RESUMO
Pediatric cutaneous mastocytosis (CM) is mainly attributed to gain-of-function mutations in KIT in mast cells. On the other hand, growing evidence suggests that CM patients exist without KIT mutations. To date, the association between the KIT mutation status and clinical phenotype has not been elucidated in pediatric CM, especially in patients with wild-type KIT. Nevertheless, genetic analysis has yet to be performed with whole KIT sequence of mast cells in Japanese patients with pediatric CM. In the present study, 11 Japanese patients with pediatric CM were analyzed to determine whether they had KIT mutations in their skin, and their clinical phenotypes were observed. The approximate frequency of patients with KIT mutation and that of wild-type KIT was almost consistent with the European analysis. The distribution of overall macules was similar between the patients with and without KIT mutations.
Assuntos
Estudos de Associação Genética , Mastocitose Cutânea/genética , Proteínas Proto-Oncogênicas c-kit/genética , Pré-Escolar , Análise Mutacional de DNA , Feminino , Mutação com Ganho de Função , Humanos , Lactente , Recém-Nascido , Masculino , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/patologia , Pele/citologia , Pele/patologiaRESUMO
AIM: In patients with diabetes or ischemia, angiogenesis and infection control are required for chronic leg ulcers, which substantially impair patients' quality of life. We developed a novel functional peptide, named AG30/5C, with angiogenic and anti-microbial properties. Treatment with AG30/5C significantly accelerated the wound healing of full-thickness defects in mice. To evaluate the safety of AG30/5C in the treatment of leg ulcers, a physician-initiated clinical study was carried out. METHODS: The first-in-human trial was designed as an open-label treatment with AG30/5C (0.1 mg/mL) given twice per day for 11 days, and with a follow-up period of 17 days. The inclusion criteria for severe skin ulcers were: (i) diabetes or critical limb ischemia; (ii) resistance to standard therapy for 1 month; and (iii) detection of methicillin-resistant Staphylococcus aureus in the skin ulcer. RESULTS: Four patients were enrolled in this study, and two patients met these criteria. For the evaluation of safety, three adverse effects were reported as possibly related to AG30/5C treatment; however, these adverse effects were not severe and resolved during or after treatment. Thus, there were no safety concerns. In both patients, the size of the ulcer decreased after treatment (44.62% and 10.23% decrease), and further decreased after the follow-up period (73.85% and 10.23% decrease). The former patient was diagnosed as Werner syndrome and the skin ulcer was resistant to standard therapy; however, it was sensitive to AG30/5C treatment. CONCLUSIONS: Topical treatment with AG30/5C for severe leg ulcers was safe, well tolerated and effective. Geriatr Gerontol Int 2017; 17: 2150-2156.
Assuntos
Proteínas Angiogênicas/uso terapêutico , Úlcera da Perna/terapia , Peptídeos/uso terapêutico , Proteínas Angiogênicas/efeitos adversos , Humanos , Peptídeos/efeitos adversos , Médicos , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Fasciite Necrosante/induzido quimicamente , Infecções Estreptocócicas/induzido quimicamente , Infecção dos Ferimentos/induzido quimicamente , Antibacterianos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biópsia , Terapia Combinada , Desbridamento , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/microbiologia , Fasciite Necrosante/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pele , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Resultado do Tratamento , Cicatrização , Infecção dos Ferimentos/diagnóstico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/terapiaAssuntos
Adenocarcinoma/complicações , Autoanticorpos/sangue , RNA Helicases DEAD-box/imunologia , Dermatomiosite/complicações , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/complicações , Neoplasias Gástricas/complicações , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Helicase IFIH1 Induzida por Interferon , Pessoa de Meia-Idade , Fatores de Transcrição/imunologiaAssuntos
Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Hipo-Hidrose/tratamento farmacológico , Sudorese/efeitos dos fármacos , Terfenadina/análogos & derivados , Administração Oral , Adulto , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Biópsia , Humanos , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/fisiopatologia , Masculino , Terfenadina/administração & dosagem , Resultado do TratamentoRESUMO
H2S has been highlighted recently as an endogenous, gaseous signaling molecule, especially in inflammations. The deposition of IC induces an acute inflammatory response with tissue injury. To assess the roles of H2S in the IC-induced diseases, the cutaneous, reverse passive Arthus reaction was conducted using NaHS as a H2S donor. Furthermore, we conducted similar experiments using selectin(-/-) mice to determine the involvement of selectin molecules in the H2S-mediated pathway. Exogenous application of NaHS dramatically attenuated inflammatory reactions in WT mice associated with Arthus reaction. Namely, mRNA expressions of TNF-α, IFN-γ, and neutrophil numbers were reduced significantly in the lesional skins of NaHS-treated WT mice relative to untreated ones. NaHS treatment significantly reduced these three parameters in the lesional skins of E- and P-selectin(-/-) mice but not in those of L-selectin(-/-) mice. Quite similar results were obtained in the blocking study using WT mice injected with mAb to E-, P-, and L-selectin. Our results indicated that the exogenous application of NaHS attenuates inflammatory responses in reverse passive Arthus reaction through a L-selectin-involved pathway but not through E- or P-selectin pathways.
Assuntos
Reação de Arthus/prevenção & controle , Sulfeto de Hidrogênio/farmacologia , Selectina L/imunologia , RNA Mensageiro/sangue , Pele/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Anticorpos/farmacologia , Complexo Antígeno-Anticorpo/imunologia , Reação de Arthus/genética , Reação de Arthus/imunologia , Reação de Arthus/patologia , Selectina E/genética , Selectina E/imunologia , Deleção de Genes , Expressão Gênica , Sulfeto de Hidrogênio/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Inflamação/prevenção & controle , Interferon gama/biossíntese , Interferon gama/imunologia , Selectina L/genética , Masculino , Camundongos , Camundongos Knockout , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Selectina-P/genética , Selectina-P/imunologia , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Sulfetos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaAssuntos
Doença Hepática Induzida por Substâncias e Drogas/complicações , Etodolac/efeitos adversos , Interleucina-10/sangue , Síndrome de Stevens-Johnson/complicações , Idoso , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Evolução Fatal , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Sepse/sangue , Sepse/complicações , Síndrome de Stevens-Johnson/sangue , Síndrome de Stevens-Johnson/patologiaRESUMO
BACKGROUND: Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. OBJECTIVE: To evaluate the role of adhesion molecules, including P-selectin glycoprotein ligand-1 (PSGL-1), P-selectin, and E-selectin. METHODS: Subcutaneous primary growth and metastasis to the lung of B16 melanoma cells were examined in mice lacking PSGL-1, P-selectin, or E-selectin. RESULTS: Primary subcutaneous growth of B16 melanoma was augmented by loss of PSGL-1, P-selectin, or E-selectin, while pulmonary metastasis was reduced by the loss of E-selectin. The enhancement of subcutaneous tumor growth was associated with a reduced accumulation of natural killer cells, CD4(+) T cells and CD8(+) T cells, while the attenuation of pulmonary metastasis was related to the numbers of CD8(+) T cells. The expressions of transforming growth factor (TGF)-ß and interleukin (IL)-6 were correlated with primary subcutaneous growth; TGF-ß, IL-6, and interferon-γ were related to number of metastatic lung nodules. Cytotoxicity against melanoma cells in splenocytes and in tumor-draining lymph node cells were not defective by the absence of adhesion molecules, suggesting that the enhancement of tumor growth and metastasis caused by the loss of selectins results from an impaired migration of effector cells into the tissue. CONCLUSIONS: The results indicate the complexity of anti-tumor responses mediated by adhesion molecules in primary subcutaneous tumors and pulmonary metastasis of murine experimental melanoma.
Assuntos
Selectina E/fisiologia , Melanoma Experimental/etiologia , Glicoproteínas de Membrana/fisiologia , Selectina-P/fisiologia , Neoplasias Cutâneas/etiologia , Animais , Citocinas/genética , Leucócitos/fisiologia , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Neoplasias Cutâneas/patologiaRESUMO
We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T(2)-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.
Assuntos
Corticosteroides/uso terapêutico , Osteomielite/tratamento farmacológico , Osteomielite/etiologia , Esclerodermia Localizada/complicações , Esclerodermia Localizada/tratamento farmacológico , Anticorpos Antinucleares/sangue , Medula Óssea/patologia , Pré-Escolar , Feminino , Humanos , Perna (Membro) , Imageamento por Ressonância Magnética , Osteomielite/patologia , Esclerodermia Localizada/patologiaRESUMO
Stress affects the pathophysiology of cutaneous immune reactions, including contact hypersensitivity (CH) in individuals sensitized with sensitizing hapten, where local endothelial cell activation plays a critical role. To clarify the effects of stress in cutaneous immune reactions, we selected a CH model using annoying sound as a stress. Furthermore, we conducted the stress experiments by using selectin-deficient mice to determine the involvement of selectin molecules regarding local endothelial activation. Auditory stress augmented CH responses in the present study. Namely, ear thickness and mast cell numbers were significantly increased in stressed CH mice. mRNA expression of preprotachykinin-A, a precursor of substance-P; interferon-gamma; interleukin (IL)-4; IL-6; and tumor necrosis factor-alpha significantly increased in stressed CH mice. Furthermore, stressed L-selectin-deficient mice showed significant decreases in all parameters mentioned above relative to stressed wild-type mice in CH response. Meanwhile, treatment with anti-L-selectin Ab resulted in a significant decrease in ear thickness and mRNA levels of interferon-gamma, IL-4, IL-6, and tumor necrosis factor-alpha, but failed to significantly reduce preprotachykinin-A mRNA levels and mast cell numbers. Our results indicated that auditory stress enhances CH response and that the augmentation of this CH response might be mediated through L-selectin, but not through P- or E-selectin pathways.