Interleukin-1 alpha in normal skin.
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Biomedical subjects
Publications and source records attributed to R W Groves.
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Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a recently described endothelial surface glycoprotein which is inducible by interleukin 1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) or bacterial lipopolysaccharide (LPS). Using an immunohistochemical technique and a monoclonal antibody (1.2B6) specific for ELAM-1 we have found marked vascular endothelial expression of ELAM-1 in many cutaneous inflammatory disorders, including allergic contact dermatitis, atopic dermatitis and psoriasis, and in dermal infiltrates associated with benign, premalignant and malignant keratinocyte proliferation. In normal skin, minimal levels of ELAM-1 expression were detected. In psoriasis, double-immunoenzyme staining studies revealed a close spatial relationship between ELAM-1 expression and neutrophil margination, suggesting a functional link. Recombinant human interferon-gamma (30 micrograms) injected intradermally in normal adult human volunteers did not substantially upregulate ELAM-1 in contrast to its marked effect on intercellular adhesion molecule-1 (ICAM-1) expression, indicating that this cytokine is probably not involved in ELAM-1 induction in vivo. These results indicate that ELAM-1 is widely induced in cutaneous inflammation with a time course of expression that is longer than that observed in vitro. As ELAM-1 acts as an adhesion ligand for neutrophils, and perhaps monocytes, the expression of this molecule in cutaneous lesions is likely to be an indication of the ability of vascular endothelium to recruit these cells from the circulation. Furthermore, the cytokine inducibility of ELAM-1 is indirect evidence for functional interactions between perivascular mononuclear cells, other resident cells and the blood vessel wall.
Gamma glutamyl transpeptidase (GGT) is an enzyme expressed by some epithelial neoplasms but not normal interfollicular epidermis. In order to examine the relationship between malignant change and de-differentiation we studied histochemically the expression of GGT in human foetal skin, various inflammatory dermatoses and epidermal neoplasms. In foetal skin GGT was detectable after 7 weeks' gestation, reached a maximum at 11 weeks and was undetectable by 24 weeks. It was expressed strongly by squamous cell carcinoma and focally in Bowen's disease and actinic keratoses. There was no GGT expression in basal cell carcinoma or most benign skin tumours, but keratoacanthomas were weakly positive. Keratinocytes in the vicinity of malignant melanocytes also expressed GGT. This study suggests that GGT expression, while not a simple marker of malignancy, may represent reversion to a less differentiated or 'foetal' phenotype.
A 20-year-old woman developed cutaneous Mycobacterium kansasii infection following steroid infiltration of two plaques of lichen simplex. The organism was resistant to many standard antituberculous drugs and following sensitivity studies treatment with erythromycin was begun. This has been effective and well tolerated. Treatment of atypical mycobacteria with drugs not traditionally associated with antituberculous activity is being increasingly reported and, so far, resistance has not been a problem. Erythromycin has good tissue penetration with excellent activity against M. kansasii and should be considered in the therapy of similar cases.
A 59-year-old Caucasian housewife presented with a 2-year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome.
Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma cortisol by mid-afternoon. This study compared plasma cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of 'well-being' by visual analogue scale correlated significantly with simultaneous plasma cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.
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A method is described for the measurement of T-cell cytotoxicity to purified preparations of insulin, their high molecular weight fractions and C-peptide derivatives. The technique assesses cellular cytotoxicity to membrane associated insulin in an autologous system. Peripheral blood lymphocytes from 19 type 1 diabetic patients were stimulated in vitro for 6 days with the pharmaceutical preparation(s) used therapeutically. At the end of this period, they were set up in a 4-h cytotoxicity assay against 51Cr labelled PHA blast transformed lymphocytes in the presence of therapeutic insulin, monocomponent insulin, B-component or C-peptide. The results presented here demonstrate cytotoxicity to insulin B-component in diabetic patients who have received pork insulin for 2-6 years. The possible reasons for this finding are discussed.
Although most wounds heal rapidly, impaired or delayed tissue repair represents a major clinical challenge. Current therapy is directed at providing a wound with the most favorable environment in which to heal, rather than aiming to increase the rate of healing pharmacologically. Recent studies have suggested that a number of drugs may act specifically to increase healing rates. In vivo studies have demonstrated that recombinant human granulocyte-macrophage colony-stimulating factor facilitates wound contraction, causes local recruitment of inflammatory cells, and induces keratinocyte proliferation. It also activates mononuclear phagocytes, promotes migration of epithelial cells, and further regulates cytokine production. In 2 recent placebo-controlled studies involving venous leg ulceration, subcutaneous perilesional injections of recombinant human granulocyte-macrophage colony-stimulating factor were found to be significantly better than placebo in the time to complete wound healing. In other studies, recombinant human granulocyte-macrophage colony-stimulating factor was administered topically to wounds. Several case reports have also demonstrated the use of recombinant human granulocyte-macrophage colony-stimulating factor for postsurgical wounds, chronic leg ulcers of sickle cell anemia patients, and refractory pyoderma gangrenosum. Despite proper attention to wound care, some wounds fail to heal in an appropriate fashion and may become chronic. Studies of wound physiology as well as experimental and clinical evidence suggest that recombinant human granulocyte-macrophage colony-stimulating factor may promote healing of these lesions.