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Biomedical subjects

K S Stenn

Publications and source records attributed to K S Stenn.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fibroblast-dependent induction of a murine skin lesion with similarity to human common blue nevus.

In an attempt to define epithelial-mesenchymal interactions in skin appendage formation, we have been studying a nude mouse grafting model that permits the combination of heterotypic and heterochronic epithelial and mesenchymal cells. In this study using neonatal hair bud cells combined with various mesenchymal cell preparations, we show that one can regenerate near-complete skin with intact epidermal and dermal layers plus mature hair follicles. It was determined that the character of the resulting regenerated skin could be manipulated as a function of the specific mesenchymal component. Lack of dermal cells resulted in a scar, whereas inclusion of a suspension of dissociated total dermal cells resulted in near-complete skin regeneration, and in the presence of follicular papilla fibroblasts (both hair-inductive and non-hair-inductive) or NIH3T3 fibroblasts, the reconstitution had similarity to the common blue nevus. The results indicate that 1) a stimulant of human common blue nevus can be produced in an animal model, 2) the underlying disorder of the lesion in mice appears to be entirely dermal in origin, arising independent of the epidermal component, and 3) complex dermal cell interactions involving lesion-initiative and lesion-suppressive activities underlie the pathogenesis. This experimental system will serve as a valuable tool in elucidating cutaneous dermal-epidermal signals in normal skin as well as the alteration of these signals in malformations such as the hamartoma described here.

3T3 Cells↗
PubMed1995

Changes in expression of apoptosis-associated genes in skin mark early catagen.

Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcriptase-polymerase chain reaction, we examined in this study the expression in total skin, throughout one hair cycle, of a series of regulatory genes associated with apoptosis. We show that gene expression within skin is hair-cycle-dependent. Transforming growth factor-beta was expressed immediately before catagen; therefore, it might be involved in the early signaling of this process. Tumor necrosis factor-beta was expressed during catagen and might be involved in follicular apoptosis. Several proto-oncogenes and transcription factors have been described in the regulation of apoptosis in other systems. Here we show that the transcript levels of c-myc, c-myb, and c-jun changed immediately before or during early catagen and thus could be involved in the signaling or regulation of catagen. Levels of p53 remained constant throughout anagen and catagen, suggesting that p53 is not involved in the developmentally induced apoptosis of the hair follicle. The variable expression throughout the hair cycle of the genes described demonstrates the dynamic changes of the skin and underscores the importance of studying the complete hair cycle when characterizing any molecule in skin.

Animals↗
PubMed1994

Transection level dictates the pattern of hair follicle sheath growth in vitro.

Using a newly developed in vitro sheep hair culture system, we found that the pattern of sheath growth is a function of the level at which the follicle is transected. Two patterns are observed. The type 1 pattern, which occurs after the follicle is transected below the sebaceous gland, shows an equal elongation of the sheath and shaft. The type 2 pattern, which occurs when the follicle is cultured either after transection above the sebaceous gland or with an intact attached epidermis, is characterized by growth of hair shaft clean of sheath. These growth patterns, dictated by the transection level, are observed in both sheep and human follicles, are not dependent on the presence of the sebaceous gland itself, and are not influenced by the presence of co-cultured epidermis or infundibulum. Thymidine autoradiography demonstrates that transecting follicles beneath the sebaceous gland leads to an increase in DNA synthesis of the cells in the external root sheath, but does not alter DNA synthesis of the cells in the follicle matrix. Besides the obvious implications to wound closure, these findings indicate that the sebaceous gland demarcates a significant region of the follicle which influences sheath-shaft interactions and that the sheath and the shaft constitute coordinated cell populations which nevertheless respond distinctly to proliferative signals.

Animals↗
PubMed1994

Molecules of the cycling hair follicle--a tabulated review.

In this review we tabulated molecules which have been experimentally identified to be associated with, or play a role in, hair follicle growth. While compiling these data we were impressed by the fact that this field is only now beginning to be developed in terms of molecular analysis. Ironically, hair was used in some of the earliest molecular approaches to biologic structure (e.g. Astbury and Street, 1931), but the field did not develop from there. From our review we have come to the following conclusions. (1) As indicated by the growing number of reports dealing with follicle-associated molecules in the past 3 years, the field of hair biology has entered a new molecular era. (2) In many reported hair biology studies not enough emphasis has been placed on the fact that the follicle is a dynamic structure. All too often a study is limited to follicles of one particular phase of the cycle or one phase of development. Students in the field have to be more sensitive to the remarkable changes that this deceptively simple structure can undergo during its cycle. (3) Although we have not been able to find any molecules unique to the follicle, some of the structural molecules come close to an ideal tool. It is our impression that even more specific molecule tags will be found. Whether this requires a subtraction library approach or gene mapping of specific mutants is not yet clear. It would appear that the large, diverse family of intermediate filament-associated proteins will prove to be an excellent source of unique follicle-labeling molecules. (4) There is an acute need for molecules which distinguish the phases of the cycle, e.g. telogen from early anagen. Telogen is by far the most difficult phase to identify morphologically since the earliest phase of anagen and the latest phase of catagen may appear structurally like telogen. That these phases are functionally distinguishable must imply a molecular difference. As the number of recognized hair follicle-associated molecules and their interactions increase, it will be essential to assemble libraries of highly specific RNA and antibody probes for localization and mapping studies. We recognize that this review, as written, is imperfect. It is particularly deficient in making any effort towards identifying unifying principles of structure and function. We look forward to returning to this subject within 3 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Expression of the bcl-2 protooncogene in the cycling adult mouse hair follicle.

The hair follicle undergoes a cycle of growing, regressing, and resting phases (anagen, catagen, telogen, respectively). As the follicle enters catagen, the cells of the lower, cycling portion undergo a process of controlled cell death (apoptosis). Understanding the mechanism of apoptosis in the follicle should give insight into one of the control steps of hair cycling. In this study we sought the expression of bcl-2, a protooncogene associated with apoptosis control, in the cycling follicle of the adult mouse. Using a monoclonal antibody to the mouse protein we immunolocalized bcl-2 gene product in the cycling pelage follicle of the C57/B6 adult mouse. The protein was expressed in the follicular papilla (a non-cycling portion of the follicle) throughout the cycle-including telogen. The cycling follicular epithelium, however, showed positive antibody staining in anagen, which decreased in catagen and disappeared in telogen. In anagen the cells of the bulb, bulge, and basal layer of the outer root sheath expressed the bcl-2 protein. Understanding the action of this apoptosis-inhibiting molecule should serve to elucidate the dynamics of follicular cycling.

Animals↗
PubMed1994

Isolation and culture of follicular papillae from murine vibrissae: an introductory approach.

The recent successes in culturing follicular papilla cells have afforded a rapid advance in our understanding of hair biology. Although the experimental manipulation of the papilla is briefly described in the original reports, a detailed description for workers starting in the field is not yet available. In this report we give a brief review of hair biology relevant to the papilla, and illustrate the method we have found successful for isolating and growing papilla cells.

Animals↗
PubMed1993

Homeobox genes and the patterning of skin diseases.

Fundamental to our understanding of skin diseases and their presentation is an understanding of the pattern of their development. When we have established the molecular basis of their development we will be in a much better position to control and treat such diseases. The homeobox genes are a family of regulatory proteins that influence pattern formation at many levels. Their presence in skin implicates them in this important role. It seems highly likely that they will be shown to be fundamental to the development of the patterns used in diagnosing skin diseases.

Genes, Homeobox↗
PubMed1993

Glucocorticoid effect on hair growth initiation: a reconsideration.

It has been demonstrated by various workers in the past that glucocorticosteroids block hair growth. Using the mouse model for studying hair growth induction we reexamined the effect of topically applied steroids on hair growth to establish at what stage the steroid block acts. In accord with studies by others, we found that these steroids block hair growth at the point of anagen initiation, but that once the steroid applications are stopped, hair growth starts. Since steroid withdrawal alone did not induce hair growth, it is clear that these steroids do not block, either spontaneous or manipulated, hair growth induction, but they do block, the apparent next step, i.e., hair formation. Moreover, since hair growth could be induced even while the animals were being treated with the steroid, the induction step appears independent of the steroid block. These studies and those of others lead us to conclude that these steroids block the expression of hair-forming genes, but do not interfere with the signal(s) that initiates those genes. This system appears to be ideal for identifying the signals (perhaps, genes) responsible for initiating hair growth.

Administration, Topical↗
PubMed1992

Ectodermal dysplasias associated with clefting: significance of scalp dermatitis.

Several clinical syndromes are characterized by ectodermal dysplasia (ED) in association with clefting of the lip and/or palate. The three most commonly recognized entities are (1) the EEC syndrome (ectodermal dysplasia, ectrodactyly, cleft lip/palate); (2) the Rapp-Hodgkin syndrome with ectodermal dysplasia, cleft lip/palate, and mid facial hypoplasia; and (3) the Hay-Wells or AEC syndrome (ankyloblepharon, ectodermal defects, cleft lip/palate). The clinical characteristics of these entities as well as several less common syndromes are reviewed and summarized. The presence of scalp dermatitis in patients with the AEC syndrome and less often the Rapp-Hodgkin syndrome is emphasized.

Cleft Lip↗
PubMed1991

Vitronectin: effects on keratinocyte motility and inhibition of collagen-induced motility.

Epibolin, a plasma protein, was initially purified on the basis of its ability to enhance spreading of keratinocytes. It is now known that epibolin is identical to serum spreading factor, S protein, and vitronectin, and the current name for the protein is vitronectin. Studies of vitronectin on cultured keratinocytes showed that it caused spreading and epiboly but not cellular adhesion to the substratum. In studies with other types of cells, vitronectin increased migration of several types of cells in a Boyden chamber. Because some agents that enhance spreading and adhesion, such as collagen and fibronectin, also increase motility, we tested whether vitronectin increased motility of keratinocytes. By photographing and quantitating motility of keratinocytes plated on a bed of colloidal gold particles, we determined that vitronectin increased local movement of keratinocytes in a concentration-dependent fashion, resulting in clearing of gold particles in a circular pattern around the cells, but did not cause the production of tracks found in cultures plated on collagen or fibronectin. The small increases in clearing of the gold particles that occurred in the presence of vitronectin were abolished by antibody to vitronectin. Furthermore, the marked increase in motility produced by type I collagen was significantly reduced when the keratinocytes were treated with vitronectin. Antibody to vitronectin also abrogated the vitronectin-induced reduction in collagen-stimulated motility, confirming that this action was specific for vitronectin. Serum, which contains vitronectin, stimulated motility in a fashion identical to purified vitronectin, but serum lacking vitronectin was inactive. These studies show that vitronectin causes a localized increase in movement associated with spreading resulting in a halo around individual cells, that vitronectin does not enhance directional motility of keratinocytes in this assay but in contrast antagonizes such motility produced by collagen, and that vitronectin is the factor in serum responsible for this effect. The findings with vitronectin and collagen show that these agents stimulate different types of motility. The roles in wound healing of agents stimulating different types of motility are unclear and require further study.

Blood Physiological Phenomena↗
PubMed1991

The epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH inhibits murine hair growth in vivo and in vitro.

Tissue growth may be controlled by negative feedback mechanisms. Recently, a pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH ('epidermal pentapeptide', EPP), which slows the growth of mouse epidermis in vivo and of mouse keratinocytes in vitro, was isolated from mouse epidermis. Since inhibitory molecules like EPP might be part of the feedback systems underlying hair growth control, we assessed the effect of synthesized EPP on the growth of hair follicles, using rodent in vivo and in vitro assays. We report for the first time that intraperitoneally injected EPP (30 nmol/animal/day over 6 days) significantly slows the growth of hair follicles in plucking-induced anagen skin of C57 B1-6 mice (as assessed by microscopic morphometry). Using an in vitro organ culture assay, EPP inhibits the incorporation of 3H-thymidine into mouse pelage anagen follicles. That this epidermal-derived peptide affects hair growth raises the possibility that hair growth may be regulated by an inhibition/disinhibition mechanism under participation of EPP-like molecules and that the epidermis may play a role in the control of hair growth.

Alopecia↗
PubMed1990

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix.

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism.

Animals↗
PubMed1990

Telogen skin contains an inhibitor of hair growth.

We have investigated whether C57B1-6 mouse skin with all its follicles in the telogen stage of the hair cycle contains a hair-growth inhibitory activity, as opposed to skin with anagen follicles. Crude aqueous extracts of whole telogen mouse skin (TE), anagen skin (AE) or vehicle alone (V) were injected intraperitoneally into mice in which anagen had previously been induced by plucking of telogen hair follicles. Injection of TE, but not AE or V, significantly retarded the development of anagen follicles, as measured by macroscopic and quantitative microscopic hair growth parameters (skin pigmentation and thickness, appearance of trichohyaline granules) and the incorporation of tritiated thymidine into mouse skin from animals previously treated with either TE or V (skin organ culture). This inhibitory activity seemed to be localized to the epidermis and was also present in rat epidermis. We suggest that this apparently non-species-specific inhibitor present in telogen skin may play a role in regulating the hair cycle in rodents.

Animals↗
PubMed1989

Nevomelanocytic proliferations in association with cutaneous malignant melanoma: a multivariate analysis.

Two hundred forty-eight cases of melanoma accessioned from 1984 through 1985 were independently reviewed by a panel of dermatopathologists for the presence of nevomelanocytic proliferations in histologic contiguity with melanoma. One hundred ninety-seven cases remained in the sample for analysis after cases with insufficient histologic material and those diagnosed without primary melanoma were excluded. We found that 32.5% of melanomas (95% confidence interval, 25.9% to 39.7%) were associated with a benign or dysplastic nevus in histologic contiguity. Melanoma type and anatomic location were significant predictors of contiguous nevomelanocytic proliferations when considered alone. After adjustment, however, only melanoma type significantly predicted the presence of a contiguous histologic evidence of a precursor nevus than was nodular melanoma (odds ratio, 11.1; 95% confidence interval, 1.4 to 86.6) and were almost 22 times more likely to be associated with a nevus than was lentigo maligna melanoma (odds ratio, 21.45; 95% confidence interval, 2.8 to 162.4). This evidence supports the concept of the heterogeneity of melanoma histogenesis.

Adult↗