Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in patients with chronic plaque psoriasis.

BACKGROUND: Psoriasis is a common inflammatory cutaneous disorder characterized by activated T-cell infiltration. T lymphocytes bearing natural killer cell receptors (NKRs) have been suggested to play an important role in the pathogenesis of psoriasis. However, the expression pattern of activating and inhibitory NKRs on T lymphocytes from psoriatic patients and its significance in psoriasis needs further study. OBJECTIVES: To investigate the pathogenesis of NKR-expressing T cells in psoriasis. MATERIALS AND METHODS: Thirty patients with chronic plaque psoriasis and 20 healthy controls were enrolled in this study. The immunophenotypic profiles of NKRs, including CD56, CD16 (activating NKRs), CD158a, CD158b, CD94 and NKG2A (inhibitory NKRs), were analysed in peripheral blood T lymphocytes, as well as psoriatic lesional infiltrating T cells, by triple-fluorescence flow cytometry. RESULTS: A significant increase of inhibitory CD8+ CD158b+, CD4 CD8 CD158b+ and CD8+ CD94/NKG2A+ T cells was found in the peripheral blood of patients with psoriasis when compared with controls. Tissue-infiltrating T lymphocytes expressing inhibitory receptors CD158b, CD94 and NKG2A were found in psoriatic lesions. There was a significant positive correlation between the increased percentage of circulating CD8+ CD94/NKG2A+ T cells and the Psoriasis Area and Severity Index. CONCLUSIONS: In the present study, we demonstrated increased proportions of particular subsets of inhibitory CD158b+ and/or CD94/NKG2A+ T cells in patients with psoriasis. The elevation of these inhibitory NKR-expressing T cells was correlated with disease severity, which may signify the possibility of chronic antigen-driven stimulation and dysregulated cytokine production in the pathogenesis of psoriasis.

Pattern of skin diseases in a geriatric patient group in Taiwan: a 7-year survey from the outpatient clinic of a university medical center.

BACKGROUND: Geriatric health care has become a worldwide concern, but relatively few statistical studies are available about geriatric skin diseases. Moreover, no information exists regarding skin disorders among the elderly population in Taiwan that has become a geriatric country. OBJECTIVE: To determine the characteristic pattern and the prevalence of various skin disorders for the elderly who visited the National Taiwan University in the last 7 years. METHODS: Using a database from the Dermatology Outpatient Clinic of the National Taiwan University Hospital, 1993-1999 file, we conducted a retrospective cross-sectional study by evaluating the age, proportion, and gender of each specific cutaneous disease category, chi(2) tests were used for analyzing statistical significance. The analysis supplied odds ratios and 95% confidence intervals. RESULTS: A total of 16,924 patients aged 65 years and older, which constituted 11% of the total patients seen at the Clinic of Dermatology from 1993 through 1999, were studied. The male to female ratio was 1.3 to 1. The most common cutaneous disorder in the elderly was dermatitis (58.7%), followed by fungal infections (38.0%), pruritus (14.2%), benign tumors (12.8%), and viral infections (12.3%). Cutaneous malignant tumors were found in 2.1%. Basal cell carcinoma occurred in 29.8%, actinic keratosis in 22.4%, Bowen's disease in 13.3% and squamous cell carcinoma 13.3%. Interestingly, our cases of extramammary Paget's disease showed a male predominance. Most melanomas were acral lentiginous melanoma located on the soles. The prevalence of common diseases in elderly patients compared with those outpatients of less than 65 years showed a 3-fold increased risk for pruritus. Moreover, the pattern of geriatric skin diseases in Taiwan was significantly different from Western countries. CONCLUSION: The prevalence of skin diseases in elderly patients emphasizes the importance of health education in geriatric people in Taiwan concerning appropriate use of emollients, proper foot care, sun protection and early detection of skin cancers.

The effect of a phorbol ester on amphibian myogenesis.

The effect of a phorbol ester (TPA) on myogenesis of urodelian embryo has been investigated. Presumptive somites were extirpated from mid-neurula, the stage when they have already attained certain degree of determination. The explants were treated with TPA (10 ng/ml in Steinberg solution with the addition of 10% Leibovitz's L-15) for 4 days, the period during which the frequency and size of gap junctions in normal myogenic cells are at the maximum. After the treatment many cells became dispersed and isolated while others spread out and remained connected in the form of a sheet. During further culture for 6 days in the solution without TPA myogenesis was blocked. Both the dispersed cells and the cells in a sheet remained at the earliest stage of muscle differentiation with irregular shape or in the form of myoblast, while cells of the control series formed myotubes containing bundles of myofibrils. The result suggests that the blockage of myogenesis is the consequence of interruption of junctional communication evoked by TPA treatment.

Coupling of gap junctions by induction of impulse conductivity in cultured epithelium of newt embryo (Cynops orientalis).

Impulse generation and propagation was previously shown to occur in skin epithelium of newt (Cynops orientalis) embryos during certain stages of development and to be correlated with morphological changes of gap junctions. These properties are not detected in embryonic epithelia explanted and grown in culture. However, early explants when transplanted to a host embryo develop conductivity, and relatively large gap junctions with loose arrangement of connexons occur as soon as the host embryo reaches the stage when conductivity is at its maximum. In contrast, morphological and physiological characteristics of impulse propagation are lost when the transplanted epithelium is extirpated from the host embryo and returned to in-vitro conditions. Therefore, it appears that impulse propagation is dependent not solely on the differentiation of epithelial cells but upon signals from non-epithelial (possibly mesodermal) tissue as well.

Gap junctions and impulse propagation in embryonic epithelium of Amphibia. A freeze-etching study.

Epithelium of amphibian embryos (Cynops orientalis, Xenopus laevis) was found in preceding experiments to generate and conduct impulses during a limited stage (26-37) of development . In order to elucidate the structural basis of impulse propagation, epithelial cells of four stages were examined by the freeze-etching method: (I) before and (II) during acquisition of conductivity; (III) when propagation was fully established, and (IV) when it was no longer present. Only few gap junctions (GJ) of small size were found in groups I and IV. GJ in epithelia of group III were increased in number and size, and appeared morphologically "coupled", i.e., with more loosely arranged connexons. the size of gap-junctional particles did not differ significantly between coupled and uncoupled stages. Zonulae occludentes seemed "leaky" in stage *, and "tight" in stages II-IV. Thus, the morphological characteristics of specialized junctions between "non excitable cells" correlated with the opening and closing of low resistance intercellular current pathways during embryonic development. Gap junctions in particular seem to form an essential link in the non-neural stimulus-response system, which may facilitate the mobility of the embryo during early phases of aquatic life before the reflex pathways have been established. Coupling and uncoupling of gap junctions may also play an important role in the regulation of cell differentiation and morphogenetic movement. The experimental model used in this study provides a useful tool for further investigations of structural correlates of gap junctional permeability under physiological conditions.