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Biomedical subjects

D T Downing

Publications and source records attributed to D T Downing.

At least 19 recordsLinked to original sources

Lamellar structures formed by stratum corneum lipids in vitro: a deuterium nuclear magnetic resonance (NMR) study.

Hydrated lipid mixtures consisting of stratum corneum ceramides, cholesterol, specifically deuterated palmitic acid, and cholesteryl sulfate were investigated by solid-state 2H NMR spectroscopy at different temperatures. The mole ratio of cholesterol to ceramides was varied from 1 to 0. 2H NMR spectra from these mixtures showed powder patterns with quadrupolar splittings smaller than those obtained from control mixtures containing dipalmitoylphosphatidylcholine (DPPC) instead of the ceramides. This result is attributed to the rigid amide group of the ceramides, with a planar configuration, which could prevent close packing of the alpha-methylenes of the acyl chains. There was a gradual loss of symmetry in the powder pattern as the amount of cholesterol was decreased and the amount of ceramides (or DPPC) was increased concomitantly. The loss was more pronounced in the ceramide-containing samples. This phenomenon is interpreted as a decrease in the axial reorientation rate of the alpha-deuterated palmitic acid in the bilayers, presumably caused by the increased hydrogen bonding resulting from the high amount of hydroxyl-bearing ceramides. Spectra obtained at temperatures above 60 degrees C indicated the formation of a hexagonal phase (HII) by the ceramide-containing mixtures. Spectra of the omega-deuterated palmitic acid in the mixture containing 76 mol% ceramides and no cholesterol indicated phase separation into a more rigid phase and a more mobile phase in the temperature range of 25 to 60 degrees C. The bilayer configuration of lipids at 25 degrees C was confirmed by thin-section electron microscopy.

Animals

Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls.

BACKGROUND AND DESIGN: Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. RESULTS: Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. CONCLUSION: Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.

Adolescent

In vivo studies of cutaneous lipid biosynthesis.

The epidermis and the sebaceous glands are both characterized as terminally differentiating tissues in which cells produced by replication in the germinative layer progress during several weeks through a programmed series of biochemical and morphological changes that end in cell death and eventual sloughing of the final metabolic products. Because of these slow changes and the presence of successive anabolic and catabolic regimes in the same tissue, classic methods of biochemistry using cell homogenates have not been widely successful. Much of what is known of the lipid metabolic pathways has therefore been obtained from experiments with biopsy materials or in intact animals. Radiotracer experiments in intact animals have been successful largely because the lipid products into which the radiolabel is incorporated are not lost to the general circulation during the several weeks in which they are retained in the tissue. Nor are they subject to continual degradation and resynthesis that would be the case in most other tissues, but progress steadily through the series of biochemical transformations that occur along with the morphologic changes characteristic of the epidermal and sebaceous tissues. Furthermore, of the radiolabel that enters the general circulation, only an insignificant proportion returns to the cutaneous tissues to obscure the local metabolic activities.

Animals

Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid.

Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland.

Acne Vulgaris

Age-related changes in sebaceous gland activity.

The sebaceous glands of man show age-related differences in their activity as determined by quantitative and qualitative examination of sebum. Sebaceous secretion is low in children and begins to increase in mid- to late childhood under the influence of androgens. This rise continues until the late teens, after which no further significant change takes place until late in life. In elderly men, sebum levels remain essentially unchanged from those of younger adults until the age of 80. In women, sebaceous secretion decreases gradually after menopause and shows no significant change after the 7th decade. The most likely explanation for the decrease in sebaceous gland secretion with age in both men and women is a concomitant decrease in the endogenous production of androgens. Although surface lipid levels fall with age, paradoxically the sebaceous glands become larger, rather than smaller, as a result of decreased cellular turnover. Nonetheless, as the higher surface lipid levels after administration of fluoxymesterone (a synthetic testosterone derivative) indicate, the glands have the capacity to respond to androgens.

Adolescent

The fatty acids of human sebaceous gland phosphatidylcholine.

The fatty acids of human sebaceous gland phosphatidylcholine were examined by gas chromatography and by analysis of the double bond positions in the C-16 and C-18 monoenes. Compared to phosphatidylcholine from other organs, sebaceous gland phosphatidylcholine was found to be deficient in essential fatty acids and poly-unsaturated fatty acids. The relatively large mono-unsaturated fatty acid fraction consisted predominantly of fatty acids with delta6- and delta8-unsaturation. Analysis indicates that the fatty acids of sebaceous gland phospholipids are predominantly of types synthesized in sebaceous glands.

Fatty Acids

Surface lipid composition in children with protein-calorie malnutrition.

The composition of skin surface lipid has been measured in a group of 21 children with the diagnosis of marasmic-kwashiokor. When compared to the values for healthy children of comparable age, the squalene content was significantly decreased (3.1% +/- 3.2% versus 9.8% +/- 3.6%) and the squalene/wax ester ratio was also significantly decreased (0.57 +/- 0.55 versus 2.13 +/- 0.91). Measurements of skin surface lipid also were made in five of these children after treatment. The altered values reverted towards normal. Since changes in the squalene content and the squalene/wax ester ratio of skin surface lipid can be correlated with other biochemical changes of protein-calorie malnutrition, the analysis of surface lipid, a procedure that is both convenient and non-invasive, can be of use in determining the nutritional status in field studies of malnourished subjects.

Child

Skin surface lipids of the dog.

The skin surface lipid of the dog has been reported to contain a high proportion of diol diesters having a lower mobility on thin layer chromatography than diesters from other species in spite of containing similar fatty acid and diol components. In the present study, dog skin surface lipid was separated by preparative thin layer chromatography into sterol esters (42%), wax diesters (32%), free sterols (9%), polar lipids (7%), and unidentified components (10%). The diesters contained 1,2-diols, each estrified with one long chain fatty acid and one isovaleric acid moiety. The diols were principally branched chain C21 and C22 compounds while the long chain fatty acids esterified with them were mainly C20 and C21 branched compounds. The fatty acids from the sterol esters were mostly saturated, branched chain C19 TO C23, together with 7% of straight chain monoenoic acids, principally C21 and C22. There were only trace amounts of free sterols other than cholesterol, while the esterified sterols contained 96% cholesterol and 4% lathosterol.

Animals

Skin surface lipid composition, acne, pubertal development, and urinary excretion of testosterone and 17-ketosteroids in children.

Fifty-two children, age 5-10, from acne-prone families, were studied for a period of 1 year to examine the interrelationship between sebum, acne, pubertal development, and urinary steroid excretion. In each of the subjects, 30 boys and 22 girls, the composition of forehead skin lipid was determined 4 times yearly by thin-layer chromatography, with measurement of triglycerides, diglycerides, free fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. Twice yearly, examination was made of the presence or absence of acne, pubertal maturation and the 24-hour urinary excretion of testosterone as determined by radioimmunnoassay, and of total 17-ketosteroids, dehydroepiandrosterone, androsterone, and etiocholanolone, as determined by paper chromatography. The relative amount of sebaceous lipids was positively correlated with age of the subjects (wax esters p less than .001, squalene p less than .05), as was the triglyceride-diglyceride component (p less than .05). No significant correlation was seen with the fatty acids. Acne, primarily comedonal, occurred in 27/52 subjects (15 girls, 12 boys) and was associated with higher sebum values. One-half of the children with acne had no signs of pubertal development. A significantly positive correlation was observed between the relative amount of sebaceous lipid and the urinary excretion of 17-ketosteroids, androsterone, and etiocholanolone in both sexes, and of testosterone and dehydroepiandrosterone in boys. The development of acne in children is an early pubertal event, often evident before other signs of pubertal maturation, and it is associated with an increase in sebum and in the urinary excretion of androgenic steroids.

17-Ketosteroids

Nutritional influences of pellagra on sebum composition.

Sebum composition has been measured in 51 patients with varying degrees of pellagra and compared with a control group of subjects in the same geographic area. In the pellagra group the wax ester percentage was 14-9 versus the normal of 21-9%. The squalene percentage was increased in the pellagra group (11-6%) versus a control value of 8-4%. A small increase in the percentage of cholesterol was also noted. These changes, which previously have been observed in starved but otherwise normal subjects, were reversible with adequate refeeding.

Adult

Analysis of soluble proteins in comedones.

The detergent-soluble fraction of purified, concentrated comedo samples was analysed for protein by disc-gel electrophoresis and fluorescamine assay. Spectrophotometer scanning revealed a characteristic pattern of 14 peaks which was essentially uniform in comedones from individuals having acne, Favre-Racouchot syndrome, or prepubertal comedones. The pattern was different in material derived from keratinous cysts and the contents of follicles from the nose. The presence of small amounts of serum proteins, notably globulins, was detected by immunodiffusion.

Acne Vulgaris

Skin surface lipids of the guinea pig.

Skin surface lipids of the guinea pig were found to contain sterol esters (33%), wax diesters (diacyl alkanediols) (24%), glycerol ether diesters (28%), free fatty alcohols (6%) and free sterols (9%). The sterol esters and diacyl alkanediols contained saturated fatty acids (40 and 67%, respectively) having straight and singly-branched chains and mono-unsaturated acids (60 and 33%,respectively) derived predominantly by delta 9-desaturation of C15 and C16 straight-chain saturated fatty-acid precursors. The 1-O-alkylglycerols and fatty acids from the glycerol ether diesters were both entirely saturated series containing straight, branched and multi-branched chains. Both the free and the esterified sterols consisted principally of cholesterol with a small proportion of lathosterol.

Animals

Octadecadienoic acids in the skin surface lipids of acne patients and normal subjects.

Measurements were made of the proportions of octadeca-5,8-dienoic acid and octadeca-9,12-dienoic acid in the scalp surface lipids of 6 normal subjects, 5 subjects with slight acne, and 9 subjects with severe acne. The group averages for the delta5,8 isomer were: 0.74, 0.85, and 0.61% and for the delta9,12 isomer were 0.56, 0.27, and 0.19%, respectively. The differences in the levels of the delta9,12 isomer between the normal subjects and the groups with slight and with severe acne were statistically significant (p less than 0.02 and 0.001), respectively) but there was no significant difference in the content of the delta5,8 compound. The ratio of the delta5,8/delta9,12 isomers showed no correlation with the rate of sebum production in 12 subjects.

Acne Vulgaris

The sebaceous glands: twenty-five years of progress.

During the last twenty-five years, research on the sebaceous glands has made significant advances. Many of the new findings are related to electron microscopy, quantitative lipid composition studies, and the hormonal and nonhormonal control of sebaceous gland secretion.

Animals

Trans-unsaturated fatty acids in human skin surface lipids.

Methyl esters of the fatty acids obtained by saponification of human skin surface lipids were subjected to thin-layer chromatography on silica gel-silver nitrate revealing the presence of trans-monounsaturated components constituting approximately 0.3% of the total fatty acids. The positions of unsaturation in the 18-carbon trans-unsaturated acids in 2 subjects resembled those present in the corresponding acids from margarine, although this was not a component of the diet of one of the subjects. Dietary origin is possible for these components, which could also arise from bacterial action in the pilosebaceous follicle.

Butter