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Biomedical subjects

K M Anderson

Publications and source records attributed to K M Anderson.

At least 145 records · Page 8Linked to original sources

Human PC-3 prostate cell line DNA synthesis is suppressed by eicosatetraynoic acid, an in vitro inhibitor of arachidonic acid metabolism.

When human PC-3 cells derived from a metastatic prostatic adenocarcinoma were incubated for 15 min to 4 h with the in vitro inhibitor of eicosanoid biosynthesis, eicosatetraynoic acid (ETYA) at 10-80 microM, DNA synthesis was suppressed. No reduction in cellular viability occurred, as judged by exclusion of trypan blue or unaltered release of 51Cr-labeled proteins, and the inhibition was partially reversible. Indomethacin (to 12.5 micrograms/ml) did not inhibit DNA synthesis or alter the suppression of DNA synthesis by ETYA, suggesting a role for a lipoxygenase product in this effect. Addition of leukotriene B4 (LTB4) at 10(-8) M did not reverse the inhibition of DNA synthesis produced by ETYA, nor did arachidonic acid (10(-5) - 10(-9) M) incubated with control cells mimic the effect of that agent. 3H-arachidonic acid incubated with PC-3 cells was rapidly incorporated into phospholipids and this labeling was differentially inhibited by ETYA. Positive modulation of PC-3 cellular DNA synthesis by lipoxygenase products and inhibition of their synthesis by ETYA is one attractive hypothesis with which to account for these results. Other consequences of producing a selective deficiency of arachidonic acid in cellular membrane phospholipids and even the probable substitution of ETYA for arachidonic acid could also contribute to the inhibition of DNA synthesis by ETYA.

5,8,11,14-Eicosatetraynoic Acid↗

Effect of collimator setting on the output of rectangular fields from linear accelerators.

The output (cGy/mu) of a rectangular field from a linear accelerator is not always the same as that of its equivalent square field. We have summarized output variations with upper and lower collimator setting for 4, 6, and 24 MV X-rays. It is concluded that an error in output on the order of a few percent is introduced for elongated fields if lower set of collimator jaws is used for setting the longer dimension of the field, and computing the output using equivalent square method. It is recommended that specific guidelines be developed regarding rectangular field setting on high energy linacs.

Humans↗

Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study.

The prevalence of and risk factors associated with echocardiographically determined left ventricular hypertrophy were examined in 4976 participants in the Framingham Heart Study (age, 17 to 90 years). Left ventricular hypertrophy was detected in 356 men (16%) and 513 women (19%). Prevalence increases dramatically with age (P less than 0.001), with 33% of men and 49% of women age 70 or older affected. A significant association between blood pressure and left ventricular hypertrophy is present and occurs at levels of systolic pressure below 140 mm Hg (age adjusted, P less than 0.001). There is a ninefold (women) to tenfold (men) increase from leanest to most obese group (age adjusted, P less than 0.001). In multivariate analysis, age, blood pressure, obesity, valve disease, and myocardial infarction are independently associated in both sexes. We conclude that left ventricular hypertrophy is a common echocardiographic finding for which several risk factors can be identified. These findings support weight reduction and blood pressure control for prevention or regression of this condition.

Adult↗

Arterial receptors for adrenal steroids and transport of electrolytes in vascular smooth muscle.

The role of arterial receptors to mineralocorticoids (MC) and glucocorticoids (GC) in the induction by MC and GC of changes in transmembrane transport of sodium (Na+) and water was investigated. Implantation of Silastic rubber strips impregnated with 11-desoxycorticosterone acetate (DOCA) in rabbits was followed by a marked increase in vascular smooth muscle cell membrane permeability to Na+ and hypertension. Both of these effects were preventable with progesterone, an anti-MC at the steroid-receptor level, implanted in relative excess simultaneously with DOCA, in approximately 50% of the implanted animals. The other 50% were hydroxylating in vivo progesterone to 11-desoxycorticosterone (DOC) efficiently enough not to yield the necessary ratio of progesterone to DOC for the sufficient MC receptor blockage. In vascular smooth muscle cell culture, grown in the presence of steroids, GC but not MC increased intracellular water space. This increase was preventable by a potent synthetic anti-GC,RU 38486, a steroid with high affinity for GC receptors, added to culture medium along with GC. These results provide evidence that both the in vivo effect of MC on Na+ permeability and the induction of hypertension, and the in vitro effect of GC on water transport in cultured vascular smooth muscle cells are elicited through the receptor-mediated molecular mechanism(s) for action of these steroids in the arterial wall.

Animals↗

Synthesis of eicosanoids by gamma-interferon-differentiated U937 cells.

Interferons induce morphological, biochemical and functional alterations in monocyte macrophage and myeloid cell lines. We studied the effect of 3 days incubation with gamma-interferon from human buffy coats on the global synthesis of arachidonic acid metabolites by U937 cells. Interferon-induced morphologic changes including cytoplasmic and nuclear changes and the appearance of multiple lysosomal-like granules consistent with cellular differentiation were observed by electron microscopy. The labeling of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine was increased and that of phosphatidylinositol, free fatty acids as 3H-arachidonic acid and neutral lipids reduced, when interferon-treated cells were incubated with 3H-arachidonic acid. Interferon caused qualitative and quantitative changes in the synthesis of cyclooxygenase and lipoxygenase products. A23187, a calcium ionophore, and the tumor promotor, phorbol myristate acetate, greatly increased the synthesis by interferon-differentiated cells of 2 cyclooxygenase products; synthesis of lipoxygenase products was reduced. In the presence of indomethacin, 'shunting' into putative lipoxygenase products occurred. The relationship between interferon-induced morphologic and functional changes, the development of altered phospholipid and eicosanoid metabolism and the identity of these metabolites are yet to be established.

Cell Differentiation↗

Sequential hormone therapy for advanced breast cancer.

Sequential hormone therapy for advanced breast cancer can offer significant and prolonged disease control with minimal morbidity. Predictors of response to sequential hormone therapy have not previously been identified. Sixty postmenopausal women with advanced or recurrent breast cancer treated with sequential megestrol acetate and tamoxifen were evaluated to identify factors which predict response to sequential therapy. The response rate to first-line therapy was 28% (17/60). Forty-seven percent of patients who responded to the first therapy responded to the second (8/17). Four of 16 patients (25%) who failed the first hormone therapy responded to the second. The response rate to a second hormone therapy was 25% (15/60). Chi-square tests were used to test the association between a response to sequential hormonal therapy and prior chemotherapy, age at first hormone trial, number of sites of disease, dominant site of disease, sequence of hormonal therapy, second response on the basis of first response, presence of soft tissue disease or bone disease alone, and receptor value. A one-tailed Fisher exact probability test revealed that a greater proportion of receptor-positive patients exhibited positive responses to sequential hormonal therapies than did receptor-negative patients. All of the patients who responded to a second hormonal therapy were estrogen receptor (ER)- and progestogen receptor (PgR)-positive. Fisher exact probability tests revealed a statistically significant association between response to initial hormone therapy and response to a subsequent hormone trial. This study suggests that patients who fail their initial hormone trial should be considered for a second hormonal trial if they are ER- and PR-positive.

Adult↗

Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study.

The association of ventricular arrhythmias with left ventricular (LV) hypertrophy was examined in 6,218 participants in the Framingham Heart Study. Electrocardiographic (ECG) LV hypertrophy was present in 171 subjects and echocardiographic hypertrophy was detected in 869. Echocardiographic LV hypertrophy was associated with increased risk for each of 6 ventricular arrhythmia grades in men (relative risk up to 8.9, p less than 0.01), and 4 of 6 grades in women (p less than 0.05). Similarly, men with ECG LV hypertrophy were at increased risk for 4 of 6 arrhythmia grades (p less than 0.05). However, owing to low prevalence ECG LV hypertrophy was not associated with arrhythmia in women. After adjustment for age, sex, systolic blood pressure, valvular heart disease, angina pectoris and acute myocardial infarction, the association of echocardiographic but not ECG LV hypertrophy with ventricular arrhythmia remained significant (p less than 0.001). Thus, echocardiographic LV hypertrophy is more prevalent and more sensitive for ventricular arrhythmias than ECG LV hypertrophy.

Adult↗

Cholesterol and mortality. 30 years of follow-up from the Framingham study.

From 1951 to 1955 serum cholesterol levels were measured in 1959 men and 2415 women aged between 31 and 65 years who were free of cardiovascular disease (CVD) and cancer. Under age 50 years, cholesterol levels are directly related with 30-year overall and CVD mortality; overall death increases 5% and CVD death 9% for each 10 mg/dL. After age 50 years there is no increased overall mortality with either high or low serum cholesterol levels. There is a direct association between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels). Under age 50 years these data suggest that having a very low cholesterol level improves longevity. After age 50 years the association of mortality with cholesterol values is confounded by people whose cholesterol levels are falling--perhaps due to diseases predisposing to death.

Adult↗

Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study.

Of 6,148 original cohort and offspring subjects of the Framingham Heart Study who underwent routine evaluation, a healthy group of 347 men (aged 42 +/- 12 years) and 517 women (aged 43 +/- 12 years) was identified to develop echocardiographic criteria for left ventricular (LV) hypertrophy. Healthy subjects were defined as normotensive, receiving no cardiac or antihypertensive medications, nonobese and free of cardiopulmonary disease. Echocardiographic criteria (in accordance with the American Society of Echocardiography convention) for LV hypertrophy, based on mean plus 2 standard deviations for LV mass, LV mass corrected for body surface area and LV mass corrected for height in this healthy sample are, respectively: 294 g, 150 g/m2 and 163 g/m in men and 198 g, 120 g/m2 and 121 g/m in women. Criteria based on LV mass/height result in higher prevalence rates of LV hypertrophy than LV mass/body surface area while still correcting for body size. The prevalence of LV hypertrophy in the entire study population (using LV mass/height criteria) is 16% in men and 19% in women. Until outcome guided criteria for LV hypertrophy are developed, application of sex-specific criteria based on a healthy population distribution of LV mass offer the best approach to echocardiographic diagnosis of LV hypertrophy.

Adult↗

Echocardiographically determined left ventricular structural and functional correlates of complex or frequent ventricular arrhythmias on one-hour ambulatory electrocardiographic monitoring.

The associations between 6 echocardiographic measurements and ventricular arrhythmias on 1-hour ambulatory electrocardiograms were evaluated in 3,348 subjects of the Framingham Heart Study who were free of symptomatic coronary artery disease, congestive heart failure and valvular heart disease and were not receiving diuretic drugs or other blood pressure or cardiac medications. Age-adjusted estimates of association between echocardiographic measurements of left ventricular (LV) structure and function and complex or frequent (Lown grade 2 or greater) ventricular arrhythmia were computed using logistic regression. In this bivariate model only LV internal diameter (systolic and diastolic) and fractional shortening were associated with arrhythmia in both sexes (p less than 0.01). When all variables were entered into a multivariate model, only age and systolic LV internal diameter remained independently associated with arrhythmia (p less than 0.001). Thus, LV chamber size and function are important predictors of risk for ventricular arrhythmia. Systolic LV internal diameter, which reflects both functional and structural information, is the only measurement independently predictive of arrhythmia risk in persons free of apparent heart disease.

Adult↗

Hormone receptor studies in axillary metastases from occult breast cancers.

The authors describe 11 patients with occult breast carcinoma, who initially presented with axillary nodal metastases of unknown origin. In all 11 cases, physical examination and mammography results were normal. Steroid hormone receptor studies were done on tissue from all 11 axillary masses and 2 masses underwent lactalbumin staining as well. In 8 of the 11 patients these studies were positive, suggesting breast as the primary tumor site. Estrogen (30 to 445 fmol/g) or progesterone (30 to 1059 fmol/g) receptors, or both, were positive in seven cases. Although a breast carcinoma was subsequently found in all 11 patients, receptor studies on the primary tumor could not be done in every instance. The authors concluded that performing steroid hormone receptor assays on axillary metastases from occult tumors not only may provide information regarding the identity of the primary tumor but also may be the sole opportunity to determine its hormone receptor status.

Adenocarcinoma↗

Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample. The Framingham Offspring Study.

Two fasting lipoprotein cholesterol measurements have been made on Framingham Offspring Study participants, first in 1971-75 and again in 1979-83. Longitudinal analysis (n = 2433, age 20-49 at first exam) using multivariate regression found aging, weight gain, vasectomy, menopause, and increased smoking are associated with worsening lipoprotein profiles, while increased alcohol consumption is associated with increased high density lipoprotein cholesterol (HDL-C). Average increases in low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in women accelerate with age; in men the increases are similar or perhaps decelerate with age. Secular trends were measured using age-adjusted mean values for individuals aged 25-54. Averages of total cholesterol, LDL-C (men only), systolic and diastolic blood pressure, body mass index, number of cigarettes per day, and alcohol consumption were lower at the second examination. Two secular trends in women indicate a possible worsening of population lipoprotein profiles: mean VLDL-C was higher and mean HDL-C lower at the second exam.

Adult↗

Is the tuberculosis screening program of hospital employees still required?

The American Thoracic Society and the Centers for Disease Control recommend that each hospital has a tuberculosis screening program. As the incidence of active tuberculosis in the United States has been decreasing during the last 30 yr, the necessity for continuing this screening program may be questioned. This prospective study evaluates whether screening hospital employees is still useful. In the state of Washington from January 1, 1982, through December 31, 1984, tuberculosis was diagnosed in 747 patients, of whom 387 (52%) were hospitalized. One hundred seventy-one of the hospitalized patients (44%) were sputum-smear-positive. Data were collected from each of the 114 hospitals in the state. During the 3-yr period, 50 hospitals admitted no patients known to have M. tuberculosis, 48 admitted 1 or more sputum-smear-positive patients, and 16 others admitted 1 or more smear-negative patients. The number of employees at each hospital ranged from 10 to 6,289 (539 +/- 757, mean +/- SD). Skin testing was performed on 13.7 to 100% (median, 84.2%) of employees. In the 3-yr period, 126,493 skin tests were placed by trained personnel; 501 employees were reported as being converters, but only 129 were found to be true converters. The conversion rates of employees in hospitals to which patients with smear-positive and smear-negative disease were admitted were 1.05 and 1.09 per 1,000, respectively. The conversion rate in hospitals where no patients with M. tuberculosis were admitted was 0.8 per 1,000. These conversion rates were no greater than that predicted for the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidemiology of diabetes mellitus in the elderly. The Framingham Study.

Factors potentially associated with adult-onset diabetes mellitus in the elderly were reviewed, using the Framingham Heart Study data and other population data. Incidence data for diabetes mellitus in the elderly are sparse, but they indicate that the prevalence of diabetes increases greatly with age. Prevalence rates commonly exceeded 10 percent in those over the age of 60. Men and women in the Framingham Study who were overweight by more than 40 percent had twice the prevalence of diabetes mellitus compared with those of normal weight. Hypertension and coexistent vascular disease were particularly common in elderly diabetic patients, with rates markedly greater than those found among younger adult-onset diabetic patients. In those 50 years of age or older, the later development of diabetes mellitus was associated with increased levels of very-low-density lipoprotein cholesterol, decreased levels of high-density lipoprotein cholesterol, obesity, elevated casual glucose levels, use of diuretics, and preexisting vascular disease.

Adult↗

In vitro stimulation by prostate extracts of rat ventral prostate stromal and epithelial cell division.

We examined the effect of prostate cell extracts on the replication of highly enriched rat ventral prostate stromal and epithelial cells cultured in RPMI-1640. Extracts from normal rat prostates completely inhibited cell division in both fractions, while a 10% (v/v) extract of Dunning R-3327G adenocarcinoma inhibited replication of stromal cells but permitted that of epithelial cells. The cytotoxic effect of prostate extracts was dialyzable, heat stable, unaffected by proteases, soluble in acid/alcohol, and insoluble in chloroform. These properties are consistent with those of polyamines incubated in the presence of fetal calf serum. Dialyzed extracts from Dunning adenocarcinomas, and from human benign hypertrophic and carcinomatous prostates stimulated rat prostate stromal and epithelial cell division, in keeping with other reports of "growth factors" in prostate tissue. This mitogenic activity was stable to temperature (70 degrees C, 4 hours), and marginally if at all affected by exposure to trypsin or to pronase coupled to Sephadex. Short-term culture of separated prostate cells should provide a useful assay system for detecting putative autocrine or paracrine stromal and/or epithelial cell growth factors and identifying suspected homo- or heterotypic cellular interactions in normal and diseased prostates.

Adenocarcinoma↗

Sensors in pacing.

Sensor driven pacing is emerging as a powerful therapeutic tool to provide paced patients with a more natural heart rhythm, and, additionally, piezoelectricity is one technology that can provide sensed information to the pacemaker--and shows promise in controlling that rhythm.

Electronics, Medical↗