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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 19 recordsLinked to original sources
PubMed1992

Plasmapheresis for severe, unremitting, chronic urticaria.

Histamine-releasing autoantibodies have been identified in chronic idiopathic urticaria. 8 patients with severe disease and histamine-releasing activity in their sera underwent plasmapheresis. Symptoms were abolished for 2 months in 1 patient and for 3 weeks in another, 2 showed almost complete resolution of symptoms, 2 had temporary relief, and the other 2 showed little change. Further investigation in 4 of the patients showed significantly reduced skin-test responses to fresh post-exchange autologous sera after plasmapheresis compared with stored pre-exchange sera, but the response to intradermal histamine remained unchanged. Blood cellular histamine increased as in-vitro serum histamine-releasing activity fell after plasmapheresis. These results favour a pathogenetic role for histamine-releasing autoantibodies in patients with chronic urticaria.

Adult↗
PubMed1992

Future modalities.

Explore the source record for details and available documents.

Cyclosporins↗
PubMed1992

Culture of human dermal fibroblasts in collagen gels: modulation of interleukin 1-induced prostaglandin E2 synthesis by an extracellular matrix.

Human dermal fibroblasts, cultured as suspensions in collagen gels and as monolayers, were stimulated with recombinant human interleukin-1 beta (rIL 1 beta) at 72 h, and prostaglandin E2 (PGE2) was assayed 24 h later. Fibroblasts in gels were less responsive to rIL 1 beta than monolayers, PGE2 synthesis increasing from less than 1 ng/microgram DNA without rIL 1 beta to maxima of 11.3 and 32.9 ng/micrograms DNA, with half maximal release occurring at 7.47 and 0.75 pM rIL 1 beta for the gel and monolayer cultures, respectively. Increased PGE2 was first detected 4 h after addition of rIL 1 beta to gels and was inhibited by 10(-5) M indomethacin. The amount of PGE2 synthesized per fibroblast increased with the time the gels had been in culture when stimulated with rIL 1 beta and was proportional to the number of fibroblasts in the gels, but inversely related to the collagen concentration. A common feature of these experiments was significantly greater induction of PGE2 synthesis at higher cell densities in collagen gels. Exogenous 10(-4) M arachidonic acid further increased PGE2 synthesis by rIL 1 beta-stimulated fibroblasts, but the differential in the amount of PGE2 released from fibroblasts at high and low population densities in the gels was maintained. These results are consistent with interleukin 1 (IL 1) stimulating PGE2 synthesis in dermal fibroblasts by increasing cyclooxygenase activity. Furthermore, the results show that dermal fibroblasts have an additional regulatory mechanism, related to the cell population densities or their interactions with an extracellular matrix, to finely modulate the amount of PGE2 synthesized in response to IL 1.

Arachidonic Acid↗
PubMed1992

Wegener's granulomatosis presenting as pyoderma gangrenosum.

We report three cases of Wegener's granulomatosis presenting with cutaneous ulceration resembling pyoderma gangrenosum. Wegener's granulomatosis classically affects the upper and lower respiratory tracts and the kidneys. Skin involvement occurs in up to 50% of patients. Increased awareness that cutaneous involvement can take the form of pyoderma gangrenosum and that it can be a presenting sign may lead to more rapid diagnosis of Wegener's granulomatosis.

Adult↗
PubMed1992

Urticaria: new molecular insights and treatments. The Parkes Weber Lecture 1991.

Chronic urticaria remains one of the major unsolved clinical problems in dermatology. My group has employed an integrated experimental approach in order to shed light on the pathophysiology and treatment of this group of disorders. Using delayed pressure urticaria as a model, evidence has emerged of the role of eosinophil major basic protein (MBP) and of interleukin-6 (IL-6) as important molecular mediators, possibly explaining the poor response to H1 antihistamines. Our recent work in chronic idiopathic urticaria has led to identification of a circulating greater than 100 kD factor which causes wealing following intradermal injection and which releases histamine from normal leukocytes in vitro. Further characterisation confirmed that this skin and histamine releasing reactivity is due mainly to an IgG anti-IgE autoantibody. That this autoantibody is functionally significant is supported not only by its ability to release histamine and cause local wealing, but also by the results of removal by plasmapheresis which we have shown to cause clinical improvement in seven out of eight patients with severe unremitting chronic urticaria. It is concluded that chronic 'idiopathic' urticaria is an autoimmune disease due, in most patients, to a functionally significant IgG anti-IgE autoantibody. Immunotherapy offers the best long-term prospects of relief in severe unremitting cases.

Adult↗
PubMed1991

Blood mononuclear cells from patients with psoriasis exhibit an enhanced adherence to cultured vascular endothelium.

Blood mononuclear cells (MNC) from patients with psoriasis were more adherent to monolayers of endothelial cells prepared from human umbilical cord vein than otherwise similar cells from control subjects. This increase in adherence occurred in the presence (mean 37% increase; p less than 0.01) and absence (mean 47% increase; p less than 0.05) of 10% autologous serum and was not related to the disease severity of the patients. The augmented adhesiveness of the patients' cells was also apparent when using monolayers of endothelial cells isolated from human skin. The levels of immune complexes, complement, alpha 2-macroglobulin, acute phase proteins (alpha 1-acid glycoprotein, C-reactive protein and alpha 1-antitrypsin), and tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interleukin-1 beta (IL-1 beta) in the patients' sera were within normal limits. When MNC were added to endothelial monolayers that had been incubated with either TNF alpha or the highest concentration of rIL-1 beta used in the study, both the patients' and control's cells exhibited a similar increase in attachment (p less than 0.01). Pretreatment of endothelium with interferon-gamma did not enhance the attachment of MNC from either group of subjects. The augmented adherence of the patient's MNC appears to be due to an abnormal adhesiveness of the lymphocytes rather than the monocytes and is not related to an enhanced expression of the cell-surface adhesion molecules CD11a/CD18. It is likely that the circulating MNC of psoriatic patients may be predisposed for extravasation into skin.

Cell Adhesion↗
PubMed1991

In-vivo studies of the action spectrum and time course for release of transforming growth factor-alpha by ultraviolet irradiation in man.

Transforming growth factor-alpha (TGF-alpha) is a growth-promoting cytokine which enhances epithelial proliferation and is secreted by a wide variety of tumour cells. It is also present in normal human epidermis and its overproduction may be responsible for epidermal hyperproliferation in psoriasis. Ultraviolet (UV) B irradiation of human skin leads to epidermal damage and significant subsequent hyperplasia after approximately 24 h, whereas UVA irradiation has little such effect and predominantly damages the dermis. The relative efficacies of UVB and UVA in releasing TGF-alpha were studied in 10 subjects of skin types I and II using a skin-chamber technique and a specific TGF-alpha radioimmunoassay. Significantly elevated concentrations of immunoreactive TGF-alpha were detected in samples after 24 h in UVB-irradiated compared with unirradiated skin. Samples at earlier time points from UVB- and UVA-exposed skin contained measurable levels of TGF-alpha but these were not significantly elevated above the levels found in samples from unirradiated areas. These results, which suggest the UVB irradiation increases release of TGF-alpha from human skin at 24 h, indicate that TGF-alpha may be implicated in UVB-induced epidermal hyperplasia.

Cell Division↗
PubMed1991

Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria.

Circulating histamine releasing factor(s) have been demonstrated previously in chronic urticaria by an immediate weal-and-flare response to intradermal autologous serum injection. We have studied 25 chronic urticaria patients by in vivo skin testing with autologous sera and an in vitro histamine release assay using mixed leukocytes of healthy donors, to define the nature and functional properties of the serum factor(s). Twenty showed a weal response to autologous serum (mean +/- s.e.m., 37.3 +/- 6.8 mm3). Weal formation was confined to ultrafiltered serum fractions greater than 100 kD in nine of nine patients. There was no response in 10 healthy controls of five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release greater than 10% (mean +/- s.e.m., 44.3% +/- 6.7) above basal levels from leukocytes of at least one of seven healthy donors. This in vitro response was also confined to ultrafiltered serum fractions greater than 100 kD in seven of seven sera and was present in IgG fractions of six of seven chronic urticaria sera that showed histamine releasing activity. Functional studies indicated that this histamine releasing autoantibody had the properties of anti-IgE: chronic urticaria sera 'desensitized' basophil leukocytes to subsequent challenge with other chronic urticaria sera and to goat anti-human IgE antibody; human myeloma IgE inhibited histamine release from leukocytes in response to chronic urticaria sera; removal of surface-bound IgE by lactic acid 'stripping' reduced histamine release in response to chronic urticaria sera and anti-IgE and subsequent passive sensitization with IgE myeloma serum partially restored it. Stainable peripheral blood basophils/mm3 in chronic urticaria patients were significantly reduced (mean +/- s.e.m, 7.9 +/- 2.0) when compared to healthy controls (39.6 +/- 4.4), P less than 0.001. These results suggest that histamine releasing autoantibodies are important in the pathogenesis of chronic urticaria by stimulating or facilitating degranulation of basophils and cutaneous mast cells through cross-linking cell surface IgE receptors.

Adult↗
PubMed1991

Contact urticaria due to the common stinging nettle (Urtica dioica)--histological, ultrastructural and pharmacological studies.

A frequent cause of contact urticaria is skin exposure to the common stinging nettle (Urtica dioica). The urticaria is accompanied by a stinging sensation lasting longer than 12 h. Little is known of the cellular and molecular mechanism of stinging-nettle urticaria. After preliminary pharmacological analysis of pro-inflammatory activity in nettle stings, the cellular response of mononuclear cells, polymorphonuclear cells and mast cells was examined in six people 5 min and 12 h after nettle contact. Only mast cell numbers were significantly increased at 12 h. Ultrastructurally, some mast cells showed evidence of degranulation at 5 min and 12 h. At 12 h mast cells were closely associated with dermal dendritic cells and lymphocytes suggesting a functional unit. The mean histamine and serotonin contents of a nettle hair were found to be 6.1 ng and 33.25 pg, respectively. Nettle-sting extracts did not demonstrate histamine release from dispersed rat mast cells in vitro. These results suggest that part of the immediate reaction to nettle stings is due to histamine introduced by the nettle. However, the persistence of the stinging sensation might suggest the presence of substances in nettle fluid directly toxic to nerves or capable of secondary release of other mediators.

Blood Vessels↗
PubMed1991

The hormonal profile of women with acne and polycystic ovaries.

Most women with acne are found to have polycystic ovaries on high resolution pelvic ultrasonography, but most of these women do not manifest the other classical clinical characteristics of the polycystic ovary syndrome. We have compared the endocrinological profile of women with acne who were found to have polycystic ovaries with that of women with polycystic ovaries who presented to an endocrine clinic with hirsutes or non-dermatological manifestations of the polycystic-ovary syndrome. The group of women with acne had normal serum hormonal concentrations. Unlike other women with polycystic ovaries, they did not have significantly elevated serum concentrations of luteinizing hormone or testosterone. By clinical and endocrinological criteria, patients with acne who have polycystic ovaries appear to be a distinct sub-population of women with polycystic ovaries.

Acne Vulgaris↗