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S Lindsey

Publications and source records attributed to S Lindsey.

30 records · Page 2Linked to original sources
PubMed1987

Taurine enhances low density lipoprotein binding. Internalization and degradation by cultured Hep G2 cells.

To evaluate the impact of taurine on hepatic cholesterol catabolism low density lipoprotein (LDL) binding, internalization and degradation were measured in cultured Hep G2 cells. Preincubation of cells with 0.1-10 mM taurine for 24 h stimulated LDL receptor activity by as much as 100%. Only the high affinity LDL receptor activity (specific) was increased by taurine preincubation, whereas the low affinity receptor activity (nonspecific) remained unchanged. Scatchard analysis of the binding data revealed that taurine doubled the number of LDL receptors without affecting receptor affinity. Taurine-enhanced LDL receptor activity was most pronounced when LDL concentrations exceeded 100 micrograms/ml, but was noted at taurine concentrations as low as 0.1 mM (plasma level). Interestingly, taurine had no effect on LDL receptor activity when it was added simultaneously with 125I-LDL to Hep G2 cells, or when non-bile acid-producing human skin fibroblasts were tested. Stimulation of LDL receptor activity was also obtained with 10 mM cysteine, a taurine precursor, but not with glycine. Increased cellular concentrations of taurine and cysteine were associated with an elevated rate of bile acid synthesis and a reduced cellular free cholesterol concentration. The data suggest that taurine enhanced LDL receptor activity by sparing cysteine, a known sulfhydryl group donor and stimulator of 7 alpha-hydroxylase activity, and that the latter stimulated bile acid production leading to increased utilization of cellular free cholesterol and enhanced LDL uptake.

Animals↗
PubMed1987

Monocyte adherence to endothelial cells in vitro is increased by beta-VLDL.

The adherence of blood monocytes to the arterial endothelium is an early event in the development of atherosclerotic lesions. The possibility was investigated that alterations in the level and composition of plasma lipoproteins may contribute to this phenomenon. The adherence of human mononuclear cells to primary bovine aortic endothelial cells was measured in an in vitro monolayer collection assay. Preincubation of endothelial cells with beta-very low density lipoprotein (beta-VLDL) from cholesterol-fed rabbits or with very low density lipoprotein (VLDL) from cholesterol/saturated fat-fed cebus monkeys resulted in a significant increase in the subsequent adherence of monocytes to the endothelial cells. The effect of beta-VLDL was maximal at 100 micrograms protein/ml. The response increased with time when endothelial cells were incubated with beta-VLDL for 0-120 minutes, then remained maximal for up to 4 hours. The adherence of a human monocytic cell line (U937) to endothelial cells was also increased by beta-VLDL. These results suggest that diet-induced alterations in lipoprotein composition may contribute to the development of atherosclerotic lesions by affecting the adherence of monocytes to the arterial endothelium.

Animals↗
PubMed1986

LDL enhances monocyte adhesion to endothelial cells in vitro.

Monocyte adhesion to the arterial endothelium is an early event in diet-induced atherogenesis. The possibility that low-density lipoprotein (LDL) may influence this adhesion was investigated by using an in vitro monolayer collection assay. Postprandial and fasting LDL was isolated from 12 normal adult human donors (8 male and 4 female) and incubated with primary cultures of bovine aortic endothelial cells (BAEC) for 6 hours. 51Cr-labeled mononuclear leukocytes (MNLs) were then added and incubated an additional 30 minutes. When results were expressed as the ratio of adherent counts per minute in LDL-treated BAEC cultures to that in PBS-treated controls, 10 of the 16 LDL samples isolated from male donors induced a significant increase (P less than 0.05) in MNL adhesion (1.06-1.27) attributable to esterase-positive cells. This increase was dose-dependent and maximal at 100 micrograms LDL protein/ml. The magnitude of the response was significantly correlated with LDL composition (r = 0.857, P less than 0.01) such that LDL rich in cholesterol and triglyceride relative to protein enhanced MNL adhesion, whereas lipid-poor LDL (typically isolated from the women) reduced adhesion.

Animals↗
PubMed1984

Regulation of low-density lipoprotein receptors in the human hepatoma cell line Hep G2.

The human hepatoma cell line Hep G2 can be maintained in continuous culture and secretes numerous plasma proteins and lipoproteins into the medium. To better characterize cholesterol homeostasis in these cells we have examined the binding, internalization and degradation of [125I]LDL by cultured Hep G2 cells. Hep G2 cells express high-affinity low-density lipoprotein (LDL) receptors which facilitate the binding, internalization and degradation of [125I]LDL; these receptors can be induced by growth in LDL-depleted medium and repressed by further incubation in medium supplemented with LDL. The degradation of [125I]LDL by derepressed Hep G2 cells was inhibited by greater than 90% by monensin. Incubation of Hep G2 cells in the presence of increasing concentrations of LDL also inhibited cholesterol biosynthesis. Our results indicate that Hep G2 cells possess high affinity LDL receptors which are subject to metabolic regulation and suggest that this cell line affords a valuable model to further examine cholesterol and lipoprotein metabolism in human liver cells.

Acetates↗
PubMed1984

Will dietary omega-3 fatty acids change the composition of human milk?

The most abundant long-chain polyunsaturated fatty acid in brain and retinal lipids is docosahexaenoic acid (DHA, C22:6 omega 3). It becomes incorporated into nerve tissues mostly in utero and during the 1st yr of life. DHA is derived in humans either performed in the diet or by hepatic synthesis from dietary linolenic acid (C18:3 omega 3). Since human milk contains DHA, this study was designed to see if increased dietary DHA would be reflected in a higher DHA content in human milk. Eight lactating women were given supplements of a fish oil concentrate rich in omega-3 fatty acids, including DHA (11% of fatty acids). Six women took 5 g/day of fish oil for 28 days; five women consumed 10 g/day for 14 days; and one woman consumed 47 g/day for 8 days. Each intake level of fish oil produced significant dose-dependent increases in the DHA content of milk and plasma. Base-line DHA levels in milk were 0.1 +/- 0.06% of total fatty acids. Five g/day of fish oil raised the levels to 0.5 +/- 0.1% (p less than 0.001); 10 g/day raised DHA levels to 0.8 +/- 0.1% (p less than 0.001); and 47 g/day produced DHA levels of 4.8%. The results of this study indicated that relatively low intakes of dietary DHA significantly elevated milk DHA content. This would clearly elevate the infant's DHA intake and might have implications for brain and retinal development.

Adult↗
PubMed1984

Adrenocortical response to adrenocorticotropin in heterozygous familial hypercholesterolemia.

Receptor-mediated uptake of low density lipoproteins (LDL) provides an important source of cholesterol for corticosteroid synthesis by human adrenocortical cells grown in tissue culture. Recent studies have indicated an impaired adrenocortical response to prolonged ACTH stimulation in patients with abetalipoproteinemia (who lack plasma LDL) and in patients with homozygous familial hypercholesterolemia (FH), who have a virtual absence of high affinity LDL receptors. In the present study we examined parameters of adrenocortical function in four women with well characterized heterozygous FH to assess whether a 50% reduction in the number of LDL receptors measured in vitro influenced the response of the adrenal cortex to prolonged stimulation with ACTH. Biochemical studies of the binding, internalization, and degradation of [125I]LDL were undertaken in cultured skin fibroblasts from each patient, and all patients had reduced LDL receptor activity. The adrenocortical response to a 36-h iv infusion of alpha ACTH-(1-24) (Cortrosyn) was evaluated in the four patients with heterozygous FH and in five normal women. Stimulation with iv ACTH resulted in rapid increases in the serum concentrations of cortisol in both groups and plateau concentrations of 55-60 micrograms/dl. The rates of increase and the plateau concentrations were similar in the control and FH patients. Similarly, rates of excretion of 17-hydroxycorticosteroids and cortisol were similar in the normal subjects and FH patients. These results indicate that a 50% reduction in the number of high affinity LDL receptors due to the presence of one abnormal gene at the LDL receptor locus does not result in any impairment in the delivery of cholesterol to the adrenal cortex during conditions of maximal corticosteroid production.

17-Hydroxycorticosteroids↗
PubMed1984

Similarities and differences in the ultrastructure of two hormone-dependent and one independent human breast carcinoma grown in athymic nude mice: comparison with the rat DMBA-induced tumor and normal secretory mammocytes.

The human breast cancer cell lines MCF-7 (ER positive), ZR 75-1 (ER positive) and MDA-MB 231 (ER negative) form solid tumors within one week following inoculation into athymic nude mice. Tumor formation by MCF-7 and ZR 75-1 cells was dependent upon estrogen, whereas MDA-MB 231 cells formed tumors in ovariectomized mice with or without supplemental estrogen. Ultrastructural comparison of tumors formed by the three human breast carcinoma lines in athymic nude mice indicated that lactoperoxidase activity, milk protein and fat globule formation were virtually absent from all three tumors. The estrogen-dependent tumors (MCF-7, ZR 75-1), however, had more desmosomes, intermediate-sized microfilaments and collagen than the estrogen-independent tumor (MDA-MB 231). When the ultrastructure of the three human tumors was compared to the hormone-dependent, DMBA-induced rat mammary carcinoma and to the normal lactating rat mammocytes, the following observations were evident: a) the estrogen-dependent human tumors closely resembled the normal rat tissue in the distribution of desmosomes and collagen, b) the rat mammary carcinoma differed from both the estrogen-dependent and -independent human tumors, in having milk protein, milk fat globules and intense lactoperoxidase activity. The results indicate that these hormone-dependent and -independent human mammary tumors maintained in athymic nude mice differ markedly in their ultrastructure from the lactating rat mammocytes and the rat DMBA-induced mammary carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Menopause, medroxyprogesterone and breathing during sleep.

Twenty-one postmenopausal women were monitored for sleep-disordered breathing and nocturnal oxygen desaturation to evaluate the contribution of progestational hormones to the occurrence of these sleep events. For approximately one month 11 subjects received 30 mg of medroxyprogesterone (MPG) daily, and 10 received placebo tablets in a randomized, double-blind controlled study. Respiration, saturation and electroencephalography were monitored during one night of sleep before and one night after therapy. Contrasted with the low incidence of disordered breathing and desaturation in premenopausal women, 71 percent of the postmenopausal women had such events. In the placebo-treated group, all measured variables of sleep and breathing were identical on the two nights, which suggested that the findings of a single night of sleep monitoring may be representative of other nights of sleep. Although several subjects appeared to show improvement with MPG, only the maximum duration of apnea was significantly reduced the second night (p less than 0.03).

Adult↗
PubMed1981

Organotypic culture of fetal rat lung: evaluation and comparison with organ culture.

Monodispersed suspensions of 19-day fetal rat lung when plated onto gelatin sponges reaggregated to form alveolarlike structures. These structures consisted almost entirely of alveolar type II cells, whereas the whole cultures contained about 65% type II cells. The phospholipid content and composition of the organotypic cultures after 8 days of incubation was very similar to that of explants of 19-day fetal rat lung grown in organ culture of 48 h, as was the pattern of incorporation of choline and acetate into phospholipids. Very little phosphatidylcholine was secreted by the organotypic cultures into the culture medium. Initial observations suggested that the organ cultures are more responsive to hormones. Organotypic cultures do not appear to offer any major advantage over the simpler and quicker organ cultures for studies of hormonal influences on fetal lung maturation. They may be useful for examining the metabolism and sympathetic pathways of the type II cell.

Acetates↗
PubMed1981

Transcutaneous noninvasive monitoring of carbon dioxide tension.

We evaluated the accuracy of a new device for continuous noninvasive measurement of cutaneous PCO2. The Hewlett-Packard capnometer (model 47210/HA) works by means of an infrared transducer applied to the forearm over an area of skin that has been stripped of the stratum corneum. Capnometer transcutaneous carbon dioxide pressure (CPCO2) was compared with arterial carbon dioxide pressure (PaCO2) during 60 simultaneously obtained measurements in 13 hemodynamically stable patients. Each patient was studied for 1 1/2 to 5 hours, and a wide range of PaCO2 values (21 to 82 mm Hg) was represented. The data show a clinically significant relationship whereby PaCO2 = CPCO2 - 4.13, with a SE of +/- 2.19 mm Hg. Clinical usefulness of noninvasive cutaneous CO2 monitoring can be foreseen in patients whose ventilatory support is being tapered, in those with respiratory depression caused by various neuromuscular disorders, and in patients with chronic obstructive pulmonary disease and acute respiratory failure. Our results indicate that continuous transcutaneous CPCO2 measurements are safe and accurate and strongly suggest that they can be of clinical usefulness in a select group of hemodynamically stable patients.

Adult↗
PubMed1980

The effect of low flow oxygen on sleep-disordered breathing and oxygen desaturation. A study of patients with chronic obstructive lung disease.

Oxygen desaturation occurs during sleep in many patients with chronic obstructive lung disease (COLD) and is often caused by sleep-disordered breathing (SDB). Nocturnal oxygen therapy should improve nighttime hypoxemia, but might also worsen SDB. Using standard polysomnographic techniques, we evaluated the frequency and duration of oxygen desaturation and SDB during sleep in 11 patients with stable COLD. During half of the night the patients breathed air through a nasal cannula and during the other half of the night they breathed oxygen at 2 liters per minute. Five patients had arterial lines inserted for determination of arterial blood gas levels during periods of SDB or desaturation. The ten men and one woman slept 70 minutes (52 percent of time in bed) while on air and 111 minutes (80 percent of time in bed) while on oxygen (p < 0.001). Oxygen therapy reduced the number of episodes of desaturation per hour and the time spent in desaturation. However, there was no difference between air and oxygen in episodes of SDB per hour, the duration of episodes of SDB, baseline sleeping PaCO2 or PaCO2 during episodes of desaturation or SDB. Therefore, in most patients with stable COLD, administration of oxygen at 2 liters per minute improves oxygenation, prolongs sleep, but does not adversely affect SDB.

Adult↗