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Biomedical subjects

K Hanley

Publications and source records attributed to K Hanley.

At least 19 recordsLinked to original sources
PubMed2002

Symptoms of vertigo in general practice: a prospective study of diagnosis.

BACKGROUND: There is little published evidence of the general practice experience of the diagnostic outcomes when symptoms of vertigo present. What research there is has been dominated by specialist centres. This gives a skewed view of the prevalence of the causes of such symptoms. AIM: To describe the likely diagnosis of symptoms of vertigo. DESIGN OF STUDY: Prospective cohort study METHODS: Thirteen GPs were recruited and trained to clinically assess and follow up all patients presenting with symptoms of vertigo over a six-month period Age-sex data were simultaneously gathered on those who consulted with non-vertiginous dizziness. RESULTS: The main diagnoses assigned by the GPs in 70 patients were benign positional vertigo, acute vestibular neuronitis and Ménière's disease, which together accounted for 93% (95% confidence interval = 71% to 100%) of patients' symptoms. Ninety-one per cent of patients were managed in general practice and 60% received a prescription for a vestibular sedative. CONCLUSION: This study suggests that presentations of symptoms of vertigo can be clinically diagnosed in most cases. The diagnoses recorded by GPs differ in proportion to those in specialist centres, with a larger number of patients suffering from benign positional vertigo and acute vestibular neuronitis in general practice, in contrast with specialist centres, which see more patients with Ménière's disease.

Diagnosis, Differential↗
PubMed2001

Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D.

Lipids that are synthesized de novo in the epidermis, including fatty acids, oxysterols, 1,25-dihydroxyvitamin D(3), and farnesol, can regulate the differentiation of normal human keratinocytes (NHK). Cholesterol sulfate (CS), an epidermal lipid that is produced in the upper nucleated layers of the epidermis coincident with terminal differentiation, has been shown to play a role in the regulation of the late stages of keratinocyte differentiation, including formation of the cornified envelope. In the present study, we determined i) whether CS regulates involucrin (INV), an early keratinocyte differentiation marker, and ii) the mechanism by which CS regulates differentiation. mRNA and protein levels of INV, a precursor protein of the cornified envelope, increased 2- to 3-fold in NHK incubated in the presence of CS. In contrast, cholesterol had no effect on INV protein or mRNA levels. Transcriptional regulation was assessed in NHK transfected with INV promoter-luciferase constructs. CS increased luciferase reporter activity approximately 2- to 3-fold in NHK transfected with a 3.7-kb INV promoter construct. Deletional analysis revealed a CS-responsive region of the INV promoter located between bp --2452 and --1880. A 5-base pair (bp) mutation of the AP-1 site (bp --2117 to --2111) within this responsive region abolished CS responsiveness, suggesting a role for the AP-1 complex in the regulation of INV transcription by CS. Electrophoretic mobility shift analysis demonstrated increased binding of nuclear extracts isolated from CS-treated NHK to AP-1 DNA as compared with vehicle-treated controls. Incubation of the nuclear extract with the appropriate antibodies showed that the AP-1 DNA-binding complex contained Fra-1, Fra-2, and Jun D. Western blots demonstrated that CS treatment increased the levels of Fra-1, Fra-2, and Jun D, and Northern analyses revealed that CS increased mRNA levels for these same AP-1 factors. These data indicate that CS, an endogenous lipid synthesized by keratinocytes, regulates the early stages of keratinocyte differentiation, and may do so through its ability to modulate levels of AP-1 proteins. -- Hanley, K., L. Wood, D. C. Ng, S. S. He, P. Lau, A. Moser, P. M. Elias, D. D. Bikle, M. L. Williams, and K. R. Feingold. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J. Lipid Res. 2001. 42: 390--398.

Binding Sites↗
PubMed2001

A systematic review of vertigo in primary care.

The symptom of vertigo is usually managed in primary care without further referral. This review examines the evidence on which general practitioners can base clinical diagnosis and management of this relatively common complaint. Research in this area has in the main been from secondary and tertiary centres and has been of variable quality. Indications are that the conditions that present in general practice are most likely to be benign positional vertigo, acute vestibular neuronitis, and Ménière's disease; however, vascular incidents and neurological causes, such as multiple sclerosis, must be kept in mind. An important practice point is that vestibular sedatives are not recommended on a prolonged basis for any type of vertigo. There is a need for basic epidemiological and clinical management research of vertigo in general practice.

Dizziness↗
PubMed2001

A measurement of the efficacy of anticoagulation monitoring in a general practice based setting.

With increasing numbers of patients on anticoagulant therapy and a trend towards moving certain hospital services to a primary care setting, we looked at how GPs are managing Warfarin therapy in their patients. This prospective study measured the efficacy of INR monitoring in 325 patients who were being managed in a general practice setting. 41% (415 of 1016) of readings fell strictly within the target ranges recommended by the British Society for Haematology. There was a low rate of haemorrhagic events (3.7%) in patients on Warfarin. Possible methods of improving readings include the introduction of Decision Support Services and formal training.

Anticoagulants↗
PubMed2000

Farnesol stimulates differentiation in epidermal keratinocytes via PPARalpha.

The isoprenoids farnesol and juvenile hormone III (JH), metabolites of the cholesterol biosynthetic pathway, have been shown to stimulate fetal epidermal development in rodents. In this study we determined whether this effect might be attributed to a direct induction of keratinocytes differentiation and examined the mechanisms responsible for these effects. Rates of cornified envelope formation, a marker of keratinocyte terminal differentiation, as well as protein and mRNA levels of two proteins required for cornified envelope formation, involucrin (INV) and transglutaminase, increased 2- to 3-fold in normal human keratinocytes (NHK) treated with either farnesol or JH, even at low calcium concentrations (0.03 mM), which otherwise inhibit differentiation. In contrast, neither cholesterol nor mevalonate affected INV or transglutaminase mRNA levels. Effects of farnesol and JH on INV and transglutaminase mRNA levels were additive with high calcium concentrations (1.2 mM) that independently stimulate keratinocyte differentiation. In contrast, keratinocyte DNA synthesis was inhibited by these compounds. Both farnesol and JH stimulated INV and transglutaminase promoter activity, suggesting regulation at the transcriptional level. A series of truncation and deletion experiments revealed a farnesol-responsive region (-2452 to -1880 base pairs (bp)) in the INV gene. This region contained an AP-1 site. A single base pair mutation of the AP-1 site at -2116 to -2110 bp abolished farnesol responsiveness, identical to effects by peroxisome proliferator-activated receptor (PPARalpha) activators. Farnesoid X-activated receptor mRNA was not detected in NHK, but farnesol treatment increased activities of both a PPAR response element and PPARalpha mRNA levels in NHK. Furthermore, the increase in PPRE activity by farnesol was dependent upon PPARalpha in CV-1 cells. Finally, topical applications of farnesol increased mRNA and protein levels of the differentiation-specific genes, profilaggrin and loricrin, determined by immunohistochemistry and in situ hybridization, in wild-type but not in PPARalpha-/- murine epidermis. These findings suggest a novel role for selected isoprenoid cholesterol intermediates in the regulation of differentiation-specific gene transcription and a convergence of PPARalpha with the cholesterol synthetic pathway.

Animals↗
PubMed2000

Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo.

Our recent studies have demonstrated that PPARalpha activators stimulate differentiation and inhibit proliferation in cultured human keratinocytes and accelerate epidermal development and permeability barrier formation in fetal rat skin explants. As the role of PPARalpha activation in adult epidermis is not known, the aim of this study was to determine if topically applied PPARalpha ligands regulate keratinocyte differentiation in murine epidermis. Topical treatment with PPARalpha activators resulted in decreased epidermal thickness. Expression of structural proteins of the upper spinous/granular layers (involucrin, profilaggrin-filaggrin, loricrin) increased following topical treatment with PPARalpha activators. Furthermore, topically applied PPARalpha activators also increased apoptosis, decreased cell proliferation, and accelerated recovery of barrier function following acute barrier abrogation. Experiments with PPARalpha-/- knockout mice showed that these effects are specifically mediated via PPARalpha. Compared with the epidermis of PPARalpha+/+ mice, involucrin, profilaggrin-filaggrin, and loricrin expression were slightly decreased in PPARalpha-/- mice. Moreover, topical clofibrate treatment did not increase epidermal differentiation in PPARalpha-/- mice. Furthermore, in cultured human keratinocytes we have demonstrated that PPARalpha activators induce an increase in involucrin mRNA levels. We have also shown that this increase in gene expression requires an intact AP-1 response element at -2117 to -2111 bp. Thus, stimulation of PPARalpha stimulates keratinocyte/epidermal differentiation and inhibits proliferation.

Administration, Cutaneous↗
PubMed2000

Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPARalpha activators restores tissue homeostasis.

We recently showed that topically applied PPARalpha activators promote epidermal differentiation in intact adult mouse skin. In this study we determined the effect of clofibrate and Wy-14,643, activators of PPARalpha, on hyperproliferative epidermis in hairless mice, induced either by repeated barrier abrogation (subacute model) or by essential fatty acid deficiency (chronic model). The hyperproliferative epidermis was characterized by an increased number of proliferating cells expressing proliferating cell nuclear antigen. Topical treatment with PPARalpha activators resulted in a substantial decrease in epidermal hyperplasia in both the subacute and chronic models of hyperproliferation. Following topical treatment, proliferating cell nuclear antigen-expressing cells were restricted to the basal layer, similar to normal epidermis. In hyperproliferative epidermis there was decreased expression of involucrin, profilaggrin-filaggrin, and loricrin as assayed by in situ hybridization and immunohistochemistry. Following topical treatment with PPAR activators staining for these mRNAs and proteins increased towards normal levels. Finally, topically applied clofibrate also increased apoptosis. This study demonstrates that topical PPAR activators have profound effects on epidermal gene expression in hyperproliferative skin disorders. Treatment with PPARalpha activators normalizes cell proliferation and promotes epidermal differentiation, correcting the cutaneous pathology. This study identifies PPARalpha activators as potential skin therapeutic agents.

Administration, Topical↗
PubMed2000

Oxysterols induce differentiation in human keratinocytes and increase Ap-1-dependent involucrin transcription.

Ligands and activators of the nuclear hormone receptor superfamily are important in the regulation of epidermal development and differentiation. Previously, we showed that naturally occurring fatty acids, as well as synthetic ligands for the peroxisome proliferator-activated receptor, induce keratinocyte differentiation in vitro. Here we asked whether oxysterols, another class of lipids formed de novo in the epidermis and that activate liver X-activated receptor, regulate keratinocyte differentiation. mRNA and protein levels of involucrin and transglutaminase 1, markers of differentiation, increased 2- to 3-fold in normal human keratinocytes incubated in the presence of 25- or 22R-hydroxycholesterol in low calcium. In high calcium, which alone induces differentiation, mRNA levels were further increased by oxysterols. Rates of cornified envelope formation, an indicator of terminal differentiation, also increased 2-fold with oxysterol treatment. In contrast, the rate of DNA synthesis was inhibited approximately 50% by oxysterols. Transcriptional regulation was assessed in keratinocytes transfected with either transglutaminase 1 or involucrin promoter-luciferase constructs. 22R-hydroxycholesterol increased transglutaminase 1 and involucrin promoter activity 2- to 3-fold. Either deletion of the -2452 bp to -1880 bp region of the involucrin promoter, or mutation of the AP-1 site within this region, abolished oxysterol responsiveness. Moreover, increased AP-1 DNA binding was observed in oxysterol-treated keratinocytes by gel shift analyses. Finally, we demonstrated the presence of liver X-activated receptor alpha and beta mRNAs, and showed that oxysterols stimulate a liver X-activated receptor response element transfected into keratinocytes. These data suggest that oxysterols induce keratinocyte differentiation, in part through increased AP-1-dependent transcription of the involucrin gene, an effect that may be mediated by liver X-activated receptor.

Calcium↗
PubMed1999

Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants.

Rapid production of protein-based tumor-specific vaccines for the treatment of malignancies is possible with the plant-based transient expression system described here. We created a modified tobamoviral vector that encodes the idiotype-specific single-chain Fv fragment (scFv) of the immunoglobulin from the 38C13 mouse B cell lymphoma. Infected Nicotiana benthamiana plants contain high levels of secreted scFv protein in the extracellular compartment. This material reacts with an anti-idiotype antibody by Western blotting, ELISA, and affinity chromatography, suggesting that the plant-produced 38C13 scFv protein is properly folded in solution. Mice vaccinated with the affinity-purified 38C13 scFv generate >10 micrograms/ml anti-idiotype immunoglobulins. These mice were protected from challenge by a lethal dose of the syngeneic 38C13 tumor, similar to mice immunized with the native 38C13 IgM-keyhole limpet hemocyanin conjugate vaccine. This rapid production system for generating tumor-specific protein vaccines may provide a viable strategy for the treatment of non-Hodgkin's lymphoma.

Amino Acid Sequence↗
PubMed1999

Induction of selected lipid metabolic enzymes and differentiation-linked structural proteins by air exposure in fetal rat skin explants.

The epidermal permeability barrier of premature infants matures rapidly following birth. Previous studies suggest that air exposure could contribute to this acceleration, because: (i) development of a structurally and functionally mature barrier accelerates when fetal rat skin explants are incubated at an air-medium interface, and (ii) occlusion with a water-impermeable membrane prevents this acceleration. To investigate further the effects of air exposure on epidermal barrier ontogenesis, we compared the activities of several key enzymes of lipid metabolism and gene expression of protein markers of epidermal differentiation in fetal rat skin explants grown immersed versus air exposed. The rate-limiting enzymes of cholesterol (HMG CoA reductase) and ceramide (serine palmitoyl transferase) synthesis were not affected. In contrast, the normal developmental increases in activities of glucosylceramide synthase and cholesterol sulfotransferase, responsible for the synthesis of glucosylceramides and cholesterol sulfate, respectively, were accelerated further by air exposure. Additionally, two enzymes required for the final stages of barrier maturation and essential for normal stratum corneum function, beta-glucocerebrosidase, which converts glucosylceramide to ceramide, and steroid sulfatase, which desulfates cholesterol sulfate, also increased with air exposure. Furthermore, filaggrin and loricrin mRNA levels, and filaggrin, loricrin, and involucrin protein levels all increased with air exposure. Finally, occlusion with a water-impermeable membrane prevented both the air-exposure-induced increase in lipid enzyme activity, and the expression of loricrin, filaggrin, and involucrin. Thus, air exposure stimulates selected lipid metabolic enzymes and the gene expression of key structural proteins in fetal epidermis, providing a biochemical basis for air-induced acceleration of permeability barrier maturation in premature infants.

Acyltransferases↗
PubMed1999

Fetal epidermal differentiation and barrier development In vivo is accelerated by nuclear hormone receptor activators.

Nuclear receptors which interact with the retinoid X receptor are involved in the regulation of epidermal differentiation and development. We have recently shown that activators of the peroxisome proliferator-activated receptor and of the farnesoid X-activated receptor accelerate epidermal barrier maturation in fetal rat skin in vitro. In this study we asked whether cutaneous development in utero was affected by peroxisome proliferator-activated receptor or farnesoid X-activated receptor activators, or by an activator of another retinoid X receptor partner, liver X receptor. Activators of the peroxisome proliferator-activated receptor (clofibrate or linoleic acid), farnesoid X-activated receptor (farnesol or juvenile hormone III), or liver X receptor (22R-hydroxycholesterol), were injected into the amniotic fluid of fetal rats on gestational day 17. Fetal epidermal barrier function and morphology was assessed on day 19. Whereas vehicle-treated fetal rats displayed no measurable barrier (transepidermal water loss > 10 mg per cm2 per h), a measurable barrier was induced by the intra-amniotic administration of all activators tested (transepidermal water loss range 4.0-8.5 mg per cm2 per h). By light microscopy, control pups lacked a well-defined stratum corneum, whereas a distinct stratum corneum and a thickened stratum granulosum were present in treated pups. By electron microscopy, the extracellular spaces of the stratum corneum in control pups revealed a paucity of mature lamellar unit structures, whereas these structures filled the stratum corneum interstices in treated pups. Additionally, protein and mRNA levels of loricrin and filaggrin, two structural proteins of stratum corneum, were increased in treated epidermis, as were the activities of two lipid catabolic enzymes critical to stratum corneum function, beta-glucocerebrosidase and steroid sulfatase. Finally, peroxisome proliferator-activated receptor-alpha and -delta and liver X receptor-alpha and -beta mRNAs were detected in fetal epidermis by reverse transcriptase-polymerase chain reaction and northern analyses. The presence of these receptors and the ability of their activators to stimulate epidermal barrier and stratum corneum development suggest a physiologic role for peroxisome proliferator-activated receptor and liver X receptor and their endogenous ligands in the regulation of cutaneous development.

Amnion↗
PubMed1999

The role of automated external defibrillators in rural general practice.

In a questionnaire survey (100% response rate) investigating the availability and use of automated external defibrillators (AEDs), it was found that the success rate (number discharged alive) compared favourably with pre-hospital defibrillation by other providers, and that AEDs aided the management of dysrhythmias not commonly seen in general practice. With appropriate training they are useful in rural general practice.

Data Collection↗
PubMed1998

Ontogeny of the epidermal permeability barrier.

A competent permeability barrier must be present by the end of gestation to allow for life in a terrestrial environment. Indeed, early preterm infants display serious complications of skin immaturity. Yet, regardless of their degree of prematurity, all infants quickly develop a competent barrier. To learn more about the mechanisms and regulation of barrier ontogeny, we have utilized late-gestation fetal rodents. In 19-21 d fetal rats, we showed that barrier competence is accompanied by both enhanced epidermal development and formation of extracellular lamellar membranes in the stratum corneum. The identical sequence and time-course occurs when fetal rat skin is cultured in a serum-free medium. Glucocorticoids, thyroid hormone (T3), and estrogen accelerate, while androgens delay barrier formation both in utero and in the in vitro system, explaining the poorer outcome of premature males versus females. But neither T3 nor glucocorticoids are absolutely required for barrier development. Lifting fetal skin cultures to an air-medium interface also accelerates barrier formation, explaining the rapid emergence of barrier competence in very premature infants. PPARalpha and FXR activators, which, like T3, heterodimerize with the nuclear receptor, RXR, also accelerate barrier development in vitro. Finally, not only the nuclear receptor family, but also Ca++ could regulate key events late in barrier development.

Animals↗
PubMed1998

Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha.

Peroxisome proliferator activated receptors (PPAR) belong to the superfamily of nuclear hormone receptors that heterodimerize with the retinoid X receptor and regulate transcription of several genes involved in lipid metabolism and adipocyte differentiation. Because of the role of 1,25-dihydroxyvitamin D3 and retinoic acid working through similar receptors (the vitamin D receptor and retinoic acid receptor, respectively) on keratinocyte differentiation, we have examined the effects of activators of PPARalpha on keratinocyte differentiation. The rate of cornified envelope formation was increased 3-fold in keratinocytes maintained in low calcium (0.03 mM) and incubated in the presence of clofibric acid, a potent PPARalpha activator. Involucrin, a cornified envelope precursor, and the cross-linking enzyme transglutaminase, were increased at both the message level (2-7-fold) and the protein level (4-12-fold) by clofibric acid. Furthermore, physiologic doses of the fatty acids oleic acid, linoleic acid, and eicosatetraynoic acid, which are also activators of PPARalpha, also induced involucrin and transglutaminase protein and mRNA. In contrast, the PPARgammaligand prostaglandin J2 had no effect on protein or mRNA levels of involucrin or transglutaminase. Levels of involucrin and transglutaminase mRNA and protein were induced by clofibric acid in keratinocytes incubated in 1.2 mM calcium, a concentration which by itself induces keratinocyte differentiation. Finally, PPARalpha activators inhibit DNA synthesis. This study demonstrates that PPARalpha activators, including putative endogenous ligands such as fatty acids, induce differentiation and inhibit proliferation in keratinocytes, and suggests a regulatory role for the PPARalpha in epidermal homeostasis.

Cell Differentiation↗
PubMed1998

Formation of the epidermal calcium gradient coincides with key milestones of barrier ontogenesis in the rodent.

The epidermal permeability barrier forms late in gestation, coincident with decreased lipid synthesis, increased lipid processing, and development of a mature, multi-layered stratum corneum. Prior studies have shown that changes in the epidermal Ca++ gradient in vivo regulate lamellar body secretion and lipid synthesis, and modulations in extracellular Ca++ in vitro also regulate keratinocyte differentiation. We asked here whether a Ca++ gradient forms in fetal epidermis in utero, and whether its emergence correlates with key developmental milestones of barrier formation and stratum corneum development. Using either ion precipitation or proton induced X-ray emission analysis of fetal mouse and rat skin, we showed that a Ca++ gradient is not present at gestational days 16-18, prior to barrier formation, and that a gradient forms coincident with the emergence of barrier competence (day 19, mouse; day 20, rat) prior to birth. These results are consistent with a role for Ca++ in the regulation of key metabolic events leading to barrier formation. Whether the calcium gradient is formed actively or passively remains to be determined.

Animals↗
PubMed1998

Ligands and activators of nuclear hormone receptors regulate epidermal differentiation during fetal rat skin development.

Because a protective barrier is essential for life, the development of the epidermis and stratum corneum must be completed prior to birth. The epidermal permeability barrier is comprised of corneocytes embedded in a lipid enriched matrix. Recent studies from our laboratory, using an explant model of fetal rat skin development that closely parallels in utero development, have shown that hormones and other activators of members of the nuclear receptor family regulate permeability barrier ontogenesis by stimulating lipid metabolism and the formation of the extracellular lipid lamellae. Using this model we sought to determine whether these hormones and nuclear activators also regulate keratinocyte differentiation during fetal development. Profilaggrin/filaggrin and loricrin expression, assessed by in situ hybridization and by immunohistochemistry, were progressively increased during epidermal ontogenesis. Whereas profilaggrin/filaggrin and loricrin were not expressed at day 17 of gestation, by day 19 both were present in the upper layers of the epidermis and both became still more abundant by day 21. These developmental changes also occurred in fetal skin explants cultured in vitro for 4 d, although the expression levels did not appear as robust as in utero. Whereas neither profilaggrin/filaggrin nor loricrin were expressed in control explants cultured for 2 d, they were seen in explants treated with either thyroid hormone, glucocorticoids, or estrogens. In contrast, dihydrotestosterone treatment delayed the expression of profilaggrin/filaggrin and loricrin. Moreover, both clofibrate, a peroxisome proliferator-activated receptor-alpha ligand, and juvenile hormone III, a farnesoid X-activated receptor activator, markedly accelerated fetal epidermal differentiation, stimulating both profilaggrin/filaggrin and loricrin expression. Our results demonstrate that several hormones and activators of nuclear hormone receptors regulate epidermal differentiation during fetal development, affecting key constituents of both keratohyalin granules and the cornified envelope. Thus, a variety of ligands/activators of nuclear receptors accelerate not only permeability barrier ontogenesis, but also the expression of structural proteins essential for stratum corneum formation.

Animals↗
PubMed1998

Glucocorticoid deficiency delays stratum corneum maturation in the fetal mouse.

The stratum corneum (SC) matures during late gestation in man and other mammals. Using the fetal rat as an experimental model, we have previously shown that glucocorticoids given in pharmacologic doses accelerate fetal SC maturation and barrier formation. To determine whether glucocorticoids are required for normal SC maturation, we examined the epidermal morphology of glucocorticoid-deficient (C-) murine pups, derived from matings of mice homozygous for null mutations of the corticotropin-releasing hormone alleles. In control pups on day 17.5 of gestation (term is 19.5 d), a multilayered SC was present and neutral lipid deposition in a membrane pattern was observed using Nile red fluorescence histochemistry. Ultrastructurally, mature lamellar unit structures predominate in the SC intercellular domains. In contrast, in C-pups only a single layer of SC was evident on day 17.5, and secreted lamellar material was not organized into mature lamellar structures. Furthermore, the expression of structural proteins necessary for cornified envelope formation, involucrin, loricrin, and filaggrin, and the activity of the lipid synthetic enzymes beta-glucocerebrosidase and steroid sulfatase, markers of barrier maturation, were reduced in day 17.5 C-pups. C-pups derived from pregnancies supplemented with physiologic amounts of cortisone, however, display normal SC ultrastructure on day 17.5 of gestation. Furthermore, at birth, both control and C-pups exhibit a multilayered SC replete with mature lamellar membrane structures. These data demonstrate that fetal glucocorticoid deficiency delays SC maturation, and suggests that normal levels of glucocorticoids are not absolutely required for SC development.

Animals↗