Biomedical subjects

D T Downing

Publications and source records attributed to D T Downing.

At least 91 records · Page 5Linked to original sources

PubMed1986

Linoleate content of epidermal acylglucosylceramide in newborn, growing and mature mice.

Epidermis was collected from newborn, growing and adult mice. Acylglucosylceramide, a structurally unique O-acylsphingolipid, was isolated from each sample, and the ester-linked fatty acids were analyzed by capillary column gas-liquid chromatography. The esterified acids of acylglucosylceramide from newborn mice contained 12% linoleate. The linoleate content of the acylsphingolipid increased rapidly, doubling within 4 days and reaching an adult level of 45% within 2 months. The increase in the linoleate content of the epidermal lipid was accompanied by decreases in 16-carbon monoenoic fatty acids and saturated fatty acids ranging from 14 up to and including 24 carbons in length. These results indicate several potential problems for experimentation involving neonatal skin. Also, the possibility that neonatal mouse epidermis may provide a useful model system for studies on the relationship between linoleic acid and epidermal cell proliferation is also raised.

Aging↗

PubMed1986

Effect of cyproterone acetate-ethinyl estradiol treatment on the proportions of linoleic and sebaleic acids in various skin surface lipid classes.

The effect of high-dose cyproterone acetate-ethinyl estradiol treatment on rates of sebum secretion and on the proportions of linoleic acid (18:2 delta 9,12) and sebaleic acid (18:2 delta 5,8) in the skin surface lipids of three female acne patients was examined. Changes in rates of sebum secretion were evaluated indirectly by measuring the ratio of wax esters/(cholesterol + cholesterol esters) in the subjects' skin surface lipid. In two of the subjects, this ratio indicated a reduction of sebum secretion rates to the childhood range. Concomitantly, there was an increase in linoleic acid and a decrease in sebaleic acid in all lipid classes. In the third subject, in whom there was only a small reduction in sebum secretion rate, the proportion of linoleic acid in the cholesterol esters more than doubled, but the changes in the other lipid classes were small or nonexistent. The results indicate that the proportions of linoleic acid and sebaleic acid in sebum are influenced by sebum secretion rates.

Acne Vulgaris↗

PubMed1986

The lipid composition of porcine epidermis and oral epithelium.

The permeability barrier of mammalian skin has been analysed in terms of its lipid composition whereas that of the oral mucosa is uncharacterized. As there are differences in permeability between different regions of the oral mucosa, and between the oral mucosa and skin, there may be corresponding differences in the nature of the barrier layer. Lipids were identified by thin-layer chromatography after solvent extraction of separated epithelium; their localization was determined in histological sections using standard histochemical stains. Keratinized oral epithelium and epidermis showed a similar pattern of lipid distribution, the majority of neutral lipids being ceramides, localized around the cells of the stratum corneum. The non-keratinized epithelium contained few neutral lipids but polar lipids, particularly cholesterol sulphate and glucosylceramides, were clearly evident. Histochemical staining suggested that these were localized in intercellular regions throughout the epithelium. The differences in the types and distribution of lipids accord well with known permeability differences, which show that keratinized oral epithelium and epidermis have a similar impermeability to water and that non-keratinized regions have greater permeability.

Animals↗

PubMed1986

Skin surface lipids of the mink.

Skin surface lipids from mink (Mustela vison) were collected in acetone and analyzed by thin-layer chromatography and gas chromatography. The principal components were wax monoesters (92%), cholesteryl esters (5%), free fatty acids (1%), fatty alcohols (1%) and cholesterol (1%). The fatty acids and alcohols contained in these lipids were composed principally of homologous series of straight chained omega 7-unsaturated structures (C16-C24), accompanied by lesser proportions of homologous series of saturated (C14-C22) and omega 9-unsaturated (C18-C22) structures.

Animals↗

PubMed1986

A survey of polar and nonpolar lipids from epidermis and epidermal appendages of the chicken (Gallus domesticus).

Total lipid was extracted from chicken (Gallus domesticus) epidermis, leg scale, claws, feathers and preen glands and analyzed by quantitative thin-layer chromatography. All of the tissue lipids contained large proportions of wax diesters, triglycerides, and free sterols and variable proportions of phospholipids, steryl esters and free fatty acids. All of the keratinized tissues, but not the preen gland, contained ceramides, acylceramides and cholesteryl sulfate. Acylglucosylceramides were found only in full thickness epidermis. Glucosylsterols and acylglucosylsterols were found in the keratinized tissues, and may be of significance in the evolutionary history of the epidermal water barrier.

Animals↗

PubMed1986

Lipids of epidermis and keratinized and non-keratinized oral epithelia.

Lipid compositions have been determined by quantitative thin-layer chromatography for epidermis, floor of mouth, gingiva, palate and buccal epithelium of the pig (Sus scrofa). All of the epithelia contained phospholipids, glycosylceramides, cholesteryl sulfate, cholesteryl esters, free sterols, fatty acids and triglycerides. Epidermis, palate and gingiva had similar lipid compositions, which were characterized by the presence of O-acylglycosylceramides, O-acylceramides and relatively high proportions of ceramides. Floor of mouth and buccal epithelium, which are not keratinized, contained no O-acylglucosylceramides or O-acylceramides and very little ceramide. The higher water permeability of the non-keratinized oral regions may reflect the absence of acylglucosylceramides and the low proportions of ceramides.

Animals↗

PubMed1986

Essential fatty acids and acne.

Acne is characterized by hyperkeratosis of the follicular epithelium, leading to horny impactions that may lie dormant as open or closed comedones or may cause inflammation of the follicle. Although persons with acne have consistently been observed to have elevated levels of sebum secretion, no mechanism relating sebum secretion rates to comedogenesis is known. Acne patients have also been shown to have low levels of linoleic acid in their skin surface lipids. To explain this observation, the hypothesis is advanced that the linoleate concentration in human sebum depends on the quantity of linoleic acid present in each sebaceous cell at the commencement of its differentiation and on the extent to which this initial charge is diluted by subsequent endogenous lipid synthesis in each sebaceous cell. A corollary hypothesis holds that low concentrations of linoleate in sebum impose a state of essential fatty acid deficiency on the cells of the follicular epithelium and induce the characteristic response of hyperkeratosis. Both hypotheses could hold, without there being a systemic deficiency of linoleic acid, simply as the result of elevated lipogenesis in individual sebaceous cells.

Acne Vulgaris↗

PubMed1986

Possible genetic control of the proportions of branched-chain fatty acids in human sebaceous wax esters.

The composition of human sebum varies among individuals with respect to the proportions of various types of fatty acids in the ester lipid classes. Iso-branched fatty acids with even numbers of carbons (iso-even) are particularly variable. However, in 13 identical twin pairs, intrapair differences in the proportions of iso-even fatty acids in sebaceous wax esters were found to be very small, while interpair differences were as large as in the nontwin population. Intrapair differences in iso-even fatty acids were also quite small in 4 of 8 fraternal twin pairs. Heritability estimates suggested that proportions of iso-even fatty acids in human sebum are controlled, at least in part, by genotype.

Adolescent↗

PubMed1986

Lipid composition of cohesive and desquamated corneocytes from mouse ear skin.

An organ culture system has been used to examine differences in the lipid compositions of materials derived from cohesive and desquamated mouse ear stratum corneum. Within this culture system, skin explants display rates of cell replication and differentiation comparable to those observed in vivo for up to 2 weeks and, during this period, loosened or dishesive material accumulates at the surface. Lipid compositions were determined for both intact and loosened stratum corneum derived from cultured skin and also for freshly prepared stratum corneum. In all 3 cases, the profiles of the nonpolar lipids and the ceramides were essentially the same; some of the nonpolar lipids appeared to be of sebaceous origin. The only changes detected upon desquamation were reductions of cholesteryl sulfate and a second unidentified lipid of similar polarity. Cholesteryl sulfate constitutes 4-5% of the polar lipid in fresh stratum corneum or stratum corneum from organ culture. This is reduced to 0.4% in the desquamated material which accumulates in the culture system. The unidentified lipid decreases from 1-2% of the polar lipid in intact fresh or cultured stratum corneum to 0.1% in the desquamated material. The possible function of cholesteryl sulfate in corneocyte cohesion is discussed.

Animals↗

PubMed1986

Preparation of liposomes from stratum corneum lipids.

Mammalian stratum corneum contains multiple intercellular lipid bilayers that constitute the epidermal water barrier. Unlike all other biologic membranes, the epidermal lamellae do not contain phospholipids, as a result of which the ability of the stratum corneum lipid mixture to form bilayers has been questioned. In the present study, a lipid mixture containing only epidermal ceramides (40%), cholesterol (25%), palmitic acid (25%), and cholesteryl sulfate (10%), approximating the composition of stratum corneum lipids, formed stable, unilamellar liposomes when sonicated at 80 degrees C in buffer containing 100 mM NaCl, 5 mM Tris, and 1 mM EDTA at pH 7.5. The size and form of the liposomes were studied by both freeze fracture and negative staining electron microscopy. Lipid mixtures from which either the palmitic acid or the cholesteryl sulfate were omitted were still capable of forming similar liposomes, but a mixture of ceramides and cholesterol, or ceramides alone, were incapable of forming liposomes. The results indicate that lipid mixtures similar to those found in stratum corneum are capable of forming bilayers at physiologic pH.

Animals↗

PubMed1986

Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides.

Sebaceous wax esters and epidermal acylceramides were isolated from skin surface lipid obtained from children and from young adults. Fatty acid methyl esters (FAME) were prepared from the esterified fatty acids of these lipid classes and analyzed to ascertain the proportions of methyl linoleate (18:2 delta 9,12), methyl sebaleate (18:2 delta 5,8), and methyl sapienate (16:1 delta 6). On the same subjects, 2 measures of sebum secretion rate were obtained, namely the sustainable wax ester secretion rate (WESR) on the forehead and the ratio of wax esters/(cholesterol + cholesterol esters) [WE/(CH + CE)] in the surface lipid. The proportions of methyl linoleate in FAME from the wax esters decreased, and the proportions of methyl sebaleate increased, with increased rates of sebum secretion. For both methyl linoleate and methyl sebaleate, a better correlation was obtained when the ratio of WE/(CH + CE) was used as a measure of sebum secretion rather than the WESR. The proportions of methyl linoleate in the FAME from the acylceramides were also inversely related to ratios of WE/(CH + CE). In acylceramides, linoleate was replaced by sapienate, a major fatty acid of human sebum. It appears, therefore, that sebum fatty acid composition may change with changes in sebaceous gland activity, and that sebum fatty acids can enter the epidermis and be incorporated into epidermal lipids.

Acne Vulgaris↗

PubMed1986

Lipid composition of cultured murine keratinocytes.

The current study was undertaken to determine whether a previously reported murine culture system is an acceptable model for the study of epidermal lipid metabolism. The lipid composition of primary neonatal mouse keratinocyte cultures was determined and compared with that of freshly isolated keratinocytes and whole epidermis. 14C-Labeled arachidonic acid (AA) and linoleic acid (LA) were added to cultures and the incorporation into specific lipids was assessed. The lipid composition of the cultures indicated that they were partially differentiated, which parallels the well-known incomplete keratinization seen in many keratinocyte culture systems. Of particular importance, the LA-rich uniquely epidermal lipids which may be of importance in water barrier function, acylglucosylceramide (AGC) and acylceramide (AC), were made by the cultures. Fatty acid analysis of total lipid, phospholipid, and AGC extracts revealed a significant decrease in LA content compared with the parent epidermis; this may have resulted from the low level of LA in fetal bovine serum, which was the serum source for these cultures. Labeled AA and LA were incorporated into the lipids of cultured keratinocytes in distinct patterns that were consistent with the fatty acid content of the lipids. Both AGC and AC showed preferential uptake of LA compared with AA. There was minimal labeling of non-linoleate-containing lipids and a low degree of conversion of labeled LA to AA. Considering the grossly different environment of the in vitro system compared with the in vivo state, the overall lipid composition was remarkably well maintained. Keratinocyte cultures should be of great value in the study of epidermal lipid metabolism.

Animals↗

PubMed1986

Changes in sebum secretion and the sebaceous gland.

New data have shown that sebum secretion is highest in young adults and then declines steadily throughout life in both men and women. This parallels the decline in androgen levels, but this cannot be the sole factor because there is so much overlap in sebaceous gland activity between men and women. The increased occurrence of dry skin in the elderly has been shown to be unrelated to the sebum secretion rate. This is not unexpected, as children, with even less sebum, rarely have this problem. Seborrheic dermatitis, which is also much more common in the elderly, is also unrelated to sebum secretion rate.

Adolescent↗

PubMed1986

Lipids of chicken epidermis.

The lipids from chicken epidermis were analyzed by a combination of quantitative thin-layer and gas-liquid chromatography and by chemical and spectroscopic methods. The lipid groups present included wax diesters (34%), triglycerides (32%), sterols (11%), phospholipids (11%), nonphosphorus-containing sphingolipids (3%), beta-D-glucosylsterols (3%), 6-O-acyl-beta-D-glucosylsterols (2%), steryl esters (1%), cholesteryl sulfate (1%), and free fatty acids (1%). The major phospholipids were phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, and the sphingolipids included ceramides, glucosylceramides, O-acylceramides, and O-acylglucosylceramides. Glucosylsterols and acylglucosylsterols have not been found in mammalian skin, and may be relevant to the evolutionary history of the epidermal water barrier. The wax diesters contained mainly 16-, 18-, and 20-carbon saturated fatty acids esterified to 20- through 24-carbon threo and erythro 2,3-diols, while the chicken epidermal triglycerides contained some very long-chain (26-40 carbon) saturated fatty acids. These wax diesters and unusual triglycerides may be of significance in human health.

Animals↗

PubMed1985

Comparison of acetate and glucose incorporation into rat and horse skin lipids.

The relative efficiency of acetate and glucose as substrates for the biosynthesis of lipids in the skin of the rat and horse was examined using in vivo pulse labelling of skin with [1-14C]acetate and [U-14C]glucose by intradermal injections. The resulting radiolabelled lipids were recovered in the rat by punch biopsy as well as by daily, long-term skin surface lipid collections and in the horse by punch biopsy of the injection sites. The lipids were examined by liquid scintillation and by a combination of thin-layer chromatography and autoradiography. In both species the recovery of radiolabel in the non-polar lipids was much higher after a pulse of [1-14C]acetate than after a pulse of [U-14C]glucose. In the rat, the skin surface lipids labelled through acetate contained sufficient radiolabel to allow observation of the time course of excretion of 14C in the major non-polar lipid classes. The results suggest that the biosynthesis of these lipid classes in the sebaceous glands of the rat are not entirely synchronous. In the skin lipid extracts of the horse, all of the major lipid classes, including phospholipids and glycolipids, were labelled through acetate. In contrast, none of the non-polar lipids and very little of the polar lipids were labelled through glucose.

Acetates↗

PubMed1985

The time-course of lipid biosynthesis in horse skin.

To observe the time-course of formation of sebaceous lipids in the horse, skin was pulse-labelled in vivo by intradermal injection of [1-14C]acetate and the injection sites were harvested at intervals for up to 12 days by skin punch biopsy. The distribution of radioactivity among the major neutral lipid classes and the phospholipids from these biopsies showed that, soon after pulse-labelling, the phospholipids were highly labelled followed by a long-term decrease in radioactivity. Over the same period, the low initial labelling of the dominant component, the equolides (giant ring omega-lactones, C32-C36), was followed by a long-term increase in radioactivity. This suggests a post-pulse transferance of radioactivity from the phospholipids to the equolides, presumably in the fatty acids. Of the phospholipid fatty acids from horse dermis, including sebaceous glands, 33% were found to contain iso-branched structures unique to horse sebaceous lipids. Of the iso-branched fatty acids, 40% were delta 9-18:1 and delta 9- and delta 11-20:1 acids, which are structurally appropriate to be precursors for the monounsaturated equolides. These findings strengthen the hypothesis that the sebaceous phospholipids of horse skin serve as long-term lipid intermediates in the biosynthesis of the equolides during sebaceous cell development.

Acetates↗

PubMed1985

Measurement of the time between biosynthesis and surface excretion of sebaceous lipids in the horse.

The time between the biosynthesis and excretion of sebum to the skin surface of the horse was examined by in vivo intradermal injection of [1-14C]acetate followed by periodic surface lipid collections. The radiolabelling of the major neutral lipid classes, equolides (giant ring omega-lactones, C32-C36) and cholesteryl esters, was evaluated by thin-layer chromatography and autoradiography. The distribution of radioactivity within the monounsaturated equolides was examined by oxidative fragmentation and evaluation of the products. A peak of radioactivity in the equolides and cholesteryl esters occurred 15-21 days and 10-16 days, respectively, after injection. The time-courses of specific radioactivity of the two types of equolide oxidation fragments were also found to be dissimilar. The results are interpreted as indicating that in the biosynthesis of a large proportion of the equolides, de novo fatty acid synthesis was not followed immediately by fatty acid chain elongation. The phospholipids of the sebaceous cells are proposed as the long-term intermediate in which fatty acids reside between these two biosynthetic processes.

Animals↗

PubMed1985

Human stratum corneum polar lipids and desquamation.

The ceramides and steryl-sulfate components from desquamated and cohesive human stratum corneum were examined using a combination of chemical and chromatographic means. Six structurally distinct series of ceramides were identified, and the relative amounts of these species, as measured by quantitative thin-layer chromatography, did not differ in cohesive and desquamated stratum corneum. In contrast, the level of cholesteryl sulfate was significantly reduced in the desquamated material. The results are in accord with the hypothesis that cholesteryl sulfate serves in cell-to-cell cohesion within the stratum corneum, and its hydrolysis may be necessary to permit shedding of cells from the surface.

Ceramides↗