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Biomedical subjects

M L Williams

Publications and source records attributed to M L Williams.

At least 163 records · Page 9Linked to original sources
PubMed1988

Lipid content and metabolism of human keratinocyte cultures grown at the air-medium interface.

The differentiation of human keratinocytes in most culture systems is incomplete; e.g., lamellar bodies, the characteristic lipid-delivery organelles of epidermis, are not present. Moreover, their lipid profile does not reflect the distinctive composition found in cornifying epidermis. In contrast, keratinocytes that grow at an air-medium interface exhibit more complete differentiation. In this study, we compared the elaboration of lamellar bodies, the lipid content, and the lipid metabolism of human keratinocytes, cultured both under standard immersed conditions and after lifting to an air-medium interface. Whereas submerged cultures neither elaborated lamellar bodies nor displayed a lipid distribution characteristic of cornifying epidermis, lifted cultures displayed advanced cornification, elaborated lamellar bodies which were deposited in intercellular domains, and a lipid profile more typical of cornifying epidermis. Moreover, lipid biosynthesis was 5-10-fold more active in lifted than in immersed cultures, and was not inhibited by exogenous lipoproteins. These findings are consistent with recent studies that demonstrate both high rates of lipogenesis in differentiating layers of the epidermis as well as autonomy of lipogenesis from the influence of circulating lipoproteins. Thus, the lipid content and metabolism of human keratinocyte cultures, grown at an air-medium interface, demonstrate features that simulate the epidermis.

Cell Differentiation↗
PubMed1988

Neutral lipid storage disease with ichthyosis: lipid content and metabolism of fibroblasts.

Neutral lipid storage disease with ichthyosis is a newly recognized heritable disorder characterized by widespread cellular triglyceride storage. Lipid metabolism in fibroblasts cultured from three affected family members was studied. The stored lipid is triglyceride composed of an unremarkable fatty acid profile and derived from both exogenously-supplied and endogenously-synthesized fatty acids. Lipid storage could not be corrected by prolonged culture in lipid-depleted media. Acetyl CoA carboxylase activity and beta-oxidation of palmitate were both normal. Taken together, these studies exclude a primary defect of fatty acid uptake, over-synthesis or impaired beta-oxidation. Moreover, triacylglycerol lipase activity of homogenates of fibroblasts from patients with NLSDI examined over the range of pH 3.5-8.5 was normal.

Fatty Acids↗
PubMed1988

Acid rain: chemistry and transport.

This review describes the more important features of the emission, chemistry, transport and deposition of pollutants involved in acid deposition. Global emissions, both natural and man-made, of sulphur and nitrogen oxides are discussed and examples of spatial distributions and trends over the last century presented. The more significant chemical and physical processes involved in the transformation of the primary emissions into their acidic end products are described, including a summary of the approximate timescales of the processes involved. Measurements and modelled calculations of spatial and temporal patterns in the deposition of acidic pollutants by both wet and dry pathways are presented.

Journal Article↗
PubMed1988

Density-dependent variations in the lipid content and metabolism of cultured human keratinocytes.

Cultured human foreskin keratinocytes have been utilized extensively to study modulations in protein content during epidermal differentiation. In this study we examined their usefulness as a model system for differentiation-linked changes in lipid content and metabolism. First-to-third passage keratinocytes were grown in 10% fetal calf serum on a mitomycin-treated 3T3 feeder layer and harvested at intervals before, during, and after reaching confluence for determination of lipid, protein, and DNA content. Lipid synthesis, determined as acetate incorporation into lipid, was most active in pre-confluent cultures and at all times closely paralleled the growth activity of the cultures. Post-confluent cultures were characterized by an increase in total lipid content and by increased triglyceride content and synthesis. Pulse-chase studies demonstrated that labeling of the triglyceride pool was labile and suggested that even in post-confluent cultures, triglycerides provide a fatty acid reservoir for phospholipid biosynthesis. A novel band, which co-migrated with monoalkyldiacylglycerol in two solvents systems was present in confluent and post-confluent cultures, but absent in pre-confluent cultures. Sphingolipids constituted less than 10% of total lipid at all stages of growth, and cholesterol sulfate was present only in small quantities. These studies illustrate the relationship of lipid synthesis to growth and demonstrate that human foreskin keratinocytes, cultured under standard conditions, reproduce incompletely the lipid composition of epidermis in vivo.

Cell Division↗
PubMed1988

Skin lipid content during early fetal development.

Although little is known about changes in the lipid composition of the skin during fetal development, information regarding the developmental sequence of fetal skin lipid content could be important for understanding the emergence of epidermal barrier function, as well as providing baseline criteria for prenatal diagnosis of certain inherited disorders of cornification. In these studies, epidermis was separated from dermis in fetal skin samples ranging from 50 to 140 d, estimated gestational ages (EGA), and its lipid composition was analyzed by quartz rod microchromatography/flame-ionization and thin layer chromatography. Lipid biochemical data were correlated with developmental milestones observed by electron microscopy (morphologic studies). The lipid composition of epidermal and dermal fractions from skin samples between 50 and 110 d EGA was similar, with both tissues exhibiting a predominance of free sterols and phospholipids. After 110 d EGA dermis became enriched in triglycerides, corresponding to the progressive development of adipocytes after this time. EGA epidermis after 110 d was enriched not only in triglycerides, but also sterol esters. Moreover, ceramides and glycosphingolipids also became increasingly prominent, changes that were greatest in epidermis from older fetuses and from cephalad regions. These changes in epidermal lipid composition corresponded morphologically to the progressive emergence of both folliculocentric epidermal cornification and sebaceous gland development.

Cholesterol↗
PubMed1988

Calorimetric and electron spin resonance examination of lipid phase transitions in human stratum corneum: molecular basis for normal cohesion and abnormal desquamation in recessive X-linked ichthyosis.

Lipids appear to play a critical role as regulators of stratum corneum desquamation. In this study, we observed discrete lipid phase transitions at physiologic temperatures in both normal human scale (NHS) and in lipid extracts of NHS by differential scanning calorimetry. In contrast, such thermal transitions were not observed in recessive x-linked ichthyosis scale (RXLIS). To gain further insight into the molecular basis of the lipid phase transitions in NHS vs. RXLIS, comparable samples were evaluated by electron spin resonance, utilizing the perdeuterated probe, di-t-butyl nitroxide. Upon electron spin resonance analysis, both NHS and RXLIS demonstrated thermal phase transitions in the physiologic range; however, the nature of the lipid environments in each type varied. Whereas the environment of the spin probe was more polar in NHS than in RXLIS, the spin probe partitioned into a more "fluid" environment in RXLIS; i.e., the spin probe was more mobile in RXLIS than in NHS lipid matrices. Because an alteration in the cholesteryl sulfate:cholesterol ratio is the primary lipid abnormality in RXLIS, model cholesterol-fatty acid-cholesteryl sulfate mixtures were prepared in proportion to the lipid composition of NHS and RXLIS. Differences were observed in both thermal transitions and in lipid microenvironments in these mixtures that paralleled those observed in scale samples. Based on these results, a model is proposed that invokes abnormal hydrogen bonding, due to increased cholesteryl sulfate, as the mechanism for the abnormal desquamation in recessive X-linked ichthyosis.

Butanes↗
PubMed1988

The expression of congenital ichthyosiform erythroderma in second trimester fetuses of the same family: morphologic and biochemical studies.

The first born offspring of first-cousin parents was affected with a keratinization disorder thought to be nonbullous congenital ichthyosiform erythroderma (CIE). In each of three subsequent pregnancies, the parents elected to have prenatal diagnosis based on evaluation of fetal skin biopsies. The epidermis of fetus 1 was identical to normal 21-wk estimated gestation age (EGA) fetal epidermis, but because keratinization begins normally around 24 wk EGA, the procedure was repeated 4 wk later. A thin epidermis with a few layers of stratum corneum indicated a normal fetus and a healthy infant was born at term. Skin biopsy samples from fetus 2 gave conflicting results; the epidermis of one sample appeared normal but the second had 5-15 layers of incompletely keratinized cells superficial to basal and intermediate layers. The hair canals of both samples were hyperkeratotic. Pelleted amniotic fluid cells contained aggregates of incompletely keratinized epidermal cells and concentric rings of keratinized cells. The fetus was thought to be affected and the pregnancy terminated. Regional variation in epidermal thickness and keratinization was noted upon gross examination of the fetus and by histology of the skin. Marked hyperkeratinization of follicles was evident in all regions. No abnormal keratins were expressed in the affected epidermis but epidermal lipids analyzed from two body regions had a lower triglyceride content and a higher content of free sterols compared with age-matched, normal fetal epidermis. Immunolabeling for markers of differentiation revealed variable stages of epidermal differentiation according to region. Four structurally identical biopsy samples were obtained from a third fetus. The epidermis appeared normal for age and hair canals were keratinized to various extents. The pregnancy was continued and at 33 wk a male infant was born with a severe ichthyosis of the face and scalp and fine, white scaling on the body. The epidermis of both the severely and mildly affected regions of the newborn had a thick, compact stratum corneum and other features of CIE. Scars from all four fetal biopsies were identified on the trunk, in areas which appeared less affected clinically. This study reports, for the first time, the criteria for prenatal diagnosis of CIE and the variable expression of this disorder in the midtrimester fetus. More importantly, it demonstrates the risks and pitfalls of this in utero diagnosis based on epidermal morphology.

Adult↗
PubMed1988

Clonal rearrangement of the T cell receptor beta gene in the circulating lymphocytes of erythrodermic follicular mucinosis.

Follicular mucinosis is a condition characterized by the abnormal accumulation of acidic mucopolysaccharides in hair follicles. It is classically described as occurring idiopathically in young persons and within the infiltrates of mycosis fungoides in older individuals. We report a 12-year-old girl who had erythrodermic follicular mucinosis, hypereosinophilia, circulating Sezary cells, and both immunophenotypic and genotypic evidence of T cell neoplasia. Erythrodermic follicular mucinosis may represent an unusual variant of the Sezary syndrome, which to date has not been described in children or adolescents.

Alopecia↗
PubMed1988

The natural history of preterm ruptured membranes: what to expect of expectant management.

We asked the question: What can be expected of expectant management in preterm ruptured membranes? Our findings showed that ruptured membranes during the first half of the third trimester occurred in only 1.7% (N = 298) of 17,877 pregnancies delivered at our institution, yet accounted for 20% of the total perinatal deaths during the study period. Expectant management was seldom successful; only 20 (7%) of pregnancies with preterm ruptured membranes did not begin labor within 48 hours. The condition of preterm ruptured membranes was also frequently associated with other obstetric complications such as twins, breech presentation, chorioamnionitis, and fetal heart rate decelerations in labor. We conclude that preterm ruptured membranes is an uncommon but complex obstetric problem that remains largely unsolved.

Breech Presentation↗
PubMed1988

Localization of sites of lipid biosynthesis in mammalian epidermis.

The end-product of epidermal differentiation is a stratified layer of corneocytes whose extracellular lipid bilayers provide a permeability barrier. It is generally accepted that the epidermis synthesizes most if not all of the lipids found in this tissue and that extra-epidermal tissues contribute very little to this lipid content. Moreover, the individual epidermal strata in which epidermal lipid biosynthesis occurs are not known. To address this question, we examined [3H]H2O incorporation into nonsaponifiable and saponifiable lipids in individual epidermal cell layers 3 hr after intraperitoneal injection into neonatal mice, and compared this to protein and DNA synthesis using intraperitoneal [3H]leucine and [3H]thymidine incorporation, respectively. Lipid biosynthesis was also assessed by [14C]acetate incorporation into lipid fractions in organ cultured skin and in epidermal subpopulations. The in vivo studies demonstrated that the biosynthetic activity of both saponifiable and nonsaponifiable lipids was comparable to, if not greater, in the stratum granulosum (SG) than in basal/spinous (SB + SS) layer, despite significantly lower levels of both protein and DNA synthesis in the SG. On a mass basis, the SG accounts for about four times the biosynthetic activity of the combined SB + SS layers. The lipid biosynthetic activity in vitro also was two- to fivefold higher in the SG, regardless of whether the epidermis was separated into individual cell layers before or after incubations with radiolabel. Moreover, this difference could not be ascribed to increased acetate pools or to elevated metabolism in the SG versus the SB + SS since the rates of CO2 production were much lower in the SG fraction. The increase in lipid biosynthesis in SG over SB + SS was greatest for phospholipids, followed by glycosphingolipids, and free sterols but was observed in almost all lipid classes. These studies show not only that mammalian epidermis is an active site of de novo lipid biosynthesis, but also that this activity remains high in the stratum granulosum, while other forms of metabolic activity are diminishing. These observations are consistent with the knowledge that lipids extruded from the stratum granulosum layer provide the hydrophobic permeability barrier, and further suggest that elevated synthetic activity in the stratum granulosum would allow rapid replenishment in the event that the barrier is damaged.

Animals↗
PubMed1987

The effect of vitamin D status on cutaneous sterologenesis in vivo and in vitro.

Recent studies have shown that cutaneous sterologenesis is autonomous from the influence of circulating sterols, and that the epidermis is an important site of sterologenesis which is regulated by permeability barrier requirements. In addition to barrier function, an additional, important function of the epidermis is to synthesize sterol precursors of vitamin D3. The present study was designed, first, to determine whether vitamin D status and/or circulating levels of 1,25-dihydroxyvitamin D3 might play a role in regulating cutaneous sterol synthesis in vivo and, second, whether 1,25-dihydroxyvitamin D3 modulates sterologenesis in cultured human keratinocytes. Hairless mice were maintained on a vitamin D-deficient diet in the dark and supplemented with various doses of vitamin D3/day. Despite demonstrating serum 25-hydroxyvitamin D3 levels ranging from less than 10 to 343 ng/ml, the incorporation of tritiated water into cholesterol and total nonsaponifiable lipids in both the epidermis and dermis was similar in the four groups of animals. Likewise, administration of various doses of 1,25-dihydroxyvitamin D3 to vitamin D-deficient mice resulted in serum levels of 1,25-dihydroxyvitamin D3 ranging from less than 10 to 85 pg/ml; yet, cholesterol and total nonsaponifiable lipid synthesis was similar in both the dermis and epidermis in all groups of animals. Moreover, administration of 0.6 micrograms/kg per day of 1,25-dihydroxyvitamin D3 to 'normal' vitamin D-replete mice also had no effect on cutaneous sterol synthesis. Furthermore, conversion of 7-dehydrocholesterol to cholesterol in vitamin D-deficient vs. supplemented animals did not differ. Finally, addition of 1,25-dihydroxyvitamin D3 to cultured keratinocytes over a concentration range of 10(-12)-10(-7) M did not affect sterologenesis, except at supraphysiologic doses (10(-7) M). Together, these results suggest that vitamin D status does not influence sterol synthesis in the skin.

Animals↗
PubMed1987

Free sterol metabolism and low density lipoprotein receptor expression as differentiation markers of cultured human keratinocytes.

In contrast to most tissues, epidermis and its derivatives appear to lack low density lipoprotein (LDL) receptors and exhibit sterologenesis rates unaffected by circulating lipoprotein (LP) cholesterol content. Since LDL receptors have been demonstrated in both cultured squamous cell carcinoma cells and human foreskin keratinocytes, when maintained in low-calcium media, LDL receptor expression may be related to keratinocyte differentiation. We compared receptor binding and internalization of LDL-gold in normal keratinocytes at different stages of growth at physiological calcium concentrations (early, 3-5 days; preconfluent, 6-10 days; postconfluent, 12-17 days), and correlated receptor expression with sterologenesis in LP-replete vs.-depleted media. Whereas in early cultures about 60% of sterologenesis was LP dependent, this fraction declined in preconfluent and confluent cultures despite continued culture growth and little decline in total sterologenesis. Accordingly, LDL receptors were most evident in early cultures, declining in preconfluent cultures in parallel with the decrease in LP-dependent sterol synthesis. In contrast, sterologenesis in human foreskin fibroblasts was profoundly influenced by exogenous LP at all stages of confluence; total and LP-dependent sterologenesis declined in parallel with growth cessation. These studies represent the first demonstration that normal keratinocytes express functional LDL receptors at physiologic calcium concentrations. Moreover, they demonstrate that LDL receptor expression in keratinocytes, in contrast to fibroblasts, can only in part be attributed to growth requirements. Instead, loss of LDL receptor expression serves as a distinctive marker of keratinocyte differentiation and may reflect the specific functional requirements of the epidermis in vivo.

Acetates↗
PubMed1987

Mycosis fungoides beginning in childhood and adolescence.

Mycosis fungoides is a form of cutaneous T cell lymphoma usually occurring in mid to late adulthood. We report 12 patients with mycosis fungoides whose eruption began before age 20 years, including one patient with histologic documentation at 5 years of age. The onset of mycosis fungoides during the first two decades may be more common than is generally recognized and should be included in the differential diagnosis of chronic dermatoses in children and adolescents.

Adolescent↗
PubMed1987

Mitomycin C-treated 3T3 fibroblasts used as feeder layers for human keratinocyte culture retain the capacity to generate eicosanoids.

Murine 3T3 fibroblasts, treated with mitomycin C in order to inhibit their proliferation, have been extensively used as feeder layers to enhance the cultivation of human keratinocytes in vitro. In order to identify possible factors responsible for this enhancing effect, studies were undertaken to determine whether eicosanoid generation by 3T3 cells was preserved following mitomycin C treatment. Accordingly, both untreated and mitomycin C-treated 3T3 cells were incubated with [1-14C]arachidonic acid and their qualitative generation of [1-14C]labeled eicosanoids assessed by thin layer chromatography. Levels of endogenously generated eicosanoids were quantitatively determined by specific radioimmunoassays performed on culture supernatants obtained from incubations of both treated and untreated cells. Results of these studies demonstrate that mitomycin C treatment, although preventing the proliferation of 3T3 cells, failed to alter their generation of prostaglandin E2 or 6-keto-prostaglandin F1 alpha. Furthermore, in parallel cultures, the untreated 3T3 cells stopped generating eicosanoids upon reaching confluence, whereas the mitomycin C-treated 3T3 cells that did not proliferate continued to generate eicosanoids.

Animals↗
PubMed1987

Neurodevelopmental outcome of preschool children born preterm with and without intracranial hemorrhage.

Thirty-five children who had been born preterm with and without intracranial hemorrhage and weighing less than or equal to 1500 g were followed prospectively to assess neurodevelopmental outcome. The 13 children with hemorrhage were inferior to the 22 without hemorrhage in terms of birthweight, Apgar scores, health complications at and after birth, neurological integrity at age five and several scales of the McCarthy Scales of Children's Abilities. The hemorrhage group performed significantly below the standardized mean on each of the McCarthy scales, whereas the group without hemorrhage performed below the mean only in Quantitative and Memory scores. The Bayley scales at one year were not clinically sensitive to hemorrhage, but were predictive of McCarthy General Cognitive Index scores at age five. A greater proportion of children with hemorrhage have had educational difficulties and have been included in alternative school programs. Preterm, very low-birthweight children, and particularly those with intracranial hemorrhage, are at high risk for motor, perceptual and cognitive defects which underlie learning difficulties.

Brain Damage, Chronic↗