facilitate identification of persons who are in the highest and lowest percentiles for their age and gender. The levels of the apolipoproteins varied for both age and gender. This is the first study to provide a reference sample for plasma levels of these apolipoproteins for male and female subjects 5 to 90 years of age selected from the general population.

Adolescent↗