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Biomedical subjects

K M Anderson

Publications and source records attributed to K M Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1990

How reliably can compact chemistry analyzers measure lipids?

Five compact chemistry analyzers were evaluated for the measurement of lipids. Fresh plasma or serum specimens from a standardized research laboratory were assayed for total cholesterol on all five analyzers. Triglycerides and high-density lipoprotein cholesterol were assayed on the three analyzers that could measure both of these analytes. Study results were interpreted by assessing accuracy and precision and by defining the percentage of patient specimens classified in the same categories as the reference laboratory, according to National Cholesterol Education Program guidelines. Two analyzers met standards for accuracy of cholesterol measurement. Three analyzers met performance standards for precision of cholesterol measurement. Agreement with National Cholesterol Education Program classification of specimens compared with the reference laboratory for total cholesterol ranged from 73% to 96% and was less for indirect low-density lipoprotein cholesterol. We conclude that under controlled conditions, compact chemistry analyzers vary in the reliability of lipid determination and classification of patients.

Autoanalysis↗
PubMed1990

Body fat distribution and breast cancer in the Framingham Study.

We examined the relation between central body fat distribution and breast cancer in a prospective cohort of women who participated in the Framingham Study. At the baseline examination in 1948, a total of 2,201 women aged 30-62 years were analyzed. An index of central to peripheral body fat (the central adiposity ratio) was calculated from the sum of the trunkal skinfolds (chest, subscapular, and abdominal) divided by the sum of the extremity skinfolds (triceps and thigh). These skinfolds were measured at the fourth examination in 1954. The cohort was followed for up to 28 years and yielded 106 cases of breast cancer. When divided into quartiles based on the central adiposity ratio, only women in the fourth quartile (those with the highest central to peripheral body fat distribution) demonstrated an increased risk for breast cancer. The age- and adiposity-adjusted relative risk estimate for having an increased central adiposity ratio (fourth quartile) compared to lower central adiposity ratios was 1.8 (95% confidence interval, 1.2-2.6). Adjustment for potential confounders of height, parity, and education did not appreciably alter this estimate (1.7, 1.1-2.5). There was no association between degree of adiposity, as measured by the sum of the five skinfolds or by body mass index (weight in kg divided by height in m2), and subsequent breast cancer. The results of this study suggest that increased central to peripheral body fat distribution predicts breast cancer risk independently of the degree of adiposity and may be a more specific marker of a premalignant hormonal pattern than degree of adiposity.

Adult↗
PubMed1990

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study.

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.

Adult↗
PubMed1990

Tumor cell mitochondrial matrix/cristae complexes as potential sites for anticancer therapy with polyunsaturated fatty acid analogues.

The consequences of incubating human cancer cells with ETYA, a competitive analogue of arachidonic acid, and the reported responses of cells cultured with polyunsaturated fatty acids indicate that polyunsaturated fatty acid analogues or their modified congeners could represent potential cytotoxic anticancer agents. The inner mitochondrial membrane and matrix may represent important targets for such agents, since they seem unusually susceptible to ETYA-induced oxidative stress.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Stratifying the patient at risk from coronary disease: new insights from the Framingham Heart Study.

Although cardiovascular disease remains the leading cause of death in the United States, cardiovascular disease mortality has decreased steadily during the past 2 decades. This trend is largely attributable to improved detection and management of cardiovascular risk factors, in which the Framingham Heart Study has played a major role. This article examines some of the risk factors associated with coronary heart disease, notably, advancing age, hypertension, left ventricular hypertrophy, smoking, elevated serum cholesterol, and reduced high-density lipoprotein, all of which have been investigated by the Framingham Heart Study. In addition, new data are presented from a multidimensional model of coronary heart disease. This is a novel approach that takes into account the interactions of multiple risk factors and their contribution to overall coronary heart disease risk.

Adult↗
PubMed1990

Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis.

von Recklinghausen neurofibromatosis (NF1) is a common hereditary disorder characterized by neural crest-derived tumors, particularly benign neurofibromas whose malignant transformation to neurofibrosarcomas can be fatal. The NF1 gene has been mapped to a small region of chromosome 17q, but neither the nature of the primary defect nor the mechanisms involved in tumor progression are understood. We have tested whether NF1 might be caused by the inactivation of a tumor suppressor gene on 17q, analogous to that on chromosome 22 in NF2, by searching for deletions of chromosome 17 in NF1-derived tumor specimens. Both neurofibrosarcomas from patients with "atypical" NF and 5 of 6 neurofibrosarcomas from NF1 patients displayed loss of alleles for polymorphic DNA markers on chromosome 17. However, the common region of deletion was on 17p and did not include the NF1 region of 17q. Since no loss of markers on chromosome 17 was observed in any of 30 benign tumors from NF1 patients, the 17p deletions seen in neurofibrosarcomas are probably associated with tumor progression and/or malignancy. This region contains a candidate gene for tumor progression, p53, which has recently been implicated in the progression of a broad array of human cancers. In a preliminary search for p53 aberrations by direct sequencing of polymerase chain reaction-amplified DNA from 7 neurofibrosarcomas, 2 tumors that contained point mutations in exon 4 of the p53 gene were found, suggesting a role for this gene in at least some neurofibrosarcomas. Thus the formation of malignant neurofibrosarcomas may result from several independent genetic events including mutation of the NF1 gene, whose mechanism of tumorigenesis remains uncertain, and subsequent loss of a "tumor suppressor" gene on 17p, most likely p53.

Base Sequence↗
PubMed1990

Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism.

Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. We studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14-eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also became more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA-treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distention and disruption of the cristae along with an increase in cytoplasmic vacuolization. We conclude that the inhibitors of eicosanoid biosynthesis, NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also induce increased astrocytic differentiation.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy.

Numerous electrocardiographic criteria, which are largely dependent on fixed voltage thresholds, have been proposed for the diagnosis of left ventricular hypertrophy (LVH). Electrocardiographic criteria for LVH were examined in 4,684 subjects of the Framingham Heart Study who underwent echocardiographic study for LVH. Echocardiographic LVH was detected in 290 men (14.2%) and 465 women (17.6%). Electrocardiographic features of LVH were present in 2.9% of men (60/2,042) and 1.5% of women (39/2,642). The overall sensitivity of the electrocardiographic diagnosis of LVH was 6.9%, whereas specificity was 98.8%. Sensitivity of the electrocardiogram (ECG) for LVH was marginally lower in women than in men (5.6% vs. 9.0%, p = 0.075). Obesity was inversely associated with sensitivity (p less than 0.05, both sexes combined, sex-adjusted). Smoking was also inversely related to sensitivity (p = 0.001, both sexes combined, sex-adjusted). In contrast, sensitivity of the ECG increased with age (p less than 0.001, both sexes combined, sex-adjusted). These findings suggest that electrocardiographic detection of LVH can be improved by incorporating information about noncardiac factors that impact on electrocardiographic sensitivity for LVH, presumably by attenuating QRS voltage. New strategies that take into consideration sex, age, smoking status, and obesity might improve the sensitivity of the ECG without diminishing specificity.

Age Factors↗
PubMed1990

5,8,11,14-eicosatetraynoic acid inhibits PC3 DNA synthesis and cellular proliferation, in part due to its 5'-lipoxygenase activity.

5,8,11,14-eicosatetraynoic acid (ETYA), a competitive analogue of arachidonic acid reversibly inhibited human prostate PC3 DNA synthesis at 4 h. This was not due to reduced cellular viability, as judged by several criteria, and resulted in reduced cell numbers at 72 h. Several less specific inhibitors of 5'-lipoxygenase, and A63162, a highly specific inhibitor, reduced labeling of DNA with 3H-thymidine. A23187, a calcium ionophore, reduced DNA synthesis, and ETYA rapidly increased [Ca2+]i measured with the Fura II technique. Comparison of the biochemical events evoked by ETYA and A63162 should identify those required for the downregulation of DNA synthesis.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1989

Impact of national guidelines for cholesterol risk factor screening. The Framingham Offspring Study.

Recently published guidelines from the National Cholesterol Education Program were applied to 792 men and 853 women aged 30 to 69 years who participated in Framingham Offspring examination 3 from 1983 to 1987. Using nationally recommended algorithms, cholesterol levels are desirable in 50% of men and women, borderline in 12% of men and 30% of women, and elevated in 35% of men and 19% of women. Assuming that diet reduces low-density lipoprotein cholesterol levels 20%, 10%, or 5%, rates of lipid medication use are projected as 2%, 5%, or 10%, respectively. Applying 6-year estimates of coronary risk derived from the original Framingham cohort to their offspring, the nationally recommended algorithm lacks specificity in women younger than 40 years and in both men and women older than 60 years. This study suggests that effective diet probably will be the cornerstone of current guidelines, and individuals aged 40 to 60 years might benefit most.

Adult↗
PubMed1989

Inhibition of U937 eicosanoid and DNA synthesis by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism and its partial reversal by leukotriene C4.

When replicating U937 cells were incubated with up to 80 microM concentrations of the in vitro inhibitor of eicosanoid biosynthesis, 5,8,11,14-eicosatetraynoic acid (ETYA), DNA synthesis measured by labeling with [3H]thymidine was inhibited in a concentration-dependent manner. No reduction in cellular viability occurred, as judged by exclusion of trypan blue, unaltered release of 51Cr-labeled proteins, and the reversibility of inhibition after incubation for 72 h with ETYA. Neither indomethacin nor acetylsalicylic acid, inhibitors of cyclooxygenase, altered DNA synthesis in control or ETYA-inhibited cells, excluding participation of the products of this enzyme in the inhibition of DNA synthesis. Incubation of inhibited cells with extracts prepared from log-phase media partially reversed the inhibition of DNA synthesis. Addition of leukotriene B4 or D4 at 10(-7) to 10(-8) M did not reverse ETYA-induced inhibition of DNA synthesis, nor did the addition of a series of long chain fatty acids, including arachidonic acid. However, leukotriene C4 at 10(-7) M partially reversed the inhibition of DNA synthesis. Extracts of media from log-phase cells were shown by high-pressure liquid chromatography to contain leukotriene C4, and synthesis of this compound was inhibited by ETYA, as judged by measurement of UV absorbance and radioactivity. Additional inhibitors of eicosanoid metabolism including nordihydroguaiaretic acid and esculetin also suppressed DNA synthesis in U937, K562, and prostate PC3 cells, without altered cellular viability; the effect is not limited to lymphohematopoietic cells or to a single inhibitor of arachidonic acid metabolism. Suppression of U937 DNA and eicosanoid synthesis by ETYA and the partial reversal of DNA synthesis by leukotriene C4 suggest that in these cells eicosanoids may modulate DNA synthesis. Other possible consequences of incubating cells with ETYA including creation of arachidonic acid-deficient membranes, and even incorporation of the agent into membrane phospholipids, may also contribute to the reversible inhibition of DNA synthesis.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1989

Is alcohol consumption related to breast cancer? Results from the Framingham Heart Study.

We studied the relation between alcohol consumption and breast cancer among women in the Framingham Heart Study cohort. A total of 2,636 women aged 31-64 years provided information on alcohol consumption at the second biennial examination. They were followed for up to 32 years; during this period, breast cancer was diagnosed in 143 of these women. Alcohol intake was also assessed at 10 and 20 years of follow-up and every 2 years thereafter. In analyses using only baseline alcohol intake, the multiple risk factor-adjusted relative risk (RR) estimate of breast cancer for any drinking, compared with nondrinking, was 0.8 [95% confidence interval (CI), 0.5-1.1]. For three levels of alcohol intake (0.1-1.4 g/day, 1.5-4.9 g/day, and greater than or equal to 5.0 g/day), the baseline analyses yielded RRs (vs. nondrinking) of 1.0 (CI, 0.6-1.5), 0.7 (CI, 0.4-1.1), and 0.6 (CI, 0.4-1.0), respectively. In analyses incorporating repeated measures of alcohol, the comparable RRs were 0.9 (CI, 0.6-1.2) for any drinking (vs. nondrinking) and 0.7 (CI, 0.4-1.4), 1.1 (CI, 0.7-1.8), and 0.8 (CI, 0.5-1.2), respectively, for the three levels of intake (vs. nondrinking). Alcohol consumption was not associated with an increased risk of breast cancer in this cohort.

Adult↗
PubMed1989

Prevalence of intraventricular block in the general population: the Framingham Study.

QRS intervals in the ECGs of members of the Framingham Heart Study cohort and offspring were measured to provide an estimate of the prevalence of intraventricular block in the general population. Intervals of greater than or equal to 0.09 second appear in men twice as commonly as in women, are rare before age 50 to 60, and shift from a predominance of right bundle branch block in the young to an indeterminate pattern in the elderly. Complete intraventricular block (QRS interval greater than or equal to 0.12 second) is seen in 11% of elderly men and 5% of elderly women. Aside from age and sex, logistic regression indicates strong associations with concurrent manifestations of coronary heart disease, congestive heart failure, and atrioventricular block, as well as hypertension, left ventricular hypertrophy, and ventricular extrasystoles. Among those subjects free of clinical coronary disease and congestive heart failure, associations between QRS interval and age, sex, atrioventricular block, and ECG left ventricular hypertrophy remain significant by multivariate analysis. Whether people with prolonged QRS intervals need special monitoring or attention cannot be told from these data.

Adult↗
PubMed1989

Effect of nordihydroguaiaretic acid on cultured rat and human glioma cell proliferation.

When cultured malignant cells derived from rat gliomas (C6 and 9L) and human gliomas (A-172 and T98G) were treated for 4 hours with 1 to 80 microns nordihydroguaiaretic acid (NDGA) or 5,8,11,14-eicosatetraynoic acid (ETYA), a dose-dependent inhibition of deoxyribonucleic acid (DNA) synthesis occurred. In a series of three experiments for each cell line, 40 microM NDGA suppressed 3H-thymidine incorporation in the rat and human glioma lines to an average of less than 3.1% and 5.6% of control uptake (counts per minute), respectively. Incubation with a higher concentration of ETYA (80 microM) resulted in inhibition of rat and human DNA synthesis to less than 53% and 62% of control levels, respectively. This inhibition was not associated with any loss of cell viability, as judged by trypan blue exclusion studies. Prolonged incubation (for 72 hours) of the rat and human glioma cells with NDGA markedly decreased cell proliferation with no loss of cell viability. The inhibition of human glioma cell division by NDGA was rapidly reversible after incubation for 24 hours and at least partially reversible after incubation for 96 hours. It is concluded that the inhibitors of eicosanoid biosynthesis, NDGA and (to a lesser extent) ETYA, reduce in vitro cell proliferation in two glioma lines from both the rat and human. Since neither indomethacin nor acetylsalicylic acid altered DNA synthesis in these cell lines, this implicates the lipoxygenase products of arachidonic acid metabolism as important positive modulators in glioma cell division. These findings warrant further study in an in vivo system.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1988

Labelling of lipids and phospholipids with [3H]arachidonic acid and the biosynthesis of eicosanoids in U937 cells differentiated by phorbol ester.

Phorbol esters induce morphologic and biochemical differentiation in U937 cells, a monocyte/macrophage-like line derived from a human histiocytic lymphoma. We are interested in the phorbol ester-stimulated release of arachidonic acid from cellular membranes and the subsequent synthesis of eicosanoids, as it may prove to correlate with the induced cellular differentiation. Undifferentiated log-phase U937 cells released little recently incorporated [3H]arachidonic acid, but phorbol 12-myristate 13-acetate increased its apparent rate of release to that of cells differentiated by exposure to phorbol myristate acetate for 3 days. Exposure of washed differentiated cells immediately prelabelled with [3H]arachidonic acid to additional phorbol myristate acetate did not augment the release of [3H]arachidonic acid. The basal release of nonradioactive fatty acids from differentiated cells was 5-10 times that of undifferentiated cells, and phorbol myristate acetate increased their release from both types of cell 2- to 3-fold. Differentiated cells immediately prelabelled with [3H]arachidonic acid exhibited greater incorporation into phosphatidylinositol and phosphatidylcholine, and contained more radioactive free arachidonic acid, compared with undifferentiated cells. Undifferentiated cells contained more radioactivity in phosphatidylserine, phosphatidylethanolamine and neutral lipids. Phorbol myristate acetate caused differentiated cells to release [3H]arachidonic acid from phosphatidylinositol, phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine, but release from neutral lipids was reduced, and the content of [3H]arachidonic acid increased. In undifferentiated cells incubated with phorbol myristate acetate, radioactivity associated with phosphatidylserine, phosphatidylethanolamine and neutral lipid was reduced and [3H]arachidonic acid was unchanged. Synthesis of cyclooxygenase products exceeded that of lipoxygenase products in both differentiated and undifferentiated cells. Phorbol myristate acetate increased the synthesis of both types of product, cyclooxygenase-dependent more than lipoxygenase-dependent, especially in differentiated cells. The biological significance of these changes in lipid metabolism that accompany phorbol myristate acetate-induced differentiation are yet to be established.

Arachidonic Acid↗