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1.
Asian Pac J Allergy Immunol ; 38(3): 186-189, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30903995

RESUMO

BACKGROUND: Dental treatment for patients with self-reported metal allergy or concern about the possibility of having such an allergy is often difficult; such patients often undergo dermatological consultations for metal patch test (PT). OBJECTIVE: This study compared PT results for metal allergens and the clinical relevance of this among patients visiting Fukuoka Dental College Hospital. METHODS: We performed PT with metal allergens on patients with oral mucosa- or skin-related symptoms, or those concerned about adverse events associated with upcoming dental treatment. RESULTS: Fifty-nine patients were patch-tested with metal allergens. Thirty-four cases (58.8%) had self-reported metal allergy. Regarding comorbidities, atopic dermatitis was the most common (7 cases), followed by hand eczema, palmoplantar pustulosis, lichen planus, and abnormal sensation in the mouth. Overall, 25 of 59 cases had at least one positive PT reaction. The most common positive allergen was nickel sulfate (17 cases), followed by cobalt chloride, zinc chloride, and palladium chloride. The rate of positivity of metal PT was significantly higher in the self-reported metal allergy cases than in the others (P < 0.001). Other comorbidities were not significantly associated with those with or without self-reported metal allergy. Five of those without self-reported metal allergy showed positive PT reaction. CONCLUSIONS: Patients with self-reported metal allergy exhibited more metal PT reactions than those without this. One fifth of those without this showed positive metal PT reaction, implying the importance of PT for both with and without self-reported metal allergy. PT results are helpful for selecting dental metals for future prosthetic and orthodontic treatments.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/imunologia , Metais/imunologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Hipersensibilidade/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Autorrelato , Testes Cutâneos , Adulto Jovem
2.
Exp Dermatol ; 25(5): 368-74, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26909655

RESUMO

Although the major autoantigens in classic pemphigus are desmogleins, sera from various types of pemphigus react with a number of other molecules, including desmocollins and plakin proteins. However, other novel pemphigus-related autoantigens remain to be identified. In this study, immunoblotting for serum from an atypical autoimmune bullous disease patient identified an unknown 175 kDa protein. Subsequent studies using two-dimensional gel electrophoresis, immunoblotting and mass-spectrometry identified the 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including indirect immunofluorescence of skin and cultured keratinocytes, two-dimensional gel electrophoresis and immunoblotting with anti-EEA1 polyclonal antibody, and preabsorption with EEA1 recombinant protein. Finally, we developed a novel BIOCHIP assay using full-length EEA1 recombinant protein to detect anti-EEA1 antibodies. However, none of 35 sera from various types of pemphigus showed anti-EEA1 antibodies in the BIOCHIP assay, with the exception of the serum from the index case. In addition, various findings in the index case did not suggest pathogenic role of anti-EEA1 autoantibodies. Therefore, although we successfully identified the 175 kDa protein reacted by a serum of an atypical pemphigus-like patient as EEA1, novel BIOCHIP study for other pemphigus sera indicated that EEA1 is not a common and pathogenic autoantigen in pemphigus.


Assuntos
Autoanticorpos/imunologia , Pênfigo/imunologia , Proteínas de Transporte Vesicular/imunologia , Animais , Células COS , Chlorocebus aethiops , Humanos , Masculino , Pessoa de Meia-Idade
3.
Am J Dermatopathol ; 38(2): 121-3, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26067456

RESUMO

Immunoreactants are found in the epidermal basement membrane in both lupus erythematosus and bullous pemphigoid (BP). To our knowledge, there are no comparative studies on direct immunofluorescence (DIF) of discoid lupus erythematosus (DLE) and BP. The authors studied DIF of lesional skins in 9 patients (2 males and 7 females) with DLE and 29 patients (11 males and 18 females) with BP to disclose the difference between these 2 diseases. IgG deposition was significantly more frequent at the epidermal basement membrane zone (BMZ) in the BP group than in the DLE group; however, IgA and IgM depositions were significantly more frequent at both the epidermal and follicular BMZs in the DLE group than in the BP group. In addition, the mean number of positive immunoreactants at both the epidermal and follicular BMZs was significantly larger in the DLE group than in the BP group. On an average, ≥3 immunoreactants were seen at the epidermal and follicular BMZs in DLE, whereas ≤2.5 immunoreactants were seen in BP. DIF may contribute to the differentiation between these 2 diseases.


Assuntos
Complemento C3/análise , Técnica Direta de Fluorescência para Anticorpo , Imunoglobulina A/análise , Imunoglobulina M/análise , Lúpus Eritematoso Discoide/imunologia , Penfigoide Bolhoso/imunologia , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/análise , Biomarcadores/análise , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Discoide/patologia , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/patologia , Valor Preditivo dos Testes , Pele/patologia , Adulto Jovem
4.
Exp Dermatol ; 24(1): 62-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25346431

RESUMO

Peroxisome proliferator-activated receptors (PPARs) are potentially useful for the treatment of skin diseases, because they stimulate keratinocyte differentiation, exert anti-inflammatory effects and improve barrier function. We examined five PPAR-γ agonists, including four thiazolidinediones (ciglitazone, troglitazone, rosiglitazone and pioglitazone) and an angiotensin-II receptor blocker (telmisartan), for their ability to upregulate filaggrin and loricrin expression at both mRNA and protein levels in cultured normal human keratinocytes (NHKs). Troglitazone, rosiglitazone, pioglitazone and telmisartan significantly increased filaggrin expression at both mRNA and protein levels in calcium-induced differentiated NHKs. Rosiglitazone and pioglitazone, but not troglitazone nor telmisartan, also significantly increased loricrin expression at both mRNA and protein levels in differentiated NHKs. These effects were not found in undifferentiated NHKs nor differentiated NHKs treated with ciglitazone. This study revealed differential effects of various PPAR-γ agonists on epidermal differentiation, and the most potent of those are rosiglitazone and pioglitazone.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Filamentos Intermediários/química , Queratinócitos/efeitos dos fármacos , Proteínas de Membrana/química , PPAR gama/agonistas , Tiazolidinedionas/química , Anti-Inflamatórios/química , Benzimidazóis/química , Benzoatos/química , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cromanos/química , Proteínas Filagrinas , Humanos , Queratinócitos/citologia , Microscopia de Fluorescência , Pioglitazona , RNA Mensageiro/metabolismo , Rosiglitazona , Pele/efeitos dos fármacos , Telmisartan , Troglitazona
5.
Exp Dermatol ; 24(3): 217-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25496384

RESUMO

In this study, we attempted to identify unknown autoantigen for intraepidermal neutrophilic IgA dermatosis-type IgA pemphigus by novel IgA-specific immunoprecipitation. Mass-spectrometry study identified polymeric immunoglobulin receptor (PIGR) as the candidate protein, and we confirmed that PIGR expressed in both epidermis and cultured keratinocytes. Eukaryotic recombinant protein of PIGR expressed in COS7 cells was reacted with both patient and normal sera, indicating that PIGR binds physiologically to IgA. To detect antigen-specific binding by IgA autoantibodies, we performed several experiments using deglycosylated PIGR and F(ab)2 fragments from patient sera. However, these analyses suggested that patient IgA bound physiologically, but not immunologically, to PIGR. Nevertheless, our study provided two important insights. Newly developed IgA-immunoprecipitation system should be a useful tool in the future study of identification of antigens for IgA autoantibodies. Detection of epidermal PIGR in this study confirmed previous results and indicated possible immunological role of PIGR in epidermis.


Assuntos
Imunoglobulina A/sangue , Imunoprecipitação/métodos , Pênfigo/imunologia , Receptores de Imunoglobulina Polimérica/sangue , Autoantígenos , Células Cultivadas , Epiderme/imunologia , Proteínas do Olho , Humanos , Queratinócitos , Neutrófilos/imunologia , Pênfigo/patologia , Fragmentos de Peptídeos
6.
J Am Acad Dermatol ; 73(1): 50-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25896671

RESUMO

BACKGROUND: Many case reports have described the coexistence of autoimmune bullous diseases (AIBDs) and psoriasis. Among them, anti-laminin γ1 (p200) pemphigoid is the best known. OBJECTIVES: We sought to characterize patients with AIBDs and psoriasis and to investigate common AIBDs occurring in these patients. METHODS: This retrospective study included 145 patients with coexisting AIBD and psoriasis given a diagnosis from January 1, 1996, to July 31, 2013, at an academic dermatology department. Of these, 134 were consultation cases regarding AIBD diagnosis. RESULTS: Ratio of male to female patients was 5.7:1. Psoriasis onset preceded AIBD onset in most patients. Mean age at AIBD onset was 65.4 years, and mean duration between psoriasis and AIBD onset was 14.6 years. Most cases had single AIBD, whereas 16 cases had combined AIBDs. Bullous pemphigoid was the most prevalent (63.4%) followed by anti-laminin γ1 pemphigoid (37.2%). LIMITATIONS: Consultation cases may not have included mild AIBD cases. CONCLUSION: This study confirmed the association of psoriasis and anti-laminin γ1 pemphigoid. However, because bullous pemphigoid is a much more common disease, it is seen more frequently in patients with psoriasis than anti-laminin γ1 pemphigoid.


Assuntos
Doenças Autoimunes/complicações , Psoríase/complicações , Dermatopatias Vesiculobolhosas/complicações , Dermatopatias Vesiculobolhosas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Exp Dermatol ; 23(3): 155-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24387643

RESUMO

Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen-activated protein kinase (p38MAPK) linearly, they suppressed activity of c-Myc and acantholysis in a non-linear, V-shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c-Myc in pemphigus vulgaris pathology.


Assuntos
Receptores ErbB/antagonistas & inibidores , Pênfigo/tratamento farmacológico , Quinazolinas/farmacologia , Animais , Humanos
8.
Exp Dermatol ; 23(6): 433-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24750515

RESUMO

We investigated protein expression and in situ activity of transglutaminases (TGs) in normal skin and various epidermal neoplasms. In normal skin, TG1 protein expression and TG activity were found at keratinocyte cell membranes in upper epidermis and granular layer, respectively. In seborrhoeic keratosis, TG1 protein was expressed evenly throughout tumors, while TG activity increased in gradient fashion from lower tumor area to cornified layer. In squamous cell carcinoma, TG1 protein was expressed at inner side of cell membranes, whereas TG activity was found in cytoplasm predominantly at horn pearls. In basal cell carcinoma, weak TG activity was found in cytoplasm of all tumor cells without the presence of TG1 protein. Immunoblotting and in situ activity assays using specific substrate peptides confirmed that TG2, but not TG1, contributed to the TG activity. These results suggested that different expression and activation of TGs may contribute to characteristics of the skin tumors.


Assuntos
Regulação Neoplásica da Expressão Gênica , Regulação da Expressão Gênica , Precursores de Proteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Pele/metabolismo , Transglutaminases/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Ceratose Seborreica/genética , Ceratose Seborreica/metabolismo , Ceratose Seborreica/patologia , Precursores de Proteínas/genética , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Transglutaminases/genética
9.
Exp Dermatol ; 23(7): 514-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24698124

RESUMO

Hailey-Hailey disease (HHD) is a dominantly inherited skin disease caused by mutations in ATP2C1 gene, which encodes secretory pathway Ca(2+) /Mn(2+) -ATPase protein 1. The precise mechanism remains unclear. In this study, to understand molecular basis of HHD, we examined expression of mRNA and protein in cultured keratinocytes derived from three HHD patients with different mutations. We showed that reduced expression of mRNA and protein in patient with p.Gln504X, but not in patients with p.Pro307His and c.1308+1G>A. RT-PCR analysis for patient with c.1308+1G>A revealed in-frame exon skipping. Reduction of mRNA and protein in p.Gln504X was considered to be caused by nonsense-mediated mRNA decay. p.Pro307His located adjacent to Ca(2+) -binding residue may induced conformational change, which leads to defective Ca(2+) transport. In-frame shorter transcript caused by c.1308+1G>A may have slightly reduced activity, which accounted for mild phenotype of the patient. These results clarified the pathogenic effects of different causative mutations in development of skin lesions.


Assuntos
Queratinócitos/metabolismo , Mutação , Pênfigo Familiar Benigno/genética , RNA Mensageiro/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Células Cultivadas , Códon sem Sentido , Citoplasma/metabolismo , Éxons , Deleção de Genes , Humanos , Queratinócitos/citologia , Masculino , Pessoa de Meia-Idade , Pênfigo Familiar Benigno/metabolismo , Fosforilação , Estrutura Terciária de Proteína
10.
Exp Dermatol ; 23(8): 596-605, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24758362

RESUMO

B-cell activating factor (BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells (DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid (BP), were analysed by flow cytometry. Compared with healthy controls (HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP.


Assuntos
Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Penfigoide Bolhoso/metabolismo , Linfócitos B/patologia , Estudos de Casos e Controles , Humanos , Células de Langerhans/metabolismo , Células de Langerhans/patologia , Microscopia Confocal , Penfigoide Bolhoso/patologia , Pênfigo/metabolismo , Pênfigo/patologia
11.
Exp Dermatol ; 23(9): 682-4, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24828603

RESUMO

Although fibronectin (FN) is known as a chemoattractant for human dermal fibroblasts (HDFs), it is unclear whether HDF migration is stimulated by FN produced by HDFs (autocrine manner) or by keratinocytes (paracrine manner). In this study, we investigated HDF migration by Boyden chamber assay using conditioned media from HDFs and HaCaT cells (keratinocyte cell line). Immunoblotting and enzyme-linked immunosorbent assay revealed that FN existed in both conditioned media. Boyden chamber assay showed both conditioned media stimulated HDF migration, which was inhibited by anti-FN antibody. Antibodies to both integrin ß1and ß3 subunits inhibited HDF migration induced by HDF-conditioned medium almost completely and that by HaCaT cell-conditioned medium with 50-60%. These results suggested that HDF migration was stimulated by FN in both autocrine and paracrine manners. However, the mechanisms of HDF migration by FN, particularly the role of integrin ß1 and ß3 subunits, were slightly different between autocrine and paracrine manners.


Assuntos
Fibroblastos/fisiologia , Fibronectinas/fisiologia , Pele/citologia , Comunicação Autócrina , Linhagem Celular , Movimento Celular/fisiologia , Meios de Cultivo Condicionados , Humanos , Integrina beta1/fisiologia , Integrina beta3/fisiologia , Queratinócitos/fisiologia , Comunicação Parácrina , Fenômenos Fisiológicos da Pele
12.
J Cutan Pathol ; 41(11): 880-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25265985

RESUMO

BACKGROUND: Acantholysis in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) occurs predominantly in the suprabasal area and the granular layer, respectively. However, acantholysis can occasionally be observed in unusual locations. METHODS: We retrospectively studied the acantholysis locations in 35 PV and 27 PF cases, and analyzed them using the index value of Desmoglein (Dsg) 1 and Dsg3 by enzyme-linked immunosorbent assay, clinical data, and inflammatory cells. We also analyzed the relationship between clinical subtype and various parameters. RESULTS: In PV, acantholysis was noted in the suprabasal area in 3 cases, in the lower half of the epidermis in 19 cases, and throughout the epidermis in 13 cases. In PF, acantholysis was observed in the granular layer in 6 cases, in the upper half of the epidermis in 14 cases, and throughout the epidermis in 7 cases. Mean index value of Dsg1 in PV patients with acantholysis throughout the epidermis was 2-fold higher than other PV patients. Neutrophils tended to infiltrate the dermis and epidermis more in PF than in PV. CONCLUSIONS: Higher Dsg1 index values seem to correlate with acantholysis in the upper part of the epidermis in PV. Neutrophils may play some role in unusual acantholysis locations in PF.


Assuntos
Acantólise/patologia , Pênfigo/patologia , Acantólise/sangue , Acantólise/imunologia , Desmogleína 1/sangue , Desmogleína 3/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Pênfigo/imunologia , Estudos Retrospectivos
13.
Dermatol Ther ; 27(3): 135-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24102897

RESUMO

In this study, we report on the efficacy of combination therapy of second-generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis or pemphigoid nodularis patients, in whom conventional therapy was ineffective. All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice a day for 4 weeks in addition to other medications they had been taking. We assessed the manifestations of the lesions and itching intensity before and after the therapy, and we evaluated each patient as (i) markedly improved, (ii) improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients (13.3%) were evaluated as markedly improved, and the lesions of one patient completely disappeared. Three patients (20.0%) were evaluated as improved, and six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved by combination therapy of fexofenadine and montelukast, in which nine cases (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were involved. No patients revealed any side effects. This study revealed that combination therapy of fexofenadine and montelukast was effective for some patients with conventional therapy-resistant prurigo nodularis and pemphigoid nodularis.


Assuntos
Acetatos/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Prurigo/tratamento farmacológico , Quinolinas/uso terapêutico , Pele/efeitos dos fármacos , Terfenadina/análogos & derivados , Acetatos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclopropanos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/diagnóstico , Prurigo/diagnóstico , Quinolinas/administração & dosagem , Pele/patologia , Sulfetos , Terfenadina/administração & dosagem , Terfenadina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
14.
Exp Dermatol ; 22(8): 515-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23879810

RESUMO

Mesenchymal stem cells (MSCs) are non-haematopoietic cells that reside in most tissues including adult bone marrow. MSCs have recently been extensively studied and used for clinical therapies, including skin wound healing. However, there are still many questions to be answered. In the viewpoint entitled 'Mesenchymal stem cell therapy in skin: why and what for?', Dr. Khosrotehrani provided a comprehensive overview for MSC properties and current progresses on clinical applications for various skin conditions. This viewpoint is therefore very helpful for both dermatologists and basic skin researchers to understand stem cells researches.


Assuntos
Dermatologia/tendências , Derme/citologia , Transplante de Células-Tronco Mesenquimais/tendências , Células-Tronco Mesenquimais/citologia , Dermatopatias/terapia , Humanos
15.
Exp Dermatol ; 22(4): 262-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23528211

RESUMO

Neurofibromatosis type I (NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors (MPNST) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high-level expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In this study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non-Schwann cell line and the upstream mTOR-HIF-1α - VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral-mediated RNA interference resulted in elevated expression of VEGF, HIF-1α and phosphorylated mTOR at the protein level. The results obtained from Nf1 gene silencing in murine Schwann cell line analogously suggest that NF1 gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of VEGF expression without the tumor microenvironment by activation of the mTOR-HIF-1α - VEGF pathway. We also showed that interleukin-6 is upregulated in Nf1 gene knock-down Schwann cells at the protein level.


Assuntos
Genes da Neurofibromatose 1 , Células de Schwann/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-6/metabolismo , Queratinócitos/metabolismo , Camundongos , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Microambiente Tumoral , Regulação para Cima
16.
Exp Dermatol ; 22(2): 83-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23039137

RESUMO

Inherited keratinizing disorders are caused by mutations in the genes encoding cornified cell envelope proteins, enzymes and their inhibitors, adhesion molecules, cytoskeletal proteins and others in the epidermis. These molecules are known to regulate differentiation, proliferation and cell adhesions. Intriguingly, some keratinizing disorders show blistering skin lesions, while some inherited blistering disorders show abnormal keratinization. Therefore, hereditary keratinizing and blistering diseases are closely related and show overlapping genetic backgrounds. In this review, we overviewed keratinizing and blistering disorders in terms of overlapping of the two disease groups. Gene mutations in desmosomal components cause striate keratoderma, Naxos disease, epidermolytic palmoplantar keratoderma and plakophilin deficiency, which first show skin fragility and blisters and later hyperkeratosis. Gene mutations in hemidesmosomal components cause various forms of epidermolysis bullosa, some of which show hyperkeratosis on the nails, palms and soles, in addition to blister formation. Diseases with gene mutations in calcium pump proteins are Darier disease and Hailey-Hailey disease, which show clinicopathological overlaps and develop both keratinizing and blistering skin lesions. Finally, gene mutations in epidermal keratins cause epidermolysis bullosa simplex, epidermolytic ichthyosis, superficial epidermolytic ichthyosis, epidermolytic palmoplantar keratoderma and pachyonychia congenita/focal palmoplantar keratoderma, which show thickening of the palms and soles with underlying blister formation. In general, responsible proteins for diseases developing both keratinizing and blistering conditions are adhesion molecules, calcium pump proteins and keratins, but not connexins, cornified cell envelop proteins, enzymes or inhibitors. It is still unknown how particular keratinizing diseases develop blisters and vice versa.


Assuntos
Vesícula/genética , Epiderme/patologia , Hiperceratose Epidermolítica/genética , Queratinas/genética , Ceratodermia Palmar e Plantar/genética , Dermatopatias/genética , Displasia Arritmogênica Ventricular Direita/genética , Cálcio/metabolismo , Diferenciação Celular , Epiderme/metabolismo , Epidermólise Bolhosa/genética , Doenças do Cabelo/genética , Humanos , Queratinas/fisiologia , Mutação , Pênfigo Familiar Benigno/genética
17.
J Pathol ; 228(1): 1-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22692770

RESUMO

Autoimmune bullous diseases (ABDs) are organ-specific autoimmune diseases, in which blisters on the skin and mucous membranes develop through binding of pathogenic autoantibodies to target antigens. There are two major ABD groups: the pemphigus group, showing autoantibodies to desmosomal components; and the subepidermal ABD group, showing autoantibodies to hemidesmosomal components in the epidermal basement membrane zone. Recent immunological, biochemical and molecular biological studies revealed many new autoantigens, including desmocollins, various plakin family proteins and integrins. A revised ABD classification includes new disease entities such as paraneoplastic pemphigus, IgA pemphigus and anti-laminin γ1 pemphigoid. In addition to systemic corticosteroids and various immunosuppressive agents, various adjuvant therapies for ABDs have developed. Among them, intravenous immunoglobulin (IVIG) is a promising therapy, although the therapeutic mechanisms are still unknown. Various disease models for ABDs have developed, particularly for pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita (EBA), and these have provided insights into the pathogenesis of various ADBs that suggest possible new treatment strategies. However, the fundamental mechanisms in disruption of immune-tolerance are still unknown. EBA shows autoimmunity to type VII collagen, the major component of anchoring fibrils, and EBA pathogenesis has been studied in various disease models. Previous studies suggested that, following binding of autoantibodies to type VII collagen, activation of complement, cytokine release, neutrophil migration, Fcγ receptors (FcgRs) and metalloproteinases play important roles in induction of subepidermal blisters. In this issue of the Journal of Pathology, Kasperkiewicz and colleagues reveal important roles of activating FcgRIV and inhibitory FcgRIIB in EBA pathogenesis that were recognized by conducting elegant studies using both genetic analysis and functional animal model methods. The expression equilibrium of the activating and inhibitory FcgRs can be modulated towards the inhibitory FcgRIIB by IVIG therapy, resulting in beneficial clinical effects of IVIG in EBA and other autoimmune skin-blistering diseases.


Assuntos
Doenças Autoimunes/etiologia , Epidermólise Bolhosa Adquirida/etiologia , Animais , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Vesícula/tratamento farmacológico , Vesícula/imunologia , Vesícula/patologia , Colágeno Tipo VII/imunologia , Modelos Animais de Doenças , Epidermólise Bolhosa Adquirida/tratamento farmacológico , Epidermólise Bolhosa Adquirida/patologia , Humanos , Tolerância Imunológica , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Camundongos , Camundongos Knockout , Especificidade de Órgãos , Receptores de IgG/imunologia , Pele/imunologia , Pele/patologia
19.
Clin Dev Immunol ; 2012: 562168, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22778765

RESUMO

We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. The mean age at onset was 43.8, and 13 years earlier for female patients. More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients.


Assuntos
Povo Asiático , Dermatite Herpetiforme/imunologia , Dermatite Herpetiforme/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dermatite Herpetiforme/genética , Feminino , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Lactente , Japão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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