Asunto(s)
Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Dermatomiositis/etiología , Siliconas/efectos adversos , Adulto , Implantación de Mama/instrumentación , Dermatomiositis/diagnóstico , Dermatomiositis/cirugía , Remoción de Dispositivos , Femenino , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Cholesterol is de novo synthesized in the upper epidermis and plays an important role in maintaining the normality of skin. Studying the impact of the inhibition of cholesterol de novo synthesis in the epidermis may help understand how skin homeostasis is regulated. OBJECTIVE: In this study, we created a gene expression profile to investigate the effect of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on epidermal homeostasis. METHODS: A microarray analysis was performed using normal keratinocytes with or without HMG-CoA reductase inhibitor (pitavastatin) treatment. Real-time PCR confirmed the reproducibility of genes with altered expression in keratinocytes treated with HMG-CoA reductase inhibitors. Among these genes, we focused on reduced expression of claudin 7 histologically confirmed by immunohistochemical staining, in situ hybridization, and immunoelectron microscopy. RESULTS: Claudin-7 was highly expressed in the stratum granulosum of psoriatic lesions but was not expressed in the normal epidermis. Immunoelectron microscopy revealed that claudin-7 was localized in the keratohyalin granules of psoriatic lesions. CONCLUSION: These results indicate that claudin-7 expression was regulated by HMG-CoA reductase in the epidermis and might play a pathogenic role in the keratohyalin granules found in the epidermal granular layer of psoriasis.
Asunto(s)
Acilcoenzima A/antagonistas & inhibidores , Claudinas/genética , Claudinas/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Psoriasis/genética , Quinolinas/farmacología , Regulación hacia Abajo/efectos de los fármacos , Epidermis/metabolismo , Homeostasis/genética , Humanos , Queratinocitos , Microscopía Inmunoelectrónica , Psoriasis/metabolismo , Psoriasis/patología , TranscriptomaRESUMEN
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.
Asunto(s)
Estudios de Asociación Genética , Mastocitosis Cutánea/genética , Proteínas Proto-Oncogénicas c-kit/genética , Preescolar , Análisis Mutacional de ADN , Femenino , Mutación con Ganancia de Función , Humanos , Lactante , Recién Nacido , Masculino , Mastocitos/patología , Mastocitosis Cutánea/diagnóstico , Mastocitosis Cutánea/patología , Piel/citología , Piel/patologíaRESUMEN
SR-0379 is a functional peptide that has wound healing effect with anti-microbial action, making it an ideal drug to prevent infection. To evaluate the safety, efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A multi-center, double-blind, randomized clinical study was conducted from October 2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes or critical limb ischemia and (2) wound size <6 cm in diameter. Twelve patients were randomized into four groups and administered 0.02%, 0.1%, or 0.5% SR-0379 or placebo treatment on skin ulcers once per day for 28 days. Efficiency was evaluated by determining the rate of wound size reduction as a primary endpoint at 4 weeks after the first treatment compared with the pre-treatment wound size. As a secondary endpoint, the DESIGN-R score index, time to wound closure, and the 50% wound size reduction ratio were also evaluated. The safety of SR-0379 was evaluated during the study period. In the evaluation of efficiency, the skin ulcer reduction rates at the last evaluation were 44.73% for the 0.02% SR-0379 group, 68.25% for the 0.1% group, and 71.61% for the 0.5% group, compared with 9.95% for the placebo group. Six adverse events were reported in four patients, of which one occurred in the placebo group, and causal relationships to study drugs were denied for all six events. Treatment with SR-0379 for chronic leg ulcers was safe, well tolerated, and effective.
RESUMEN
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.
Asunto(s)
Proteínas Angiogénicas/uso terapéutico , Úlcera de la Pierna/terapia , Péptidos/uso terapéutico , Proteínas Angiogénicas/efectos adversos , Humanos , Péptidos/efectos adversos , Médicos , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal , Inmunoglobulinas Intravenosas/uso terapéutico , Seudoobstrucción Intestinal/tratamiento farmacológico , Polimiositis/tratamiento farmacológico , Esclerodermia Sistémica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.
Asunto(s)
Bacterias/enzimología , Inmunoglobulinas/metabolismo , Péptido Hidrolasas/metabolismo , Receptores Inmunológicos/inmunología , Animales , Bacterias/metabolismo , Citocinas/metabolismo , Humanos , Inmunidad Innata , Inmunoglobulinas/farmacología , Legionella pneumophila/efectos de los fármacos , Legionella pneumophila/enzimología , Legionella pneumophila/crecimiento & desarrollo , Legionella pneumophila/inmunología , Enfermedad de los Legionarios , Ratones , Monocitos/efectos de los fármacos , Monocitos/microbiología , Mycoplasma hyorhinis/enzimología , Neutrófilos/efectos de los fármacos , Receptores Inmunológicos/metabolismo , Streptococcus pneumoniae/enzimologíaRESUMEN
Behçet's disease (BD) is a relapsing systemic inflammatory disorder of unknown etiology involving systemic vasculitis. Vasculitis in BD results from the involvement of arteries, veins and blood vessels of all sizes, which leads to the three major manifestations of this condition: venous occlusion, arterial occlusion and aneurysm formation. Therefore, whole-body vascular involvement should always be considered in BD patients. Here, we describe the first appearance of an internal carotid-posterior communicating artery aneurysm, resulting in complete oculomotor nerve palsy in a BD patient. A 44-year-old Japanese man suffered from recurrent episodes of erythema nodosum that had presented on the lower extremities for the past 2 years. His condition was diagnosed as an incomplete type of BD based on relapsing oral and genital ulcers, skin eruptions, such as erythema nodosum and folliculitis, a positive pathergy test and systemic arthralgia. Ten years after his initial clinical presentation, he had manifestations of right-sided ptosis and cyclic dull pain in his right temporal region. Magnetic resonance imaging and angiography revealed a right internal carotid artery-posterior communicating artery aneurysm. Although oculomotor nerve palsy associated with internal carotid artery-posterior communicating artery aneurysm in a BD patient has not been reported previously, our report highlights the fact that this abnormal manifestation should be considered in those with vasculo-BD.
Asunto(s)
Síndrome de Behçet/complicaciones , Enfermedades de las Arterias Carótidas/complicaciones , Arteria Carótida Interna , Aneurisma Intracraneal/complicaciones , Enfermedades del Nervio Oculomotor/etiología , Adulto , Enfermedades de las Arterias Carótidas/diagnóstico , Humanos , Aneurisma Intracraneal/diagnóstico , Angiografía por Resonancia Magnética , MasculinoAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Fascitis Necrotizante/inducido químicamente , Infecciones Estreptocócicas/inducido químicamente , Infección de Heridas/inducido químicamente , Antibacterianos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biopsia , Terapia Combinada , Desbridamiento , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/terapia , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Piel , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/terapia , Resultado del Tratamiento , Cicatrización de Heridas , Infección de Heridas/diagnóstico , Infección de Heridas/microbiología , Infección de Heridas/terapiaAsunto(s)
Adenocarcinoma/complicaciones , Autoanticuerpos/sangre , ARN Helicasas DEAD-box/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/inmunología , Enfermedades Pulmonares Intersticiales/complicaciones , Neoplasias Gástricas/complicaciones , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Helicasa Inducida por Interferón IFIH1 , Persona de Mediana Edad , Factores de Transcripción/inmunologíaAsunto(s)
Enfermedades del Sistema Nervioso Autónomo/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Hipohidrosis/tratamiento farmacológico , Sudoración/efectos de los fármacos , Terfenadina/análogos & derivados , Administración Oral , Adulto , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Biopsia , Humanos , Hipohidrosis/diagnóstico , Hipohidrosis/fisiopatología , Masculino , Terfenadina/administración & dosificación , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Reacción de Arthus/prevención & control , Sulfuro de Hidrógeno/farmacología , Selectina L/inmunología , ARN Mensajero/sangre , Piel/efectos de los fármacos , Sulfuros/farmacología , Animales , Anticuerpos/farmacología , Complejo Antígeno-Anticuerpo/inmunología , Reacción de Arthus/genética , Reacción de Arthus/inmunología , Reacción de Arthus/patología , Selectina E/genética , Selectina E/inmunología , Eliminación de Gen , Expresión Génica , Sulfuro de Hidrógeno/metabolismo , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Inflamación/prevención & control , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Selectina L/genética , Masculino , Ratones , Ratones Noqueados , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/patología , Selectina-P/genética , Selectina-P/inmunología , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Piel/inmunología , Piel/patología , Sulfuros/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Increases in allergic diseases have been reported from various epidemiological surveys. However, a few reports demonstrate the comorbidity of food allergy (FA) and allergic march. The aim of this study was to assess the prevalence and comorbidity of allergic diseases in Japanese students. METHODS: First-year students (n = 3,321; 2,209 male and 1,112 female) at Osaka University were asked about allergic diseases using postal interview sheets. Personal and family histories of doctor-diagnosed allergic diseases, clinical courses, and aggravating factors were included in the questionnaires. RESULTS: The lifetime prevalence of allergic rhinitis (AR), atopic dermatitis (AD), bronchial asthma (BA), and FA was 35.7%, 16.5%, 9.9%, and 7.0%, respectively. Disease-specific family histories existed for AR, AD, and BA. There was a positive correlation between the number of family histories of allergic disease and comorbidity (R = 0.370, P <0.001). Comorbidity with AD significantly lowered the onset age of both BA (P = 0.010) and AR (P <0.001). In addition, the onset age of AD was remarkably lowered by comorbidity with FA (P <0.001). Comorbidity with FA was the highest risk factor for the progression of allergic march. Although most students showed improvement in AD, BA, and AR over time, the peak recurrence period was observed in adolescence. CONCLUSIONS: These findings indicate that AD associated with FA accelerates the subsequent progression of allergic march. Early appropriate management for genetically high-risk groups is important for the prevention of allergic march.
Asunto(s)
Autoanticuerpos/inmunología , Dermatomiositis/inmunología , Enzimas Activadoras de Ubiquitina/inmunología , Adulto , Pueblo Asiatico , Autoanticuerpos/sangre , Niño , Estudios de Cohortes , Dermatomiositis/sangre , Femenino , Humanos , Inmunoprecipitación , Masculino , Reino Unido , Población BlancaRESUMEN
BACKGROUND: Increases in allergic diseases have been reported from various epidemiological surveys. However, a few reports demonstrate the comorbidity of food allergy (FA) and allergic march. The aim of this study was to assess the prevalence and comorbidity of allergic diseases in Japanese students. METHODS: First-year students (n = 3,321; 2,209 male and 1,112 female) at Osaka University were asked about allergic diseases using postal interview sheets. Personal and family histories of doctor-diagnosed allergic diseases, clinical courses, and aggravating factors were included in the questionnaires. RESULTS: The lifetime prevalence of allergic rhinitis (AR), atopic dermatitis (AD), bronchial asthma (BA), and FA was 35.7%, 16.5%, 9.9%, and 7.0%, respectively. Disease-specific family histories existed for AR, AD, and BA. There was a positive correlation between the number of family histories of allergic disease and comorbidity (R = 0.370, P < 0.001). Comorbidity with AD significantly lowered the onset age of both BA (P = 0.010) and AR (P < 0.001). In addition, the onset age of AD was remarkably lowered by comorbidity with FA (P < 0.001). Comorbidity with FA was the highest risk factor for the progression of allergic march. Although most students showed improvement in AD, BA, and AR over time, the peak recurrence period was observed in adolescence. CONCLUSIONS: These findings indicate that AD associated with FA accelerates the subsequent progression of allergic march. Early appropriate management for genetically high-risk groups is important for the prevention of allergic march.