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Biomedical subjects

A V Powles

Publications and source records attributed to A V Powles.

At least 19 recordsLinked to original sources
PubMed1995

A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro.

Keratinocytes from normal and psoriatic skin were tested for their in vitro proliferative response to a range of concentrations of rIL-6, rTGF alpha, rIL-8 and rGM-CSF using a serum-free culture system. With one exception, all normal cultures (11/12) were stimulated by 1000 ng/ml IL-6 (P < 0.001). Six out of ten psoriatic keratinocyte cultures were also stimulated at this concentration, but this just failed to reach significance (P = 0.05). As a group, the response by psoriatic keratinocytes to IL-6 was significantly less than that of normal keratinocytes (P = 0.02). TGF alpha at 1 ng/ml induced proliferation in approximately 60% of both normal (8/12, P < 0.05) and psoriatic (6/10, P < 0.01) keratinocyte cultures; there was no significant difference between the responses of the two groups to this cytokine. In addition, small numbers of both normal and psoriatic cultures responded to TGF alpha over a concentration range of 0.1 to 100 ng/ml. Approximately half of the normal and psoriatic cultures were stimulated by 10-1000 ng/ml IL-8. However, the effect was not significant for the group at any of the concentrations tested. GM-CSF had minimal to no effect on most of the normal and psoriatic cultures tested. This study showed that psoriatic keratinocytes are equally responsive to the stimulatory effects of TGF alpha and IL-8, but are less susceptible to IL-6 compared to keratinocytes from normal skin. These findings are consistent with a role for these cytokines in the maintenance of a hyperproliferative epidermis in psoriasis.

Adult↗
PubMed1992

Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.

Animals↗
PubMed1991

Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

Adolescent↗
PubMed1991

Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy.

A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.

Adult↗
PubMed1990

Four years of experience with cyclosporin A for psoriasis.

Forty-four patients with severe psoriasis have been treated with cyclosporin A (CyA) for 2-50 months (mean 17 months). During the study, 31 (70%) of these patients achieved a greater than 70% reduction in PASI score, 39 (88%) achieved a greater than 60% reduction and 42 (95%) a greater than 50% reduction. The mean initial dose of CyA was 3 mg/kg/day and the mean dose was 3.3 mg/kg/day throughout the study. Twenty-five (57%) patients were maintained on less than or equal to 3 mg and six (14%) required greater than 5 mg/kg/day for limited periods to obtain significant improvement. In three of these patients, this was achieved with 6 mg/kg/day but, of the remainder, one required 7 mg and two required 10 mg/kg/day. Of the 44 patients, 32 (73%) are still taking CyA. Patients were discontinued because of: side-effects directly attributable to treatment (n = 4); remission of psoriasis (n = 4); death (n = I); defaulting (n = I); infrequent attendance (n = I); high doses of NSAID were necessary for arthritis (n = I). Before starting CyA, 39 patients were normotensive; 21 (54%) developed mild hypertension. In 28 patients where the GFRs were estimated before and during treatment, there was a 16% reduction (P less than 0.0001) during a mean period of 8 months. Two patients developed malignancies. The incidence of hypertension and percentage decrease in GFR were strongly correlated with the dose required to control the psoriasis.

Adult↗
PubMed1990

Renal function after long-term low-dose cyclosporin for psoriasis.

Two groups of patients receiving cyclosporin A (CyA) for psoriasis had their renal function assessed by measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The first group comprised 13 patients who had taken low dose (average 3 mg/kg per day) CyA for an average period of 2.5 years. Seven of the 13 had a normal GFR of 108 (77-121) ml/min (median; range). In the other six patients the GFR was low at 63 (50-77) ml/min and CyA was discontinued for periods ranging from 3 to 17 weeks. The GFR rose in all six patients, to 79 (60-91) ml/min; this change was significant (P less than 0.05). The six patients restarted CyA because their psoriasis recurred and after a mean interval of 15 weeks the GFR had fallen in all six to 63 (46-80) ml/min (P less than 0.05) and the ERPF decreased from 339 (231-414) ml/min to 244 (177-321) ml/min (P less than 0.05). In the second group of 11 patients measurements were made prior to starting CyA and after taking CyA for a mean of 9 weeks. The GFR fell in eight out of 11 subjects, the GFR for the 11 patients being 117 (72-128) ml/min before taking CyA and 97 (51-122) ml/min after CyA (P less than 0.02). The ERPF was measured in nine of the 11 patients and fell in seven of the nine. The ERPF for the nine patients before CyA was 490 (296-642) ml/min and for the 11 patients after CyA was 410 (195-543) ml/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Intradermal antigen tests in psoriasis.

To assess whether elicitation of delayed hypersensitivity may be superior to trauma in inducing the Koebner reaction in psoriasis, 12 affected patients and 9 control subjects were tested with 0.1 ml intradermal injections of streptokinase/streptodornase (20 mu/5 mu per 0.1 ml), PPD (1 in 1000) and saline control solutions in a double-blind study; Koebner status was also established in the psoriatic patients. Injected sites were examined at 48 h and 7, 14, 21 and 28 days for local development of psoriasis, erythema and induration (diameter). One patient was Koebner-positive and developed psoriasis at all three injection sites. The other, Koebner-negative psoriatic subjects did not develop psoriasis locally. However, compared with non-psoriatic controls they showed a marked delay in resolution of the delayed hypersensitivity reaction to the PPD antigen and a similar but less marked phenomenon was observed for streptokinase/streptodornase. These findings indicate that intradermal antigen, of the nature and amount used in this study, is no more effective in inducing the Koebner phenomenon than injury alone. However, the ability of psoriasis patients to switch off cell-mediated immune reaction appears to be impaired.

Adult↗
PubMed1990

Epidermal rupture is the initiating factor for the Koebner response in psoriasis.

The Koebner phenomenon was studied using low pressure suction and/or sellotape stripping. Each of 10 patients with psoriasis had 5 suction blisters induced and sellotape stripping. In each patient the roof of 4 of the 5 blisters was removed. In 6 of the 10 patients, psoriasis developed where the blister roof was removed, but not where the blister was left intact. However, only 3 of these 10 patients were also Koebner-positive at the tape-stripped site. Similarly, in a group of 37 psoriasis patients who were sellotape-stripped alone, only 8 (21.6%) were Koebner-positive at the tape-stripped site. In another experiment, 5 suction blisters were produced in each of 4 patients. The roof of 4 blisters was removed, one of which was occluded. Psoriasis developed in 3 of the 4 patients, but only where the blister roof had been removed and left unoccluded. These findings suggest that rupture of the epidermis can initiate the Koebner response, but that secondary dermal events are necessary for a psoriatic lesion to form.

Adult↗
PubMed1989

Intralesional cyclosporin in psoriasis: effects on T lymphocyte and dendritic cell subpopulations.

On each of 10 patients with untreated plaque psoriasis, two symmetrical plaques were injected with cyclosporin A or placebo on six occasions over 12 days, in a double-blind manner. Biopsies taken from these lesions at 14 days were examined for differences in cellular composition using a double-labelling immunofluorescent technique. The cyclosporin-injected plaques cleared significantly better than those injected with placebo (P less than 0.001). In the epidermis of the cyclosporin-injected plaques, total and HLA-DR+ CD4+ and CD8+ T cell numbers were significantly decreased compared to corresponding plaques treated with placebo (total CD4+, total CD8+, DR+ CD4+, P less than 0.01; DR+ CD8+, P less than 0.02). Similarly, T lymphocyte numbers in the dermis were decreased in the cyclosporin compared to placebo-treated plaques; the reduction in total CD4+ and DR+ CD8+ T cell numbers was statistically significant (P less than 0.05). Although total numbers of epidermal dendritic cells were not significantly altered, the DR+CD1- dendritic cell subpopulation was markedly decreased (P less than 0.01) and DR-CD1+ dendritic cells increased (P less than 0.05) in the plaques injected with cyclosporin compared to corresponding placebo-treated plaques. These findings show that cyclosporin injected in situ is effective in clearing psoriasis and probably exerts this beneficial effect by its action on T lymphocytes. A suitable topical preparation that allows penetration of the drug should prove helpful in the treatment of psoriasis.

Adult↗
PubMed1989

Long-term cyclosporin for psoriasis.

Thirteen patients with severe persistent psoriasis, intolerant of, or unresponsive to, other current treatments have been treated with cyclosporin (Cys) for periods varying from 12-25 (mean 18) months. The dose ranged from 1-4 mg/kg/day (mean 2.8 mg). There was a 72% reduction in the mean PASI score at 4 weeks, and at the end of the study, an 81% reduction. Adjuvant therapy with topical steroids was used in 11 of the 13 patients after the first 3 months of Cys treatment to persistent patches on an intermittent basis with beneficial effect. Six patients developed mild to moderate hypertension, in three this was controlled by a reduction in the dose of Cys, and in the other three by hypotensive agents. The mean serum creatinine rose from 72 to 90 microM/l during the study. Hypertrichosis occurred in seven of the 13 patients. Low dosage Cys is an effective treatment for clearing psoriasis and maintaining improvement on a long-term basis.

Adult↗
PubMed1989

Sulphamethoxypyridazine for dermatitis herpetiformis, linear IgA disease and cicatricial pemphigoid.

One-hundred and sixty-eight cases of dermatitis herpetiformis were reviewed to compare the clinical response to and incidence of side-effects from dapsone and sulphamethoxypyridazine. Thirty-seven received sulphamethoxypyridazine (0.25-1.5 g/day) as a single agent therapy at some stage during their care and 161 had dapsone only (50-450 mg/day). Thirty of these patients received both drugs, but at different times. Both were highly effective in controlling the skin disease in 97% of patients on dapsone and 89% on sulphamethoxypyridazine. While 36 (22%) of dapsone-treated subjects had intolerable side effects warranting a change in therapy, this occurred in only five (13.5%) of those treated with sulphamethoxypyridazine. Sulphamethoxypyridazine was also effective as a single agent in three patients with linear IgA disease who had suffered adverse effects from dapsone, and in 10 out of 15 patients with oral and cutaneous lesions of cicatricial pemphigoid.

Adolescent↗
PubMed1989

Effect of simulated sunlight on Langerhans' cells in malignant melanoma patients.

The effect of artificial sunlight on the number and HLA class II expression of Langerhans' cells was studied in 10 patients with malignant melanoma and 10 control volunteers. The total number of Langerhans' cell decreased in both groups but at 96 h there was a greater and significant decrease (p less than 0.01) in the number of Langerhans' cells in the melanoma group, compared with controls. This decrease persisted and was still greater in the melanoma group (p less than 0.02) at one week post-irradiation. There was a rise in Langerhans' cell count over the following 3 weeks in both groups. Unexpectedly, during this period in the melanoma group-but not controls-there was a significant median peak rise above pre-irradiation levels (p less than 0.001). Alteration in the response of Langerhans' cells to sunlight may play a part in the aetiology of malignant melanoma.

Adult↗