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Attila Dobozy

Publications and source records attributed to Attila Dobozy.

At least 19 recordsLinked to original sources
PubMed2007

Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children.

Tacrolimus ointment is a topical calcineurin inhibitor for the treatment of atopic dermatitis. The primary objective of this open-label study was to assess the long-term safety of tacrolimus ointment. The primary end-point was the incidence of adverse events. Secondary end-points included the Eczema Area and Severity Index and a modified version of this index. A total of 466 children with atopic dermatitis, aged 2-15 years, applied 0.03% or 0.1% tacrolimus ointment twice daily for up to 29.5 months. Skin burning and pruritus were the most common application site events; their prevalence decreased over time. There was no increase in viral infections or other adverse events over time. Laboratory profiles were consistent with those reported in atopic populations. Substantial improvement in all efficacy end-points was observed by week 2 and maintained throughout the study. Long-term treatment with tacrolimus ointment is safe and effective in these patients with atopic dermatitis.

Administration, Topical↗
PubMed2006

Effects of the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and galanin on the production of nerve growth factor and inflammatory cytokines in cultured human keratinocytes.

Neuropeptides released from the cutaneous sensory nerve endings have neurotransmitter and immunoregulatory roles; they exert mitogenic actions and can influence the functions of different cell types in the skin. The aims of this study were a systematic investigation of the effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL) on the inflammatory cytokine production (IL-1alpha, IL-8 and TNF-alpha) of the keratinocytes, and a study of their role in the production and secretion of nerve growth factor (NGF) and its precursor molecule (proNGF). Cultures of normal human keratinocytes were treated with 10(-8)M SP, CGRP, VIP or GAL for 30 min. After different time intervals, cells were harvested for total RNA isolation; in addition, cell lysates and supernatants were collected. The effects of the neuropeptides on the mRNA expressions of the different cytokines and NGF were investigated by Q-RT-PCR and the protein levels were studied by means of ELISA assays and Western blotting. Each of the four neuropeptides induced increases in the expressions of IL-1alpha, IL-8 and TNF-alpha mRNA. Increases appeared in the amount of the IL-1alpha protein in the supernatants of neuropeptide-treated cells, and the IL-8 secretion was mildly elevated, while secretion of TNF-alpha remained undetectable. The four neuropeptides increased the NGF mRNA expression to different extents. In the cell lysates of the keratinocytes, only proNGF could be detected, its concentration in the neuropeptide-treated cells being approximately twice that in the time-matched controls. Both control cultures and neuropeptide-treated cultures were found to secrete proNGF and mature NGF, but neuropeptide-treated cell cultures produced markedly higher (3-7-fold) amounts of NGF-like immunoreactive materials. The results demonstrated that neuropeptides released from cutaneous nerves after an injurious stimulus are able to induce an upregulation of IL-1alpha and IL-8 production; they are additionally able to influence the expressions of proNGF/NGF and their secretion from the keratinocytes. These findings may contribute toward an understanding of the neural influence on skin health and disease.

Calcitonin Gene-Related Peptide↗
PubMed2006

PUVA treatment of the nasal cavity improves the clinical symptoms of allergic rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin.

We earlier reported that intranasal irradiation with the 308 nm xenon chloride (XeCl) ultraviolet-B laser and irradiation with a combination of ultraviolet-B (UVB), ultraviolet-A (UVA) and visible light (VIS) is highly effective in the treatment of allergic rhinitis and inhibit the immediate-type hypersensitivity reaction in the skin. Since photochemotherapy with 8-methoxypsoralen (8-MOP) plus UVA light (PUVA) is widely used in the treatment of different inflammatory skin disorders due to its immunosuppressive effect, in the present study we investigated the efficacy of intranasal PUVA treatment in allergic rhinitis and the effect of PUVA treatment on the skin prick test (SPT) reaction. An open study was performed in 17 patients with hay fever. Intranasal PUVA therapy was given four times weekly for 3 weeks. The treatment was started with a fluence of 0.5x of the individual minimal phototoxic dose (MPD) and the dosages were gradually increased. Evaluation was based on the symptom scores. The effect of PUVA treatment on the allergen-induced wheal formation was also studied in the SPT. PUVA treatment of the nasal cavity significantly decreased the nasal symptoms of the patients with allergic rhinitis. Treatment of the skin with PUVA also significantly suppressed the allergen-induced wheal formation in the SPT reaction. These data suggest that intranasal PUVA phototherapy is also an effective modality in the treatment of allergic rhinitis.

Administration, Intranasal↗
PubMed2006

Necrolytic migratory erythema.

BACKGROUND: Necrolytic migratory erythema is considered to be a paraneoplastic dermatosis. The classical symptoms are associated with alpha-cell pancreatic islet cell tumor or 'glucagonoma'. Generally, extracutaneous hallmarks of this disease include weight loss, diabetes, anaemia and diarrhoea. OBSERVATION: We report a case of a 39-year-old woman with a 3-year history of recalcitrant psoriasiform eruption, who had no other associated symptoms on routine examination. Histologic examinations suggested necrolytic migratory erythema. Abdominal computer tomography was performed, which revealed a tumor in the tail of the pancreas. After distal resection of the pancreas her skin symptoms resolved in a few days time. Histology was consistent with glucagonoma. She is clinically well and symptomless and no signs of metastasis after 4 years. CONCLUSIONS: It is infrequent to have only necrolytic migratory erythema, hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in glucagonoma syndrome. To our knowledge, ours is the second such case reported in the literature. Skin symptoms are important, often they are the clue to the diagnosis of glucagonoma syndrome.

Adult↗
PubMed2006

Galanin receptor expression in cultured human keratinocytes and in normal human skin.

Galanin (GAL) is a biologically active neuropeptide that is widely distributed in the nervous system. GAL exerts diverse action via the GAL receptors (GALR1, GALR2, and GALR3), which belong in the superfamily of G-protein-coupled transmembrane receptors. In human skin, GAL-like immunoreactivity has been reported in free nerve endings and fibers of the dermis. The extraneuronal expression of GAL has also been demonstrated. Although the GALRs are essential for biological functions, the expressions of different GALR subtypes in cultured human keratinocytes have not yet been investigated. The aim of our study was to investigate the mRNA and protein expressions of the different GALRs in the HaCaT immortalized keratinocyte cell line and in cultured human keratinocytes. When reverse transcription (RT)-polymerase chain reaction (PCR) was used with different GALR-specific primers, only GALR2 mRNA was identified in cultured HaCaT cells and keratinocytes. Sequencing of the PCR products proved the presence of GALR2 mRNA in the keratinocytes. The presence of GALR2 protein was next investigated, using a polyclonal antibody against human GALR2. Both the HaCaT cells and the cultured keratinocytes displayed specific immunohistochemical staining, with higher intensity on the surface of the keratinocytes. Immunohistochemical investigations of normal human skin specimens revealed that GALR2 was expressed with high intensity in the basal layer of the epidermis and also around the hair follicles in the dermis. GAL treatment of the keratinocytes resulted in an increase in cytosolic Ca2+ concentration, suggesting that GALR2 is a functional receptor. Further studies are necessary to clarify the biological effects of GAL in the skin.

Adult↗
PubMed2006

The expression of keratinocyte growth factor receptor (FGFR2-IIIb) correlates with the high proliferative rate of HaCaT keratinocytes.

Keratinocyte growth factor receptor (KGFR = FGFR2-IIIb) is a tyrosine kinase receptor expressed by keratinocytes, which mediates the effects of fibroblast growth factors (FGF). There are contradictory data in the literature regarding the role of FGFR2-IIIb during the proliferation/differentiation programme of keratinocytes. In this study, we aimed to investigate whether overexpression of FGFR2-IIIb may have a role in the regulation of keratinocyte proliferation. We analysed the expression of FGFR2-IIIb in an in vitro HaCaT model system representing different stages of proliferation and differentiation of keratinocytes. Real-time RT-PCR and Western blot analyses demonstrated a correlation between FGFR2-IIIb mRNA and protein expression and the proportion of cells in S/G2/M phase in synchronized HaCaT keratinocytes and thus with proliferation activity (r = 0.96). After treatment with the antipsoriatic drug, dithranol, FGFR2-IIIb is downregulated dose dependently both at mRNA and protein levels. Moreover, when the rate of proliferation is decreased by the lack of cell attachment to the culturing surface, FGFR2-IIIb mRNA (P = 0.0315) and protein expressions were also reduced (P = 0.0242), while a differentiation marker, keratin 10, mRNA (P = 0.0003) and protein levels (P = 0.001) were increased (r = -0.92). Based on our results we conclude that FGFR2-IIIb expression in HaCaT keratinocytes corresponds with the proliferative activation of the cells and is not related to the differentiation programme.

Anthralin↗
PubMed2005

Alzheimer's lymphocytes are resistant to ultraviolet B-induced apoptosis.

In the present pilot investigation, the susceptibility of T-lymphocytes from Alzheimer's disease (AD) subjects (n=22) and aged-matched, non-demented controls (CNT) (n=12) was examined with ultraviolet (UV) B light-induced apoptosis in vitro. The basal apoptotic ratios were similar in both groups. However, the AD lymphocytes displayed significantly (p<0.0001) lower apoptotic levels than those of the CNT lymphocytes at all of the applied UVB exposure doses (100, 200 and 300 mJ/cm(2)). These observations indicate that AD lymphocytes are more resistant than CNT lymphocytes to UVB irradiation.

Aged↗
PubMed2005

[Connection between uveal melanoma and dysplastic naevus syndrome].

The dysplastic naevus syndrome increases the risk of cutaneous (RR: 4.36; CI: 1.84-10.36) as well as uveal melanoma (RR: 4.22; CI: 1.81-9.84). A significantly higher occurrence rate of conjunctival naevi (3.2% vs. 0%; p=0.029), choroidal naevi (5.2% vs. 0.7%; p=0.023) and iris freckles (17.1% vs. 5.6%; p=0.002) could be detected in the dysplastic naevus syndrome patients compared to subjects in the control group. The presence of cutaneous dysplastic naevi in uveal melanoma patients increases the risk of the prognostically worse--epitheloid or mixed--forms of uveal melanoma (RR: 5.97%; CI: 1.61-22.14), compared to patients without cutaneous atypical naevi.

Adult↗
PubMed2005

[Intranasal phototherapy for the treatment of allergic rhinitis].

INTRODUCTION: Allergic rhinitis is a frequent disease, accompanied by significant social-economic costs and a negative impact on the quality of life. Phototherapy has a profound immunosuppressive effect and is effectively used in the treatment of several immune mediated skin diseases such as atopic dermatitis. AIMS: The authors investigated the efficacy of intranasal phototherapy with a combination of low doses of ultraviolet-B, ultraviolet-A and visible light in allergic rhinitis. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with a history of at least 2 years of moderate to severe ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs. Intranasal phototherapy was performed 3 times a week for 3 weeks. As placebo low intensity visible light was used. RESULTS: Phototherapy resulted in a significant improvement of clinical symptoms for nasal itching, rhinorrhea, sneezing and total nasal score. Scores for nasal obstruction slightly improved during phototherapy while a significant increased was found in the placebo group. In the overall efficacy assessment, both patients and investigators found phototherapy significantly more efficient than placebo. Phototherapy was well tolerated, the only side effect was the slight dryness of the nasal mucosa. CONCLUSIONS: These results suggest that intranasal phototherapy is effective for the treatment of allergic rhinitis, and opens up new opportunities for the treatment of immune-mediated mucosal diseases.

Adult↗
PubMed2005

Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS.

To identify genetic factors contributing to psoriasis susceptibility, gene expression profiles of uninvolved epidermis from psoriatic patients and epidermis from healthy individuals were compared. Besides already characterized genes, we identified a cDNA with yet unknown functions, which we further characterized and named PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). In silico structural and homology studies suggested that PRINS may function as a noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA polymerase II, and it is expressed at different levels in various human tissues. Real time reverse transcription-PCR analysis showed that PRINS was expressed higher in the uninvolved epidermis of psoriatic patients compared with both psoriatic lesional and healthy epidermis, suggesting a role for PRINS in psoriasis susceptibility. PRINS is regulated by the proliferation and differentiation state of keratinocytes. Treatment with T-lymphokines, known to precipitate psoriatic symptoms, decreased PRINS expression in the uninvolved psoriatic but not in healthy epidermis. Real time reverse transcription-PCR analysis showed that stress signals such as ultraviolet-B irradiation, viral infection (herpes simplex virus), and translational inhibition increased the RNA level of PRINS. Gene-specific silencing of PRINS by RNA interference revealed that down-regulation of PRINS impairs cell viability after serum starvation but not under normal serum conditions. Our findings suggest that PRINS functions as a noncoding regulatory RNA, playing a protective role in cells exposed to stress. Furthermore, elevated PRINS expression in the epidermis may contribute to psoriasis susceptibility.

Base Sequence↗
PubMed2005

Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells.

Vaginal epithelium has a powerful innate immune system that protects the female reproductive organs from bacterial and fungal infections. In the present study, we aimed to explore whether the Toll-like receptor (TLR) signaling pathway and the induction of pro-inflammatory cytokines and antimicrobial peptides could contribute to the protection against pathogenic microorganisms in vaginal epithelia, using an immortalized vaginal epithelial cell line PK E6/E7 as a model. We found that TLR2 and TLR4 receptors are expressed in vivo in the vaginal epithelia and in vitro in PK E6/E7 vaginal epithelial cell line. The Gram-negative cell wall compound lipopolysaccharide (LPS), the Gram-positive compound peptidoglycan (PGN), heat-killed Candida albicans and zymosan significantly (P<0.05) induced the expression of pro-inflammatory cytokines and chemokines such as TNF-alpha and IL-8/CXCL8 in vaginal epithelial cells. Furthermore, the expression and production of human beta-defensin-2 (hBD2), an antimicrobial peptide with chemotactic functions, was also up-regulated in PK E6/E7 cells after treatment with LPS, PGN or C. albicans. Treatment of vaginal epithelial cells with microbial compounds induced the activation and nuclear translocation of NF-kappaB transcription factor, a key element of innate and adaptive immune responses. In our work, we provide evidence that microbial compounds induce the production of pro-inflammatory cytokines, chemokines and antimicrobial peptides in vaginal epithelial cells. In vivo, vaginal epithelial cell-derived inflammatory mediators and antimicrobial peptides may play important roles in vaginal immune responses and in the elimination of pathogens from the female reproductive tract.

Candida albicans↗
PubMed2005

Rhinophototherapy: a new therapeutic tool for the management of allergic rhinitis.

BACKGROUND: Phototherapy has a profound immunosuppressive effect and is able to inhibit hypersensibility reactions in the skin. OBJECTIVE: We evaluated whether phototherapy using a combination of UV-B (5%), UV-A (25%), and visible light (70%), referred to as mUV/VIS, is effective in treating allergic rhinitis. METHODS: We conducted a randomized, double-blind study, in 49 patients with hay fever. The study was performed during the ragweed season. Each intranasal cavity was illuminated 3 times a week for 3 weeks with mUV/VIS or with low-intensity visible light. Symptom scores, inflammatory cells, and their mediators were assessed in nasal lavages. In vitro effects of mUV/VIS irradiation on T-cell and eosinophil apoptosis and its inhibitory effect on mediator release from basophils were examined. RESULTS: Rhinophototherapy was tolerated well and resulted in a significant improvement of clinical symptoms for sneezing (P < .016), rhinorrhea (P < .007), nasal itching (P < .014), and total nasal score (P < .004). None of the scores improved significantly in the control group. Scores for nasal obstruction slightly improved after mUV/VIS treatment and significantly increased in the control group (P < .017). In the nasal lavage, phototherapy significantly reduced the number of eosinophils and the level of eosinophil cationic protein and IL-5. In vitro irradiation of T cells and eosinophils with mUV/VIS light dose-dependently induced apoptosis. Furthermore, mUV/VIS irradiation inhibited the mediator release from RBL-2H3 basophils. CONCLUSION: These results suggest that phototherapy is an effective modality to treat allergic rhinitis and offer new options for the treatment of immune-mediated mucosal diseases.

Apoptosis↗
PubMed2005

Experimental bullous pemphigoid generated in mice with an antigenic epitope of the human hemidesmosomal protein BP230.

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease that targets the hemidesmosomal proteins BP230 and BP180. To investigate the pathogenic role of anti-BP230 antibodies, rabbit polyclonal antibodies were generated against an antigenic sequence of the human BP230 antigen (BPAG 1, 2479-2499), which shows 67% homology in the human and the mouse BP230. Purified IgG from the rabbit anti-serum was transferred subcutaneously into the dorsal skin of neonatal isogeneic CBA/Ca (CBA) mice in a dose of 5 mg (n=7) or 1.2 mg IgG/50 microl (n=16). After 24 h, 1 of the mice injected with 5 mg IgG exhibited blisters, but the dorsal skin of all 7 of them was erythematous, and gentle friction produced a fine persistent wrinkling of the epidermis in 4 mice. The mice injected with 1.2 mg IgG developed less severe symptoms. Immunohistological examinations revealed linear rabbit IgG and mouse C3 depositions along the basement membrane of the perilesional skin and subepidermal blister formation. An intradermal inflammatory reaction (granulocyte infiltration) was also detected. None of these symptoms was seen in mice injected with IgG from a control rabbit anti-serum. These findings demonstrate that antibodies against BP230 can elicit the clinical and immunopathological features of BP in neonatal mice, suggesting that anti-BP230 antibodies may possibly play a pathogenic role in this disease.

Amino Acid Sequence↗
PubMed2005

Autoantibodies to human alpha6 integrin in patients with bullous pemphigoid.

Bullous pemphigoid (BP) is characterized immunologically by tissue-bound and circulating autoantibodies targeting the hemidesmosomal proteins BP230 and BP180. Recent evidence suggests a pathophysiological role for autoantibodies against alpha6 integrin in the subepidermal blister formation of oral pemphigoid. The objective of our study was to investigate the presence of anti-alpha6 integrin antibodies in patients with classical BP. The autoantibody profiles of 30 patients with BP, 10 patients with pemphigus vulgaris, and 20 healthy persons were identified. With the use of PeptideStructure and PlotStructure software, four different antigenic epitopes for alpha6 integrin were predicted, and their fusion recombinant constructs were prepared in an E. coli expression system. Sera were tested for alpha6 integrin autoantibodies by an ELISA technique. Altogether, 52% of the patients with BP displayed circulating antibodies against at least one recombinant protein. Our findings provide the first evidence for the presence of anti-alpha6 integrin antibodies in patients with classical BP.

Adult↗
PubMed2004

Inhibition of immediate type hypersensitivity reaction by combined irradiation with ultraviolet and visible light.

Recently we found that ultraviolet B (UVB) irradiation in erythematous doses significantly inhibited the immediate type hypersensibility reaction in the skin. In the present study we investigated the effects of different wavelengths on the skin prick test reaction (SPT). The forearm of ragweed allergic patients was irradiated with increasing doses of ultraviolet A (UVA), visible light (VIS) or combined UVB, UVA and VIS light, referred to as mUV/VIS. SPTs were performed 24 h after irradiation both on irradiated and non-irradiated control skin areas using ragweed extract. UVA and VIS irradiation led to a slight, not significant inhibition of allergen-induced wheal formation. Mixed irradiation with mUV/VIS light resulted in a dose-dependent inhibition of the allergen-induced wheal formation. The inhibition was significant already at suberythematous doses. As there is a good correlation between SPT and the nasal symptoms in patients with hay fever these data suggest that phototherapy with mUV/VIS light might be an effective and safe treatment modality for immediate type hypersensibility reactions in the skin and nasal mucosa.

Adult↗