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Presents an abstract of the article "Are Moles Just Naevus Cells?," by C. B. Bentley-Phillips and R. Marks.

Presents an abstract of the article "Identification of Lymphoid Cells in the Cutaneous Infiltrate of Skin Reticuloses and Lichen Planus," by R. S. -H. Tan, J. P. Hayes and N. A. Byrom.

Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in bumans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA. were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to tbe infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of bumans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens. [ABSTRACT FROM AUTHOR]

There is considerable evidence that electrolytes can penetrate the stratum corneum but there is no evidence on whether this penetration occurs through or between the corneum cells. In this paper evidence is presented which shows that the equilibrium water content of intact corneum immersed in electrolyte solutions depends upon the electrolyte concentration and obeys the laws of osmosis. Removal of lipid by solvent extraction destroys the osmotic properties. This evidence indicates that the osmotic properties of corneum depend upon the presence of a lipid-containing semipermeable membrane system. Other evidence indicates that this membrane system is the cell walls of the corneum cells themselves. If electrolytes cannot enter the corneum cells in these osmotic experiments it follows that they cannot enter the corneum cells during penetration through the stratum corneum and that they must therefore pass between the cells. [ABSTRACT FROM AUTHOR]

In a case of pyoderma gangrenosum without associated disease, clumping of cells was noted during routine leucocyte counts. It was probably due to a cryoglobulin in the patient's plasma. [ABSTRACT FROM AUTHOR]

The article discusses the paper "The Problem of Cellular Naevi," by C. Voss. This paper concludes that the cellular naevus is a complex neurogenic malformation, of neuroectodermal and neuromesodermal origin. Dendritic chromatophores and dendritic cells belong to the same system.

The nature of melanocytic naevi is unknown notwithstanding their considerable significance for clinician and pathologist and despite the wealth of existing knowledge about melanocyte biology.To investigate how far a simple mutational model can explain the clinical and pathological features of melanocytic naevi, in particular their pattern of onset and frequency.I have constructed a model of the development of the adult melanocyte population from a single stem cell. The total cutaneous melanocyte population in a human adult is already known, as well as the range of spontaneous mutation rates at a given gene site. For each cycle of mitosis during the post stem-cell expansion of the melanocyte population, I calculate the accumulated number of cells likely to be mutated at a particular (although unknown) gene site. The results are interpreted in the light of a hypothesis that each of these mutant melanocytes will go on to form a melanocytic naevus. Comparisons are made with neurofibromas, occurring in type 1 neurofibromatosis and as sporadic lesions.A single genetic mutation in melanocyte precursors is found to be sufficient to explain the clinical and pathological features of melanocytic naevi.I propose that melanocytic naevi are a consequence of single spontaneous genetic mutations which inevitably occur during the development of the adult population of cutaneous melanocytes. [ABSTRACT FROM AUTHOR]

This article presents information about the research paper entitled "Psoriatic fibroblasts fail to induce epidermal hyperplasia," presented by W. R. Otto and R. Dover at the British Society for Investigative Dermatology Annual Meeting, Cambridge, September 1987. The role of the dermal component may be important in the development of the psoriatic lesion. These workers embedded full thickness biopsies from psoriatic skin into collagen gels seeded with normal or psoriatic fibroblasts, and obtained increased keratinocyte outgrowth from the latter. However, no control was made for the influence of the biopsy dermal remnant, nor was a histological analysis made.

This article presents information about the research paper entitled "Survival of sex-mismatched cultured allogenic keratinocytes in the treatment of shaved tattoos assessed by a biotinylated Y probe," presented by Anne Brain, P. Coates, and Trisha Purkis at the British Society for Investigative Dermatology Annual Meeting, Cambridge, September 1987. There was no evidence of survival of male cells in the biopsies of the female recipients and the percentage of male cells in the biopsies of male recipients was within the normal range. Therefore, there is no evidence of survival of allogenic keratinocytes from 1 week after their use as skin grafts and beneficial results must result from a biological dressing effect.

This article presents information about the research paper entitled "Cellular sensitivity to UVA in photosensitivity dermatitis/actinic reticuloid (PD/AR)," presented by B. E. Johnson, E. M. Walker, J. Ferguson and W. Frain-Bell and others at the British Society for Investigative Dermatology Annual Meeting, Cambridge, September 1987. Cells from subjects with actinic reticuloid are reported to be more UVA sensitive than those from normals. They have therefore compared the UVA sensitivity of fibroblasts from 18 subjects with clinical, phototest and patch test evidence for the diagnosis of photosensitivity PD/AR with that of cells from 16 non-photosensitive controls.

The article focuses immunological abnormalities in patients with candidiasis and their relationship to severity of infection. Full immunological assessment has been performed on six patients with persistent oral candidiasis and compared with three patients with diffuse chronic mucocutaneous candidiasis, and a father and daughter with familial chronic mucocutaneous candidiasis. The only abnormality detected in non-specific tests of immunological function was that of low levels of E rosette forming cells in all five patients with familial or diffuse mucocutaneous candidiasis.

Different chemicals that specifically and selectively inhibit or activate protein kinases have been used to define the possible roles of these enzymes in the different steps of epidermal differentiation. Using HaCaT keratinocytes as a model, and under conditions in which cell proliferation is minimally affected, we found that tyrosine kinase inhibition leads to an inhibition of early (spinous; keratin k10 expression) and late (granulosum; involucrin expression) differentiation processes. cGMP- and cAMP-dependent protein kinases appear to modulate the transition from spinous to granular differentiation, a process which seems to be negatively controlled by protein phosphatases. Finally, enzymes belonging to the protein kinase C family appear to facilitate the transition from spinous to granular differentiation programmes while inhibiting the early steps of epidermal differentiation. [ABSTRACT FROM AUTHOR]

Adherence of Malassezia yeast cells to human keratinocytes was assessed by a novel technique using double-sided Sellotape. Although adherence using double-sided Sellotape is still merely a model for in vivo adherence. It approximates to the conditions found on the skin surface. There were no differences in adhesive properties to human keratinocytes between Malassezia strains originating from HIV-positive and HIV-negative patients with seborrhoeic dermatitis, nor was there a relationship between the severity of seborrhoeic dermatitis and in vitro adherence to human keratinocytes. [ABSTRACT FROM AUTHOR]

We have previously identified a novel 105-kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune-mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non-lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western-blotted proteins revealed that a comigrating 105-kDa protein is present in both cytosol extracts (n = 6) and conditioned media (n = 3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defective in vivo expression of this novel 105-kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105-kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed. In any case, the reduced in vivo expression of the 105-kDa protein represents additional evidence for a defect in BMZ composition in dystrophic EB which extends to a number of molecular components. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the fact that several cell types residing in or travelling through the skin are targets and/or sources of nerve growth factor (NGF), little is known about the role of NGF in skin development, physiology and disease. Employing a previously defined skin organ culture assay for studying the proliferation of murine keratinocytes in their natural tissue environment, we have assessed the effect of murine NGF (7S) on keratinocyte proliferation in intact skin derived from two defined stages of the murine hair cycle. We found that 10–200 ng/ml NGF stimulated epidermal keratinocyte proliferation in organ-cultured C57 BL-6 mouse skin in the telogen phase of the hair cycle. Follicle keratinocyte proliferation was stimulated by 100 ng/ml NGF in telogen skin organ culture, but this concentration of NGF inhibited both epidermal and follicle keratinocyte proliferation in organ culture of anagen skin. The latter inhibitory effect of NGF was abrogated by co-incubation with neutralizing anti-NGF antibodies or with the protein kinase C inhibitor staurosporine. The proliferation-modulatory effects of NGF were associated with the induction of significant mast cell degranulation. and were inhibited by cromoglycate co-administration. This is the first report of a modulatory. hair cycle-dependent effect of NGF on keratinocyte proliferation in situ. which may require the presence of mast cells. Our study supports the notion of auto- and paracrine functions of NGF in murine skin physiology, which can be further assessed in the physiologically relevant mouse model delineated here. [ABSTRACT FROM AUTHOR]

Dynamic expression of pemphigus antigens by cultured human and mouse keratinocytes was compared with that of desmosome-associated molecules and cellular markers relating to epidermal differentiation. Plakoglobin was detected in localized areas of keratinocyte sheets in low Ca2+ (0.15 mM) KGM medium. In minimum essential medium (MEM) containing 1.8 mM Ca2+, plakoglobin was expressed in the intercellular spaces (ICS) throughout the keratinocyte sheet. Desmoplakin I and II, which were present in the cytoplasm of keratinocytes in the low Ca2+ medium, moved to the cell surface after the medium was changed to MEM. Desmoglein 1 and pemphigus vulgaris (PV) antigens were observed in the ICS of both the monolayers and stratified areas in the MEM. Pemphigus foliaceus (PF) antigens, frequently together with desmoglein 1, involucrin and keratins specific for the upper layer of the epidermis, were expressed by stratified keratinocytes but not the cells in the monolayers. The Western blotting study of the cultured keratinocyte extract showed 160- and 1 30-kDa bands positive for desmoglein 1 antigens and a 130-kDa band stained with PV sera. These findings suggest that although desmoglein 1 molecules bear PF antigenic sites, their expression pattern by cultured keratinocytes is closely related to that of PV rather than PF antigens. The PF antigenic sites may be formed on desmoglein 1 during epidermal differentiation. [ABSTRACT FROM AUTHOR]

Interferon-γ (IFN-γ) induces major histocompatibility complex (MHC) class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression on human epidermal keratinocytes. Griseofulvin, an extensively used antifungal agent, has been used effectively in the treatment of lichen planus, in which keratinocytes express both HLA-DR and ICAM-1 antigens. In this study, we investigated the effect of griscofulvin on IFN-γ-induced MHC class II antigen and ICAM-1 expression of keratinocytes, and demonstrated that griseofulvin decreased IFN-γ-induced HLA-DR but not ICAM-1 expression. [ABSTRACT FROM AUTHOR]

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Nonspecific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics. [ABSTRACT FROM AUTHOR]

We report two patients with chronic, recurrent, nodular panniculitis lesions that later developed areas of lipoatrophy. Histologically, there was a consistent lobular lipophagic replacement of fat cells with lipophagic giant cells. The clinical appearance was that of tender, erythematous. superficial or subcutaneous, symmetrical nodules and plaques of 1-2 weeks' duration. The lesions could occur with episodes of fever. One patient had hepatomegaly and the other had an increased sedimentation rate and leucocytosis. The histology and the clinical pattern of the panniculitus syndrome resembled those of lipophagic lipoatrophy of childhood. This is a panniculitis of unknown cause in which the principal inflammatory cell response in the subcutaneous tissue is the macrophage. [ABSTRACT FROM AUTHOR]

The mechanism of the occurrence of natural antikeratin antibodies in human sera was studied using hybrid spleen cells obtained from experimentally naive or from immunized mice. Antikeratin antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 5.9-9.5% of the culture supernatants of fused spleen cells taken from naive mice. When mice were immunized with keratins, the number of supernatants containing antikeratin antibodies was increased to eight out of 51 (15.7%). When immunized with non-keratin materials such as activated human T cells, adult T-cell leukaemia cell lysates, and human T-cell lymphotropic virus type-1 (HTLV-1), 16.7-20.8% of the supernatants were found to contain antikeratin antibodies by ELISA. The antikeratin antibodies in the supernatants showed cytoplasmic staining of keratinocytes in human as well as mouse skin by indirect immunofluorescence. The antibodies reacted with extracted human epidermal keratins by dot-blot and Western blot analysis. Most antikeratin antibodies in the supernatants did not show cross-reactivity with exogenous antigens used for immunization and vimentin-type intermediate-sized filaments. These findings demonstrate that B cells producing antikeratin antibodies are common in naive mice, and produce various types of antikeratin antibodies following specific activation with epidermal keratins and non-specific immunological stimuli. [ABSTRACT FROM AUTHOR]

Normal human keratinocytes and the keratinocyte-derived cell lines NCTC 2544 and A 431, were exposed for different periods (1–5 days) to various concentrations (0.023–46.6 μg/ml) of nickel (Ni2+). A dose- and time-dependent inhibition of cell growth and viability was observed. Cultures exposed to 2.3 μg Ni2+/ml showed approximately 50% cell survival at 5 days. An increase in release of interleukin 1 by keratinocytes was detected following culture for 24 h with a Ni2+ concentration of 2.3–11.5 μg/ml. Short periods of incubation (30 min) with these concentrations induced an activation of lipoxygenase in leucocytes from healthy subjects, without modifying cell viability. The results suggest that the percutaneous penetration of small amounts of Ni2+ can result in damage to keratinocytes and can initiate sensitization. [ABSTRACT FROM AUTHOR]

Foetal antigen 2 (FA-2) is a connective-tissue-associated antigen isolated from second trimester human amniotic fluid. FA-2 has an α-electrophoretic mobility and is a single-chain molecule with a molecular weight of 26 kDa as determined by polyacrylamide gel electrophoresis (PAGE). Using indirect immunofluorescence and the immunoperoxidase technique, FA-2 was found to be in the lamina densal sublamina densa region of the basement membrane zone (BMZ) in adult as well as in foetal skin. FA-2 was found throughout the dermis in beta! skin, whereas in adult skin it was found to be associated with the BMZ and around the blood vessels, hair follicles and eccrine glands. Intracellular FA-2 antigen was demonstrated in proliferating fibroblasts by the indirect immunoperoxidase technique and immunoelectron microscopy of the fibroblasts revealed staining of the antigen in the cisternae of the rough endoplasmatic reticulum at the trans-side of the Golgi complex as well as in vesicles close to the plasma membranes. FA-2, a hitherto undescribed antigen associated with human BMZ, is probably being synthesized by proliferating fibroblasts. [ABSTRACT FROM AUTHOR]

A case of infantile digital fibromatosis (IDF) in a 3-year-old girl is reported. Two tumours were present on the left fourth toe and one over the lateral aspect of the left heel. Histological examination revealed that the turnout cells contained intracytoplasmic inclusion bodies, characteristic for this condition. The tumours showed spontaneous regression without therapy. [ABSTRACT FROM AUTHOR]

We investigated the co-distribution of lymphocyte subpopulations and non-lymphoid ‘accessory’ cells in 35 cases of cutaneous lymphoproliferative diseases (T-cell lymphoma, 10 cases; B-cell lymphoma, 17 cases; pseudolymphoma, 8 cases) using immunohistochemical methods. T-zone histiocytes and particularly Langerhans cells were abundant in all cutaneous T-cell lymphomas, but were also found in B-cell lymphomas. T-zone histiocytes were associated with T-lymphocytes, especially T-helper cells., but not with T-suppressor cells. Dendritic rcticulum cells were essentially confined to well differentiated germinal centres. Macrophages occurred in both lymphomas and pseudolymphomas without definite relationship with either B- or T-cells. In malignant lymphomas of high grade malignancy, macrophages represented the only non-lymphoid cell type. Our results indicate that malignant lymphoid cells, like normal lymphocytes, require definite micro-environments which are, at least in part, maintained by certain non-lymphoid cells. [ABSTRACT FROM AUTHOR]

We Studied the localization of P230, an immunoanalogue of erythroid α-spectrin, in normal and psoriatic human epidermis and in cultured human keratinocytes. In immunofluorescence microscopy of frozen sections of normal human skin a bright cytoplasmic staining was seen in the cortical area of the keratinocytes. Similar staining was also seen in lesional and uninvolved areas of psoriatic epidermis. The pericytoplasmic localization of P230 could also be seen in cultured human keratinocytes: a lamina-like reticular staining was seen mostly confined to the ventral cytoplasmic aspect and to junctional areas of the cells. Immunoblotting of electrophoretically separated polypeptides of epidermal cells revealed a distinct polypeptide of Mr 230 kD. The results indicate that α-spectrin-like polypeptides form a major cytoskeletal framework in human epidermal ceils in both normal and psoriatic skin. [ABSTRACT FROM AUTHOR]

Melanocytes isolated from normal adult human skin were cultured in vitro. Separation of the epidermis from the dermis by trypsin flotation proved better than collagenase treatment for providing viable cultures of melanocytes with a minimum of fibroblast contamination. Centrifugation on a discontinuous, rather than a continuous Percoll gradient, was more efficient in separating the epidermal cell types. Most of the melanocytes were usually found in one particular layer, and most of the viable keratinocytes were in the sediment. None of the layers produced a uniformly high percentage of melanocytes on routine culture, but enriched melanocyte cultures could be obtained by seeding the epidermal cells in magnesium- and calcium-free medium for 24 to 48 hours, and then transferring them to fibroblast-conditioned medium containing horse serum and polyamines. Melanocytes were identified by their dendritic morphology, ultrastructure, reaction to cholera toxin and pigment production after treatment with melanocyte stimulating hormone. Pure cultures of melanocytes have been cultivated by this method for more than 43 weeks (ten passages). [ABSTRACT FROM AUTHOR]

Interferon-like activity could be detected in the sera of nineteen psoriatic patients (interferon titres between 8 and 64 i.u./ml), whereas healthy controls were negative. Following PUVA treatment the interferon levels increased significantly (interferon titres between 32 and 128 i.u./ml). An enhanced interferon production could explain some of the immunological phenomena connected with PUVA treatment. Interferon (IFN) has been detected in the circulation of patients with auto-immune diseases (Skurkovich & Eremkina, 1975; Hooks et al., 1979; Ohno et al., 1982) and this prompted us to look for IFN activity in the sera of psoriatic patients and to study its response to PUVA therapy. According to Lindner-Frimmel (1974) and Mozes & Vilček (1974), ultraviolet radiation should be capable of potentiating an induced IFN production in human cells. [ABSTRACT FROM AUTHOR]

The antigenicity of premelanosomes, which are specific organelles for melanin biosynthesis in the cytoplasm of malignant melanoma cells, has been revealed by the blastogenic responses of lymphocytes from melanoma-bearing Syrian (golden) hamsters, using the lymphocyte stimulation assay. The lymphocytes from these hamsters have also been found to exhibit cytotoxic effects on cultured melanoma cells as shown by the microcytotoxic assay technique. [ABSTRACT FROM AUTHOR]

A method is proposed for the evaluation of the cell cycle time of in vivo steady state populations. It requires only an accurate estimation of either the labelling index or the mitotic index and an approximate evaluation of the period between the initiation of the S phase and the completion of mitosis. The method proposed takes into account the fact that the cell cycle is non-deterministic, the angle at which cells divide and the effect of cell extrusion from the basal layer, plus the fact that the cells can only be extruded when in certain phases of the cell cycle. Limitations of other methods recently reported are discussed. [ABSTRACT FROM AUTHOR]

Stratum corneum was removed from the surface of pig skin using a wet brushing technique. The material so obtained was fractionated into cell clumps, discrete cells and fine material by differential filtration through nylon gauzes. Ceramide, cholesterol and free fatty acid accounted for about 95% of the lipid present in each fraction: phospholipid and glycolipid were not detected. Material removed by successive brushings showed no detectable differences in lipid composition. [ABSTRACT FROM AUTHOR]

Examines the effects of anthralin and analogues on growth and thymidine incorporation in human skin fibroblasts. Manifestation of psoriasis by excessive scaling due to epidermal hyperplasia; Inhibition of cellular DNA synthesis; Comparison of the benefits of anthralin and its oxidative decomposition products.

An infant with GM1 gangliosidosis was found to have an eruption at birth consisting of extensive and unusual slate blue macules resembling mongolian spots. All areas of skin were involved except face, scalp, palms, and soles. A biopsy of a macule obtained at 5 months of age demonstrated melanocytic cells in the dermis consistent with mongolian spot but also a perivascular bistiocytic infiltrate. At 8 months of age, absence of β-galactosidase activity was documented in both peripheral leukocytes and skin fibroblasts confirming the diagnosis of GM1 gangliosidosis. The dermal histiocytic cells noted on skin biopsy were interpreted as a manifestation of this storage disease. The coexistence of the hyperpigmented lesions and the heritable enzyme defect was believed to be coincidental. [ABSTRACT FROM AUTHOR]

For the first time a method for culturing human hair follicle cells is described. The bovine eye lens capsule, a basement membrane-like structure, is used as the substrate for the cultures. In a culture medium supplemented with hydrocortisone and insulin about 70% of the original follicles will form growing colonies of diploid keratinocytes. [ABSTRACT FROM AUTHOR]

Double fertilization of the egg may lead to a chimaeric state, in which the cell composition of the individual derives from two zygotes. Some special types of naevoid hyperpigmentation may result Two new cases are added to the three published cases of chimaerism with skin manifestations. [ABSTRACT FROM AUTHOR]

360 nm ultraviolet light (UVA) plus coal tar depresses mitosis and DNA synthesis in epidermal cells. UVA has no effect by itself. In some models coal tar alone can partially depress DNA synthesis. 254 nm ultraviolet light (UVC) .and 290-320 nm ultraviolet light (UVB) do not enhance depression of DNA synthesis by coal tar. Dithranol will suppress mitosis and DNA synthesis of epidermal cells but there appears to be no photo-activation by UVA. Dithranol suppression and suppression of DNA synthesis by UVB or UVC are additive when used together. [ABSTRACT FROM AUTHOR]

Fractions of IgG from sera of patients with pemphigoid and pemphigus added to monolayer cultures of mouse epidermal cells resulted in a sparse distribution of cells. Direct immunofluorescence studies of these monolayers revealed epidermal cell surface antigens reacting with pemphigoid and pemphigus antibodies. We suggest that these antibodies may bind to epidermal cell surface antigenic molecules which are important in maintaining epidermal cell adhesion in culture. [ABSTRACT FROM AUTHOR]

An ultrastructural dopa reaction, with glutaraldehydeaformaldehyde prefixation, was carried out on ten specimens of malignant melanoma showing a wide variation in melanosomal morphology. All tumours, but only a minority of tumour cells, contained reaction product. In all tumours the reaction product was distributed similarly in the Golgi apparatus and Golgi associated endoplasmic reticulum (GERL). However, differences were noted in its deposition in melanosomes. Whereas vacuolar and lamellar profiles sometimes contained reaction product, it was not seen in normal, granwar and abortive melanosomes. Tumour cells without metanosomes were also seen to contain reaction product. [ABSTRACT FROM AUTHOR]

A primary (non-allergic) inflammatory response was elicited in the skin of albino rats by exaggerated application of sodium laurate solution, and the liberation of histamine, a known mediator of cutaneous inflammation in many species, was studied by a histofluorimetric stain specific for this amine which forms a complex with orthophthalaldehyde. Within the first 2 h after irritation both the epidermis and the upper dermis exhibited widespread diffuse, extracellular yellow fluorescence of the histamine- orthophthalaldehyde complex; dilated blood vessels and many fibroblasts were also fluorescent. The extracellular and vascular staining increased in intensity up to about 6 h and then gradually faded. By about 12 h after irritation, yellow histamine fluorescence was located only as a narrow band in the upper dermis close to the dermo-epidermal junction. The fluorescence was probably contained within cells, tentatively identified as leukocytes. Other than occasional mast cells in deeper regions of the dermis, no other histamine-fluorescent cells were seen throughout the response. None of these features was observed in normal, control rat skin treated only with distilled water, and routinely we failed to observe more than just an occasional fluorescent mast cell in irritated or control skin alike. The morphological features of the inflammation closely resembled those described by others for chemical irritation of skin. This study indicates the presence of histamine in the early stages of cutaneous inflammation of the rat, and suggests routes of its dispersal at later stages, when other inflammatory mediators are known to be involved. [ABSTRACT FROM AUTHOR]

The effect of dexamethasone on the regeneration of new epithelium over the base of an excised suction blister has been studied over a period of 9 days. It was found that dexamethasone did not significantly affect the migration of epidermis over the blister base but it did significantly reduce the number of cells in DNA synthesis and post wounding acanthosis of wound edge and regenerating epithelium. In order to develop drugs which influence wound healing it is necessary to have a technique which can measure its rate of progress. One of the greatest problems in this area is the complexity of the wound healing process: collagen formation, clot removal, tissue refashioning and re-epithelialization all play a role. We believe that a wound of the skin remains a wound as long as it is uncovered by mature functioning epidermis. We are therefore attempting to understand the process of re-epithelialization and have produced a model in which it can be easily measured. The model that we have chosen is that of the re-epithelializing area produced by suction blistering in the hairless hamster. [ABSTRACT FROM AUTHOR]

Lymphocytes from healthy human donors were used as a model system for studying the combined effect of 8-methoxypsoralen (8-MOP) plus UVA. Two hours after oral administration of therapeutic doses of the drug enough 8-MOP was taken up in vivo by the circulating peripheral lymphocytes to cause significant inhibition of phytohaemagglutinin induced lymphocyte proliferation when the cells were exposed in vitro to UVA irradiation. The inhibition of proliferation as monitored by a reduced ³H-thymidine incorporation into cellular DNA was shown to be UVA-dose dependent. Control cultures of 8-MOP containing lymphocytes which were not UVA irradiated showed normal blast transformation. In lymphocytes obtained from the same donors prior to 8-MOP intake, PHA-induced lymphocyte transformation was not impaired by UVA irradiation. In 8-MOP containing lymphocytes exposed repeatedly to UVA during the 72 h culture period a cumulative effect of irradiation could be observed. A varying sensitivity towards S-MOP plus UVA was noted when the cells were irradiated at different times after PHA stimulation. The cells were most vulnerable to UVA irradiation during the DNA-synthesis phase of the proliferating lymphocytes. The results suggest that dermal inflammatory infiltrates containing locally proliferating lymphocytes are influenced by systemic photochemotherapy since UVA penetrates well into the dermis. [ABSTRACT FROM AUTHOR]

The identification of mononuclear cells extracted from cutaneous tumours (basal cell carcinoma, squamous cell carcinoma and superficial spreading melanoma) has been investigated. The relative numbers of T cells and B cells have been determined using the E-rosette test and the EAC-rosette test. The results have been compared to those of delayed hypersensitivity type reactions. Different cell distribution patterns (E/EAC ratio) have been found in the infiltrates according to the type of tumour. An immunocytochemical technique has been developed for the identification in situ of immunoglobulin- producing cells in the inflammatory infiltrates. In each case the class of immunoglobulin (IgM, IgG or IgA) has been identified and the relative frequency of Ig-producing cells has been determined. The results indicate humoral and cellular immune responses with variations attributable to the type of tumour. In weakly malignant tumours, the infiltrate is characterized by an elevated number of T lymphocytes and numerous plasma cells which secrete all classes of Ig; in highly malignant tumours it is characterized by a reduced number of both T lymphocytes (E rosette) and plasma cells which do not secrete all classes of Ig. [ABSTRACT FROM AUTHOR]

A silicone rubber impression technique, together with scanning electron microscopy, was used to study the surface detail of porokeratosis of Mibelli. The lesions are propagated by a bud-like spreading of the active edge. The keratotic rim is produced by the condensation of squamous cells from both within and without the lesion. [ABSTRACT FROM AUTHOR]

Recent evidence suggested that cyclic adenosine 3',5'-monophosphate (cAMP) may be involved in the regulation of cell proliferation and differentiation. The effects of theophylline and dibutyryl cAMP on cell division and keratinization of human epidermal cultures were examined. Nine to 12-day-old cultures were treated with these agents, separately and in combination, for various intervals. Both agents, either singly or in combination, depressed mitoses. The maximum mitotic inhibition was obtained in cultures treated with theophylline or theophylline plus dibutyryl cAMP. Tritiated thymidine studies showed that the test agents had no effect on labelling index (LI) at 4 h, but a 74% inhibition of LI was observed at 24 h. The maximum inhibition of LI (93%) occurred at 96 hours. In contrast to the control cultures, which rarely contain keratohyaline granules (KG), a marked increase in the production of these granules occurred in cultures treated with dibutyryl cAMP plus theophylline. The KG were present over the whole outgrowth. Theophylline alone also stimulated the production of KG, whereas dibutyryl cAMP had no effect. These data show that these agents inhibit cell division and this inhibition may be accompanied by an increased production of KG. [ABSTRACT FROM AUTHOR]

Cells, obtained from human leg by successive treatments with trypsin, were air dried on microscope slides before mounting in glycerol. Dry weights and projected areas of individual cells were measured using a Vickers M 86 scanning microinterferometer. The dry weights of cells varied from 100 pg for basal cells to 700 pg for large squames. Corresponding projected areas varied from 100 to 1500 μm². [ABSTRACT FROM AUTHOR]

Studies on primary cultures of normal adult melanocytes from the ear skin of a black strain of guineapigs are reported. Melanocytes have a low proliferation rate and tend to form cohesive groups on a glass surface. The cells undergo division while maintaining close contacts with each other whereas DNA synthesis is rare in melanocytes with multiple contacts. [ABSTRACT FROM AUTHOR]

Freshly harvested epidermal cells from the dorsal skin of albino guinea-pigs have been cultured for several days on glass slides and on collagen films within Leighton tubes. Routinely it has been observed that the keratinocytcs which initially attach to the substratum rapidly detach again during the first 6 days and the presence of collagen does not influence their overall survival. However, the keratinocytes cultured on collagen films exhibit greatly enhanced cellular metabolism, in particular, dehydrogenase activity, DNA synthesis and phospholipid turnover. These findings support those published by others that collagen (and, presumably, other components of dermis) greatly influences the epidermis in vitro. [ABSTRACT FROM AUTHOR]

Two out of sixteen biopsies from verrucous lesions of xeroderma pigrnentosum revealed unusual electronmicroscopic changes. Structures resembling anchoring fibrils and the basal lamina were noted within the grossly dilated rough endoplasmic reticulum of some basal and suprabasal keratinocytes. [ABSTRACT FROM AUTHOR]

Biopsies from affected skin of sixty-two patients with stable psoriasis were investigated by in vitro labelling with tritiated thymidine and by routine histological techniques. In the same patient there were considerable variations in the number of DNA-synthesizing ceils in biopsies taken from different but similarly located lesions of the same macroscopic appearance, whereas variations in the number of DNA-synthesizing cells in biopsies taken from the same lesions were less pronounced. With due regard given to this finding, it is shown that treatment with dithranol for I and 2 weeks significantly reduces the number of DNA-synthesizing cells. There was an inverse relationship comparing the development of the granular layer with the number of DNA-synthesizing cells and parakeratosis. The variations in the number of DNA-synthesizing cells in different lesions in the same patient may also have implications for paired comparisons of topical treatment efficiency. [ABSTRACT FROM AUTHOR]

The epidermal component of lichen planus seems to result from a continuous process of erosion of the basal zone, and repopulation of the `wounded' area by cells from nearby uninvolved epidermis. In order to investigate these migrating cells further, we have studied tissue slices from forty papules of lichen planus derived from twenty-nine patients. The tissue slices were cultured for periods of 24 or 48 h. Marked migration of fusiform and spindle-shaped cells into the eroded dermo-epidermal zone appeared to have taken place. In general, the changes represented an exaggeration of those usually present in vivo. Cytochalasin B, in concentrations of 5 μg/mI or greater in the culture medium, prevented cell migration. This effect, and the fact that autoradiographic studies showed few cells to be synthesizing DNA, suggested that cell migration took place by movement rather than by mitotic activity. [ABSTRACT FROM AUTHOR]