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D A Buckley

Publications and source records attributed to D A Buckley.

At least 37 records · Page 2Linked to original sources

NMR structure of an F-actin-binding "headpiece" motif from villin.

A growing family of F-actin-bundling proteins harbors a modular F-actin-binding headpiece domain at the C terminus. Headpiece provides one of the two F-actin-binding sites essential for filament bundling. Here, we report the first structure of a functional headpiece domain. The NMR structure of chicken villin headpiece (HP67) reveals two subdomains that share a tightly packed hydrophobic core. The N-terminal subdomain contains bends, turns, and a four-residue alpha-helix as well as a buried histidine residue that imparts a pH-dependent folding. The C-terminal subdomain is composed of three alpha-helices and its folding is pH-independent. Two residues previously implicated in F-actin-binding form a buried salt-bridge between the N and C-terminal subdomains. The rest of the identified actin-binding residues are solvent-exposed and map onto a unique F-actin-binding surface.

Actins↗

Large increments in psoralen-ultraviolet A (PUVA) therapy are unsuitable for fair-skinned individuals with psoriasis.

The ideal psoralen-ultraviolet A (PUVA) regimen for chronic plaque psoriasis has yet to be established. There are four components to a PUVA regimen: the dose of psoralen, the starting dose of UVA, the frequency of treatment and the incremental UVA dose protocol. Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side-effects and the risk of cutaneous carcinogenesis, believed to be independently related to the cumulative dose of UVA and the total number of treatments. The British Photodermatology Group recommends two twice-weekly PUVA regimens: one starts with 50% of the minimal phototoxic dose (MPD) and uses weekly increments of 40%, 30%, 25%, 20%, 15%, 10% and 5% of the previous dose to a maximum of 14.5 J/cm2; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40%, decreasing to 20% once erythema develops. We undertook a prospective randomized controlled trial comparing these regimens in 85 Irish patients. The clearance rate with the MPD regimen was lower than with the skin type regimen, 67.5% vs. 95% (P < 0.05). The reasons for treatment failure were grade 3 erythema and severe PUVA itch. There was a trend suggesting that patients with skin types I and II, but not skin type III, required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen, although this did not reach statistical significance. Grades 2 or 3 erythema were very common in both treatment groups (52. 5% of the skin type group and 45% of the MPD group). This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50-70% of the MPD (rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II) and when large dose increments are used. We suggest that smaller dose increments should be used in patients with skin types I and II.

Adult↗

Recalcitrant viral warts treated by diphencyprone immunotherapy.

Recalcitrant viral warts are a troublesome therapeutic problem. Immunotherapy with the universal allergic contact sensitizer diphencyprone (DCP) has been used successfully in such cases. We have reviewed our experience of the use of DCP in the treatment of resistant hand and foot warts during an 8-year period. Sixty patients were sensitized to DCP during this time; the median duration of warts was 3 years. Twelve patients defaulted from treatment. Of the remaining 48 individuals, 42 (88%) cleared of all warts. The median number of treatments to clear was five (range one to 22) and the median time to clear was 5 months (range 0.5-14). Adverse effects occurred in 27 of 48 patients (56%), most commonly painful local blistering (n = 11), blistering at the sensitization site (n = 9), pompholyx-like reactions (n = 7) and eczematous eruptions (n = 4). Three of those who defaulted did so due to side-effects, one became pregnant and eight dropped out for unknown reasons. Three of the 48 patients who cleared or had at least six treatments also discontinued DCP therapy due to side-effects, but most tolerated treatment well. Twenty-five patients were followed up for periods of 1 month to 8 years (median 2 years) and none had a recurrence. DCP immunotherapy is an effective option for the treatment of recalcitrant viral warts but patients must be motivated to attend for sequential applications and must be warned about potential uncomfortable side-effects.

Adolescent↗

Topical immunotherapy in dermatology.

Topical immunotherapy of skin diseases has been used since the 1970s to treat conditions thought to result from an altered immunological state, mainly extensive alopecia areata and resistant viral warts. Despite its effectiveness, only a handful of dermatology departments in the UK currently provide such treatment. Any of three universal contact sensitisers may be used for topical immunotherapy; but diphencyprone (DCP) has advantages over dinitrochlorobenzene (DNCB) and squaric acid dibutyl ester (SADBE). Sensitisation of medical, nursing and pharmacy staff may be avoided by careful handling of the solutions. Local blistering and eczematous eruptions are the most common risks in patients undergoing treatment; vitiligo and erythema multiforme-like reactions are rare complications. Topical immunotherapy using DCP with close supervision is a useful option for severe alopecia areata and resistant viral warts.

Administration, Topical↗

Spinal cord trauma.

New technology is helpful in the treatment of patients with spinal cord injury, but we are still unable to reverse the effects of the initial injury. The major focus in the acute treatment of spinal cord trauma has remained prevention of secondary injury and complications thereafter. This article describes different types of spinal cord injuries, treatment, and statistics.

Activities of Daily Living↗

Persistent infection of the chin with an unusual skin pathogen (Streptococcus milleri): a sign of intraoral carcinoma.

Streptococcus milleri is a commensal of the oropharynx and gastrointestinal tract which is not generally associated with skin disease. We now report a patient who presented with a pustular mass of the chin with lower lip anaesthesia. He was initially thought to have sycosis barbae, but response to treatment was poor and lesional swabs repeatedly cultured S. milleri. After some delay, squamous cell carcinoma of the mouth, involving the mandible and overlying skin, was detected. We consider that the S. milleri either invaded through the tumour from the mouth or root canal or colonized the skin from saliva dribbled over the numb lower lip. Isolation of an unusual organism and numbness of the chin are features that should suggest the need for early radiography.

Aged↗

The use of azathioprine in severe adult atopic eczema.

AIM: To evaluate the use of azathioprine in the treatment of severe adult atopic eczema and review the relevant literature. BACKGROUND: Effective treatment of severe adult atopic eczema may necessitate the use of agents such as systemic steroids, PUVA or cyclosporin, which are associated with significant morbidity. Azathioprine is an effective alternative which can induce disease remission and may be less toxic. METHODS: Ten patients treated with azathioprine 0.7-2.5 mg/kg per day for a minimum period of 12 months were evaluated in a retrospective follow-up study. RESULTS: Clearance or marked improvement was noted in eight patients; three of these later became refractory to the drug. Side-effects were few and were well-tolerated. One patient was found to have lymphoma 8 months after stopping treatment. CONCLUSION: Azathioprine is an effective and cheaper alternative to cyclosporin in the treatment of severe adult atopic eczema. Its long-term toxicity remains unclear.

Adult↗

Vulvar lymphangiectasia due to recurrent cellulitis.

We describe a 42-year-old woman in whom extensive lymphangiectasia of the vulva developed after recurrent severe episodes of cellulitis, producing changes rather similar to those seen in lymphangioma circumscriptum. We suspect that an underlying lymphatic abnormality predisposed her to cellulitis, resulting in local lymphatic fibrosis and vulvar lymphangiectasia.

Adult↗

Multiple keratoses and squamous carcinoma after PUVA treatment of vitiligo.

PUVA is known to be carcinogenic when used in the treatment of psoriasis. To date skin cancer has not been demonstrated after PUVA treatment of vitiligo. We report a patient in whom multiple squamous cell carcinomata and keratoses developed in vitiligo areas after a prolonged course of PUVA. PUVA therapy of vitiligo induces repigmentation of affected skin in some patients. An increased frequency of cutaneous neoplasms in depigmented areas is a potential hazard, as in these sites the photoprotective effect of melanin is lacking.

Carcinoma, Squamous Cell↗

A comparison of twice-weekly MPD-PUVA and three times-weekly skin typing-PUVA regimens for the treatment of psoriasis.

The most frequent PUVA treatment regimen in current use is three times weekly, using skin typing to estimate the starting dose. Recently, it was suggested that twice-weekly treatment, using the minimal phototoxic dose (MPD) to calculate suberythemal starting doses of UVA, achieved similar clearance rates with fewer treatments and a lower cumulative UVA dose. We have carried out a trial on 83 patients, comparing twice-weekly MPD-PUVA with three times-weekly skin typing-PUVA, in order to test this hypothesis. Although clearance rates were comparable between the two regimens, there was no overall significant difference in the number of treatments or in the cumulative UVA doses at clearance. However, for patients with skin types I and II the cumulative UVA dose was significantly higher using the twice-weekly MPD regimen (70.0 J/cm2 vs. 55.8 J/cm2; P < 0.05). Our results do not confirm that there is a reduction in cumulative UVA dosage with twice-weekly MPD-PUVA.

Adult↗

Cyclosporin-responsive hidradenitis suppurativa.

Hidradenitis suppurativa, a chronic inflammatory condition of the apocrine gland follicles, may rarely be complicated by pyoderma gangrenosum (PG). We report such a case, in which the immunosuppressant cyclosporin A (CyA) was given to treat PG and a dramatic improvement occurred in the patient's intractable perineal HS.

Cyclosporine↗

Resolution of xanthomas in Alagille syndrome after liver transplantation.

Alagille syndrome (arteriohepatic dysplasia) is a genetic disorder with autosomal dominant transmission which has been localized to chromosome 20p. Cutaneous manifestations include jaundice, pruritus, and widespread xanthomata. We report a child with severe Alagille syndrome in whom orthotopic liver transplantation caused rapid resolution of disfiguring xanthomas.

Alagille Syndrome↗