Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Piodermia Gangrenosa , Quinolinas , Humanos , Piodermia Gangrenosa/inducido químicamente , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/efectos adversosRESUMEN
Paradoxical reaction (PR) occurs when a drug elicits a reaction contrary to what was expected. To clarify the clinical features and genetic background of individuals susceptible to PR, we analyzed the clinical course of patients in whom psoriatic eruptions worsened or newly developed during tumor necrosis factor (TNF) antagonist administration and the role of focal infections and genetic variations. Of 125 patients who received TNF antagonist therapy for psoriasis, acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), or palmoplantar pustular psoriasis (PPP), eight patients with PR were surveyed at our hospital Dermatology Department between 2010 and 2021. A survey was also done on six patients who received TNF antagonist therapy for Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and hidradenitis suppurativa and were referred to our department due to PR. Additionally, Sanger sequencing analysis was performed for all exons and flanking introns of IL36RN (interleukin 36 receptor antagonist), CARD14 (caspase recruitment domain-containing protein 14), and AP1S3 (adaptor-related protein complex 1 subunit sigma 3). The clinical assessment of the 14 patients demonstrated an average age at PR onset of 48.4 years, a male : female ratio of 5:9, and a mean administration period until onset of 9.2 months. The clinical types of PR were plaque psoriasis, PPP, GPP, pustulosis, acne, ACH, hair loss, and exacerbation of arthralgia. Histopathology revealed psoriasiform dermatitis in three patients. One patient continued TNF antagonist therapy. All of the patients with psoriasis and GPP had dental infections, suggesting that focal infection may be a risk factor of the development of PR following TNF antagonist therapy. Gene analysis demonstrated CARD14 gene variants associated with RA, CD, AS, or PPP in four patients. In addition, all of the patients with ACH and PPP experienced PR, suggesting that these diseases may predispose patients to PR to TNF antagonist therapy.
Asunto(s)
Artritis Reumatoide , Enfermedad de Crohn , Psoriasis , Espondilitis Anquilosante , Proteínas Adaptadoras de Señalización CARD , Femenino , Guanilato Ciclasa , Humanos , Interleucinas , Masculino , Proteínas de la Membrana , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
To date, almost all case reports of insulin-derived amyloidosis described the presence of a subcutaneous mass that was observable on physical examination. This report presents two cases of insulin-derived amyloidosis without palpable masses at insulin injection sites. In both cases, blood glucose concentrations improved, and the insulin dose could be reduced by an average of 45% after changing the insulin injection sites. The insulin absorption at the site was reduced to at most 40% of that at a normal site in one case. Magnetic resonance imaging and ultrasonography were useful to screen and differentiate insulin-derived amyloidosis without a palpable mass. This report showed that insulin-derived amyloidosis without a palpable mass can be present at the insulin injection site, and has similar clinical effects to insulin-derived amyloidosis with palpable masses.
Asunto(s)
Amiloidosis/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Inyecciones Subcutáneas/efectos adversos , Insulinas/efectos adversos , Abdomen/patología , Anciano de 80 o más Años , Amiloidosis/inducido químicamente , Humanos , Hipoglucemiantes/administración & dosificación , Insulinas/administración & dosificación , MasculinoAsunto(s)
Infecciones por Mycobacterium no Tuberculosas/microbiología , Síndromes Mielodisplásicos/inmunología , Micobacterias no Tuberculosas/aislamiento & purificación , Enfermedades Cutáneas Infecciosas/microbiología , Antibacterianos/uso terapéutico , Biopsia , Quimioterapia Combinada , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Hibridación de Ácido Nucleico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológicoRESUMEN
BACKGROUND: UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified. OBJECTIVE: To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62(-/-)) mice. METHODS: p62(-/-) and wild-type (p62(+/+)) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots. RESULTS: Apoptosis was decreased in the p62(-/-) MEFs compared to p62(+/+) MEFs in response to UVB treatment. Compared with p62(+/+) MEFs, p62(-/-) MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3. CONCLUSION: p62 deficiency [corrected] reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation.
Asunto(s)
Apoptosis/efectos de la radiación , Fibroblastos/efectos de la radiación , Proteína Sequestosoma-1/metabolismo , Transducción de Señal/efectos de la radiación , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación de la Expresión Génica/efectos de la radiación , Genotipo , Ratones Noqueados , Fenotipo , Fosforilación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , Factor de Transcripción STAT3/metabolismo , Proteína Sequestosoma-1/deficiencia , Proteína Sequestosoma-1/genética , Piel/metabolismo , Piel/patología , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Familia-src Quinasas/metabolismoAsunto(s)
Dermatofibrosarcoma/diagnóstico , Sarcoidosis/diagnóstico , Enfermedades de la Piel/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Dermatofibrosarcoma/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Sarcoidosis/complicaciones , Sarcoidosis Pulmonar/complicaciones , Enfermedades de la Piel/complicaciones , Neoplasias Cutáneas/complicacionesRESUMEN
B-Myb (Mybl2) is a member of the Myb gene family of transcription factors involved in the control of cell growth, differentiation, and apoptosis. The effects of B-Myb on keratinocyte proliferation and differentiation have not yet been clarified. The present study was performed to examine the role of B-Myb in proliferation and differentiation of the spontaneously immortalized human skin keratinocyte cell line HaCaT and normal human keratinocytes with formation of a stratified epidermoid structure in air-liquid interface three-dimensional culture. B-Myb was expressed specifically in undifferentiated normal keratinocytes and downregulated during differentiation. The constitutive overexpression of B-Myb in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, i.e., thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity with activation of cell cycle regulatory proteins in the S and G2/M phases. In contrast, suppression of B-Myb caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that B-Myb plays an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer.
Asunto(s)
Proteínas de Ciclo Celular/genética , Diferenciación Celular/genética , Proliferación Celular/genética , Transactivadores/genética , Técnicas de Cultivo de Célula , Proteínas de Ciclo Celular/biosíntesis , Línea Celular , Epitelio/patología , Humanos , Queratinocitos/citología , Puntos de Control de la Fase M del Ciclo Celular/genética , Interferencia de ARN , ARN Interferente Pequeño , Piel/citología , Piel/patología , Transactivadores/biosíntesisRESUMEN
BACKGROUND: Exposure of skin to long-wave UV radiation (UVA) increases the cellular levels of reactive oxygen species (ROS), which have been linked to apoptosis induction through the damage of lipids, proteins, and nucleic acids. Peroxiredoxin I (Prx I) is one of a family of antioxidant proteins that plays a protective role against oxidative damage; however the role of Prx I in UVA-induced damage remains to be clarified. OBJECTIVE: Here we investigated the protective role of Prx I against UVA-induced changes using mouse embryonic fibroblasts (MEFs) derived from Prx I homozygous knockout (Prx I (-/-)) mice. METHODS: Prx I (-/-) and wild-type (Prx I (+/+)) MEFs were subjected to UVA irradiation, and the resulting apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blotting. RESULTS: Prx I (-/-) MEFs showed enhanced sensitivity to UVA treatment, exhibiting increased apoptosis and ROS production compared to Prx I (+/+) MEFs. Consistent with the increase in apoptosis, p53 expression was significantly higher, while Bcl-2, Bcl-xL, and Nrf2 expressions were all lower in Prx I (-/-) versus (+/+) MEFs. The UVA-induced inflammatory response was upregulated in Prx I (-/-) MEFs, as indicated by increased expressions of IκB, TNFα, and IL-6. Evidence was presented indicating that Prx I impacts these pathways by modifying critical signaling intermediates including p53, IκB, and Nrf2. CONCLUSION: Our results indicate that Prx I plays a protective role against UVA-induced oxidative damage by controlling ROS accumulation. Both the UVA-induced apoptotic and inflammatory signals were found to be modulated by Prx I.
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Estrés Oxidativo , Peroxirredoxinas/fisiología , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Antioxidantes/metabolismo , Apoptosis , Supervivencia Celular , Fibroblastos/metabolismo , Citometría de Flujo , Homocigoto , Ratones , Ratones Noqueados , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Piel/metabolismo , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Coagulación Intravascular Diseminada/complicaciones , Hemangiosarcoma/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias del Bazo/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Docetaxel , Hemangiosarcoma/complicaciones , Hemangiosarcoma/secundario , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Neoplasias del Bazo/complicaciones , Neoplasias del Bazo/patologíaRESUMEN
OBJECTIVE: To show the efficacy of taxane-based chemotherapy for the treatment of cutaneous angiosarcoma. METHODS: A case-control study comparing patients who received taxanes without wide local excision (group A, n = 5) and patients who received conventional surgery-based therapy (group B, n = 8) in one university hospital in eastern Japan. Data were collected from a total of 13 patients with cutaneous angiosarcoma treated from November 1997 through July 2009. RESULTS: Group A received taxanes: four patients received docetaxel, and one patient received paclitaxel. Radiation was used concomitantly in two patients. Marginal local excision was performed in two patients. Group B received wide local excision followed by radiation (six patients), docetaxel (three patients), and interleukin-2 (two patients). No patients in group A had local recurrence, whereas five out of the eight patients in group B did (p < 0.05, chi-square test). Median overall survival was 31 months in group A and 10 months in group B. Estimated overall survival using the Kaplan-Meier method was significantly longer in group A (p < 0.05, log-rank test). CONCLUSION: In our series, taxane-based chemotherapy was superior to conventional surgery-based therapy. Our results indicated that taxane regimens without mutilating surgery offered both local control and prevention of metastasis, which led to prolonged survival.
Asunto(s)
Antineoplásicos/uso terapéutico , Hemangiosarcoma/terapia , Neoplasias Cutáneas/terapia , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Hidrocarburos Aromáticos con Puentes , Estudios de Casos y Controles , Femenino , Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/cirugía , Humanos , Interleucina-2/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugíaRESUMEN
Mucoepidermoid carcinoma (MEC) usually originates from the salivary glands. However, there has been no report on mucoepidermoid carcinoma of the columella. In this study, we report the case of a high-grade MEC of the columella that was successfully reconstructed after surgical resection with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. A 66-year-old man presented with a nodule on the columella. Histological findings were suggestive of a high-grade mucoepidermoid carcinoma. Wide excision was performed, and the defects of the columella and the nasal floor were reconstructed with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. The postoperative cosmetic result was good with excellent tissue texture. The reconstructed columella had an appropriate, not bulky, width as well as satisfactory height and depth. This reconstructive technique is particularly useful for correcting the large defect of the columella with nasal septum and/or nasal floor defects.
Asunto(s)
Carcinoma Mucoepidermoide/cirugía , Cartílago Auricular/trasplante , Surco Nasolabial/cirugía , Neoplasias Nasales/cirugía , Rinoplastia/métodos , Colgajos Quirúrgicos/cirugía , Anciano , Humanos , MasculinoRESUMEN
Graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT) that can be classified as acute or chronic. Characteristic cutaneous manifestations of acute GVHD, which generally occurs within 3 months following BMT, include maculopapular exanthema and perifollicular papular lesions. Psoriasiform skin eruption as a manifestation of acute GVHD is rare. We report the case of a 4-year-old boy who developed a generalized psoriasiform eruption shortly after undergoing an allogeneic BMT. Histologic features of both psoriasis and acute GVHD were present.
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Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/fisiopatología , Psoriasis/etiología , Enfermedades de la Piel/etiología , Preescolar , Humanos , Masculino , Psoriasis/patología , Enfermedades de la Piel/patología , Factores de Tiempo , Trasplante HomólogoAsunto(s)
Músculo Esquelético/patología , Paniculitis de Lupus Eritematoso/tratamiento farmacológico , Úlcera Cutánea/patología , Úlcera Cutánea/cirugía , Grasa Subcutánea/patología , Antiinflamatorios/uso terapéutico , Nalgas , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Músculo Esquelético/cirugía , Necrosis , Paniculitis de Lupus Eritematoso/complicaciones , Paniculitis de Lupus Eritematoso/patología , Prednisolona/uso terapéutico , Úlcera Cutánea/complicaciones , Grasa Subcutánea/cirugíaAsunto(s)
Isquemia/etiología , Úlcera de la Pierna/etiología , Neurofibromatosis 1/complicaciones , Piel/irrigación sanguínea , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnóstico por imagen , Alprostadil/uso terapéutico , Angiografía , Desbridamiento , Humanos , Úlcera de la Pierna/patología , Úlcera de la Pierna/terapia , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Vasodilatadores/uso terapéuticoRESUMEN
Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the pathophysiology of psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.