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PubMed1991

A retrospective analysis of primary eye cancer at the University of Alabama 1958-1988. Part 2: Eyelid tumors.

Records of 117 patients with eyelid tumors on file at the University of Alabama at Birmingham were reviewed. Basal cell carcinoma was the single most common tumor, followed by squamous cell carcinoma, cutaneous melanoma, meibomian gland carcinoma and sebaceous gland carcinoma. A high percentage of patients with eyelid tumors were found to have secondary skin and non-skin tumors (41 percent).

Adult↗

PubMed1986

Preferential expression of a Mr 155,000 milk-fat-globule membrane glycoprotein on luminal epithelium of lobules in human breast.

An integral membrane glycoprotein with an apparent molecular weight of 155,000 and isoelectric points ranging from 7.2 to 7.6 has been found to be predominantly expressed on the apical plasma membrane of luminal epithelial cell lining the lobules and terminal ducts in breast. The glycoprotein was purified to homogeneity from human milk-fat-globule membrane and was termed MFGM-gp 155. Polyclonal antibodies were raised which specifically reacted to a single component that electrophoretically comigrated with this glycoprotein in immunoblotting experiments. These antibodies appear to recognize epitopes which are expressed on the protein segment of the glycoprotein. Using an indirect immunohistological method, the glycoprotein was localized predominantly on the apical plasma membrane of luminal epithelial cells lining the alveoli of normal breasts. The expression of the antigen was maintained in both morphologically well- and poorly differentiated lobular carcinoma cells. The antigen was weakly detectable on normal epithelial cells lining the terminal ducts and malignant cells of infiltrating ductal and medullary carcinomas. Expression of the glycoprotein is not organ specific as it is detectable in normal epithelial cells of kidney, pancreas, salivary gland, and stomach and in malignant cells of colon and stomach. The antibodies did not react with large ductal, myoepithelial, stromal, endothelial, epidermal squamous epithelial cells, melanocytes, eccrine sweat glands and ducts, sebaceous glands, erythrocytes, and lymphocytes in breast and skin tissues. Thus, antibodies to this glycoprotein appear to be useful phenotype markers to study differentiation of mammary epithelial cells and the pathogenesis of different histological types of mammary carcinomas, including Paget's disease and signet-ring cell carcinoma of mammary gland.

Antibodies↗

PubMed1988

Structure and function of the skin. Are there differences between black and white skin?

In concluding my remarks on structure and function of the skin, I wish to make one additional observation. Most dermatologists have acknowledged the role of the skin and its ability to protect the human organism from invasion by pathogenic organisms. There is good scientific evidence that skin plays an important protective role. Although an intact epidermis is of utmost importance as a protective unit, the contribution of the "acid mantle" is of considerable magnitude. The acidity or alkalinity and stability of this mantle is contributed to, in large measure, by the presence of eccrine gland secretions and sebaceous gland secretions. It is then not logical to assume that if black skin contains larger numbers of large and overly active adnexal glands, it would have a most effective mechanism for control of bacterial, viral, and other infections? That this is not the situation becomes apparent in the discussions that follow on cutaneous infections in black skin.

Black People↗

PubMed1986

Distribution of the Mr 52,000 estrogen-regulated protein in benign breast diseases and other tissues by immunohistochemistry.

A secreted glycoprotein with a molecular weight of 52,000 is induced by estrogen in breast cancer cells and has been purified to prepare monoclonal antibodies. The protein has been detected in some breast cancers but not in normal breast and uterus. In order to study its potential value as a marker, we have tested by immunohistochemistry frozen sections of several normal and malignant tissues and of benign mastopathies. Among different tissues tested, the Mr 52,000 protein was detected only in liver, sweat glands, and some sebaceous glands, and in malignant melanomas and some breast tumors. Other estrogen-responsive tissues (ovary, placenta, endometrium, etc.) gave negative results. Immunoradiometric assay of the Mr 52,000 protein in biological fluid revealed an elevated concentration in cyst fluid (0.5 to 7.4 micrograms/ml), pleural effusions of certain metastatic breast cancer, and sweat. By immunohistochemistry, the Mr 52,000 antigen was also detected in 42% of 129 benign mastopathies. Gynecomastia, fibrous disease, fibroadenoma, and adenosis were mainly negative, whereas ductal hyperplasia and cysts were positive. The Mr 52,000 protein was found mostly in proliferative ducts and in cysts but not in lobular hyperplasia and nonproliferative lesions without cyst. More Mr 52,000 protein was found in postmenopausal patients than in premenopausal patients. We conclude that the Mr 52,000 protein is a marker associated with mammary cysts and proliferative ducts. On the basis of the increased risk of breast cancer in proliferative mastopathies, we suggest that the Mr 52,000 protein is useful for predicting high-risk mastopathies acting as a marker associated with the proliferation of ductal tissue.

Age Factors↗

PubMed1992

Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages.

Biotinylated hyaluronan (HA) binding complex (HABC) from bovine articular cartilage proteoglycan was used as a histological probe to study the localization of HA in human skin. The distribution of HA was compared with its presumptive cell surface receptor, CD44, using monoclonal antibodies. In epidermis both HA and CD44 were found in the basal and spinous cell layers, but neither was present in the stratum granulosum and stratum corneum. In the keratinizing parts of hair follicles, i.e. in the outer and inner epidermal root sheath, pilosebaceous duct and the actual hair, HA and CD44 were found between the vital but not the terminally differentiated cells. In the sebaceous glands a small amount of HA was found around all cells, whereas CD44 was restricted to the basal cell layer. The secretory acini of the sweat glands stained intensively with anti-CD44 antibodies but only weakly with HABC. In the sweat gland, CD44 was localized on the basal and lateral surfaces of the clear cells, whereas the dark cells and the myoepithelial cells were negative. Both the lower and upper layers of the sweat gland ducts showed a faint but constant staining for CD44 and only minor amounts of HA. While in the keratinizing skin epithelia both HA and its CD44 receptor showed an intense staining with a close co-distribution, in the sweat and sebaceous glands their distribution patterns were not similar. It is suggested that in epithelia with divergent differentiation programs the functions of CD44 and HA may be different.

Biotin↗

PubMed2004

Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin.

Lymphoid Enhancer Factor 1 (Lef-1) is an important developmental transcription factor required for the inductive formation of several epithelial-derived organs including hair follicles. Inductive expression of Lef-1 mRNA is tightly regulated during embryo development, suggesting the involvement of a highly regulated promoter. In vitro analysis of the Lef-1 gene has demonstrated the existence of at least two spatially distinct promoters with multiple transcriptional start sites that are responsive to the canonical Wnt/beta-catenin pathway. Regions of the Lef-1 promoter required for inductive regulation in vivo, however, have yet to be determined. To this end, we utilized LacZ-reporter transgenic mice to define segments of the human Lef-1 promoter capable of reproducing mesenchymal- or epithelial-restricted transcriptional patterns of Lef-1 expression during hair and vibrissa follicle development. These studies have revealed that a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos. This 2.5 kb Lef-1 promoter also demonstrated inductive mesenchymal expression during postnatal anagen stage hair-follicle cycling. Additionally, analysis of Lef-1 promoter expression revealed previously uncharacterized regions of endogenous Lef-1 expression seen in the sebaceous glands of vibrissa and hair follicles in transgenic lines harboring the minimal Lef-1 promoter and additional intronic sequences. In summary, these studies have begun to dissect the transcriptional diversity of the human Lef-1 promoter during the hair/vibrissa follicle and sebaceous gland formation.

Animals↗

PubMed1993

Histopathology of cutaneous changes in drug-induced coma.

Present knowledge of the histopathology of cutaneous changes seen in drug-induced coma is very incomplete: Only 1 of the 11 papers on this subject mentions follicular or sebaceous gland damage, with very little attention focused on vascular changes. We made a careful study of serial sections from eight cutaneous biopsy specimens from seven patients who suffered drug-induced coma with the following findings: (a) The secretory portion of the eccrine sweat coil is the epithelium most susceptible to necrosis. It is followed by, ex aequo, eccrine sweat duct, hair follicle, and sebaceous gland, and, lastly, the epidermis. (b) In the eccrine sweat duct, the outer root sheath of the hair follicle, and the epidermis, necrosis does not usually appear first in the outermost (basal cell) layer. (c) Necrosis of the outer root sheath of the telogen "club" follicle is usually more advanced than that of the secondary hair germ, and, at times, a spared anagen bulb can be seen in closest proximity. (d) Vascular changes correlate proportionately with epidermal damage and consist of a largely neutrophilic inflammatory infiltrate and blood vessel wall damage, mainly involving arterioles. Our findings contradict the widely accepted hypothesis that pressure is the main cause of the cutaneous changes in drug-induced coma.

Adult↗

PubMed1976

Histology and cytochemistry of human skin. XXXVI. The nose and lips.

The skin of the nose is characterized by often conspicuously dilated openings of the ducts of many subaceous follicles. Histological sections are dominated by gigantic sebaceous follicles, but there are also numerous vellus hairs with small sebaceous glands. All hair follicles on the surface of the nose and in the vestibule are completely invested with nerve end organs. In the vestibule, the glabrous upper surface has intraepidermal nerves and a few mucocutaneous end organs. the vermillion zone of the lip, which seperates the skin of the external lip and the mucosa of the inner lip, is keratinizing glabrous epithelium, often with numerous sebaceous glands in the upperlip. The transitional area between the keratinizing epithelium of the vermillion and the nonkeratinizing epithelium of the labial mucosa is abundantly supplied with mucocutaneous end organs, with only a few in the labial mucosa. The mucoserous glands of the labial mucosa are richly innervated.

Adult↗

PubMed1998

A keratinocyte-specific epoxygenase, CYP2B12, metabolizes arachidonic acid with unusual selectivity, producing a single major epoxyeicosatrienoic acid.

The CYP monooxygenase, CYP2B12, is the first identified skin-specific cytochrome P450 enzyme. It is characterized by high, constitutive expression in an extrahepatic tissue, the sebaceous glands of cutaneous tissues. It is expressed exclusively in a subset of differentiated keratinocytes called sebocytes, as demonstrated by Northern blot analysis, in situ hybridization, and polymerase chain reaction. The onset of its expression coincides with the morphological appearance of sebaceous glands in the neonatal rat. Recombinant CYP2B12 produced in Escherichia coli epoxidizes arachidonic acid to 11,12- and 8,9-epoxyeicosatrienoic acids (80 and 20% of total metabolites, respectively). The identification of arachidonic acid as a substrate for this skin-specific CYP monooxygenase suggests an endogenous function in keratinocytes in the generation of bioactive lipids and intracellular signaling.

8,11,14-Eicosatrienoic Acid↗

PubMed1976

Pathogenesis associated with hair follicle mites (Demodex spp.) in Australian Aborigines.

Demodex folliculorum and D. brevis are found in different habitats in the skin: the former in the hair follicles, the latter in the sebaceous glands. Both seem minor pathogens--merely harvesting the cells of their respective habitats. D. folliculorum was found aggregated (all stages) and plugging the follicular orifices; D. brevis, on the other hand, was usually solitary. In one case marked degeneration of the sebaceous gland, with leukocyte invasion, was associated with D. brevis. No correlations were discovered between either of these species and the gross condition of the skin. Positive samples were obtained from both mainland and island populationf of Aborigines. Incidence values obtained were 66.6% for males and 80% for females; in the latter, the sample was small (5) and their ages over 34 years.

Adult↗

PubMed1982

Is the metabolism of testosterone to 5 alpha-dihydrotestosterone required for androgen action in the skin?

The assumption that the metabolism of testosterone to 5 alpha-dihydrotestosterone (5 alpha-DHT) is required for androgen action in the skin was investigated by studying the uptake and metabolism of testosterone by skin and other tissues of the rat in vivo. The skin resembled the classical androgen target organs in the uptake and retention of radioactivity, but the proportions of the steroids present were markedly different. In the ventral prostate most of the testosterone was metabolized, mainly to 5 alpha-DHT, after only 20 min. In the skin testosterone was always the predominant steroid identified and androstenedione, 5 alpha-DHT, 5 alpha-androstane-3 alpha, 17 beta-diol, androsterone and 5 alpha-androstane-3 beta, 17 beta-diol were only present in much smaller quantities, even after 5 h. Hypophysectomy, known to reduce the response of the sebaceous glands to testosterone in the rat, did not alter the steroid composition in the classical target organs, the preputial glands, or the plasma, but in the skin it increased testosterone metabolism without altering the levels of 5 alpha-DHT or the 5 alpha-androstane-diols. These results suggest that the 5 alpha-reduction of testosterone to 5 alpha-DHT may not be so important in the skin, or at least in the sebaceous glands, as it is in the prostate.

Animals↗

PubMed1982

Isotretinoin in the treatment of acne: histologic changes, sebum production, and clinical observations.

Isotretinoin was administered orally for 16 weeks, in a dosage of 1 mg/kg/day, to seven men with severe acne. A 36.2% reduction of nodulocystic lesions was observed at the conclusion of treatment and a 47.2% reduction was noted at the end of a 16-week follow-up period. However, there was an 88.4% decrease in sebum production and a marked reduction histologically in sebaceous gland size after 16 weeks of treatment, with a partial recovery of glandular activity at 32 weeks. The failure to observe a more striking overall response clinically resulted primarily from two of the seven patients showing worsening or no improvement of their disease, despite profound sebaceous gland inhibition. These findings suggest that the marked sebostatic effect of isotretinoin may not be the sole explanation for its mechanism of action in reducing the severity of acne.

Acne Vulgaris↗

PubMed1980

The influence of sex hormones on acne.

The sebaceous glands are stimulated by androgens produced in the skin itself. This explains why elevated androgen levels are seldom found in blood and urine from patients with acne. The most potent androgen is dihydrotestosterone (DHT), which is formed in the target cells, i.e. in the sebaceous glands, by a 5 alpha-reduction of testosterone. DHT is then bound to a specific receptor protein and translocated into the cell nucleus. In young persons genetically predisposed to acne a temporarily increased local DHT-formation has been postulated. In women androstenedione appears to be the major pre-hormone for DHT-formation. Adrenal androgens may account for prepubertal acne. Estrogens and progesterone influence acne only in high, unphysiological doses. Therapeutically we are waiting for a safe effective anti-androgen for topical use.

Acne Vulgaris↗

PubMed2006

Activation of platelet-activating factor receptor in SZ95 sebocytes results in inflammatory cytokine and prostaglandin E2 production.

Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects mediated by the PAF receptor (PAF-R). Activation of the epidermal PAF-R induces the expression of inflammatory mediators, including cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The upregulation of COX-2 expression has been shown to be involved in sebocyte proliferation, sebaceous gland inflammation and carcinogenesis. The present study was designed to investigate whether PAF-R activation could induce the expression of COX-2 and production of PGE(2), as well as secretion of the inflammatory cytokine, interleukin-8 (IL-8), in the immortalized sebaceous gland cell line SZ95. Using calcium mobilization studies, we first confirmed that PAF can signal through PAF-R in SZ95 sebocytes. We then found that the production of IL-8 was induced following treatment with PAF-R agonist, however blocked by a specific PAF-R antagonist. Induction of COX-2 expression and increased PGE(2) production were observed in SZ95 sebocytes after PAF-R activation. Finally, it was demonstrated that the production of PGE(2), induced by PAF-R activation and mediated by COX-2 expression, was blocked following PAF-R antagonism in SZ95 sebocytes. These studies suggest that SZ95 sebocytes express functional PAF-Rs and PAF-Rs are involved in regulating the expression of inflammatory mediators, including COX-2, PGE(2) and IL-8.

Calcium Signaling↗

PubMed1987

Efficacy of topically applied 17 alpha-propylmesterolone in acne patients.

A new substance--17 alpha-propylmesterolone--was tested in the treatment of acne. 8 male and 5 females patients applied a 3% alcoholic solution of the substance twice daily on the face for a mean period of 13 weeks. Besides clinical controls with acne grading also the determinations of the sebum excretion rate (SER) and separation of the lipid fractions was done before onset of treatment, after 14 days and then monthly. Concomitantly, the levels of several hormones (serum testosterone, prolactine, follicle stimulating hormone, luteinizing hormone and estradiol) were determined. Clinical results were moderate to excellent in most of the patients. In two patients no therapy effects became apparent after 8 weeks. SER was decreased in all patients to values between 70 and 4% of pretreatment values. Sebaceous gland lipids and epidermal lipids were both inhibited effectively. Hormonal parameters showed no significant difference of pretreatment and posttreatment values. For the first time positive effects of a topical new antiandrogen--17 alpha-propylmesterolone--could be demonstrated. The interesting finding of decrease of dermal and epidermal lipids suggests that not only sebaceous glands but also overstimulated epidermal structures may be inhibited by this antiandrogen.

Acne Vulgaris↗

PubMed1978

The evolution and distribution of hydroxysteroid dehydrogenase activity in human foetal skin throughout gestation.

Specimens of skin from human foetuses from 6--41 weeks gestation were incubated to demonstrate the presence of hydroxysteroid dehydrogenases (HSDs) by histochemical methods. When present HSDs were noted only within the acini of the sebaceous glands and in the secretory duct. Seventeen-beta-HSD activity was first demonstrated at 16 weeks gestation, co-incident with full function in the glands. Three-beta- and 16beta-HSD activity did not appear until 22--24 weeks. There were differences between the foetal pattern of distribution of the enzymes within gland acini and that already known in skin from subjects in extrauterine life. The time of changeover to the latter pattern has been established as 38 weeks gestation. No correlation was noted between HSD activity and the sex of the foetus or body site. It is concluded that foetal skin is involved in steroid metabolism, and possible physiological roles for this activity are discussed, with speculation over skin as an excretory route or detoxication centre for steroids and the role of steriod metabolic activity in the local stimulation and functional control of foetal sebaceous glands.

Female↗

PubMed2004

Neuroendocrine regulation of sebocytes -- a pathogenetic link between stress and acne.

A causative link between emotional stress and acne has long been postulated. There is mounting evidence that the molecular mechanism underlying this observation is related to the expression of receptors for several neuroendocrine mediators by the sebaceous gland. Recent and ongoing studies have indicated that human sebocytes express functional receptors for corticotropin-releasing hormone, melanocortins, beta-endorphin, vasoactive intestinal polypeptide, neuropeptide Y and calcitonin gene-related peptide. After ligand binding, these receptors modulate the production of inflammatory cytokines, proliferation, differentiation, lipogenesis and androgen metabolism in sebocytes. By means of their autocrine, paracrine and endocrine actions, these neuroendocrine factors appear to mediate centrally and topically induced stress towards the sebaceous gland, ultimately affecting the clinical course of acne.

Acne Vulgaris↗

PubMed1994

Alkaline phosphatase activity and localization during the murine hair cycle.

For unknown reasons, the pilosebaceous unit displays prominent alkaline phosphatase (AP) activity, and alterations in AP activity are seen in alopecia areata. The role of AP in hair biology and pathology has been obscured by contradictory reports on the localization and activity of AP during the hair cycle, and by a paucity of instructive models for studying AP functions. Using the C57 BL-6 mouse model for hair research, we have characterized endogenous AP with a simple histochemical developing solution routinely employed for AP immunohistology. This method was selective for AP, and revealed distinctive hair cycle-dependent changes in AP activity and localization. Although the dermal papilla displays unusually strong AP activity during the entire hair cycle, the outer root sheath is AP-positive only during late anagen and early catagen. Strong, rather homogeneous AP activity is seen in the sebaceous gland (SG) only during catagen and telogen. This AP staining pattern indicates hair cycle-dependent changes in SG functions, and differs to some extent from the previously reported AP activity during the hair cycle of various species. We propose a simple and effective technique for follicle classification based on the AP histochemistry of dermal papilla and sebaceous gland, and discuss uses of the C57 BL-6 mouse model for functional AP studies.

Alkaline Phosphatase↗