The extra domain A of fibronectin (EDA+ oncofetal isoform of fibronectin was recently reported to be overexpressed in psoriatic uninvolved epidermis. It has been proposed that the abnormal presence of EDA+ oncofetal protein at the dermal-epidermal junction in the uninvolved skin may provide the "psoriatic" environment in which keratinocytes are in a preactivated state with regard to mitogenic signals (e.g., T cell lymphokines). To determine the possible sources of cellular fibronectin in the non-lesional psoriatic skin, we aimed to investigate whether keratinocytes could produce the EDA+ oncofetal form of fibronectin. RT-PCR studies revealed that both cultured normal keratinocytes and HaCaT cells express the EDA+ splice variant of fibronectin mRNA, and in HaCaT cells the EDA+/EDA- transcript ratio was elevated compared with normal keratinocytes. Cultured keratinocytes and HaCaT cells showed intracytoplasmic staining with an EDA+ fibronectin-specific antibody and among the positively stained cells many showed mitosis. Using RT-PCR, western blot analysis, and flow cytometry, we showed that in synchronized HaCaT cells the amount of both total fibronectin and its EDA+ isoform change with the proliferation/differentiation state of HaCaT cells and peak in highly proliferating cells. We show that in short-term ex vivo cultures, a small population of EDA+ fibronectin containing cell population appear among psoriatic uninvolved, but not normal epidermal cells. We also demonstrate that cell attachment has a strong influence on the expression of both total and EDA+ fibronectin. Our results suggest that proliferating keratinocytes could be the sources of the psoriasis susceptibility-related EDA+ oncofetal fibronectin in the epidermis.
Antidrug antibodies have been shown to be associated with a loss of response during biologic therapy. Despite the potential association, there has been no report on the simultaneous monitoring of the following parameters in psoriasis: presence of neutralizing antibodies, plasma tumor necrosis factor (TNF)-a concentration, TNFi concentration and disease activity. Plasma concentrations of adalimumab, infliximab, etanercept and their respective antidrug antibodies, as well as plasma concentrations of TNF-a were measured in 77 psoriasis patients receiving biologic therapy, and the values were correlated with the clinical activity of the skin disease. Antidrug antibodies were identified in the plasma of 25% of infliximab-treated patients and 29.6% of adalimumab-treated patients, but not in the etanercept group. Clinical severity scores were significantly higher in the antibody-positive patients. In patients receiving infliximab or adalimumab therapy, the presence of antidrug antibodies was directly associated with reduced plasma TNF-inhibitor concentration and elevated plasma TNF-a level.
The aim of this study was to investigate the efficacy of the sequential combined 585 nm PDL and the 1064 nm neodymium:yttrium-aluminium-garnet laser (PDL/Nd:YAG) in the treatment of surgical scars and to evaluate the short-term effects by in vivo confocal microscopy (RCM) and the long-term effects by clinical assessment of the scars. Twenty-five patients were enrolled with 39 postoperative linear scars; each scar was divided into two fields. One half was treated with the combined PDL/Nd:YAG laser, whereas the other half remained untreated. Each scar was treated three times at monthly intervals. Scars were evaluated by an independent examiner, using the Vancouver Scar Scale. The combined PDL/Nd:YAG laser significantly improved the appearance of the scars. In order to study the short-term effects of combined laser treatment, six additional patients were enrolled with 7 postoperative linear scars. One half of scars was treated once with the combined PDL/Nd:YAG laser. One week after this laser treatment, both the treated and the nontreated parts of the scars were examined by dermoscopy and RCM. The dermoscopic pictures revealed improvements even in treated areas. In conclusion, the combined PDL/Nd:YAG laser was found to be effective in improving the quality and appearance of the surgical scars.
We report on two sisters with Perrault's syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They were deaf-mute and of normal height with a few minor somatic anomalies. Both had streak gonads and an apparently normal female 46,XX chromosome constitution. The parents were apparently not consanguineous. The mother had normal hearing. Other relatives were not available for study. Epilepsy, which occurred in three relatives including one of the index patients, may have been inherited coincidentally from the mother's family.
The occurrence of endometriosis in streak gonad syndrome is extremely rare and to our knowledge, our patient is only the 4th case reported so far. Since hormonal replacement is important for patients with ovarian failure, the surgical approach is suggested as the treatment of choice for endometriosis in streak gonad syndrome.
Non-melanoma skin cancers are the most common skin tumors. Because of their frequent localization on the face and hand, aesthetic aspects of the therapeutic procedures should also be considered. Surgical excision still remains the first choice, but recently several new alternative therapies have emerged, especially for the treatment of superficial skin cancer. Photodynamic therapy has become a widely accepted therapeutic method for certain non-melanoma skin tumors. Photodynamic therapy involves the use of light to activate a photosensitizer, localized in diseased tissues. Photosensitizers are tumor-selective: their accumulation in rapidly proliferating cells and newly formed blood vessels is significantly higher than in the surrounding healthy tissues. During photodynamic therapy, cytotoxic reactive oxygen species are formed from the photosensitizer, leading to changes in subcellular pathways or apoptosis of the cells. Efficacy of the photodynamic therapy has been proven in solar keratosis, superficial basal cell carcinoma and morbus Bowen, with significantly better cosmetic outcome than that of the conventional therapeutic methods. Side effects, like erythema, crusting, serous discharge, or oedema, are usually moderate, and dissolve rapidly. The present article summarizes the authors' experiences with photodynamic treatment (212 non-melanoma skin cancer patients were treated with PDT between December 2003 and January 2006), at the Department of Dermatology and Allergology, University of Szeged, Hungary, and reviews the literature of photodynamic therapy in dermatooncology.
The detailed cytogenetic study of six Xq isochromosomes, i(Xq), and two isodicentric Xq chromosomes revealed that both their banding and their inactivation patterns differ as a result of differences in their mechanisms of origin. The arms of Xq isochromosomes may be expected to be mirror images in respect of their morphologic pattern and DNA replication sequence only in dicentric Xq isochromosomes.
Lymphangiography of the lower extremities was performed in 21 patients with ovarian dysgenesis. Seventeen subjects turned out to have hypoplastic superficial lymph vessels of the lower limbs. Aplasia of the lymphatics of the legs occurred in four instances. Hypoplastic lymph pathways were also observed in the pelvis and in the retroperitoneal space. Although the impairment of the lymphatic channels occurred in all cases of ovarian dysgenesis, it appears that it is more severe in patients with streak gonads. There was no correlation between the lymphatic defect and the karyotype. Patients with and without lymphedema had similar lymphatic defects. Our findings suggest that hypoplasia of the superficial lymph vessels of the lower limbs is a common abnormality in patients with ovarian dysgenesis irrespective of their chromosomal complements. The hypothesis that lymphedema in ovarian dysgenesis is mainly attributable to hypoplasia of the lymphatic channels is supported by this study. However, it appears that other factor(s) may also play a role in the pathogenesis of the lymphedema, since, despite lymphatic hypoplasia, lymphedema does not develop in all instances.
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