Langerhans' cells in hair follicles of the depigmenting C57Bl/Ler-vit.vit mouse. A model for human vitiligo

The C57Bl/Ler-vit.vit mouse grows a black pelage after birth. During successive hair molts, the fur loses its pigmentation. By 6 months of age, most of the fur of the animal is white. The epidermis of the ears and tail also loses its pigmentation. Histologic studies confirm that in the epidermis and hair follicles there is an absence of pigment cells identifiable by various histochemical or electron microscopic techniques. This mouse may be an excellent model in which to study the role of Langerhans' cells and the immune response in the pathogenesis of vitiligo, a study not easily done in humans. From results of prior studies, we postulated that if Langerhans' cells were involved in the destruction of melanocytes, they would be abnormal (either more or less numerous) in number during the active phase of depigmentation and normal in number after depigmentation was complete. To determine whether the Langerhans cell (Ia+/adenosine triphosphatase dendritic epidermal cell) might be involved in destruction of pigment cells, we quantified the number of Ia+ and adenosine triphosphatase dendritic cells in the hair follicles in skin from the ear, abdomen, back, and tail from male C57Bl/Ler-vit.vit mice while the fur and skin were depigmenting and after depigmentation was almost completed. We found that Langerhans' cells were normal in number during depigmentation and were most numerous after depigmentation. Previous studies indicate that Langerhans' cells in these mice are functionally defective and respond poorly to some contact allergens. From these morphologic and functional data, we conclude that Langerhans' cells probably are uninvolved in causing depigmentation in these mice. We also observed that the epithelium of hair follicles has a significantly higher (up to 1600/mm2) population density of Langerhans' cells than interfollicular skin.     

Three-dimensional comparative study of Merkel cell distribution in various body sites of guinea pigs and rats

Abstract The hair cycling pattern differs between humans and mice: for the former it is mosaic, while the latter show a wave pattern. We focused on the presence or absence of synchronization of the hair cycle based on the distribution of Merkel cells. The three-dimensional distribution and number of Merkel cells in the skin at various sites were determined in guinea pigs and rats. Using ethylenediaminetetraacetic acid, various types of hair follicles were obtained from the facial, abdominal, nipple, back, tail, perianal and plantar skin. Epidermal sheets containing numerous hair follicles were immunostained using monoclonal murine antibody CK20 which is generally accepted to be a specific immunocytochemical marker for Merkel cells of various species. Merkel cells were absent in the trunk skin of guinea pigs and rats, in complete contrast to the situation in humans. In vibrissa and other hair follicles within specialized sensitive areas, Merkel cells were found in varying numbers. Some differences in their distribution and number were observed between guinea pigs and rats. The absence of Merkel cells in the hair follicles of the trunk skin of rats and guinea pigs implies that Merkel cells are not essential for the induction and promotion of hair growth but have some different functional significance in hair follicles. Received: 7 April 1999 / Revised: 8 June 1999 / Accepted: 8 October 1999     

Selective cytotoxicity of N-acetyl-4-S-cysteaminylphenol on follicular melanocytes of black mice

Previous in vivo studies have shown that 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) have antimelanoma effects and that N-Ac-4-S-CAP produced a 98% depigmentation of hair follicles of black mice. This study investigated the process of selective melanocytotoxicity by N-Ac-4-S-CAP through light and electron microscopy studies of hair follicles obtained from newborn black mice treated with N-Ac-4-S-CAP. Visible changes in follicular melanocytes were found 4 h after intraperitoneal (i.p.) administration. Clumps of melanin granules and areas of melanocytic nuclear condensation were seen in the hair follicles. On electron microscopy there was progressive destruction of melanocytes with swelling of membranous organelles, nuclear condensation, and vacuolation of the cytoplasm, culminating in completely necrotic cells. None of these changes were demonstrated in the surrounding keratinocytes. N-Ac-4-S-CAP appears to have specific, cytotoxic effects on melanocytes actively producing eumelanin. The drug may not affect precursor or dormant melanocytes which retain the ability to become active, melanin-producing cells.     

THE SELECTIVE DEPIGMENTING ACTION OF 8-HYDROXYQUINOLINE ON HAIR GROWTH IN THE MOUSE

Summary.— Topical applications of 8-hydroxyquinoiine to mouse skin cause depigmented hair to grow in patterns which change with time and appear to be closely associated with the hair growth cycles. Sufficiently frequent applications result in virtually complete depigmentation in young adult C57BL female mice, while single applications cause isolated bands of depigmented hair. Female mice are more sensitive than males, but some treated newborn mice were unaffected, 8-Hydroxyquinaldine has a similar action. Compounds not showing this effect include 2 recognized depigmenting agents, some compounds related to 8-hydroxyquinoline and some other analytical reagents for copper.     

MEASUREMENT OF LIPID SYNTHESIS IN MOUSE AURICULAR SKIN CULTURED IN VITRO

Split-thickness mouse auricular skin has been cultured in vitro for up to 48 hours in the presence of ¹⁴C-sodium acetate, ¹⁴C-leucine, ¹⁴C-isoleucine and ¹⁴C-valine, and the incorporation of radioactivity into various tissue fractions measured in the heat-separated epidermis and dermis. Lipid fractions were analysed by chromatography. It was found consistently that the epidermis contained higher proportions of labelled sterol esters and lower proportions of labelled triglyceride than the corresponding dermis. The radioactive acyl moieties of certain lipid classes were further studied by gasliquid radiochromatography. With ¹⁴C-acetate as the tracer, sterol esters of both epidermis and dermis were seen to be enriched with respect to branched chain and odd-numbered chain fatty acids compared with triglycerides and phospholipids. With ¹⁴C-leucine, which is the specific precursor of odd-numbered chain iso-branched acids, sterol esters contained the majority of this type of fatty acid, although the major part of the radioactive substrate was metabolized to ¹⁴C-acetate and incorporated into normal, even-number chain saturated and unsaturated acids. With ¹⁴C-valine, a specific precursor of even-number chain iso-branched acids, epidermal and dermal sterol esters again contained the majority of these acids, although there was evidence of some degradation of the valine to acetate, and incorporation into normal fatty acids. With ¹⁴C-isoleucine, a specific precursor of odd-numbered chain anteisobranched acids, virtually all of the precursor was degraded to ¹⁴C-acetate, and the resultant radioactivity patterns were quite similar to those obtained with ¹⁴C-acetate cultures per se. Slight traces of radioactive anteiso acids were detected in certain lipid classes, however.     

Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses

The size of a hair follicle is thought to be determined by the volume of its dermal papilla. The volume of the dermal papilla depends on the number of cells it contains and on the volume of the extracellular matrix. To establish which of these two variables is related to differences in hair follicle size we performed a stereologic study on 235 hair follicles from different sites, including male facial skin (beard), female facial skin, and scalp. In facial follicles there was a strong correlation between the area of the hair cortex and the volume of the dermal papilla. The area of the hair cortex also correlated with the number of cells in the dermal papilla and with the volume of dermal papilla per cell. In scalp hair follicles, where there was a smaller range of sizes, the correlations between these variables were weaker. In large male facial follicles the mean total dermal papilla volume was almost 40-fold higher than in vellus follicles from female facial skin. This difference was associated with a mean 17-fold greater number of cells in the dermal papilla and a 2.4-fold greater volume associated with each cell. Intermediate results were obtained in scalp follicles. In many regions of the skin hair follicles enlarge in response to androgens during adult life hair. Our results imply that the increase in the volume of the dermal papilla in these follicles is due to an increase in the number of cells, either through proliferation or through the migration of cells from the follicular dermal sheath, and to an increase in the amount of extracellular matrix per cell. As androgens are thought to act primarily on the dermal papilla, these changes may have a direct bearing on the mechanism of androgen-mediated alterations in hair follicle size.     

The HLA-dermatosis connection

A number of dermatological diseases are associated with distinct HLA types. These associations vary in different populations and ethnic groups. HLA determination can be related to different disease courses, various anatomical predilection sites and can be used as a diagnostic tool. However, the pathogenic role of HLA in susceptibility to specific dermatological diseases often remains unclear.     

Depigmentation therapies for normal skin in vitiligo universalis

If vitiligo involves most of the body, it might be easier to depigment the normal remaining skin rather than to attempt repigmentation. We reviewed the literature to date regarding available therapies for depigmenting the normal skin in vitiligo universalis. Our review revealed that the threshold regarding what percentage of body surface area qualifies as depigmentation is variable among practitioners. Monobenzyl ether of hydroquinone (MBEH) is the most widely used depigmenting agent and has few side‐effects. Tretinoin in combination with MBEH is able to speed depigmentation of the skin. Monomethylether of hydroquinone has also been used successfully for depigmentation. Eighty‐eight per cent phenol is also effective in depigmenting the skin but its application on large areas is toxic for liver and kidney. Different types of lasers are also available to destruct the melanocytes selectively, but this technique can be painful and expensive. Cryotherapy is a cheap depigmenting therapy but, because of scarring risk, it should only be used by experienced dermatologists. No trials have compared the efficacy of the above‐mentioned well‐established depigmentation agents/techniques. Certain drugs such as imatinib, imiquimod and diphencyprone, which are used to treat other diseases, caused depigmentation as a side‐effect. Some depigmentation agents used for branding cattle can also serve as topical depigmentation agents. In conclusion, comparative clinical trials are needed to compare the efficacy of various depigmentation agents/techniques. In particular, topical imatinib, imiquimod and diphencyprone may be considered as potential depigmenting agents, which require further investigation. This review revealed that MBEH is safe and effective depigmenting agent.     

Determination of density of follicles on various regions of the face by cyanoacrylate biopsy: correlation with sebum output

The density of follicles on various regions of the human face has received scant attention. We used cyanoacrylate follicular biopsies to determine the number of follicles on the forehead, cheek, chin and nose of 12 healthy adult white women. Sebum output was assessed on the same regions by means of Sebutape®. The density of follicles and sebum output followed a centrolateral decreasing gradient. There was no correlation between these two parameters. These regional patterns are important for studies of the pathogenesis of common disorders of the face and their response to treatment.     

Immunohistochemical analysis of cytokeratin expression in various trichogenic tumors.

The immunophenotypes, especially expression of cytokeratins, in 13 cases of trichogenic tumors were examined to investigate their histogenesis. Four cases of multiple trichoepithelioma, five cases of classical solitary trichoepithelioma, one case of desmoplastic trichoepithelioma, one case of trichogenic trichoblastoma, one case of trichoblastic fibroma, and one case of giant solitary trichoepithelioma were retrieved. The immunoreactivities of the epithelial nests and the keratinous cysts in these tumors were similar to those of the outer root sheath and the infundibulum of normal hair follicles, respectively. From the comparative studies of the immunophenotypes with those of normal hair follicles, we speculated that all trichogenic tumors differentiate mainly toward the outermost layer of the outer root sheath between the lower part of the permanent portion and the upper part of the transient portion and some parts of them differentiate toward various other parts of the follicles. Although differentiation toward the other follicular structures can vary from case to case, there is no particular staining pattern specific for each kind of trichogenic tumor and no significant differences in immunoreactivity among them. Our observations support a recent notion that all neoplasms of follicular germinative cells should be grouped as a single entity.     

DIFFERENTIAL EFFECTS OF 5-BROMODEOXYURIDINE ON B16 MOUSE MELANOMA CELLS

The effects of 5-bromodeoxyuridine (BrdU) on B16 mouse melanoma were studied and the following results were obtained.

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Depigmentation therapy

ABSTRACT: Depigmentation therapy is a treatment option for patients with widespread, treatment-resistant vitiligo. The most commonly employed technique is the application of monobenzylether of hydroquinone (MBEH), also known as monobenzone, to areas with residual pigment. Prior to instituting therapy, the patient must be aware of the cost, treatment time course, risk of distant sites of depigmentation, probable permanency of depigmentation, side effects such as contact dermatitis, and the potential for repigmentation via follicular melanocytes. The social ramifications of depigmentation therapy also must be discussed, especially for patients with skin types IV and V. The sequential use of 4-methoxyphenol and Q-switched ruby laser also has been reported as a successful form of depigmentation therapy.     

Earlier‐ born secondary hair follicles exhibit phenotypic plasticity

The mouse pelage is composed of four distinct hair types. The fact that the follicles that generate these hair types form in successive waves during late embryonic development suggested the model that distinct epigenetic states of the inductive mesenchyme fixed when the follicles are formed specify the distinctive hair morphologies. This model is inconsistent with the observation that many follicles produce different hair types in successive hair cycles. In this study, the characteristics of the hair follicles that switch between the production of different hair types were examined. These follicles were born earlier than those that do not switch between hair types and made longer hairs. They also expressed a higher level of Sox2 in the dermal papilla and had more DP cells per follicle. These observations are consistent with the hypothesis that different birthdates specify the potential of different follicles. However, rather than directly specifying hair type, birthdate correlates with three types: guard hairs, a plastic population that can make awl, auchene or zigzag hairs, and a population that normally makes only zigzag hairs. Although Sox2 expression levels in the DP identify this subset during the morphogenetic cycle, Sox2 expression is not a fixed epigenetic state specified when the follicle is first formed.     

HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo

Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive depigmentation accelerates in response to stress. Personal trauma, contact with bleaching phenols, overexposure to UV, and mechanical injury can lead to progressive loss of melanocytes. This study was focused on the role of stress protein heat shock protein (HSP)70 for translating stress into an autoimmune disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant, preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by live cells, and in prior in vitro studies, HSP70 has been shown to activate dendritic cells and elicit an immune response to chaperoned proteins and peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was assessed in vivo in a mouse model of autoimmune vitiligo. In this model, depigmentation was introduced by gene gun vaccination with eukaryotic expression plasmids encoding melanocyte differentiation antigens. Inclusion of human and mouse-derived inducible HSP70 in the vaccination protocol significantly increased and accelerated depigmentation in this model, accompanied by the induction of prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with depigmentation. The data presented strongly support a role for HSP70i in progressive depigmentation in vivo.     

Follicule to follicule heterogeneity of sebum excretion

We have evaluated the normal variations in the sebum excretion rate from follicle to follicle on the forehead by using the noninvasive techniques of the Lipometre and Sebutape. For a given overall amount of sebum excreted to the surface of the skin during a limited period of time, both the number of active sebaceous follicles and the amount of lipids excreted by them may vary. Significant intraindividual and interindividual differences may be found for these parameters. Such a noninvasive approach to the biology of sebaceous glands represents a new tool allowing a precise evaluation of diseases of the sebum excretion and of their treatments.     

Delayed-amelanotic (DAM or Smyth) chicken: melanocyte dysfunction in vivo and in vitro

Chickens of the autoimmune delayed-amelanotic (DAM or Smyth) line develop postnatal feather amelanosis and severe visual defects, both of which are presumed to be due to a dysfunction of melanocytes and a subsequent autoimmune response that eliminates pigment cells. In this report we elucidate further the melanocytic defect. We present a morphologic analysis of the mildly affected erratic (eDAM) group of Smyth chicken whose partial depigmentation and lack of visual impairment resemble human vitiligo more so than do the complete amelanosis and blindness in the classical Smyth line. Histologically, the sequential events leading to amelanosis in the young Smyth chicken occur simultaneously in the feathers of adult eDAM Smyth chickens, and the infiltration of the feather pulp with mononuclear leukocytes correlates with the extent of local pigmentary abnormality. Cytochemical localizations of dopa-oxidase and acid-phosphatase activities in eDAM feather melanocytes suggest that melanogenesis and autophagocytosis of melanosomes occur in tandem and that the rates of both are higher in these cells than in melanocytes of normally pigmented control chickens. Assays for tyrosinase activity in feather follicles indicate a hypermelanization in eDAM feathers and in the pigmented feathers of young Smyth chicks prior to the onset of depigmentation. Finally, we report on the establishment of pure, proliferative cultures of neural crest-derived melanocytes from control and Smyth chicken embryos. The degenerative events in Smyth chicken melanocyte cultures mimic in part those of the cells in vivo and are therefore indicative of a genetic defect that is independent of the immune system.     

Human papillomavirus and skin cancer

Human papillomavirus (HPV) appears to be the most ubiquitous of the human viruses. Over 100 HPV types have been identified. A minority of HPV cause cutaneous warts and mucosal condylomata. The HPV that cause mucosal condylomata put the patient at various degrees of risk for developing cancers, particularly cervical cancer. The majority of HPV infect the skin of normal and immunocompromised individuals. In normal people, most of these HPV appear to establish a latent infection of the skin, most likely as normal flora residing in hair follicles; however, in patients with various systemic and localized depressions of cell-mediated immunity, some HPV infections appear to be involved in the development of nonmelanotic skin cancer and its precursor lesions in skin, usually in sunlight-exposed areas. Circumstantial evidence suggests that these HPV may have a role in promoting proliferative lesions of the skin, although their sites of active infection and mode of transmission to susceptible individuals remain unknown.     

Hair density in African Americans.

BACKGROUND: The meager data on normal hair density in humans have been gathered from a predominantly white population. Examination of scalp biopsy specimens from African Americans suggests that hair density in this group may be lower than in whites. This study was performed to quantify any differences between white and African American patients. DESIGN: A retrospective case series of subjects who had undergone a biopsy of clinically healthy scalp skin. The 4-mm punch biopsy specimens were sectioned, and all follicles contained within the specimens were counted at various levels (suprabulbar, isthmus, and infundibulum) to arrive at the number and type of hairs present. SETTING: Outpatient clinic in a tertiary care medical center. PATIENTS: A consecutive sample of 22 African American and 12 white patients with clinically healthy scalp skin specimens that were studied and compared with previously reported data. MAIN OUTCOME MEASURES: Patients' age and total number of follicles, terminal follicles, vellus follicles, terminal anagen hairs, and terminal telogen hairs. RESULTS: Total hair density (number of follicles per 4-mm punch biopsy specimen) and total number of terminal follicles and terminal anagen hairs were significantly lower in African Americans (P<.001) than in whites and in a previously reported, predominantly white, population. CONCLUSIONS: Hair density in African Americans is significantly lower than that in whites, which must be taken into consideration when evaluating a biopsy specimen from an African American patient. Data previously collected from white patients may not provide adequate guidance when evaluating scalp biopsy specimens from African Americans and could lead to an incorrect diagnosis.     

文眉致白癜风七例

【摘要】 目的 报道文眉所致白癜风7例。方法 收集2017年12月至2019年5月河南省人民医院皮肤科诊治的7例文眉引起的白癜风,回顾其临床特点。结果 7例患者文眉后1个月至1年出现数根眉毛变白,早期均表现为眉毛变白,眉部皮肤正常,眉周逐渐出现白斑,边界不清。眉部皮损反射式共聚焦扫描显微镜特征：基底层及毛囊周围色素缺失,真皮浅、中层可见高折光无定形物（色料）。斑贴试验：文眉色料均为阴性,十二醇硫酸钠均呈阳性。结论 文眉后引起的白癜风,早期眉部皮肤未见色素减退斑,结合眉部皮损反射式共聚焦扫描显微镜特征可减少误诊。     

THE FLAG SIGN IN THE HAIR OF AN ALCOHOLIC

A patient is presented with the “flag sign” which was associated with episodic malnutrition in an alcoholic. Diminished hair diameter, flating and loss of normal cuticle were found in areas of depigmentation but were sometimes dissociated suggesting different mechanisms within the general terms of “malnutrition”.