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Biomedical subjects

M A Austin

Publications and source records attributed to M A Austin.

At least 91 records · Page 5Linked to original sources
PubMed1991

Breast cancer in men: aspects of familial aggregation.

Familial aggregation of breast cancer in males was investigated in a population-based case-control study. Cases were ascertained from 10 Surveillance, Epidemiology, and End Results Program registries in the United States between 1983 and 1986. Controls were identified by random-digit dialing and from lists of Medicare recipients. The relative odds of developing breast cancer were similar in men with affected paternal and maternal relatives and in men with affected mothers and sisters. The risk increased with the number of affected relatives. The relative odds of developing breast cancer were greater in men with first-degree relatives who developed their mammary neoplasm before the age of 45 than in men with older first-degree affected relatives; the enhancement of risk in men with an affected sister was greater in those under age 60 than in older men. These results are similar to those observed by others in studies of breast cancer in women.

Breast Neoplasms↗
PubMed1991

Concordance for dyslipidemic hypertension in male twins.

Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome.

Adult↗
PubMed1991

Linkage analysis of low-density lipoprotein subclass phenotypes and the apolipoprotein B gene.

A common heritable phenotype has recently been identified which is characterized by a relative abundance of small, dense low-density lipoproteins (LDL), and mild elevations of plasma triglycerides and reductions in plasma high-density lipoproteins (HDL) cholesterol. This phenotype, designated LDL subclass phenotype B, has been associated with up to a three-fold increase in coronary disease risk. Complex segregation analysis in two large family studies has demonstrated that LDL subclass phenotype B is influenced by an allele at a single genetic locus with a population frequency of 0.25-0.3, and autosomal dominant inheritance, but with full penetrance only in males age 20 and over and in postmenopausal women. Since apolipoprotein B (apoB) is the principal protein component of LDL, linkage analysis was used to investigate possible linkage between the phenotype B phenotype and the apoB gene, using a variable number of tandem repeats site located 0.5 kb from the 3' end of the apoB gene. In 6 informative families including only family members in the penetrant classes, a total LOD score of -7.49 was found at a recombination fraction of 0.001. Thus, under the assumptions of the single gene model, it is unlikely that the apoB locus controls LDL subclass phenotype B.

Adult↗
PubMed1991

Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia.

Low-density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = -13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with FCHL.

Alleles↗
PubMed1991

Functional endoscopic sinus surgery: a brief review.

As a rule, functional endoscopic sinus surgery (FESS) is recommended for patients with chronic sinus problems that do not respond to medical treatment. For discussion of the surgical treatment to be useful we must first look at the importance of sinusitis, the medical diagnosis and treatment of sinusitis, the anatomic and pathologic considerations for the surgical treatment of sinusitis, the modern diagnosis of recurrent or persistent sinusitis and lastly, the surgical technique of functional endoscopic sinus surgery.

Endoscopy↗
PubMed1990

The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins.

The effect on plasma lipoproteins of exchanging fat type within currently recommended reduced-fat diets was studied in a free-living group of 19 men and 20 women who consumed both a polyunsaturated fat-enriched diet and a monounsaturated fat-enriched diet, each for a 12-week period, with saturated fat and cholesterol held constant. Mean plasma concentrations of low-density lipoprotein cholesterol and low-density lipoprotein total mass (analytic ultracentrifuge), and high-density lipoprotein (HDL) cholesterol and HDL total mass, did not change significantly on exchanging fat type. However, HDL2 cholesterol concentration was 50% higher and HDL3 cholesterol concentration was 7% lower for polyunsaturated compared with monounsaturated fat. Mean total mass of HDL2 was also 23.5% higher and concentration of apolipoprotein B was 5.4% lower on transfer to the polyunsaturated fat diet. Contrary to frequent assertions, we find no advantage with respect to plasma HDL concentrations in using predominantly monounsaturated rather than polyunsaturated fats in subjects who consumed reduced-fat, solid-food diets.

Adult↗
PubMed1990

Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.

In a community-based study of 301 subjects from 61 nuclear families, two distinct phenotypes (denoted A and B) were identified by nondenaturing gradient gel electrophoretic analysis of low density lipoprotein (LDL) subclasses. Phenotype A was characterized by predominance of large, buoyant LDL particles, and phenotype B consisted of a major peak of small, dense LDL particles. Previous analysis of the family data by complex segregation analysis demonstrated that these phenotypes appear to be inherited as a single-gene trait. In the present study, the phenotypes were found to be closely associated with variations in plasma levels of other lipid, lipoprotein, and apolipoprotein measurements. Specifically, phenotype B was associated with increases in plasma levels of triglyceride and apolipoprotein B, with mass of very low and intermediate density lipoproteins, and with decreases in high density lipoprotein (HDL) cholesterol, HDL2 mass, and plasma levels of apolipoprotein A-I. Thus, the proposed genetic locus responsible for LDL subclass phenotypes also results in an atherogenic lipoprotein phenotype.

Adolescent↗
PubMed1989

Plasma triglyceride as a risk factor for coronary heart disease. The epidemiologic evidence and beyond.

Elevated plasma triglyceride has been found to be a univariate risk factor for coronary heart disease in many epidemiologic studies, but this increased risk is not independent of other lipid and lipoprotein measures. Rather than dismiss triglyceride as a risk factor, we can see this disparity between univariate and multivariate results as a clue to better understanding of the potential role of triglyceride in atherosclerosis. From a statistical point of view, triglyceride often is not a significant predictor of coronary heart disease in multivariate statistical models because of the large variation in triglyceride measurements and the strong inverse relation between HDL cholesterol and triglyceride. Heterogeneity in both the biologic mechanisms producing hypertriglyceridemia and the manifestations of cardiovascular disease complicates the study of triglyceride as a risk factor. recently, subclasses of both HDL and LDL have been shown to be related to triglyceride metabolism and may provide more precise variables for predicting risk. However, none of this evidence precludes the involvement of triglyceride in the development of atherosclerosis. The final answer as to whether triglyceride is a causal risk factor for coronary heart disease must come from the biologic sciences, and the complexity of the epidemiologic results likely reflects the intricate metabolic processes involved.

Cholesterol↗
PubMed1988

Low-density lipoprotein subclass patterns and risk of myocardial infarction.

The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.

Aged↗
PubMed1988

Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families.

Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer. Patterns of breast cancer occurrence in families were investigated by complex segregation analysis. In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering. From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 0.0006 in the general population, and lifetime risk of breast cancer was 0.82 among susceptible women and 0.08 among women without the susceptibility allele. Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance. The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer. Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole.

Adult↗
PubMed1988

Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis.

Heterogeneity in the size of low-density lipoprotein (LDL) particles was used to identify two distinct patterns based on gradient gel electrophoresis analysis. These two phenotypes, LDL subclass pattern A and pattern B, were characterized by a predominance of large, buoyant LDL particles and small, dense LDL particles, respectively. The inheritance of these LDL subclass patterns was investigated in a sample of 61 healthy families including 301 individuals. LDL subclass pattern B was present in 31% of the subjects, with the prevalence varying by gender, age, and (in women) menopausal status. Complex segregation analysis suggested a major locus controlling LDL subclass patterns. The model providing the best fit to the data included a dominant mode of inheritance with a frequency of .25 for the allele determining LDL subclass pattern B and reduced penetrance for men under age 20 and for premenopausal women. Thus, the allele for the LDL subclass pattern characterized by a predominance of small, dense LDL particles appears to be very common in the population, although not usually expressed until adulthood in men and until after menopause in women. The presence of a major gene controlling LDL subclass could explain much of the familial aggregation of lipid and apolipoprotein levels and may be involved in increased risk of coronary heart disease.

Adolescent↗
PubMed1987

Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences.

The contributions of shared genes and shared environments to familial aggregation of coronary heart disease risk factors were investigated by genetic and epidemiologic analysis of 434 adult female twin pairs from the Kaiser-Permanente Twin Registry in Oakland, California, during 1978 and 1979. Initial estimates of genetic heritability were statistically significant for serum levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and Quetelet index, but were only marginally significant for systolic and diastolic blood pressures. These estimates were biased, however, because sisters in the same identical twin pair were more similar than sisters in the same fraternal twin pair not only with respect to shared genes but also with respect to shared environmental and behavioral influences. Heritability was estimated again after adjusting for shared environmental and behavioral effects by multiple regression analysis. Genetic heritability remained significant for HDL cholesterol (0.66), LDL cholesterol (0.88), triglycerides (0.53), and relative weight (0.55) but not for systolic (0.42) and diastolic (0.25) blood pressures. The strong genetic components of the levels of LDL cholesterol, HDL cholesterol, and relative weight may in part explain why some women have high levels of these coronary disease risk factors despite following recommended health behaviors.

Adult↗
PubMed1986

Genetic control of low-density-lipoprotein subclasses.

In a study of lipoprotein subclasses in 79 healthy members of sixteen nuclear families evidence was obtained that low-density-lipoprotein (LDL) subclass patterns determined by gradient-gel electrophoresis are influenced by a common allele at a single genetic locus. The estimated frequency of the allele leading to the phenotype characterised by predominance of small, dense LDL subclasses was about 15%. Expression of this phenotype appears to be age dependent, in that most affected subjects in this population were older than 40 years. Although plasma lipid levels were normal in most subjects with this trait, levels of plasma apoprotein B and triglyceride were higher and levels of apoprotein AI and HDL2 lower than in unaffected family members. It is possible that this genetic trait may interact with other genetic or environmental variables in predisposing affected individuals to atherogenic lipoprotein and apoprotein profiles.

Adolescent↗
PubMed1986

High-density lipoprotein subclass distribution and human cord blood lipid levels.

The high-density lipoprotein (HDL) subclass distribution was examined by gradient gel electrophoresis (gge) in 154 human cord blood samples, and determinations of triglyceride, total cholesterol, and HDL-cholesterol levels were performed. Three distinct gge patterns were recognizable. The first pattern, termed the normal (gge) pattern, was distinguished by a prominent double peak in the (HDL2a)gge region and a pronounced peak in the (HDL3b)gge region. Minor peaks, or shoulders, were also seen in the (HDL2b)gge and (HDL3c)gge regions, and a valley was present in the (HDL3a)gge region. This pattern was associated with normal lipid levels for cord blood plasma (mean triglycerides: 30-42 mg/dl; mean total cholesterol 62-85 mg/dl; mean HDL-cholesterol: 34-41 mg/dl). The second pattern, termed the 2b(gge) pattern, contained a major peak in the (HDL2b)gge region rather than the shoulder seen in the normal (gge) pattern, while the (HDL2a)gge, (HDL3b)gge, and (HDL3c)gge regions were less pronounced. This pattern was associated with elevated total cholesterol and HDL-C levels (means 85-102 and 49-56 mg/dl, respectively). The third pattern, termed the 3b(gge) pattern, was characterized by a paucity of material in the (HDL2b)gge region, a single peak in the (HDL2a)gge region, and either a relative increase in the (HDL3b)gge region, or a simultaneous increase in both (HDL3b)gge and (HDL3c)gge. This pattern was associated with elevated triglyceride levels (means 78-88 mg/dl) and decreased HDL-C levels (means 20-30 mg/dl). Only two infants had a simultaneous elevation of triglycerides and total cholesterol and both cases exhibited the 3b(gge) pattern. Our study demonstrates that although the triglyceride and cholesterol levels in the newborn are much lower than those in adults, they are the important factors associated with the HDL subclass distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗