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Biomedical subjects

R S Barnetson

Publications and source records attributed to R S Barnetson.

At least 55 records · Page 3Linked to original sources

All-trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation.

Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.

Animals↗

Skin diseases in the tropics.

Australian physicians may encounter a number of tropical skin diseases. Migrants or visitors may travel here with a skin disease, or people living in the tropical or subtropical regions of Australia may develop skin conditions. The most important of these are cutaneous leishmaniasis, cutaneous amoebiasis, tinea imbricata, favus, sporotrichosis, chromomycosis, cutaneous tuberculosis, Buruli ulcer, cutaneous larva migrans and dracontiasis.

Australia↗

The use of corticosteroids in dermatological practice.

OBJECTIVE: To discuss the various uses of corticosteroids in patients with skin diseases. DATA SOURCES: All relevant literature published since 1950 was reviewed and 33 studies were selected. CONCLUSIONS: Systemic and topical corticosteroid preparations are used commonly in patients with skin diseases. Oral administration of steroids is particularly useful in acute hypersensitivity diseases, connective tissue diseases, immunological blistering diseases, and the commoner dermatoses when they are very severe and widespread. Topical steroid preparations are mainly used in the different forms of dermatitis, but are also useful in psoriasis and a number of other skin diseases. If potent topical steroid preparations are used for too long, or in excessive quantities, side effects will be encountered as a direct effect on the skin, for example atrophy, and as a result of systemic absorption, for example, hypothalamic-pituitary-adrenal suppression and Cushing's syndrome.

Administration, Oral↗

Lymphomatoid granulomatosis.

Lymphomatoid granulomatosis or angiocentric T-cell lymphoma is a systemic disease that affects multiple organs. The histopathologic findings include a characteristic infiltrate that is both angiocentric and angiodestructive. The prognosis is poor but may be improved by early recognition and aggressive chemotherapy. We report a case of cutaneous lymphomatoid granulomatosis and emphasize that dermatologists play an important role in the early diagnosis of this disease.

Adult↗

Topical retinoic acid augments ultraviolet light-induced melanogenesis.

Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light-induced melanogenesis, suggesting a role for vitamin A in this process.

Animals↗

Sunscreens protect epidermal Langerhans cells and Thy-1+ cells but not local contact sensitization from the effects of ultraviolet light.

This study compares the ability of two commonly used sunscreens--octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC)--to protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+ dEC), and local contact sensitivity (CS) from the effects of ultraviolet (UV) light. Chronic exposure of mice 5 d per week for 4 weeks with an intermediate dose of solar-simulated sunlight from which any UVC had been filtered reduced the LC and Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed to simulate closely the daily exposure of humans to sunlight. This effect on LC and Thy-1+ dEC occurred in both albino and pigmented mice that develop a tan during the irradiation procedure, indicating that a tan does not protect these cells from the effects of UV light. Sunscreen preparations with Padimate O and 2-EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2-EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis of both mouse strains. Padimate O and 2-EHMC in organic solvent were used to ensure that these were the active ingredients in the sunscreen preparations. In contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-1+ dEC from UV exposure in both mouse strains, but neither protected against the development of local immunosuppression using a contact sensitivity model. Thus, even in a mouse strain that is sensitive to UV-induced immunosuppression, local immunosuppression can occur in the presence of normal densities of LC and Thy-1+ dEC.

Animals↗

Regulation of the skin immune system by retinoids during carcinogenesis.

One of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear, however, it is possible that RA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis.

Animals↗

A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne.

Alpha hydroxy acids (AHA's) or "fruit acids" are a special group of organic acids found in many natural foods. They have been described in the literature for the treatment of a number of conditions in which abnormal keratinization consistently contributes to pathogenesis. These include the icthyoses, warts, psoriasis, eczema and acne. We have performed a double-blind clinical trial on 150 patients to evaluate the efficacy and skin tolerance of the alpha hydroxy acid gluconolactone 14% in solution (Nuvoderm lotion) in the treatment of mild to moderate acne when compared with its vehicle (placebo) and 5% benzoyl peroxide lotion. The results of this study showed that both gluconolactone and benzoyl peroxide had a significant effect in improving patients' acne by reducing the number of lesions (inflamed and non-inflamed). Furthermore, fewer side-effects were experienced by patients treated with gluconolactone when compared with benzoyl peroxide.

Acne Vulgaris↗

Tea tree oil in the treatment of tinea pedis.

Tea tree oil (an essential oil derived primarily from the Australian native Melaleuca alternifolia) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections; however, to date, the evidence for its efficacy in fungal infections is still largely anecdotal. One hundred and four patients completed a randomized, double-blind trial to evaluate the efficacy of 10% w/w tea tree oil cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis. Significantly more tolnaftate-treated patients (85%) than tea tree oil (30%) and placebo-treated patients (21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no statistically significant difference between tea tree oil and placebo groups. All three groups demonstrated improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching and burning. The tea tree oil group (24/37) and the tolnaftate group (19/33) showed significant improvement in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018 respectively). Tea tree oil cream (10% w/w) appears to reduce the symptomatology of tinea pedis as effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure. This may be the basis for the popular use of tea tree oil in the treatment of tinea pedis.

Adolescent↗

Control of Langerhans' cell density by a skin tumour-derived cytokine.

Langerhans' cells (LC) are bone marrow-derived dendritic antigen-presenting cells (APC) found in the epidermis of mammals. It is not known why they accumulate in the epidermis. Human and murine skin tumours are infiltrated with large numbers of LC, however previous experiments have shown that this does not seem to be associated with immune responses against the tumours. Here we show that a squamous-derived tumour cell line (T7) produces a cytokine which increases the number of LC in normal epidermis. T7 supernatant increased the density of LC in both mice syngeneic to the T7 cells (Skh:HR-1) as well as in BALB/c mice, indicating that the cytokine is not genetically restricted. The cytokine is a protein, not a prostaglandin, with a MW of > 12,000 as its production was inhibited by cycloheximide but not indomethacin and it could not be removed by dialysis against a 12,000 MW cut-off membrane. The increased numbers of LC found in tumour supernatant-treated epidermis expressed Ia as well as the molecule defined by the J11d monoclonal antibody, which is expressed by LC but not macrophages, confirming that these cells are LC. Another squamous-derived skin tumour, T79, which is not infiltrated with large numbers of LC when inoculated into syngeneic mice, did not produce a factor capable of increasing the density of LC. Hence these studies demonstrate either the activity of a novel cytokine or a new biological activity of a previously described cytokine. It is most likely that this cytokine increased the number of LC by attracting precursors into the epidermis. As the cytokine was produced by transformed squamous cells it is also possible that this cytokine is responsible for attracting LC into normal epidermis.

Animals↗

The coexistence of lymphangiosarcoma and Kaposi's sarcoma in a renal transplant recipient.

A case of coexisting lymphangiosarcoma and Kaposi's sarcoma that occurred in a female renal transplant recipient is presented. Both sarcomas were localized to the skin and were slowly progressive over several years. The coexistence of these two sarcomas may indicate that they arose from a common precursor endothelial cell and that systemic immune suppression may be important in the pathogenesis of both these malignancies.

Female↗

Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma.

Spontaneous regression occurs in a small proportion of malignant melanomas, and it is important to understand the processes involved in its induction as this may give a guide to future therapies for this disease. We have examined 36 primary malignant melanomas (19 regressing, 17 non-regressing) and identified the cellular phenotypes and activation states of the cells infiltrating regressing and non-regressing primary melanomas by immunochemistry. We have found a significantly increased number of CD3-positive cells and an increased ratio of CD4/CD8-positive cells infiltrating regressing compared to non-regressing tumors. In addition, the expression of the interleukin 2 receptor, an activation marker for T cells, was increased. However, there were no significant differences in class II MHC, CD1, intercellular adhesion molecule 1 (ICAM1), or melanoma-associated differentiation-antigen expression in these tumors. These data are consistent with melanoma regression being induced by activated CD4 T cells and do not seem to be related to the differentiation markers we have examined on these tumors.

Antibodies, Monoclonal↗

Langerhans cell migration into ultraviolet light-induced squamous skin tumors is unrelated to anti-tumor immunity.

There has been much speculation as to the role of Langerhans cells (LC) in the induction of anti-tumor immunity. Whereas there is considerable circumstantial evidence that disruptions in the density and function of these cells during the early stages of ultraviolet (UV) light- and chemical carcinogen-induced carcinogenesis may be important for enabling developing neoplasms to escape immune destruction, the role of the large number of these cells found infiltrating developed skin tumors is less clear. To investigate this we have compared the LC density infiltrating transplanted non-immunogenic and immunogenic UV-induced murine tumors as well as LC in the epidermis overlying the tumors. Whereas two non-immunogenic tumor lines attracted large numbers of Ia+ dendritic cells, an immunogenic tumor line did not. Similar results were obtained whether the tumors were transplanted into syngeneic immunocompetent or athymic immunodeficient mice. Hence, there was no relationship between tumor immunogenicity or host immunocompetence and Ia+ dendritic cell density. Furthermore, there was no correlation with the pattern of T-cell infiltration of the tumors or CD4/CD8 cell ratio. Our results also indicate that whereas UV light decreased Ia+ cell density, both in the epidermis and the tumors, it did not inhibit the tumors from attracting Ia+ dendritic cells. Thus, the Ia+ dendritic cells infiltrating skin tumors are unlikely to indicate a host immune response to the tumor, but are more likely to be attracted by tumor-derived cytokines.

Animals↗

Topical and oral retinoids protect Langerhans' cells and epidermal Thy-1+ dendritic cells from being depleted by ultraviolet radiation.

Murine epidermis contains two types of bone marrow-derived cells of the immune system, Langerhans' cells (LC), which are dendritic antigen-presenting cells, and Thy-1+ dendritic cells (Thy-1+ DEC), which express the gamma/delta T-cell receptor for antigen and hence are probably T cells whose function in the epidermis is unknown. Ultraviolet (UV) light greatly reduces the density of both of these cell types, and hence this may be one of the mechanisms by which UV light induces immunosuppression. It is important to develop strategies for protecting these cells from the effects of UV light. In this study we show that topical all-trans-retinoic acid (RA) and an orally administered retinoid, temarotene, protect both LC and Thy-1+ DEC from being depleted by UV light. However, neither retinoid inhibited the development of immunosuppression in response to application of a contact sensitizer. We also compared two congenic mouse strains, one albino, the other lightly pigmented and capable of tanning in response to UV light. There was no difference in the ability of UV light to deplete LC or Thy-1+ DEC in these two strains or of retinoids to inhibit their depletion. These studies demonstrate that retinoids but not melanin are able to inhibit UV light from depleting LC and Thy-1+ DEC; however, there are other immunosuppressive effects of UV light which are not protected by the retinoids.

Animals↗

A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne.

Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions. We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower. Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.

Acne Vulgaris↗

Trial of nedocromil sodium in atopic eczema.

The efficacy of orally administered nedocromil sodium, a mast-cell stabilizer, was assessed in the treatment of adults with atopic eczema plus food allergy. Twenty adults with atopic eczema and allergy to hens' eggs, cows' milk or wheat took part in this double-blind, cross-over study of nedocromil sodium versus placebo, each treatment period lasting 4 weeks. No significant differences were found between the two treatments on clinical assessment, or by measurement of total and specific IgE levels.

Administration, Oral↗

Naproxen-induced bullous photodermatitis.

A case of naproxen-induced bullous photodermatitis ("pseudoporphyria") is presented. A 37-year-old woman with systemic lupus erythematosus developed tense bullae on her hands and lips, and was found to have a clinical and histological condition that was similar to porphyria cutanea tarda without the associated haematological abnormalities. The lesions remitted upon the cessation of naproxen therapy. Although this adverse effect of naproxen has been seen most frequently in patients from Australia and New Zealand, it has not been reported in the Australian medical literature previously.

Adult↗