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1.
Biomed Pharmacother ; 108: 1425-1434, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30372845

RESUMEN

In recent decades, biological agents such as tumor necrosis factor-α (TNF-α) inhibitors, have revolutionized the treatment of psoriasis. However, inhibition of a single cytokine may not achieve satisfactory therapeutic results. It is against this background that this research was undertaken to investigate the anti-psoriatic effect of a novel fusion protein (DTF) dual targeting TNF-α and interleukin-17 A (IL-17 A). Imiquimod (IMQ) was topically applied to the skin of mice to develop psoriasis-like skin and treated with etanercept or different doses of DTF. Results showed that DTF treatment (1 mg/kg, 3 mg/kg, 5 mg/kg) significantly attenuated IMQ-induced typical psoriasis-like inflammation, severity score, and epidermis thickening in a dose-dependent manner, and was again more efficient than etanercept (3 mg/kg) in alleviating all these parameters at the same dose. Furthermore, DTF was more potent than etanercept in suppressing the expression of inflammatory factors (IL-17 A, IL-6, IL-1ß, IL-23, IL-22 and IL-12) in the serum, spleen and psoriasis-like skin compared with etanercept at the same dose. In addition, DTF was more efficient than etanercept in reducing the expression of keratins, decreasing the mRNA expression of Ly-6 G and Ly-6C, and enhancing the expression of filaggrin and caspase 14 in IMQ-induced psoriasis-like skin. We conclude that DTF alleviates IMQ-induced psoriasis by attenuating inflammatory cascades, reducing keratinocytes proliferation and improving epidermal barrier function through suppressing TNF-α and IL-17 A signal pathways. These data suggest that DTF has potential to be a novel therapeutic candidate for psoriasis.


Asunto(s)
Imiquimod/toxicidad , Interleucina-17/antagonistas & inhibidores , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antígenos Ly/genética , Caspasa 14/genética , Etanercept/uso terapéutico , Femenino , Proteínas Filagrina , Proteínas de Filamentos Intermediarios/genética , Queratina-16/análisis , Queratina-17/análisis , Queratina-6/análisis , Ratones , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente
2.
An Bras Dermatol ; 92(5): 682-685, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29166506

RESUMEN

Inflammatory linear verrucous epidermal nevus and linear psoriasis are sometimes hard to differentiate clinically and pathologically. Although immunohistochemical expression of keratin 10 (K10), K16, Ki-67, and involucrin may be useful for differentiating both entities, these results have been reported in only a few cases. We collected data from 8 patients with inflammatory linear verrucous epidermal nevus, 11 with psoriasis vulgaris, and 8 healthy controls and evaluated immunohistochemical expression of Ki-67, K16, involucrin, and filaggrin among them. Ki-67 and K16 overexpression was similar in inflammatory linear verrucous epidermal nevus and psoriasis vulgaris compared with normal skin. Although staining for involucrin showed discontinuous expression in parakeratotic regions in 4 inflammatory linear verrucous epidermal nevus cases, it was continuous in the other 4 cases and in all psoriasis vulgaris cases. Filaggrin expression was present in hyperkeratotic regions but scarce in parakeratotic areas in both inflammatory linear verrucous epidermal nevus and psoriasis vulgaris. The immunostaining pattern of Ki-67, K16, involucrin, and filaggrin may be insufficient to discriminate inflammatory linear verrucous epidermal nevus from psoriasis vulgaris.


Asunto(s)
Proteínas de Filamentos Intermediarios/análisis , Queratina-16/análisis , Antígeno Ki-67/análisis , Nevo Sebáceo de Jadassohn/diagnóstico , Precursores de Proteínas/análisis , Psoriasis/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/análisis , Estudios de Casos y Controles , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Proteínas Filagrina , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Nevo Sebáceo de Jadassohn/patología , Psoriasis/patología
3.
An. bras. dermatol ; 92(5): 682-685, Sept.-Oct. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-887043

RESUMEN

Abstract: Inflammatory linear verrucous epidermal nevus and linear psoriasis are sometimes hard to differentiate clinically and pathologically. Although immunohistochemical expression of keratin 10 (K10), K16, Ki-67, and involucrin may be useful for differentiating both entities, these results have been reported in only a few cases. We collected data from 8 patients with inflammatory linear verrucous epidermal nevus, 11 with psoriasis vulgaris, and 8 healthy controls and evaluated immunohistochemical expression of Ki-67, K16, involucrin, and filaggrin among them. Ki-67 and K16 overexpression was similar in inflammatory linear verrucous epidermal nevus and psoriasis vulgaris compared with normal skin. Although staining for involucrin showed discontinuous expression in parakeratotic regions in 4 inflammatory linear verrucous epidermal nevus cases, it was continuous in the other 4 cases and in all psoriasis vulgaris cases. Filaggrin expression was present in hyperkeratotic regions but scarce in parakeratotic areas in both inflammatory linear verrucous epidermal nevus and psoriasis vulgaris. The immunostaining pattern of Ki-67, K16, involucrin, and filaggrin may be insufficient to discriminate inflammatory linear verrucous epidermal nevus from psoriasis vulgaris.


Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Precursores de Proteínas/análisis , Psoriasis/diagnóstico , Antígeno Ki-67/análisis , Queratina-16/análisis , Nevo Sebáceo de Jadassohn/diagnóstico , Proteínas de Filamentos Intermediarios/análisis , Psoriasis/patología , Inmunohistoquímica , Biomarcadores/análisis , Estudios de Casos y Controles , Diagnóstico Diferencial , Nevo Sebáceo de Jadassohn/patología
4.
J Am Acad Dermatol ; 75(1): 69-76.e2, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26946987

RESUMEN

BACKGROUND: A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). OBJECTIVE: We sought to systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. METHODS: This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of 2 late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis. RESULTS: Similar to classic psoriasis, KD-associated eruptions were characterized clinically by well-demarcated, scaly pink plaques and histopathologically by intraepidermal neutrophils, suprabasilar keratin 16 expression, and increased Ki-67 expression. They showed less frequent diaper area involvement, more crust and serous exudate, and an enduring remission (91% vs 23% with confirmed resolution; P < .001). Frequency of LCE3C_LCE3B-del and major KD outcomes were similar between cases and controls. LIMITATIONS: The study was limited by the small number of cases, treatment variation, and availability of skin biopsy specimens. CONCLUSIONS: Although the overall clinical and histopathologic findings were similar to conventional psoriasis, this appears to be a distinct phenotype with significantly greater propensity for remission. No adverse effect on KD outcomes was noted.


Asunto(s)
Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/patología , Psoriasis/etiología , Psoriasis/patología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Proteínas Ricas en Prolina del Estrato Córneo/genética , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Queratina-16/análisis , Antígeno Ki-67/análisis , Masculino , Síndrome Mucocutáneo Linfonodular/genética , Fenotipo , Pronóstico , Psoriasis/genética , Psoriasis/metabolismo , Estudios Retrospectivos , Eliminación de Secuencia
5.
Rev Mal Respir ; 33(7): 594-9, 2016 Sep.
Artículo en Francés | MEDLINE | ID: mdl-26777111

RESUMEN

INTRODUCTION: In a first study, we identified signatures of 3 mRNAs (semaphorin 3D [SEMA3D], cytokeratin 16 [KRT16] and UL16 binding protein 2 [ULBP2]) associated to response to a cisplatin-vinorelbin chemotherapy and to survival of advanced non-small cell lung cancers (NSCLC). MATERIAL AND METHODS: The aim of this study was to develop immunohistochemistry tests for KRT16, ULBP2 and SEMA3D and to test proteins expression for prediction of response and survival in biopsies of the same patients. RESULTS: We were not able to reproduce by the protein expression study the signature predicting response to chemotherapy in advanced NSCLC. CONCLUSION: We highlight the difficulties of translational research in thoracic oncology emphasizing the complexity in obtaining adequate tissue samples and the difficulties in conduction and transposing in routine practice high throughput technique for transcriptomic analyses.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Queratina-16/metabolismo , Neoplasias Pulmonares/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Semaforinas/metabolismo , Investigación Biomédica Traslacional , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/administración & dosificación , Proteínas Ligadas a GPI/análisis , Proteínas Ligadas a GPI/metabolismo , Humanos , Inmunohistoquímica/métodos , Péptidos y Proteínas de Señalización Intercelular/análisis , Queratina-16/análisis , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Semaforinas/análisis , Sensibilidad y Especificidad , Análisis de Supervivencia , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/normas , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina
6.
Int J Dermatol ; 55(4): e204-10, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26785261

RESUMEN

BACKGROUND: Lichen striatus (LS) and linear lichen planus (LLP) are separate uncommon disorders belonging to linear inflammatory dermatoses. The immunotyping of inflammatory cells has been investigated in LS and lichen planus (LP), but epidermal proliferation and differentiation have little been described in LS and LLP. METHODS: The clinical and pathological data of eight patients with LS and seven with LLP were retrospectively collected. Immunotyping of infiltrated cells and expression of Ki-67, K16, involucrin, and filaggrin were stained by immunohistochemistry in skin lesions of these patients and normal skin of eight healthy controls. RESULTS: Dermal infiltrates contained primarily CD3+ and CD68+ cells in three groups. CD4+ cells were predominantly located in the perivascular area, while CD8+ cells were frequently close to the junctional zone. Compared with control skin, epidermal and dermal CD1a+ cells, and dermal CD3+, CD4+, CD8+, and CD68+ cells were increased in LS and LLP (P < 0.05), while Ki-67+ cells were significantly high in LLP (P < 0.05) but not in LS. K16 and involucrin expression in LLP were more extensive than in LS, and filaggrin expression was similar between both entities. CONCLUSIONS: Our results indicate that the predominance of CD8+ cells and increased epidermal proliferation and abnormal keratinization are present in both dermatoses, although the levels of the above indexes are mild in LS as compared to LLP. These two entities might be due to the interaction of infiltrated cells and keratinocytes, and CD8+ cells could play a pivotal role in their pathogenesis.


Asunto(s)
Antígenos CD/análisis , Epidermis/fisiopatología , Erupciones Liquenoides/inmunología , Erupciones Liquenoides/patología , Linfocitos T/patología , Adolescente , Adulto , Anciano , Diferenciación Celular , Proliferación Celular , Niño , Preescolar , Femenino , Proteínas Filagrina , Humanos , Lactante , Proteínas de Filamentos Intermediarios/análisis , Queratina-16/análisis , Queratinocitos/fisiología , Antígeno Ki-67/análisis , Liquen Plano/patología , Erupciones Liquenoides/metabolismo , Masculino , Persona de Mediana Edad , Precursores de Proteínas/análisis , Estudios Retrospectivos , Linfocitos T/química , Adulto Joven
7.
Artículo en Inglés | MEDLINE | ID: mdl-23522646

RESUMEN

OBJECTIVE: To characterize the subtypes of ameloblastoma by differentiation markers. STUDY DESIGN: Expression of 9 major acidic epithelial keratins was immunohistochemically examined in 28 ameloblastomas. RESULTS: Keratin 15 (K15) expression patterns corresponded to histological variants: follicular, plexiform and acanthomatous. Tumor nests comprising K15-expressing basal cells mimicked oral epithelium or dental lamina, and tumor nests comprising K15-negative basal cells mimicked outer enamel epithelium. Keratin 19 (K19) was consistently expressed in solid/multicystic ameloblastoma and unicystic ameloblastoma, while peripheral ameloblastoma and desmoplastic ameloblastoma contained K19-negative cells. CONCLUSIONS: The 4 current subtypes had unvaried expression patterns within each group. However, they could be divided into 2 groups by K19 expression pattern: solid/multicystic and unicystic versus extraosseous/peripheral and desmoplastic. K15 expression pattern represented various types of differentiation for tumor nests mimicking tooth germ and oral epithelium. The results clarify the homogeneity and heterogeneity of ameloblastoma cell lineage and differentiation.


Asunto(s)
Ameloblastoma/patología , Queratinas Tipo I/análisis , Adolescente , Adulto , Anciano , Ameloblastoma/clasificación , Biomarcadores de Tumor/análisis , Cadherinas/análisis , Diferenciación Celular , Linaje de la Célula , Esmalte Dental/patología , Células Epiteliales/patología , Epitelio/patología , Femenino , Humanos , Inmunohistoquímica , Queratina-13/análisis , Queratina-14/análisis , Queratina-15/análisis , Queratina-16/análisis , Queratina-17/análisis , Queratina-18/análisis , Queratina-19/análisis , Queratinocitos/patología , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Germen Dentario/patología , Adulto Joven
8.
J Oral Pathol Med ; 42(5): 396-404, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22947066

RESUMEN

BACKGROUND: The aim of this study was to develop and characterize standardized in vitro three-dimensional organotypic models of human junctional epithelium (JE) and sulcular epithelium (SE). METHODS: Organotypic models were constructed by growing human normal gingival keratinocytes on top of collagen matrices populated with gingival fibroblasts (GF) or periodontal ligament fibroblasts (PLF). Tissues obtained were harvested at different time points and assessed for epithelial morphology, proliferation (Ki67), expression of JE-specific markers (ODAM and FDC-SP), cytokeratins (CK), transglutaminase, filaggrin, and basement membrane proteins (collagen IV and laminin1). RESULTS: The epithelial component in 3- and 5-day organotypics showed limited differentiation and expressed Ki-67, ODAM, FDC-SP, CK 8, 13, 16, 19, and transglutaminase in a similar fashion to control JE samples. PLF supported better than GF expression of CK19 and suprabasal proliferation, although statistically significant only at day 5. Basement membrane proteins started to be deposited only from day 5. The rate of proliferating cells as well as the percentage of CK19-expressing cells decreased significantly in 7- and 9-day cultures. Day 7 organotypics presented higher number of epithelial cell layers, proliferating cells in suprabasal layers, and CK expression pattern similar to SE. CONCLUSION: Both time in culture and fibroblast type had impact on epithelial phenotype. Five-day cultures with PLF are suggested as JE models, 7-day cultures with PLF or GF as SE models, while 9-day cultures with GF as gingival epithelium (GE) models. Such standard, reproducible models represent useful tools to study periodontal bacteria-host interactions in vitro.


Asunto(s)
Inserción Epitelial/anatomía & histología , Encía/anatomía & histología , Amiloide , Membrana Basal/anatomía & histología , Biomarcadores/análisis , Proteínas Portadoras/análisis , Recuento de Células , Proliferación Celular , Forma de la Célula , Técnicas de Cocultivo , Colágeno , Colágeno Tipo IV/análisis , Inserción Epitelial/citología , Células Epiteliales/citología , Epitelio/anatomía & histología , Fibroblastos/fisiología , Proteínas Filagrina , Encía/citología , Humanos , Proteínas de Filamentos Intermediarios/análisis , Péptidos y Proteínas de Señalización Intracelular , Queratina-13/análisis , Queratina-16/análisis , Queratina-19/análisis , Queratina-8/análisis , Queratinocitos/fisiología , Antígeno Ki-67/análisis , Laminina/análisis , Proteínas de Neoplasias , Ligamento Periodontal/citología , Proteínas/análisis , Factores de Tiempo , Técnicas de Cultivo de Tejidos , Transglutaminasas/análisis
9.
Oral Dis ; 18(8): 793-801, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22747944

RESUMEN

OBJECTIVES: The objectives of this study were to determine (i) the expression of oral cytokeratins (CKs) among human immunodeficiency virus (HIV)-infected subjects compared with non-HIV controls, (ii) the oral CK expression in the subjects with highly active antiretroviral therapy (HAART) compared with those without HAART, and (iii) factors associated with the expression of oral CKs. MATERIALS AND METHODS: Oral tissues from buccal mucosa were obtained by punched biopsy in HIV-infected subjects with and without HAART, and non-HIV individuals. The samples were processed for immunohistochemical studies of CK1, CK13, CK14, CK16, and involucrin. The staining intensity was scored and recorded. Logistic regression analysis and multi-way ANOVA test were performed. RESULTS: The expression of CK13, CK14, and CK16 was found to be significantly different between HIV-infected subjects and non-HIV individuals (P < 0.05). The expression of those CKs was also significantly different between those who were and were not on HAART (P < 0.05). No significant difference between the groups was observed regarding CK1 and involucrin. CONCLUSIONS: Oral epithelial cell differentiation as marked by the CK expression is affected by HIV infection and use of HAART. CKs may be the useful biomarkers to identify HIV-infected subjects who are at risk of malignant transformation of the oral mucosa because of HIV infection and HAART.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Queratinas/análisis , Mucosa Bucal/patología , 3,3'-Diaminobencidina , Adulto , Consumo de Bebidas Alcohólicas , Biopsia con Aguja , Recuento de Linfocito CD4 , Compuestos Cromogénicos , Estudios Transversales , Células Epiteliales/patología , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/patología , Seropositividad para VIH/patología , Humanos , Queratina-1/análisis , Queratina-13/análisis , Queratina-14/análisis , Queratina-16/análisis , Masculino , Persona de Mediana Edad , Precursores de Proteínas/análisis , Fumar , Carga Viral , Adulto Joven
10.
J Dent Res ; 91(8): 764-70, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22699208

RESUMEN

During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-ß is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-ß, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-ß/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.


Asunto(s)
Encía/fisiología , Proteína Smad2/fisiología , Animales , Bromodesoxiuridina , Movimiento Celular/fisiología , Proliferación Celular , Colágeno/metabolismo , Células Epiteliales/patología , Epitelio/crecimiento & desarrollo , Regulación de la Expresión Génica/genética , Encía/lesiones , Encía/patología , Queratina-14/genética , Queratina-14/fisiología , Queratina-16/análisis , Queratinocitos/patología , Queratinocitos/fisiología , Ratones , Ratones Transgénicos , Fosforilación , Regiones Promotoras Genéticas/genética , Transducción de Señal/fisiología , Proteína Smad2/genética , Factores de Tiempo , Factor de Crecimiento Transformador beta/fisiología , Cicatrización de Heridas/fisiología
11.
Mod Pathol ; 25(6): 784-94, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22301701

RESUMEN

Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in-situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events.


Asunto(s)
Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma in Situ/química , Carcinoma in Situ/genética , Queratina-13/análisis , Queratina-13/genética , Neoplasias de la Boca/química , Neoplasias de la Boca/genética , Adhesión en Parafina , Carcinoma in Situ/patología , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación in Situ , Japón , Queratina-16/análisis , Queratina-16/genética , Captura por Microdisección con Láser , Mucosa Bucal/química , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Valor Predictivo de las Pruebas , Procesamiento Proteico-Postraduccional , Estabilidad Proteica , Estabilidad del ARN , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ARN
12.
Anal Quant Cytol Histol ; 33(1): 19-24, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22125842

RESUMEN

OBJECTIVE: To compare the expression of cytokeratins (CKs) 6, 16, 19 and pan-cytokeratin (PAN) in oral mucosa cells between smokers and nonsmokers to determine the proliferative activity and expression indicative of a potential for malignant transformation. STUDY DESIGN: Smears were obtained from the left lateral border of the tongue with a cytobrush from 25 smokers and 20 nonsmokers seen at the clinics of São José dos Campos Dental School, São Paulo State University, São José dos Campos, São Paulo, Brazil, and processed for immunohistochemistry. Conventional microscopy was used for qualitative analysis. Proportions were compared statistically by the z-test and Fisher's exact test. RESULTS: The expression of CK6 (p = 0.002), CK16 (p = 0.003), CK19 (p = 0.0001) and PAN (p = 0.008) was higher in oral mucosa smears from smokers compared to nonsmokers. CONCLUSION: The expression of CK6 and CK16 demonstrated increased epithelial proliferation in the oral mucosa of smokers, and expression of CK19 indicated alterations in epithelial maturation. The expression of PAN indicates the need for the investigation of other types of CK in further studies.


Asunto(s)
Queratina-16/metabolismo , Queratina-19/metabolismo , Queratina-6/metabolismo , Mucosa Bucal/metabolismo , Fumar/metabolismo , Adulto , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Femenino , Humanos , Queratina-16/análisis , Queratina-19/análisis , Queratina-6/análisis , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Fumar/patología , Adulto Joven
13.
Braz J Otorhinolaryngol ; 76(5): 667-71, 2010.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-20963355

RESUMEN

UNLABELLED: Several studies involving immunohistochemical methods to assess external auditory canal epidermis have been performed with different objectives. With this method it is possible to assess the expression of various antigens such as cytokeratins, cytokines, and hyperproliferation markers among others. AIM: to revise, describe and analyze the knowledge generated by identifiable papers published on the worldwide literature about immunohistochemical hyperproliferation markers in normal external auditory canal epidermis. MATERIALS AND METHODS: systematic review of the papers published until 2009, in indexed international journals. RESULTS: Various antigens related to hyperproliferation were investigated by immunohistochemical methods among the included papers. The most studied ones were cytokeratin 16, Ki-67 and PCNA. CONCLUSIONS: most of the studies utilized external auditory canal epidermis as control sample to study external ear or middle ear cholesteatoma with immunohistochemical methods. There is a hyperproliferative antigen concentration, such as CK16, Ki-67 and PCNA, in the annulus tympanicus, adjacent meatus and tympanic regions, mainly in the lower areas.


Asunto(s)
Colesteatoma del Oído Medio/metabolismo , Conducto Auditivo Externo/metabolismo , Epidermis/metabolismo , Queratina-16/análisis , Antígeno Ki-67/análisis , Biomarcadores/análisis , Proliferación Celular , Humanos , Inmunohistoquímica , Antígeno Nuclear de Célula en Proliferación/análisis , Membrana Timpánica
14.
J Proteome Res ; 9(10): 5153-63, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-20722389

RESUMEN

Several lines of evidence support an autoimmune basis for alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from 10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.


Asunto(s)
Alopecia Areata/inmunología , Autoantígenos/análisis , Precursores de Proteínas/análisis , Adulto , Alopecia Areata/sangre , Autoantígenos/sangre , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Folículo Piloso/inmunología , Folículo Piloso/patología , Humanos , Proteínas de Filamentos Intermediarios , Queratina-16/análisis , Queratina-16/sangre , Masculino , Precursores de Proteínas/sangre , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
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