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  • 1
    Electronic Resource
    Electronic Resource
    Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters (2000)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities. Objectives Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity. Patients and methods PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex®, Bristol Myers Squibb, Princeton, NJ, U.S.A.), a vitamin D3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects. Results PhK activity in units mg−1 protein was highest in active untreated psoriasis (1204 ± 804·3; mean ± SD), lower in the calcipotriol-treated group (550·7 ± 192·9), lower in curcumin-treated group (207·2 ± 97·6), and lowest in normal skin (105·4 ± 44·6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F3,36 = 48·79, P 〈 0·0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells. Conclusions Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2000.03767.x
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  • 2
    Electronic Resource
    Electronic Resource
    Basement membrane changes in psoriatic patients on long-term topical corticosteroid therapy (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 15 (1990), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been observed that the beneficial anti-inflammatory effects of topical steroids in psoriasis are counteracted by increasing instability of the disease, with rebound phenomena associated with the cessation of these drugs. We report the occurrence of multi-layered fragmentation and disorganization of the basal laminae in active, untreated psoriatic lesions, resolving and uninvolved, inadvertently steroid-treated psoriatic skin, as well as in a variety of non-psoriatic dermatoses treated with fluorinated topical steroids for prolonged periods. These changes, which were associated with a moderate to severe loss of dermal collagen, were not found in untreated and treated psoriatic controls, with or without concomitant α1-antitrypsin deficiency, who had not received steroids, suggesting that they were probably the consequence of prolonged fluorinated steroid use. This conclusion is supported by the observation that the largest number of layers (10-15) of fragmented basal laminae was noted in the patients who had received fluorinated steroids for 6 years or more, while those on 4 years or less of fluorinated steroid therapy exhibited only three to seven layers of fragmented basal laminae. In psoriatic lesions, the fragmentation of the basal lamina was associated with the presence of basal keratinocyte herniations (BKH), the frequency of which has been shown to parallel clinical psoriatic activity. The persistence of these electron-microscopic markers of psoriatic activity (i.e. BKH) in psoriatic plaques treated with prolonged fluorinated steroids suggests that loss of integrity of the basement membrane, as indicated by the presence of multi-layered fragmentation of the basal lamina, may account for the instability of the psoriatic lesions treated with prolonged topical fluorinated steroids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1990.tb02038.x
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  • 3
    Electronic Resource
    Electronic Resource
    Tannic-acid staining material on high endothelial venules and lymphocytes in skin and peripheral lymph nodes in Staphylococcus aureus-associated erythroderma (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 15 (1990), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The recognition and binding of glycoprotein receptors on lymphocytes to specific antigens present on high endo-thelial venules (HEV) precedes the egress of lymphocytes from the blood stream into the tissues. In this paper, we report the presence of HEVs with tannic-acid staining material (TASM+ HEVs) in Staphylococcus aureus-associated erythroderma, which allow the migration of CD8+ lymphocytes from the bloodstream into the epidermis. TASM positivity is also expressed on lymphocytes within the regional lymph nodes, and by intravascular lymphocytes prior to leaving the TASM+ HEV. It is proposed that TASM positivity may represent a molecule, which may function in binding lymphocytes to HEVs prior to egress from the HEV. (TASM is lost from lymphocytes after leaving the HEVs.) The expression of TASM positivity may form an essential part of the CDS+ lymphocyte-HEV recognition system, and may be the means whereby CD8+ lymphocytes generated in the regional lymph nodes by various mitogens (in this case by staphylococcal mitogens) may ‘home’ to specific sites within the epidermis. TASM positivity on both the HEVs and lymphocytes may serve as a convenient marker of such a system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1990.tb02134.x
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  • 4
    Electronic Resource
    Electronic Resource
    An electron microscopic study of the epidermal infiltrate in recurrent herpes simplex (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 14 (1989), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Host immunity has been suspected of playing a role in recurrent herpes simplex. In this preliminary ultrastructural study of two patients with acute herpetic eruption, it was noted that the keratinocytes exhibiting the most severe damage are those adjacent to large granular lymphocytes. In contrast, many keratinocytes filled with viral particles of herpes simplex show little or no signs of keratinocyte damage. These observations suggest that in recurrent herpes simplex the epidermal damage may be due, at least in part, to cell-mediated host immunity as well as to the viral infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1989.tb00931.x
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  • 5
    Electronic Resource
    Electronic Resource
    Reciprocity between tissue calmodulin and cAMP levels: modulation by excess zinc (1993)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 129 (1993), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Signal transduction of many intracellular events is initiated by a minute influx of calcium ions into the cells, resulting in the formation of calcium-calmodulin complex and cAMP. Because zinc appears to have an inhibitory effect on a number of tissue reactions, it is postulated that this occurs through modulation of intracellular calcium influx. To test the hypothesis that the inhibitory effects of zinc are mediated through the calcium calmodulin-cAMP pathway, zinc was administered by various routes to five groups of nude mice (control, intragastric, intraperitoneal. intradermal and oral groups), and calmodulin and cAMP concentrations were measured in the cytosol of epidermal cells. Calmodulin levels decreased significantly in the groups given intraperitoneal zinc (P〉0.025) and intradermal zinc (P〉0.001) injections. Significant elevations of cAMP levels were noted with intradermal zinc (P〉0.025). Overall, the relationship between calmodulin and cAMP appeared to be inversely logarithmic, with the lowest calmodulin levels associated with the highest cAMP concentrations. In addition, there was a significant trend towards a smaller calmodulin/cAMP ratio in all zinc-treated groups, except the mice fed dietary zinc. These results appear to correlate with tissue zinc levels obtained with these various forms of zinc administration. Our results therefore indicate that there is a reciprocity between epidermal calmodulin and cAMP levels, which may be modulated by external factors such as zinc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1993.tb11847.x
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  • 6
    Electronic Resource
    Electronic Resource
    Elevated phosphorylase kinase activity in psoriatic epidermis: correlation with increased phosphorylation and psoriatic activity (1994)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 130 (1994), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary To determine whether abnormal activity of a calmodulin-containing enzyme which catalyses phosphorylation reactions may play a pathogenetic role in psoriasis, the presence and activity of phosphorylase kinase (PK) in human epidermis were determined in patients with untreated/active psoriasis (n=10), treated/resolving psoriasis (n= 10), and non-psoriatic controls (n= 10). Biopsies were taken from involved and uninvolved skin for PK, organic phosphorus, and inorganic phosphate estimation, and light and electron microscopy. The enzyme was present in involved and uninvolved skin of every patient in the study. PK activity (units/mg protein) was significantly higher in active psoriasis than in resolving psoriasis and controls. PK activity correlated directly with organic phosphorus levels, and inversely with the extent of cellular glycogenolysis measured by the depletion of glycogen granules within the keratinocytes. The study demonstrates that PK is present in both psoriatic and normal epidermis, with significantly higher levels in active psoriasis. Furthermore, higher levels of PK activity, glycogenolysis and phosphorylation are associated with increased clinical psoriatic activity. We conclude that PK, a calmodulin-containing enzyme, is involved in regulating calcium-dependent phosphorylation events in human epidermis, and disturbance of its activity may play a key role in the clinical manifestations of psoriasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1994.tb02924.x
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  • 7
    Electronic Resource
    Electronic Resource
    Haemorrhagic cellulitis: a syndrome associated with tumour necrosis factor-α (1994)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 130 (1994), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary A newly defined clinical syndrome, haemorrhagic cellulitis, is described in 12 patients. The syndrome consists of an acute onset of extremely painful erythema affecting dependent areas, followed by dermal haemorrhage and sloughing of the overlying epidermis, and requiring both antibiotics and systemic corticosteroids for complete resolution. The patients usually have demonstrable Gram-negative or Gram-positive infection, of non-cutaneous origin, and underlying systemic disease. Vacuolopathic necrosis of epidermal keratinocytes, and damaged vascular endothelium of the dermal blood vessels can be demonstrated by light and electron microscopy, as well as by lectin studies. Immunocytochemical studies reveal the presence of activated macrophages and T lymphocytes. We believe the syndrome is due to lipopolysaccharide-induced or bacterial mitogen-induced tumour necrosis factor-alpha (TNF-α), secreted by previously primed activated macrophages in a second-set response. TNF-α characteristically injures endothelial cells and epidermal keratinocytes. It is thought to induce its cytotoxic effects partly via neutrophil degranulation, and partly via DNAase activation, with resultant DNA fragmentation and cell lysis. Corticosteroids have been shown not only to inhibit TNF-α secretion by activated macrophages. but also to block its cytotoxicity, thus accounting for the extremely rapid clinical response to this drug in conjunction with adequate and appropriate antibiotic therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1994.tb06885.x
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