Surgical planing of the skin; dichlorotetrafluoro-ethane as a freezing agent

Surgical skin planing is, in the hands of an experienced operator, a safe and highly effective procedure for treating a number of cutaneous defects, most notably pitted acne scars. The operation is facilitated by the use of a new instrument (jet-spray handpiece) which allows the operator to freeze the skin and plane it almost simultaneously, and by a new freezing agent, dichlorotetrafluoro-ethane, which adds to the safety by eliminating the old hazards of inflammability, explosion, and the toxic inhalation of ethyl chloride. The ability to sharply differentiate between keloid and hypertrophic scar is fundamental to surgical skin planing. A hypertrophic scar results from the removal or destruction of the cutaneous appendages (hair follicles, oil and sweat glands and ducts); whereas a keloid is an idiosyncratic response without regard to damage of the appendages.Properly performed surgical planing does not entirely remove these appendages and therefore healing occurs without scarring.     

Dichloro-tetrafluoro-ethane as a Freezing Agent

Surgical skin planing is, in the hands of an experienced operator, a safe and highly effective procedure for treating a number of cutaneous defects, most notably pitted acne scars.The operation is facilitated by the use of a new instrument (jet-spray handpiece) which allows the operator to freeze the skin and plane it almost simultaneously, and by a new freezing agent, dichlorotetrafluoro-ethane, which adds to the safety by eliminating the old hazards of inflammability, explosion, and the toxic inhalation of ethyl chloride.The ability to sharply differentiate between keloid and hypertrophic scar is fundamental to surgical skin planing. A hypertrophic scar results from the removal or destruction of the cutaneous appendages (hair follicles, oil and sweat glands and ducts); whereas a keloid is an idiosyncratic response without regard to damage of the appendages.Properly performed surgical planing does not entirely remove these appendages and therefore healing occurs without scarring.     

Altered distribution of phospholipase C-gamma 1 in benign hyperproliferative epidermal diseases.

Phospholipase C-gamma 1 (PLC-gamma 1) is a well characterized substrate for the epidermal growth factor receptor tyrosine kinase and has been implicated in the intracellular biochemical signaling cascade which occurs following stimulation of cells with epidermal growth factor. The in vivo localization of PLC-gamma 1 was examined by immunohistochemistry in sections of normal human skin and in skin sections from a diverse series of hyperproliferative epidermal conditions (psoriasis, seborrheic keratoses, acrochordons, and margins near second-degree burns). Immunoreactive PLC-gamma 1 was detected only in the basal compartment of normal skin but was readily detectable in both the basal and outer epidermal compartment in hyperproliferative skin conditions. In addition, immunoreactive PLC-gamma 1 colocalizes with immunoreactive epidermal growth factor receptor in both normal and hyperproliferative epidermis.     

Surgical planing of the skin; evaluation of a method for reducing scars and other defects

Skin defects such as pitted acne scars, unsightly moles and birthmarks, and other disfiguring skin deformities can be effectively corrected with good cosmetic results. This is accomplished as an office procedure by abrading or planing the skin with a rapidly rotating wire brush using a local anesthetic. The treatment does not require hospitalization and is relatively simple and painless.     

Evaluation of a Method for Reducing Scars and Other Defects

Skin defects such as pitted acne scars, unsightly moles and birthmarks, and other disfiguring skin deformities can be effectively corrected with good cosmetic results. This is accomplished as an office procedure by abrading or planing the skin with a rapidly rotating wire brush using a local anesthetic. The treatment does not require hospitalization and is relatively simple and painless.     

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Most in vitro studies in experimental skin biology have been done in 2-dimensional (2D) monocultures, while accumulating evidence suggests that cells behave differently when they are grown within a 3D extra-cellular matrix and also interact with other cells (1-5). Mouse models have been broadly utilized to study tissue morphogenesis in vivo. However mouse and human skin have significant differences in cellular architecture and physiology, which makes it difficult to extrapolate mouse studies to humans. Since melanocytes in mouse skin are mostly localized in hair follicles, they have distinct biological properties from those of humans, which locate primarily at the basal layer of the epidermis. The recent development of 3D human skin reconstruct models has enabled the field to investigate cell-matrix and cell-cell interactions between different cell types. The reconstructs consist of a "dermis" with fibroblasts embedded in a collagen I matrix, an "epidermis", which is comprised of stratified, differentiated keratinocytes and a functional basement membrane, which separates epidermis from dermis. Collagen provides scaffolding, nutrient delivery, and potential for cell-to-cell interaction. The 3D skin models incorporating melanocytic cells recapitulate natural features of melanocyte homeostasis and melanoma progression in human skin. As in vivo, melanocytes in reconstructed skin are localized at the basement membrane interspersed with basal layer keratinocytes. Melanoma cells exhibit the same characteristics reflecting the original tumor stage (RGP, VGP and metastatic melanoma cells) in vivo. Recently, dermal stem cells have been identified in the human dermis (6). These multi-potent stem cells can migrate to the epidermis and differentiate to melanocytes.     

Surgical planing of the skin; complications and reevaluation of indications

One hundred plastic planing operations on the skin by means of a motor-driven wire brush were reviewed. Complications noted were pruritic erythematous eczematous dermatitis on a possible autosensitization basis, hyperpigmentation and milia. These occurred in a small proportion of cases and in no case were they permanent sequelae. Flat postacne scarring is more easily improved than steep "ice-pick" type scars. The planing procedure is contraindicated in the management of certain tumors of the skin, portwine nevi, decorative tattoos, and generalized dermadromes. The psychiatric and emotional impact of the patient's scarring on his personality is often a great one and the operator must bear in mind that plastic planing is no panacea for a severely neurotic patient. Therefore it is important that patients be carefully selected and that improvement rather than complete cure be stressed.     

A quantitative histochemical study of three oxidative enzymes in solar keratoses and Bowen's disease

Synopsis Succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) activities have been studied using quantitative enzyme histochemical techniques in the epidermis of five patients with solar keratoses and Bowen's disease. Non sun-exposed buttock skin was compared with the skin from the actual lesion and adjacent, clinically normal paralesional skin. SDH activity was significantly increased in the basal layer and decreased in the granular layer in the epidermis of both lesion and paralesional skin, although the total epidermal activities were unchanged when compared to non-exposed buttock skin. G6PDH activity was increased in the granular layer of paralesional epidermis and of lesions. No change in LDH activity was detected. Inclusion of phenazine methosulphate in the reaction mixtures resulted in a three-fold increase in formazan deposition without altering the localization.It is concluded that the quantitative changes and alteration in localization of SDH and G6PDH reported in solar keratoses are accompanied by similar changes in adjacent, clinically normal sun-exposed skin and differ from normal non-exposed skin. It is suggested that these changes may precede the development of the solar keratoses and that these findings may indicate a significant metabolic alteration in the events that lead to neoplasia.     

Monoclonal antibodies to native basement membranes reveal heterogeneous immunoreactivity patterns

In this paper we describe the development of basement membrane (BM) reactive monoclonal antibodies (MA), by immunization of mice with intact denuded BM. The MA raised against denuded amniotic BM (clones 1052, 1053 and 1065) showed heterogeneous staining patterns. MA 1052 and 1053 reacted with epithelial BM of the epidermis and epidermal adnexa and furthermore with the epithelial alveolar BM in the lung and the superficial part of the epithelial BM in the gastrointestinal tract. MA 1065 showed immunoreactivity with the epithelial BM of epidermis and epidermal adnexa and the epithelial BM of trachea and oesophagus, and furthermore pericellular staining of the basal keratinocytes and basal corneal epithelial cells. MA 1087, raised against human glomerular BM, showed immunoreactivity with all BM, except the central epithelial BM in the cornea. The precise localization of the target epitopes in the BM was investigated on chemically cleaved human skin. Reactivity for the MA occurred predominantly in the BM lamina adherent to the dermis, suggesting that the target epitopes reside in the lamina densa and/or lamina fibroreticularis. We furthermore examined the nature of the epitopes by preincubation of tissue sections with various enzymes prior to immunohistochemistry. The reactivity of the target epitopes was not affected by bacterial collagenase, but after various protease treatments the reactivity disappeared, suggesting that the epitopes are not localized on the triple helical part of collagenous proteins.     

Monoclonal antibody analysis of skin in chronic murine graft vs host disease produced across minor histocompatibility barriers

Chronic graft vs host disease (GVHD) across minor histocompatibility barriers was produced in BALB/c mice by the injection of spleen cells from B10.D2 mice. Changes in the skin were analyzed in frozen sections using a panel of monoclonal antibodies detected by immunoperoxidase methods. Compared to control animals, a number of changes occurred in the skin of animals with chronic GVHD. In the epidermis, there were increased numbers of Thy-1-positive dendritic cells; keratinocytes expressed Thy-1 and Ia antigens. T lymphocytes appeared in both dermis and epidermis. In the early stages, cells with "helper" and "suppressor" phenotypes were present, while at later times "helper" cells remained in the epidermis and "suppressor" cells remained in the dermis. Cells bearing markers of macrophages were prominent in both dermis and epidermis after the second week. Of great interest was the appearance of spindle-shaped cells in the dermis which expressed Thy-1 and Ia. These cells resembled fibroblasts which may be activated to produce the excess collagen seen in the skin of chronic GVHD.     

Neuroimmunoregulation of androgens in the adrenal gland and the skin

Human adrenals produce large quantities of androgens, especially DHEA which is the most abundant circulating hormone in the human body. Adrenal androgens are regulated by several factors, including pituitary ACTH and an intricate intraadrenal network involving immune cells, cytokines and neuroendocrine factors. The skin is a major target of androgens and androgen receptors are expressed in the epidermis, dermis, sebaceous glands and hair. In addition, the skin has the capacity to metabolize androgens into more powerful compounds. Similar to the adrenal gland, there is an intradermal neuro-immune network involving the local expression of cytokines and neuropeptides. Dysregulation of androgens in the adrenals and/or the skin is associated with acne, hirsutism and androgenic alopecia. Therefore, understanding the mechanisms of these intricate networks is of both basic and clinical relevance and may help to develop new strategies for the treatment of androgen-dependent skin disorders.     

Monoclonal antibodies to native basement membranes reveal heterogeneous immunoreactivity patterns

Summary In this paper we describe the development of basement membrane (BM) reactive monoclonal antibodies (MA), by immunization of mice with intact denuded BM. The MA raised against denuded amniotic BM (clones 1052, 1053 and 1065) showed heterogeneous staining patterns. MA 1052 and 1053 reacted with epithelial BM of the epidermis and epidermal adnexa and furthermore with the epithelial alveolar BM in the lung and the superficial part of the epithelial BM in the gastrointestinal tract. MA 1065 showed immunoreactivity with the epithelial BM of epidermis and epidermal adnexa and the epithelial BM of trachea and oesophagus, and furthermore pericellular staining of the basal keratinocytes and basal corneal epithelial cells. MA 1087, raised against human glomerular BM, showed numunoreactivity with all BM, except the central epithelial BM in the cornea. The precise localization of the target epitopes in the BM was investigated on chemically cleaved human skin. Reactivity for the MA occurred predominantly in the BM lamina adherent to the dermis, suggesting that the target epitopes reside in the lamina densa and/or lamina fibroreticularis.We furthermore examined the nature of the epitopes by preincubation of tissue sections with various enzymes prior to immunohistochemistry. The reactivity of the target epitopes was not affected by bacterial collagenase, but after various protease treatments the reactivity disappeared, suggesting that the epitopes are not localized on the triple helical part of collagenous proteins.Presented in part at the 20th Annual Symposium of the Histochemische Gesellschaft, Basel, September 1987     

DERMABRASIVE ABLATION OF ACNE SCARS

Dermabrasion offers cosmetic improvement of acne pits and scars, but only well-adjusted patients should be selected for this esthetic improvement. In the dermabrasion operation the deep cup-shaped pits are made shallow by saucerization, for the deep sharp shadows are eliminated as the pits are shallowed. It is the elimination of the shadow effect which is so gratifying to the patient.Although dermabrasion is a superficial skin operation, it involves dangerous instruments and thousands of minute incisions. The procedure is a surgical operation, whether done in an office or in a hospital. The author performs the operation entirely as a hospital procedure, using pentothal anesthesia with meperidine added in small increments during the operation. Thus the operation may be unhurriedly and meticulously performed.     

Dynamic nature and function of epidermal Langerhans cells in vivo and in vitro: a review, with emphasis on human Langerhans cells.

Summary Epidermal Langerhans cells (LC) are Birbeck granule-containing bone-marrow-derived cells, which are located mainly in the suprabasal layer of the epidermis. They can be readily identified by their strong expression of CDIa and MHC class II molecules. In addition to these classical properties, an extensive phenotypic profile of normal human LC, summarized in this review, is now available. The powerful capacity of LC to activate T lymphocytes is clearly documented and, to date, LC are recognized as the prominent antigen-presenting cells of the skin immune system. They are generally believed to pick up antigens encountered in the epidermis and to migrate subsequently from the epidermis to the skin-draining lymph nodes. Upon arrival in the paracortex of lymph nodes, the antigen-laden LC transform into interdigitating cells and they present antigen to naive T lymphocytes in a MHC class II-restricted fashion; this results in the generation of antigen-specific immune responses. It has also been demonstrated that transformation of LC into interdigitating cells occurs when LC are culturedin vitro. Bothin vivo andin vitro studies have indicated that properties of LC, such as phenotype, morphology and the stimulatory potential to activate T lymphocytes, are dependent on the local microenvironment in which the LC reside. The essential role of LC in the induction of contact allergic skin reactions and skin transplant rejection is well established.     

Expression of acyl-CoA synthetase 5 in human epidermis

The human epidermis is characterized by a constant renewal of keratinocytes embedded in a matrix enriched with lipids. Numerous proteins involved in lipid metabolism are found in human epidermis, especially in keratinocytes. Long-chain acyl-CoA derivatives, which are catalyzed by human ACSL5, are important metabolites in several biochemical pathways, including ceramide de novo synthesis. The aim of the present study was to investigate expression of acyl-CoA synthetase isoform 5 (ACSL5) in human epidermis by an in situ, as well as a molecular approach. We show that ACSL5 mRNA and protein are found in human epidermis, as well as in non-differentiated and differentiated HaCaT cells. Keratinocytes of stratum spinosum are the main source for ACSL5 expression in both meshed facial or abdominal skin and ridged skin of upper or lower extremities including TUNEL-positive cells in upper cellular layers. Single keratinocytes of chronic solar-exposed meshed facial epidermis occasionally display a stronger ACSL5 immunostaining. In conclusion, our study indicates that epidermal ACSL5 expression might be involved in differentiation and the stress response of keratinocytes.     

Understanding the melanocyte distribution in human epidermis: an agent-based computational model approach

The strikingly even color of human skin is maintained by the uniform distribution of melanocytes among keratinocytes in the basal layer of the human epidermis. In this work, we investigated three possible hypotheses on the mechanism by which the melanocytes and keratinocytes organize themselves to generate this pattern. We let the melanocyte migration be aided by (1) negative chemotaxis due to a substance produced by the melanocytes themselves, or (2) positive chemotaxis due to a substance produced by keratinocytes lacking direct physical contact with a melanocyte, or (3) positive chemotaxis due to a substance produced by keratinocytes in a distance-to-melanocytes dependent manner. The three hypotheses were implemented in an agent-based computational model of cellular interactions in the basal layer of the human epidermis. We found that they generate mutually exclusive predictions that can be tested by existing experimental protocols. This model forms a basis for further understanding of the communication between melanocytes and other skin cells in skin homeostasis.     

FGFR3 Mutations in Benign Skin Tumors

Activating FGFR3 germline mutations cause skeletal dysplasia and craniosynostosis syndromes. Somatic FGFR3 mutations have been identified in several cancer entities such as urothelial carcinoma and multiple myeloma. Recently, the same FGFR3 mutations known from skeletal dysplasia syndromes and urothelial carcinoma have been shown to cause benign human skin tumors such as seborrheic keratoses and epidermal nevi. The underlying mechanisms for the somatic FGFR3 mutations in the epidermis are unknown so far, as well as details of the involved signaling pathways in the mutant keratinocytes leading to the formation of acanthotic skin tumors. Herein we discuss potential mechanisms and functional consequences of activating FGFR3 mutations in human skin. Further studies are required to provide insights in the pathogenesis of benign skin tumors caused by FGFR3 mutations. These studies will add to new non-invasive therapeutical strategies for benign acanthotic skin tumors in dermatology.