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Biomedical subjects

K S Stenn

Publications and source records attributed to K S Stenn.

At least 19 recordsLinked to original sources
PubMed2003

Molecular insights into the hair follicle and its pathology: a review of recent developments.

In the last few years by means of the elucidation of the human genome and the acquisition of powerful investigative tools we have begun to understand the molecular basis of hair follicle growth control. In this article I will describe some of the salient recent contributions to the field and review the implications these findings have had on our understanding of mechanisms in dermatology and dermatopathology.

Animals↗
PubMed2001

Scd3--a novel gene of the stearoyl-CoA desaturase family with restricted expression in skin.

Stearoyl-coenzyme A (CoA) desaturase (SCD) is a key enzyme involved in the conversion of saturated fatty acids into monounsaturated fatty acids. Previously, two members of this gene family, namely, Scd1 and Scd2, have been reported. Here we report the identification and characterization of a novel member of this family, Scd3, whose expression is restricted to mouse skin, specifically to the sebaceous gland. The Scd3 gene codes for a transcript of approximately 4.9 kb with an open reading frame that results in a 359-amino-acid protein. Scd3 shares 91 and 88% identity in the protein-coding region with Scd1 and Scd2, respectively, and maps to mouse chromosome 19 in very close proximity to Scd1 and Scd2. Unlike Scd1, Scd3 expression is higher in male mouse skin than in female mouse skin. The promoter sequence of Scd3 reveals similarity with Scd1 in the proximal region but also possesses several distinctive features including the polyunsaturated fatty acid-response element. Scd3 is expressed in the skin of young asebia mutant mice (Scd1(ab2J)/Scd1(ab2J)) in the absence of Scd1. Scd3 expression changes during the mouse hair cycle but not as dramatically as Scd1. The tissue-specific and sex-dependent expression of Scd3 suggests the presence of gene- and hormonal-specific control mechanisms.

5' Untranslated Regions↗
PubMed2001

Insights from the asebia mouse: a molecular sebaceous gland defect leading to cicatricial alopecia.

The primary cicatricial alopecias have proven to be challenging for the clinician, dermatopathologist and the researcher--let alone the patient. If we are to improve our diagnostic and therapeutic tools for these very difficult disorders, we will need greater insight into their etiology. Recent work with the mouse mutant, asebia, provides a model for cicatricial alopecia. In this model the pathology--perifollicular inflammation, sebaceous gland "destruction", hair shaft granuloma, and cicatricial follicle drop-out--results from the mutation of one very important sebaceous gland gene. In the absence of this gene, the sebaceous gland is hypoplastic and normal sebum production is minimal to absent. In this paper the relevance of this mutant to human alopecias is discussed and the point emphasized that the pathogenesis of some forms of human cicatricial alopecia could involve the sebaceous gland.

Alopecia↗
PubMed2001

A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages.

Numerous strains of mice with defined mutations display pronounced abnormalities of hair follicle cycling, even in the absence of overt alterations of the skin and hair phenotype; however, in order to recognize even subtle, hair cycle-related abnormalities, it is critically important to be able to determine accurately and classify the major stages of the normal murine hair cycle. In this comprehensive guide, we present pragmatic basic and auxiliary criteria for recognizing key stages of hair follicle growth (anagen), regression (catagen) and quiescence (telogen) in C57BL/6NCrlBR mice, which are largely based on previous work from other authors. For each stage, a schematic drawing and representative micrographs are provided in order to illustrate these criteria. The basic criteria can be employed for all mouse strains and require only routine histochemical techniques. The auxiliary criteria depend on the immunohistochemical analysis of three markers (interleukin-1 receptor type I, transforming growth factor-beta receptor type II, and neural cell-adhesion molecule), which allow a refined analysis of anatomical hair follicle compartments during all hair cycle stages. In contrast to prior staging systems, we suggest dividing anagen III into three distinct substages, based on morphologic differences, onset and progression of melanogenesis, and the position of the dermal papilla in the subcutis. The computer-generated schematic representations of each stage are presented with the aim of standardizing reports on follicular gene and protein expression patterns. This guide should become a useful tool when screening new mouse mutants or mice treated with pharmaceuticals for discrete morphologic abnormalities of hair follicle cycling in a highly reproducible, easily applicable, and quantifiable manner.

Animals↗
PubMed2001

Controls of hair follicle cycling.

Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-beta, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.

Animals↗
PubMed1999

Androgen-induced delay of hair growth in the golden Syrian hamster.

The golden Syrian hamster flank organ has been used to study the stimulatory effect of androgens on sebaceous glands and hair. Androgens cause the sebaceous glands and hair follicles in this organ to grow. We have made the novel observation that exogenously administered androgen, testosterone propionate (TP), suppresses hair growth in the area surrounding the flank organ. When given in a time-release (systemic) subcutaneous dosage form (pellet), 25 mg TP inhibited the regrowth of clipped hair in peri-flank organ skin for up to 21 days; however, by 28 days hair grew back to the same extent as in controls. The peak serum level of testosterone in TP-treated animals occurred at 14 days, and declined thereafter. When two separate TP pellets (25 mg/pellet) were administered 14 days apart in order to maintain high serum levels for 28 days, the amount of hair regrowth after 35 days was identical to animals receiving a single TP pellet or placebo. This suggests that the systemic level of testosterone was not the only factor in hair regulation. Hair growing within the flank organ appeared to be unaffected by TP administration. In the golden Syrian hamster, androgen, as in humans, can exert stimulatory and inhibitory effects on hair growth depending on the body site. We conclude that this animal model could serve as a useful system to investigate the mechanisms responsible for the opposing effects of androgen on hair growth.

Analysis of Variance↗
PubMed1999

What controls hair follicle cycling?

Despite more than a hundred years of professional hair research, and substantial recent progress in unravelling the molecular controls of hair follicle morphogenesis, the chronobiological control system that cyclically drives the hair follicle through dramatic remodelling processes between phases of growth (anagen), regression (catagen), and relative resting (telogen) have remained disappointingly obscure. In view of the vast literature that has become available over the past decades on numerous genetic, biochemical, cellular and pharmacological aspects of hair growth follicle control under physiological and pathological conditions, it is astounding how comparatively few researchers in the field have published theoretical concepts that explore how hair follicle cycling might be controlled. Since this question is at the very heart of basic and clinically applied hair biology, it deserves a much more systematic and serious public exploration, which the following contributions are designed to stimulate.

Animals↗
PubMed1998

Differential subtraction display: a unified approach for isolation of cDNAs from differentially expressed genes.

We have developed a novel efficient approach, termed differential subtraction display, for the identification of differentially expressed genes. Several critical parameters for the reproducibility and enhanced sensitivity of display, as well as steps to reduce the number of false positive cDNA species, have been defined. These include- (a) use of standardized oligo(dT)-primed cDNA pools rather than total RNA as the starting material for differential display, (b) critical role of optimal cDNA input for each distinct class of primers, (c) phenomena of primer dominance and interference, and (d) design of a novel set of enhanced specificity anchor primers. Introduction of an efficient subtractive hybridization step prior to cloning of cDNA species enriches the bona fide cDNA species that are either exclusively present in one sample (+/-) or show altered expression (up-/down-regulation) in RNA samples from two different tissues or cell types. This approach, in comparison to differential display, has several advantages in terms of reproducibility and enhanced sensitivity of display coupled to the cloning of enriched bona fide cDNA species corresponding to differentially expressed RNAs.

Animals↗
PubMed1997

Expression of two Ig family adhesion molecules in the murine hair cycle: DCC in the bulge epithelia and NCAM in the follicular papilla.

The hair cycle involves remodeling of cells and of cell groups into a complex follicular structure. During skin appendage development, adhesion molecules such as neural cell adhesion molecule (NCAM) and deleted in colon carcinoma (DC) participate in the formation of cell groups. NCAM has been found to be expressed in the mesenchyme during mouse hair follicle induction. DCC expression has been observed in the epithelial cells of the developing feather. We postulate that these two molecules may also define cell groups in the cycling hair follicle. Here we report their spatio-temporal expression patterns during the depilation-induced murine hair cycle. NCAM expression was also examined in positive and negative hair-inductive follicular papilla cell lines. Throughout the hair cycle, DCC expression was confined to the basal keratinocytes of the epidermis and the epithelial portion of the hair follicle. During mid-anagen, two types of deleted in colon carcinoma staining were observed. One was a cell surface pattern seen in the epithelial cells in the bulge region where the follicular stem cells reside. The other was a diffuse cytoplasmic staining pattern in the transient hair follicle epithelia located below the bulge region. Prominent NCAM staining was observed in the follicular papilla throughout the hair cycle and was accompanied by weak staining of the matrix epithelia. NCAM expression correlated with hair induction by a follicular papilla cell line. The results suggest that DCC and NCAM define the permanent cell groups of the hair follicle and that NCAM is important for hair induction.

Animals↗
PubMed1997

Fibroblast-dependent induction of a murine skin lesion similar to human nevus sebaceus of Jadassohn.

Using a nude mouse grafting model, we have demonstrated that normal-haired skin is regenerated in a graft containing hair buds and dissociated dermis. Altering the dermal component leads to changes typical of the human nevus sebaceus of Jadassohn (NSJ). The murine lesion is characterized by sebaceous gland hyperplasia, abortive hair follicles, and epidermal hyperplasia. The development of the NSJ-like lesion is independent of the epidermal component but dependent on a specific dermal fibroblast combination, namely, a hair-inductive follicular papilla fibroblast cell line plus BALB/c 3T3 fibroblasts. Non-hair-inductive follicular papilla cell lines in combination with BALB/c 3T3 fibroblasts are unable to induce the NSJ-like structure, indicating that hair-inductive signals play a central role in its pathogenesis. BALB/c 3T3 fibroblasts in combination with total cells from dissociated neonatal dermis produce abortive hair follicles, but the sebaceous gland hyperplasia is suppressed, suggesting the presence of suppressive endogenous dermal factors. The data suggest that (a) pilosebaceous induction is a multistep process and (b) the pathogenesis of NSJ involves perturbation of a complex array of inductive mesenchymal (dermal) signals. This paper describes the first animal model of NSJ and provides evidence that development of the human lesion could depend entirely on aberrant dermal cells.

3T3 Cells↗
PubMed1996

Hair follicle growth controls.

Research in hair biology has embarked in the pursuit for molecules that control hair growth. Many molecules already have been associated with the controls of hair patterning, hair maturation, and hair cycling and differentiation. Knowing how these molecules work gives us the tools for understanding and treating patients with hair disorders.

Adult↗
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↗