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Biomedical subjects

J C Szepietowski

Publications and source records attributed to J C Szepietowski.

17 recordsLinked to original sources

Vascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patients.

BACKGROUND: Vascular adhesion protein (VAP)-1 is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes. OBJECTIVES: The aim of this study was to investigate the expression of VAP-1 in the skin and serum of psoriatic patients. MATERIAL AND METHODS: Seventy-one patients suffering from psoriasis aged between 23 and 89 years were included in the study. The mean psoriasis severity assessed according to the psoriasis area and severity index was 14.2+/-9.6 points. The soluble VAP-1 serum concentration was evaluated by ELISA and VAP-1 expression in the skin (nine patients) immunohistochemically. RESULTS: The serum concentration of soluble VAP-1 was significantly higher in psoriatic patients than in healthy controls (403.4+/-130.8 ng/mL vs. 246.4+/-68.0 ng/mL; P<0.0001). No significant relationships were found between sVAP-1 concentration and studied clinical parameters, except the presence of pruritus. Mean number of VAP-1 positive vessels in psoriatic skin, both lesional (19.8+/-1.4) and non-lesional (9.4+/-1.4), was significantly higher than in healthy skin (5.4+/-1.5; P<0.005). Lesional psoriatic skin demonstrated significantly more VAP-1 positive vessels than non-lesional skin (P<0.01). CONCLUSIONS: Significant overexpression of VAP-1 in both lesional and non-lesional psoriatic skin and higher serum level of soluble VAP-1 in psoriatic patients may indicate the role of VAP-1 in chronic inflammation occurring in psoriasis. However, because of lack of correlation between soluble VAP-1 serum levels and psoriasis severity this hypothesis needs further investigation.

Adult↗

The multifunctional role of leukaemia inhibitory factor in cutaneous biology.

Leukaemia Inhibitory Factor (LIF) is a polyfunctional cytokine, that belongs to the family of haemopoietic growth factors. LIF plays a role in growth-promotion and differentiation, regulates calcium and bone metabolism, induces acute phase proteins and causes cachexia in organisms with neoplastic disorders. LIF is also to be found in normal skin, where it may be involved in the differentiation process of keratinocytes. In addition, recent data in medical literature indicates that LIF is engaged in the pathogenesis of some skin disorders as well. It has been clearly demonstrated that LIF may act as a proinflammatory cytokine. In allergic contact dermatitis, the expression of LIF mRNA is augmented to a significant degree, indicating that LIF may play a role in the early phase of allergic contact dermatitis. LIF also plays an important role in psoriatic lesions. As the mechanism is not yet fully understood, however, it is hypothesized that the LIF function in psoriatic processes is solely connected with IL-8, as it is known that LIF is able to induce the release of IL-8. Also, some reports have suggested that LIF may also play a role in the carcinogenesis of the skin.

Journal Article↗

Itch: scratching more than the surface.

In origin, itch can be cutaneous ("pruritoceptive", e.g. dermatitis), neuropathic (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or psychogenic. Although itch of cutaneous origin shares a common neural pathway with pain, the afferent C-fibres subserving this type of itch are a functionally distinct subset: they respond to histamine, acetylcholine and other pruritogens, but are insensitive to mechanical stimuli. Histamine is the main mediator for itch in insect bite reactions and in most forms of urticaria, and in these circumstances the itch responds well to H(1)-antihistamines. However, in most dermatoses and in systemic disease, low-sedative H(1)-antihistamines are ineffective. Opioid antagonists relieve itch caused by spinal opioids, cholestasis and, possibly, uraemia. Ondansetron relieves itch caused by spinal opioids (but not cholestasis and uraemia). Other drug treatments for itch include rifampicin, colestyramine and 17-alpha alkyl androgens (cholestasis), thalidomide (uraemia), cimetidine and corticosteroids (Hodgkin's lymphoma), paroxetine (paraneoplastic itch), aspirin and paroxetine (polycythaemia vera) and indometacin (some HIV+ patients). If the remedies specified fail, paroxetine and mirtazapine should be considered. Ultraviolet B therapy, particularly narrow-band UVB, may be superior to drug treatment for itch in uraemia.

Analgesics, Opioid↗

Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus.

The pathogenesis of uraemic pruritus is unclear, although there is some evidence that an increased number of skin-infiltrating mast cells may play a role. Ultraviolet B reduces itchy sensation of uraemic patients by leading to depletion of cutaneous mast cells. This study presents data that both broad-band and narrow-band ultraviolet B irradiation are able to induce apoptosis in transformed mast cells (murine mastocytoma cell line P815) in a dose-dependent manner at a time point of 24 hours. The positive apoptotic rates were as follows: sham-exposed cells (controls) -- 13.3% +/- 0.6%; with broad-band ultraviolet B irradiation -24.5% +/- 1.1% with 10mJ/cm(2), 57.9% +/- 4.6% with 20mJ/cm(2) and 70.9% +/- 4.5% with 30mJ/cm(2); with narrow-band ultraviolet B irradiation -- 29.6% +/- 2.3% with 100mJ/cm(2), 57.3% +/- 4.1% with 200mJ/cm(2) and 81.5% +/- 1.9% with 300mJ/cm(2). The difference between the number of apoptotic cells in all groups of ultraviolet B-irradiated cells and sham-exposed cells was highly significant (P<0.001). Based on these findings, it is hypothesized that ultraviolet B induced mast cell apoptosis could be an important factor in phototherapy for the diseases dependent on increased number of cutaneous mast cells, including uraemic pruritus.

Animals↗

Leukaemia inhibitory factor and interleukin-8 expression in nonmelanoma skin cancers.

Leukaemia inhibitory factor (LIF) and interleukin (IL)-8 possess activities which may contribute to the development of carcinomas. LIF can stimulate proliferation of some tumour cell lines and IL-8 is angiogenic. Using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we measured the expression of LIF and IL-8 mRNA in cultured normal keratinocytes (NKC) and the malignant carcinoma cells lines A431, SiHa, HeLa, and in biopsies of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin. Protein expression for LIF was assessed by immunohistochemistry in the biopsies. LIF mRNA expression was increased significantly (P < 0.01) in all carcinoma lines, except SiHa, compared with NKC but the IL-8 mRNA expression in carcinoma cell lines was similar to that in NKC. Expression of LIF mRNA was elevated in BCC and SCC compared with normal skin, but a significant difference was observed only between SCC and normal skin (P < 0.01). Both BCC and SCC showed significantly greater expression of IL-8 compared with normal skin (P < 0.01). There was no correlation between LIF and IL-8 mRNA expression either in BCCs or in SCCs. Immunoreactivity for LIF was absent throughout BCC and SCC, however, normal epidermis surrounding the tumour stained positive, as in normal skin. These data may suggest a role for LIF and IL-8 in the development of skin carcinomas, but without co-ordinate regulation of these two cytokines in this process.

Adult↗

Brooke-Spiegler syndrome.

The Brooke-Spiegler syndrome is an autosomal dominant one characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. Within a given family, some members may have cylindromas whereas others may have trichoepitheliomas or both. We describe the coexistence of trichoepithelioma papulosum multiplex (also known as epithelioma adenoides cysticum of Brooke) and cylindromas in a 30-year-old man, and discuss the relationship between these two autosomal dominant syndromes.

Adult↗

Increased interleukin-7 levels in the sera of psoriatic patients: lack of correlations with interleukin-6 levels and disease intensity.

Interleukin (IL)-7 is a multifunctional cytokine which is involved in the regulation of keratinocyte-T lymphocyte interactions; the latter is an important factor in the pathogenesis of psoriasis. In vitro, IL-7 is able to induce release of cytokines, including IL-6; IL-6 expression is known to be enhanced in psoriatic patients. Serum levels of IL-7 and IL-6 were measured by ELISA in 40 psoriatic patients and compared with cytokine levels in 18 healthy individuals. Serum levels of IL-7 were also evaluated in 24 psoriatic patients during the remission of the disease after effective treatment. The IL-7 and IL-6 serum levels were significantly higher in psoriatic patients than in healthy subjects and the IL-7 serum levels did not significantly decrease after treatment. Serum levels of IL-7 did not correlate with PASI scores; however, a significant positive relationship was observed between IL-6 levels and PASI scores. There was no correlation between increased levels of IL-7 and IL-6 in the sera of psoriatic patients, suggesting the lack of a direct link between these two cytokines in the psoriatic process. In conclusion, increased IL-7 serum levels suggest that IL-7, like IL-6, may be involved in the pathogenesis of psoriasis, but in contrast with IL-6, serum IL-7 levels could not be used as a marker of disease activity in psoriatic patients.

Administration, Topical↗

Is renal function altered in patients with psoriasis vulgaris?--A short review.

Psoriasis is a chronic inflammatory dermatosis with distinct microvascular changes. Although it is generally accepted that the psoriatic process is limited to the skin, it is not excluded that similar vascular lesions might be present in internal organs, such as the kidneys. This review summarizes data on renal function in psoriatic patients who were never treated with the potentially nephrotoxic drugs used for treatment of psoriasis. The limited number of such studies is mainly concentrated on microalbuminuria. Enhanced urinary albumin excretion at the level of microalbuminuria has been found in some psoriatic individuals. All other routine laboratory renal tests were within their normal ranges. As microalbuminuria is regarded as a subclinical marker of glomerular dysfunction, the authors hypothesize that some psoriatic patients may present subclinical glomerular changes. However, kidney histopathology is necessary to confirm this hypothesis.

Albuminuria↗

Uremic pruritus.

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Humans↗

Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis.

The influence of atopy on delayed-type hypersensitivity remains unclear. The expression of cytokine mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in biopsy skin taken 24 h after the application of a 5% NiSO4 patch to five patients with atopic dermatitis and seven non-atopic subjects with previously proven contact allergy to nickel. Control specimens were obtained from untested and vehicle-tested skin from the same individuals. There was a significant increase in the mRNA expression for interferon-gamma (IFN-gamma), interleukin (IL)-2 and IL-4 together after nickel challenge in both patients (analysis of variance P = 0.007) and non-atopic-individuals (P = 0.005). In contrast, IL-10 mRNA increased in the non-atopic group only. These results show that atopic patients and normal subjects have a similar immunological reaction to nickel challenge. Moreover, it is suggested that both Th1- and Th2-type cytokines are involved in the immunopathogenesis of contact dermatitis.

Adult↗

Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

Adult↗