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Biomedical subjects

B Kirby

Publications and source records attributed to B Kirby.

At least 19 recordsLinked to original sources
PubMed2002

Natural killer and natural killer-T cells in psoriasis.

Psoriasis is characterized by a dermal and epidermal infiltrate comprised predominantly of CD4(+) and CD8(+) T cells, respectively. These cells behave in an antigen-dependent manner, which suggests that psoriasis may be a T-cell-mediated autoimmune disease. Psoriasis shares certain immunological features with recognized autoimmune conditions such as type I diabetes mellitus and multiple sclerosis, in both of which a pathogenic role is postulated for natural killer (NK) cells and natural killer-like T (NK-T) cells. However, there are few studies assessing the role of NK and NK-T cells in psoriasis. We sought to determine whether NK and NK-T cells are present in psoriasis. Skin biopsies were taken from the active edge of a psoriasis plaque and from uninvolved skin at least 5 cm away from involved skin of ten patients with chronic plaque psoriasis. Skin from four normal subjects was used as controls. Using an immunoperoxidase technique, cryostat sections were stained using antibodies to T-cell markers CD2, CD3, CD4 and CD8; cutaneous leucocyte associated antigen; NK cell markers CD16, CD56, CD57, CD94 and CD158a; and the NK-T cell marker CD161. There were significantly more cells expressing T cell markers, NK cell markers CD16, CD57, CD94 and CD158a and NK-T cell marker CD161 in involved skin than in uninvolved or normal skin ( P<0.01). There was no difference in the number of cells expressing CD56. Cells expressing NK markers were found most commonly in the papillary dermis immediately subjacent to the dermoepidermal junction. Cells expressing CD57 were found in significantly higher numbers in the epidermis and reticular dermis of involved skin. This study demonstrates that cells expressing NK markers and NK-T cell markers are present in plaques of psoriasis. The exact roles of NK and NK-T cells in psoriasis are unclear, although they may modulate autoimmune inflammation and act as a source of Th(1) cytokines important in the psoriatic process.

Adult↗
PubMed2002

A cognitive-behavioural symptom management programme as an adjunct in psoriasis therapy.

BACKGROUND: Patients with psoriasis may experience significant psychological and social disabilities. Stress or distress are proposed aggravators of the disease process in psoriasis. Preliminary studies to date have suggested that adjunctive psychological therapies may be effective in the clinical management of psoriasis. OBJECTIVES: To examine whether a 6-week multidisciplinary management approach, the Psoriasis Symptom Management Programme (PSMP) for patients with psoriasis improves clinical severity of psoriasis and its associated psychological distress and disability. METHODS: In a case-control study, patients with psoriasis attending an out-patient psoriasis specialty clinic chose to receive standard psoriasis treatment alone (n = 53) or to enter the PSMP as an adjunct to standard therapy (n = 40). They were assessed at baseline, at the end of the 6-week PSMP and after 6 months follow-up. RESULTS: As compared with standard treatment alone, analysis of covariance indicated that participation in the PSMP resulted in a greater reduction in clinical severity of psoriasis (P = 0.001), anxiety (P = 0.001), depression (P = 0.001), psoriasis-related stress (P = 0.001) and disability (P = 0.04) at 6 weeks and 6 months follow-up. CONCLUSIONS: The management of the physical aspects of psoriasis and its psychological effects are significantly improved for patients who opt for a 6-week integrated multidisciplinary approach. Furthermore, the techniques learnt by participation in the PSMP facilitate continued control of psoriasis for at least 6 months.

Administration, Topical↗
PubMed2002

Novel immune-based therapies for psoriasis.

The primacy of the immune system in the pathogenesis of psoriasis is a well-established concept to the extent that psoriasis has been classified as a T-cell-mediated, autoimmune disease. An explosion of knowledge concerning immunological events in psoriasis and the clinical efficacy of immunologically directed therapies, such as cyclosporin, support this concept. Armed with this understanding and modern biotechnology, novel interventions have been developed to treat psoriasis. The aim of these therapies is to provide selective, immunologically directed intervention with the hope that such specificity will result in fewer side-effects than traditional therapies. Of interest and importance, these pharmaceutical interventions also act as a form of investigational tool in psoriasis. Their relative efficacy in the psoriatic process provides useful insights into the hierarchial importance of immune events in the disease process and recent evidence suggests that innate rather than acquired immunity has a key role. This article reviews recent developments in immune-based therapies for psoriasis.

Cytokines↗
PubMed2002

Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis.

BACKGROUND: Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. OBJECTIVES: To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. METHODS: Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. RESULTS: In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05). CONCLUSIONS: The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Adolescent↗
PubMed2001

Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury.

EDI-immunoreactive macrophages, absent from the superior cervical ganglia (SCG) of normal rats, appear in these ganglia within 48h after postganglionic axotomy. Further, resident macrophages show changes after axotomy. Since chemokines function as chemoattractants and activators of leukocytes, the effects of axotomy on chemokine expression in the SCG were examined. Within 6 h after nerve transection, increases were seen in mRNA levels for monocyte chemoattractant protein (MCP)-1. MCP-1 mRNA was concentrated in a population of neurons, while MCP-1 protein was localized to endothelial cells. This axotomy-induced neuronal MCP-1 expression may trigger the infiltration and/or activation of macrophages in SCG after injury.

Animals↗
PubMed2001

Cytokine gene polymorphisms in psoriasis.

BACKGROUND: Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file. RESULTS: Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo. CONCLUSIONS: Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.

Adolescent↗
PubMed2001

Psoriasis: the future.

The aetiology of psoriasis is still unclear but our knowledge of the psoriatic process has grown substantially over the last two decades. The future will undoubtedly bring advances in our understanding of the pathogenesis of psoriasis and, as a consequence, new therapies. Defining the molecular genetics of psoriasis will enhance our understanding of the disease process and hopefully facilitate the development of a representative animal model. This in itself will be a key step in the development and testing of new therapies. Precise identification of the immunological events involved in psoriasis will allow specific T-cell- and cytokine-targeted, and perhaps less toxic. immunotherapies. Anti-angiogenic agents that are in development for use in oncology may also be effective in psoriasis. The adaptation of current topical therapies such as retinoids and vitamin D analogues to produce more effective and better-tolerated formulations will also play a significant role in our future first-line management of patients. The increased recognition and better management of environmental trigger factors such as psychological distress will become an important factor in future psoriasis care. The development of physical therapies including photodynamic therapy and excimer lasers has the potential to expand the remit of psoriasis therapy. There is little doubt that the future for our patients with psoriasis is bright. However, this will only be achievable by a concerted research effort to understand all facets of this enigmatic disease ranging from the molecular to the environmental.

Angiogenesis Inhibitors↗
PubMed2001

Aggressive, extensive, vasculitic leg ulceration associated with hydroxyurea therapy and a fatal outcome.

The association of lower leg ulcer development and hydroxyurea therapy in patients with myeloproliferative disorders has been reported previously. In most of these cases the ulcers healed with cessation of the hydroxyurea together with meticulous attention to wound care. We report a patient who developed painful vasculitic ulcers secondary to hydroxyurea on both lower legs whilst on long-term hydroxyurea therapy for idiopathic thrombocytosis. The ulcers extended relentlessly despite stopping hydroxyurea, maximizing topical therapies and starting intensive systemic treatment. We discuss the association of hydroxyurea therapy with the development of painful ulceration.

Aged↗
PubMed2001

Physical and psychologic measures are necessary to assess overall psoriasis severity.

BACKGROUND: The assessment of psoriasis severity is complex and involves both the physical and psychologic assessment of the individual patient. OBJECTIVE: We compared the Salford Psoriasis Index and several other tools for assessing psoriasis severity for their abilities to assess both the physical and psychologic effects of psoriasis. METHODS: A total of 101 patients (44 women, 57 men) were assessed by means of the Salford Psoriasis Index (SPI), Psoriasis Area and Severity Index (PASI), Self-Administered PASI (SAPASI), Psoriasis Disability Index (PDI), Hospital Anxiety and Depression Scale (HADS), and Illness Perception Questionnaire (IPQ). RESULTS: The "signs" score of SPI (which measures the clinical extent of psoriasis), PASI, and SAPASI correlated well with each other (r = 0.69-0.99; P <.01). They also correlated significantly, but not as strongly, with scores of psoriasis-induced disability, the PDI and SPI "psychosocial disability" score (r = 0.46-0.51; P <.01), but not with general measures of psychologic distress. There was no significant correlation between the historical treatment, "intervention," score in SPI and either the physical or the psychologic score in the SPI. The PDI and "psychosocial disability" score of SPI correlated well with each other (r = 0.69; P <.01) as well as with the depression and anxiety subscale scores of HADS (r = 0.33 and r = 0.37; P <.01, respectively), the total number of symptoms suffered by the patient (r = 0.38; P <.01), and the belief that stress or worry were associated with psoriasis (r = 0.33; P <.01). CONCLUSION: Physical scores of psoriasis severity such as PASI, SAPASI, and the "signs" component of SPI give a partial indication of psychosocial disability caused by psoriasis. In many patients, however, the physical score does not reflect psychosocial disability. Patients should be assessed by a more holistic approach, which takes into account both physical and psychologic measurements, such as used in SPI, when assessing the severity of psoriasis.

Adolescent↗