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Biomedical subjects

S E Dana

Publications and source records attributed to S E Dana.

16 recordsLinked to original sources
PubMed1992

Handedness and the bilateral asymmetry of the jugular foramen.

This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an indicator of handedness observable from cranial morphology. The jugular foramina of 54 subjects were observed for size asymmetry during routine autopsy procedures. Hand preference data were collected on each subject from family members. Of the 54 subjects, 47 were documented as being right-handed and 7 as being left-handed. These values approximate the average percentage of right-handed versus left-handed individuals from larger populations. Jugular foramen asymmetry was qualitatively identified for 36 subjects (66.7%) and was judged equivocal for the other 18 (33.3%). Of the 36 subjects exhibiting asymmetry, 28 (77.7%) showed positive correlation between the asymmetry direction and handedness. This moderate level of congruence, coupled with the result that 4 of the 7 left-handers exhibited dominant right-side foramina, casts doubt on the reliable use of jugular foramen asymmetry for estimating handedness.

Adolescent↗
PubMed1991

Sudden death caused by coronary artery aneurysms: a late complication of Kawasaki disease.

The authors describe three cases (two blacks and one Latin American) of sudden death caused by late complications of Kawasaki disease (mucocutaneous lymph node syndrome). At autopsy each heart contained multiple coronary artery aneurysms with luminal stenosis caused by intimal hyperplasia and thrombi. Although virtually all fatal cases of Kawasaki disease occur within six months of the onset of symptoms, there have been other reported deaths up to 14 years after the acute illness. The coronary artery aneurysms of Kawasaki disease may persist and cause death years after the acute illness.

Adolescent↗
PubMed1987

Deaths caused by carbon monoxide poisoning in an open environment (outdoors).

Three deaths as a result of inhalation of carbon monoxide from the exhaust fumes of automobiles are reported. All deaths occurred outside and not in a structure. The individuals were white males, ages 24 to 26 years. Blood carboxyhemoglobin concentrations ranged from 58 (in a decomposing body) to 81%. The three cases illustrate the fact that even in the outdoors death from carbon monoxide inhalation can occur if an individual is in close proximity to a rich source of carbon monoxide.

Adult↗
PubMed1987

Use of scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDXA) in identification of foreign material on bullets.

The authors report two cases in which examination of foreign material embedded in or adherent to bullets provided critical information in the reconstruction of a crime scene. Analysis of small particles by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDXA) can be accomplished without destruction or injury of the particles. In one case, the detection and identification of mineral fragments embedded near the nose of a bullet provided conclusive evidence that the bullet had ricocheted from a fireplace before striking the victim. In the second case, analysis of particles from two bullets identified them as them as bone fragments, thus proving which shots fired from a police officer's gun had killed a suspected burglar. SEM-EDXA has not been widely used to identify such material on bullets, but should be considered a potentially powerful tool in forensic science.

Adolescent↗
PubMed1975

Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease.

The hydrolysis of cholesteryl esters contained in plasma low density lipoprotein was reduced in cultured fibroblasts derived from a patient with cholesteryl ester storage disease, an inborn error of metabolism in which lysosomal acid lipase activity is deficient. While these mutant cells showed a normal ability to bind low density lipoprotein at its high affinity cell surface receptor site, to take up the bound lipoprotein through endocytosis, and to hydrolyze the protein component of the lipoprotein in lysosomes, their defective lysosomal hydrolysis of the cholesteryl ester component of the lipoprotein led to the accumulation within the cell of unhydrolyzed cholesteryl esters, the fatty acid distribution of which resembled that of plasma lipoprotein. When the cholesteryl ester storage disease cells were incubated with low density lipoprotein, the reduced rate of liberation of free cholesterol by these mutant cells was associated with a delay in the occurrence of two lipoprotein-mediated regulatory events, suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and activation of endogenous cholesteryl ester formation. In contrast to their defective hydrolysis of exogenously derived lipoprotein-bound cholesteryl esters, the choleseryl ester storage disease cells showed a normal rate of hydrolysis of cholesteryl esters that had been synthesized within the cell. These data lend support to the concept that in cultured human fibroblasts cholesteryl esters entering the cell bound to low density lipoprotein are hydrolyzed within the lysosome and that one of the functions of this intracellular organelle is to supply the cell with free cholesterol.

Cells, Cultured↗
PubMed1975

Cholesterol ester formation in cultured human fibroblasts. Stimulation by oxygenated sterols.

Incubation of monolayers of cultured human fibroblasts with oxygenated sterols (25-hydroxycholesterol, 7-ketocholesterol, or 6-ketocholestanol) markedly enhanced the rate at which the cells esterified their endogenous cholesterol and produced an increase in the cellular content of cholesterol esters. The enhanced esterification capacity was associated with an increase in the activity of a membrane-bound fatty acyl-CoA:cholesteryl acyltransferase. Incubation of cells for 5 hours with 5 mug/ml of 25-hydroxycholesterol produced an 8-fold increase in the specific activity of this enzyme when assayed in cell-free extracts. Since the oxygenated sterols that elevated the activity of fatty acyl-CoA:cholesteryl acyl-transferase also suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the data suggest that the processes of cholesterol ester formation and cholesterol synthesis in human fibroblasts are regulated in a reciprocal manner by coordinate changes in the activities of these two membrane-bound enzymes.

Acyltransferases↗
PubMed1975

Use of mutant fibroblasts in the analysis of the regulation of cholesterol metabolism in human cells.

Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipoproteins (LDL) has led to the delineation of an important, hitherto unrecognized, regulatory process for cholesterol metabolism. On normal cells, binding of LDL to this receptor regulates cholesterol metabolism by two mechanisms: (a) suppression of cholesterol synthesis and (b) facilitation of the rate of proteolytic degradation of the lipoprotein. In cells from homozygotes with the autosomal dominant disorder Familial Hypercholesterolemia, a nearly total reduction in LDL receptors results in two secondary abnormalities: (a) overproduction of cholesterol due to an inability of LDL to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) impairment in the rate of proteolytic degradation of LDL. Cells from heterozygotes possess about 50 per cent of the normal number of LDL recpetors; this leads to a concentration-dependent defect in regulation, so that attainment of rates of cholesterol synthesis and LDL degradation equal to that in normal cells requires a two to three-fold higher concentration of extracellular LDL in the heterozygote. The identification of this genetic regulatory defect in fibroblasts of heterozygotes with Familial Hypercholesterolemia makes available an in vitro system for studying the molecular mechanism by which a dominant mutation affects gene expression in mammalian cells.

Blood Proteins↗
PubMed1975

Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor.

Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylgultaryl-CoA reductase (NADPH) [mevalonate:NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the 125-I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous defects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipoprotein receptor.

Adolescent↗
PubMed1975

Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein.

Selective radioactive labeling of the cholesteryl esters contained within human plasma low density lipoprotein has allowed the study of the metabolism of these molecules in monolayers and extracts of cultured human fibroblasts. In monolayers of normal cells, binding of low density lipoprotein to its cell surface receptor was followed by rapid hydrolysis of the [3H]cholesteryl linoleate contained within the lipoprotein and accumulation of the liberated [3H]cholesterol within the cell. The stoichiometry of the degradative process suggested that the protein and cholesteryl ester components of the lipoprotein were hydrolyzed in parallel. Incubation of intact fibroblasts with chloroquine, a known inhibitor of lysosomal degradative processes, inhibited the hydrolysis of the lipoprotein-bound cholesteryl esters. Fibroblasts from subjects with the homozygous form of familial hypercholesterolemia, which lack functional low density lipoprotein receptors and thus are unable to take up this lipoprotein when it is present in the culture medium at low concentrations, were therefore unable to hydrolyze the lipoprotein-bound [3H]cholesteryl linoleate. However, cell-free extracts from these mutant cells were capable of hydrolyzing the lipoprotein-bound [3H]cholesteryl linoleate at the same rapid rate as normal cells when incubated at acid pH. These data illustrate the essential role of the low density lipoprotein receptor and of lysosomal acid hydrolases in the metabolic utilization of low density lipoproteins by cultured human fibroblasts.

Adult↗
PubMed1974

Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia.

A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [(14)C]acetate or [(14)C]oleate into the fatty acid fraction of cholesteryl [(14)C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.

Acetates↗
PubMed1973

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins.

The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), the rate-limiting enzyme of hepatic cholesterol biosynthesis, is suppressed in human fibroblasts cultured in the presence of serum. This enzyme activity increases by more than 10-fold after the removal of serum from the medium. The rise in enzyme activity requires de novo protein synthesis and is not accompanied by changes in the activities of several other cellular enzymes. The factor responsible for the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts is present in the sera of at least four mammalian species, and in human serum it is found in the low-density lipoproteins. Human high-density lipoproteins, very low-density lipoproteins from chicken egg yolk, and the fraction of human serum containing no lipoproteins do not suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Alcohol Oxidoreductases↗