RESUMEN
The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.
Asunto(s)
Carcinoma de Células Escamosas , Conducto Auditivo Externo , Humanos , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Receptores ErbB/metabolismo , Carcinoma de Células Escamosas/patología , PronósticoRESUMEN
Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor characterized by unique histomorphologic and immunohistochemical features as well as recurrent MEF2C::SS18 gene fusion. Since 2019, 24 cases have been reported in the literature, primarily arising in the oral cavity, with a single reported case arising in the parotid gland. Here, we present a case of MSA that arose in the external ear canal in an 89-year-old woman and was discovered during management of vertigo symptoms. Excisional biopsy of the lesion showed multiple fragments of squamous epithelium with hyperplastic changes and a distinct subepithelial infiltrating neoplasm composed of bland cells forming tubules and cords. Neoplastic cells expressed keratin, S100 protein, p63, and TLE1 and did not express p40, mammaglobin, pan-TRK, synaptophysin, or chromogranin by immunohistochemistry. SS18 gene rearrangement was shown with break-apart fluorescent in situ hybridization. Overall, the histomorphologic, immunohistochemical, and cytogenetic findings confirm a diagnosis of MSA arising in a unique extraoral location.
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Adenocarcinoma , Neoplasias de las Glándulas Salivales , Femenino , Humanos , Anciano de 80 o más Años , Hibridación Fluorescente in Situ , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Adenocarcinoma/patología , Inmunohistoquímica , Proteínas S100/genética , Neoplasias de las Glándulas Salivales/genética , Biomarcadores de Tumor/genéticaRESUMEN
External auditory canal (EAC) stenosis or atresia usually requires a skin graft to repair, but due to the lack of a graft containing functional glands, postoperative complications such as infection and eczema are common. The aim of this study was to isolate and characterize seed cells for the construction of tissue engineered EAC skin containing ceruminous gland by isolating and cultivating cells of ceruminous gland. In this study, EAC skin samples were harvested from adult goats for ceruminous gland cell isolation. Cell morphology and proliferation rates, expression of CK7, CK8, CK18, and CK19 (glandular cell specific-markers), and secretion of ß-defensin-1, lysozyme, and polysaccharides were evaluated at different passages to verify the presence of ceruminous gland cells and determine whether function and proliferation potential were maintained. Ceruminous glands were successfully isolated and extracted from goat EAC skin. Furthermore, the isolated glandular cells maintained robust proliferation potential, exhibited high expression of CK7, CK8, CK18, and CK19, and vigorously secreted ß-defensin-1, lysozyme, and polysaccharides in this culture system. However, expression of glandular cell specific-markers and secretory function gradually declined with increasing passage number, indicating dedifferentiation of the subcultured ceruminous gland cells after five passages. In conclusion, ceruminous glands were successfully isolated, cultured, and expanded from goat EAC skin using the serumcontaining culture system. Importantly, the isolated glandular cells retained robust proliferation potential and maintained their phenotype and function in early passages (P1-P3), indicating the method's potential application for ceruminous gland regeneration.
Asunto(s)
Conducto Auditivo Externo , beta-Defensinas , Animales , Glándulas Apocrinas/metabolismo , Conducto Auditivo Externo/metabolismo , Cabras/metabolismo , Muramidasa/metabolismo , Piel/metabolismo , beta-Defensinas/metabolismoRESUMEN
Defects in ear canal development can cause severe hearing loss as sound waves fail to reach the middle ear. Here, we reveal new mechanisms that control human canal development and highlight for the first time the complex system of canal closure and reopening. These processes can be perturbed in mutant mice and in explant culture, mimicking the defects associated with canal atresia. The more superficial part of the canal forms from an open primary canal that closes and then reopens. In contrast, the deeper part of the canal forms from an extending solid meatal plate that opens later. Closure and fusion of the primary canal was linked to loss of periderm, with failure in periderm formation in Grhl3 mutant mice associated with premature closure of the canal. Conversely, inhibition of cell death in the periderm resulted in an arrest of closure. Once closed, re-opening of the canal occurred in a wave, triggered by terminal differentiation of the epithelium. Understanding these complex processes involved in canal development sheds light on the underlying causes of canal atresia.
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Proteínas de Unión al ADN/genética , Conducto Auditivo Externo/crecimiento & desarrollo , Encefalitis/genética , Pérdida Auditiva/genética , Factores de Transcripción/genética , Animales , Diferenciación Celular/genética , Modelos Animales de Enfermedad , Conducto Auditivo Externo/anomalías , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Encefalitis/patología , Células Epiteliales/metabolismo , Epitelio/crecimiento & desarrollo , Pérdida Auditiva/patología , Humanos , Ratones , Proteínas Mutantes/genéticaRESUMEN
The jugular ganglion (JG) contains sensory neurons of the vagus nerve which innervate somatic and visceral structures in cranial and cervical regions. In this study, the number of sensory neurons in the human JG was investigated. And, the morphology of sensory neurons in the human JG and nodose ganglion (NG) was compared. The estimated number of JG neurons was 2721.8-9301.1 (average number of sensory neurons⯱â¯S.D.â¯=â¯7975.1⯱â¯3312.8). There was no significant difference in sizes of the neuronal cell body and nucleus within the JG (cell body, 1128.8⯱â¯99.7 µâ¯m2; nucleus, 127.7⯱â¯20.8 µâ¯m2) and NG (cell body, 963.8⯱â¯225.7 µâ¯m2; nucleus, 123.2⯱â¯32.3 µâ¯m2). These findings indicate that most of sensory neurons show the similar morphology in the JG and NG. Our immunohistochemical method also demonstrated the distribution of ion channels, neurotransmitter agents and calcium-binding proteins in the human JG. Numerous JG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1 (TRPV1, mean⯱â¯SDâ¯=â¯19.9⯱â¯11.5 %) and calcitonin gene-related peptide (CGRP, 28.4⯱â¯6.7 %). A moderate number of JG neurons contained TRPV2 (12.0⯱â¯4.7 %), substance P (SP, 15.7⯱â¯6.9 %) and secreted protein, acidic and rich in cysteine-like 1 (SPARCL1, 14.6⯱â¯7.4 %). A few JG neurons had vesicular glutamate transporter 2 (VGLUT2, 5.6⯱â¯2.9 %) and parvalbumin (PV, 2.3⯱â¯1.4 %). SP- and TRPV2-containing JG neurons had mainly small and medium-sized cell bodies, respectively. TRPV1- and VGLUT2- containing JG neurons were small to medium-sized. CGRP- and SPARCL1-containing JG neurons were of various cell body sizes. Sensory neurons in the human JG were mostly free of vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY). In the external auditory canal skin, subepithelial nerve fibers contained TRPV1, TRPV2, SP, CGRP and VGLUT2. Perivascular nerve fibers also had TRPV1, TRPV2, SP, CGRP, VIP, NPY and TH. However, PV- and SPARCL1-containing nerve endings could not be seen in the external auditory canal. It is likely that sensory neurons in the human JG can transduce nociceptive and mechanoreceptive information from the external auditory canal. Theses neurons may be also associated with neurogenic inflammation in the external auditory canal and ear-cough reflex through the vagus nerve.
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Ganglios , Neuropéptidos/metabolismo , Canales Catiónicos TRPV/metabolismo , Anciano , Autopsia , Péptido Relacionado con Gen de Calcitonina/metabolismo , Conducto Auditivo Externo/citología , Conducto Auditivo Externo/metabolismo , Femenino , Ganglios/citología , Ganglios/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neurotransmisores/metabolismo , Células Receptoras Sensoriales/citología , Células Receptoras Sensoriales/metabolismo , Sustancia P/metabolismo , Nervio Vago/citología , Nervio Vago/metabolismo , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
A 4-month-old female Irish Terrier presented with a well demarcated ulcerative and crusting lesion in the right ear canal. Histological analysis revealed epidermal hyperplasia with severe acantholysis affecting all suprabasal layers of the epidermis, which prompted a presumptive diagnosis of canine Darier disease. The lesion was successfully treated by repeated laser ablation of the affected epidermis. Over the course of three years, the dog additionally developed three dermal nodules of up to 4 cm in diameter that were excised and healed without complications. Histology of the excised tissue revealed multiple infundibular cysts extending from the upper dermis to the subcutis. The cysts were lined by squamous epithelium, which presented with abundant acantholysis of suprabasal keratinocytes. Infundibular cysts represent a novel finding not previously reported in Darier patients. Whole genome sequencing of the affected dog was performed, and the functional candidate genes for Darier disease (ATP2A2) and Hailey-Hailey disease (ATP2C1) were investigated. The analysis revealed a heterozygous SINE insertion into the ATP2A2 gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the ATP2A2 mRNA from skin of the affected dog demonstrated a splicing defect and marked allelic imbalance, suggesting nonsense-mediated decay of the resulting aberrant transcripts. As Darier disease in humans is caused by haploinsufficiency of ATP2A2, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease.
Asunto(s)
ATPasas Transportadoras de Calcio/genética , Enfermedad de Darier/genética , Pénfigo Familiar Benigno/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Acantólisis/genética , Acantólisis/patología , Animales , Enfermedad de Darier/patología , Enfermedad de Darier/veterinaria , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Epidermis/metabolismo , Epidermis/patología , Femenino , Haploinsuficiencia/genética , Heterocigoto , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Pénfigo Familiar Benigno/patología , Pénfigo Familiar Benigno/veterinaria , Piel/metabolismo , Piel/patologíaRESUMEN
OBJECTIVE: To investigate the expression of basic fibroblast growth factor in the matrix of human acquired cholesteatoma compared to the deep meatal skin. This topic does not appear to have been fully investigated before. METHODS: An immunochemical study was conducted. Cholesteatoma tissues from adult patients were collected during surgery (n = 19). Control specimens were taken from the deep meatal skin (n = 8) and compared. RESULTS: A highly significant difference in basic fibroblast growth factor expression was identified between cholesteatoma and skin (mean ± standard error = 58.53 ± 3.6 per cent in cholesteatoma vs 40.6 ± 3.5 per cent in skin; p = 0.005). Both basal and parabasal keratinocytes were stained positive with basic fibroblast growth factor. Additionally, there was specific staining in the basal columnar middle-ear epithelium and mast cell membrane. CONCLUSION: Basic fibroblast growth factor plays an active role in proliferative activity of cholesteatoma through its overexpression in basal and parabasal layers of cholesteatoma matrix. Moreover, its expression in the mast cell membrane supports its role in bone resorption activity.
Asunto(s)
Colesteatoma/metabolismo , Enfermedades del Oído/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colesteatoma del Oído Medio/metabolismo , Conducto Auditivo Externo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: To assess the role of Rho/Rho-kinase pathway in the pathogenesis of cholesteatoma. MATERIALS AND METHODS: Thirty-eight patients with cholesteatoma, who had gone mastoidectomies were enrolled in this prospective study. Cholesteatomas matrix (CM) and a piece of the external ear canal skin (EECS as control) were taken and transferred to the liquid nitrogen and kept at -86â°C for Rho A and Rho-kinase (ROCK) analysis with Western blotting and commercial ELISA kits (Cell Biolabs Inc., San Diego, CA). The tissues were homogenized by an appropriate ice-cold lysis buffer. Following centrifugation, the supernatant was taken and total protein amount was detected by the Bradford method. Thereafter, tissue homogenates were subjected to sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis electrophoresis then transferred to nitrocellulose membrane where it was treated with specific monoclonal primary antibody against to ROCK-2 and HRP-conjugated seconder antibody, respectively. The protein blots were visualized with commercial x-ray film and dansitometrically analyzed by the Scion Image Program (Cell Biolabs Inc., San Diego, CA). In another series of experiments, Rho-kinase activities were assessed by ROCK-2 ELISA kits. RESULTS: There were no statistical differences in Rho A translocation between CM and EECS. However, ROCK activity was found to be lower in CM than EECS as detected by ELISA kits. Furthermore, ROCK protein expression was also significantly lower in CM than EECS as demonstrated by Western blotting. CONCLUSION: Given Rho-kinase could take essential roles in cell differentiation, the results of this study implicate that down-regulated Rho-kinase could be responsible for the keratinocyte undifferentiation seen in cholesteatoma pathogenesis.
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Colesteatoma del Oído Medio/metabolismo , Conducto Auditivo Externo/metabolismo , Transducción de Señal/fisiología , Quinasas Asociadas a rho/metabolismo , Adolescente , Adulto , Niño , Colesteatoma del Oído Medio/etiología , Colesteatoma del Oído Medio/patología , Conducto Auditivo Externo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: In order to investigate the interaction between the cytokines and keratinocyte and determine the role of cytokines in hyperproliferative of chronic otitis media with cholesteatoma, we observe the expression of matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and its receptor (KGFR) in middle ear cholesteatoma. METHOD: We examined the expression of MMP9, VEGF, KGF, KGFR and Ki-67 by immunohistochemistry in 50 specimens from chronic otitis media with cholesteatoma and 15 specimens from the normal skin of external auditory meatus. Ki-67 as an evaluation of cholesteatoma proliferation markers were used to detect the keratinocyte proliferative activity. RESULT: (1) The expression of VEGF and MMP9 in cholesteatoma specimens was higher than normal skin, and the difference was statistically significant (t = 4.914, P < 0.01; t = 3.284, P < 0.01). (2) The expression of KGF and KGFR in middle ear tissues was higher than normal skin, and the difference was statistically significant (t = 4.814, P < 0.01; t = 3.104, P < 0.01); The expression of KGF and KGFR increased, and the expression of Ki-67 also correspondly increased in the cholesteatoma. (3) In the tissue MMP9 and VEGF were positive. Mean optical density increased as well. KGF expression also increased accordingly. CONCLUSION: MMP9, VEGF, KGF and KGFR proteins played an important role in hyperproliferation of cholesteatoma tissues. VEGF, MMP9 and KGF had a synergistic effect in hyperproliferation of cholesteatoma tissues.
Asunto(s)
Colesteatoma del Oído Medio/patología , Citocinas/metabolismo , Queratinocitos/citología , Conducto Auditivo Externo/metabolismo , Oído Medio/metabolismo , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Otitis Media/patología , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To determine whether the use of tissue spears to remove otorrhoea from Aboriginal children's ear canals improves hearing in the affected ear. DESIGN: Case series study with controls. METHODS: The study comprised 61 Aboriginal children from communities in the remote arid zone of South Australia who had otorrhoea obscuring the tympanic membrane in 1 or both ears. Eighty ears were treated with tissue spears, and hearing was assessed before and after treatment. RESULTS: Forty-two children had unilateral and 19 had bilateral active disease. An additional 13 ears without otorrhoea served as controls. Improvement by 5 dB HL or greater in a four-frequency pure tone average occurred in 41.3 per cent of treated ears. Subsequently, blinded audiologists made qualitative judgements that a functional improvement in hearing had occurred after tissue spear use in 28.4 per cent of ears. CONCLUSION: Tissue spears can improve hearing thresholds in a significant proportion of children with otorrhoea. However, the duration of the effect is unknown.
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Conducto Auditivo Externo/cirugía , Audición , Nativos de Hawái y Otras Islas del Pacífico , Otitis Media Supurativa/cirugía , Procedimientos Quirúrgicos Otológicos/instrumentación , Adolescente , Audiometría de Tonos Puros , Umbral Auditivo , Estudios de Casos y Controles , Cerumen , Niño , Preescolar , Conducto Auditivo Externo/metabolismo , Femenino , Humanos , Masculino , Otitis Media Supurativa/fisiopatología , Australia del SurRESUMEN
CONCLUSION: We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma. OBJECTIVES: Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo. METHODS: Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection. RESULTS: The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.
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Colesteatoma del Oído Medio/prevención & control , Pirroles/uso terapéutico , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Animales , Benzamidas , Colesteatoma del Oído Medio/metabolismo , Difenilamina/análogos & derivados , Evaluación Preclínica de Medicamentos , Conducto Auditivo Externo/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Vectores Genéticos , Masculino , Ratas Sprague-Dawley , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , TransfecciónRESUMEN
Canine aural cholesteatoma is an epidermoid cyst that forms in the middle ear cavity as a rare complication of otitis media but the aetiopathogenesis remains controversial. In the present study, 13 cases of canine aural cholesteatoma were investigated histologically and immunohistochemically and compared with cases of chronic otitis. The immunohistochemical investigation was performed using the following monoclonal antibodies: anti-cytokeratins (CK) 14, 16, 8/18, and 19, and anti-Ki67. The proliferative indexes (PIs) of cholesteatomata and otitis epithelium were calculated as the percentage of Ki67 positive nuclei/total nuclei. Histologically, the cholesteatomata were composed of a hyperplastic, hyperkeratotic epithelium (matrix) resting on a fibrous perimatrix, infiltrated by inflammatory cells and devoid of cutaneous adnexa. Immunohistochemically, the cholesteatoma epithelium was CK14- and CK16-positive, and CK8/18- and CK19-negative. A similar pattern of CK expression was found in otitis externa. In otitis media, ciliated epithelium stained CK8/18- and CK19-positive in all layers, CK14-positive in the basal layers, and CK16-negative. The mean PIs in cholesteatomata and otitides were 18.8 and 17.8, respectively. The immunohistochemical pattern of CK expression in cholesteatomata, when compared with chronic otitis, was suggestive of hyperproliferative epithelium, but its origin could not be demonstrated. Comparable PI values were obtained in cholesteatoma and in chronic otitis, which confirmed that Ki67 is a valuable indicator of a hyperproliferative state, but not a predictor of aggressiveness.
Asunto(s)
Colesteatoma del Oído Medio/veterinaria , Enfermedades de los Perros/patología , Queratinas/metabolismo , Antígeno Ki-67/metabolismo , Otitis Externa/veterinaria , Otitis Media/veterinaria , Animales , Colesteatoma del Oído Medio/patología , Perros , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Femenino , Inmunohistoquímica/veterinaria , Masculino , Otitis Externa/patología , Otitis Media/patologíaRESUMEN
PURPOSE: Heavily T2-weighted, 3-dimensional, fluid-attenuated inversion recovery (hT2W-3D-FLAIR) imaging has been reported to detect low concentrations of gadolinium-based contrast media (GBCM) in the anterior eye segment (AES), subarachnoid space (SAS), and labyrinthine perilymph as well as in the cerebrospinal fluid (CSF) of the internal auditory canal (IAC) 4 hours after intravenous administration of a single dose (IV-SD-GBCM) in patients with inner ear disorders. To elucidate the time course of contrast enhancement in healthy volunteers, we obtained hT2W-3D-FLAIR serially after IV-SD-GBCM. MATERIALS AND METHODS: We obtained hT2W-3D-FLAIR before and 0.5, 1.5, 3, 4.5 and 6 hours after IV-SD-GBCM in 6 healthy volunteers and measured signal intensity of the AES, SAS surrounding the optic nerve (SAS-ON), SAS in Meckel's cave (SAS-MC), pontine parenchyma, CSF in the IAC (CSF-IAC), CSF in the ambient cistern (CSF-AC), CSF in the lateral ventricles (CSF-LV), perilymph (PL), and endolymph (EL) in the labyrinth. We then compared averaged values among all time points using analysis of variance (ANOVA). RESULTS: After IV-SD-GBCM, we observed no change in signal intensity in the pontine parenchyma, CSF-LV, or EL and significant enhancement in all other structures. Maximum enhancement was most frequent at 4.5 hours after IV-SD-GBCM in the SAS-ON and PL, at 1.5 hours in the AES and SAS-MC, and at 3 hours in the CSF-IAC and CSF-AC. CONCLUSIONS: Contrast enhancement can be detected by hT2W-3D-FLAIR in the AES, SAS-ON, SAS-MC, PL, CSF-IAC, and CSF-AC in healthy volunteers after IV-SD-GBCM. Timing of maximum enhancement differed among locations. These data might serve as basic knowledge for future clinical research.
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Medios de Contraste/farmacocinética , Compuestos Heterocíclicos/farmacocinética , Imagen por Resonancia Magnética , Compuestos Organometálicos/farmacocinética , Adulto , Segmento Anterior del Ojo/metabolismo , Conducto Auditivo Externo/metabolismo , Gadolinio/líquido cefalorraquídeo , Gadolinio/farmacocinética , Voluntarios Sanos , Compuestos Heterocíclicos/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/líquido cefalorraquídeo , Perilinfa/metabolismo , Espacio Subaracnoideo/metabolismo , Factores de TiempoRESUMEN
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) was recently identified as a member of the TNF superfamily of structurally related cytokines. It regulates TNF-α and numerous cellular responses. We investigated whether TWEAK is upregulated in human middle ear cholesteatoma compared to the skin of the normal external auditory canal (EAC). The expression of TWEAK was analyzed using reverse transcription-polymerase chain reaction, Western blotting and immunohistochemical staining. TWEAK expression was correlated with that of TNF-α as determined by Western blotting. The expression of TWEAK and TNF-α protein was stronger in cholesteatoma tissue than in EAC skin. TWEAK was expressed to a greater degree in the suprabasal layer in the cholesteatoma than in EAC skin. The expression of TWEAK was correlated more closely with single-stranded DNA than Ki-67 immunohistochemically. These findings imply that TWEAK plays an important role in modulating TNF-α expression and apoptosis in cholesteatoma.
Asunto(s)
Colesteatoma del Oído Medio/metabolismo , Conducto Auditivo Externo/metabolismo , Oído Medio/metabolismo , Regulación de la Expresión Génica/fisiología , Receptores del Factor de Necrosis Tumoral/genética , Adulto , Western Blotting , Oído Medio/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor de TWEAK , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: The aim of our study was to investigate the relationship between the destruction of temporal bone structures, ossicular chain destruction, dissemination of cholesteatoma and the expressions of bone morphogenetic proteins (BMPs), BMP-2, BMP-4 and BMP-6 in patients with acquired cholesteatoma. MATERIAL AND METHODS: This study was performed in a total of 80 patients with cholesteatoma and without cholesteatoma who had undergone surgery due to chronic otitis media. The patients were grouped as the study and the control groups. The study group comprised patients with primary acquired cholesteatoma, and the control group consisted of chronic otitis media patients without cholesteatoma. The samples were obtained from cholesteatoma tissue and the external acoustic meatus skin in study group patients and they were obtained from the external acoustic meatus skin only in control group patients. The Reverse Transcriptase Polymerase Chain Reaction method was used for the measurements of BMPs, BMP-2, BMP-4 and BMP-6 expressions. Polymerase Chain Reaction was studied by isolation of Ribonucleic Acid from the tissue samples. RESULTS: When the expressions of BMP in the external acoustic meatus skin were compared between the study and the control groups, the BMPs, BMP-2 and BMP-6 were determined to have a statistically significant relation in the study group (p<0.05), but BMP-4 was not significant (p>0.05). When the expression of BMP in cholesteatoma tissue was investigated in the study group patients, the BMPs, BMP-2 and BMP-6 were determined with statistically significant positivity (p<0.05), but there was no significant positivity for BMP-4 (p>0.05). In the study group, there was no statistical significance between the expressions of BMPs, BMP-2, BMP-4 and BMP-6 in cholesteatoma tissue, in the external acoustic meatus skin, and temporal and ossicular chain destruction, and dissemination of cholesteatoma (p>0.05). A statistically significant positivity for BMPs expression in cholesteatoma tissue was determined in patients with destruction of the incus+malleus+stapes (p<0.05). CONCLUSION: The expressions of BMPs, BMP-2 and BMP-6, were elevated in cholesteatoma tissue. Furthermore, the positivity of BMPs expression was statistically significant in patients with destruction of all the ossicles, and we think that this marker can be used for evaluation of the aggressiveness of cholesteatoma.
Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Colesteatoma del Oído Medio/metabolismo , Colesteatoma del Oído Medio/patología , Adolescente , Adulto , Proteínas Morfogenéticas Óseas/genética , Estudios de Casos y Controles , Conducto Auditivo Externo/metabolismo , Osículos del Oído/patología , Electroforesis en Gel de Agar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Otitis Media/patología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: Ceruminous adenoma of the external auditory canal (EAC) is a rare type of tumour that is diagnosed histologically. However, the clinical behaviour of these tumours remains controversial. Here, we report a case of ceruminous adenoma of the EAC and expression of a hypoxia marker. CASE REPORT: A 78-year-old man presented with a 6-month history of recurrent otorrhoea in the right ear. Surgery was performed by the transmeatal approach with total removal of the mass. Histopathology revealed a ceruminous adenoma. Tumour cells were positive for CK, S-100 protein, Glut-1, HIF-1α, PI3K and p-Akt. There was no evidence of recurrence at last follow-up 27 months after the operation. CONCLUSIONS: Ceruminous adenoma of the EAC is a rare tumour. The treatment of choice is wide local excision with clear margins. To our knowledge, this is the first report of Glut-1 expression and the PI3K/Akt pathway in ceruminous adenoma of the EAC.
Asunto(s)
Adenoma/metabolismo , Neoplasias del Oído/metabolismo , Transportador de Glucosa de Tipo 1/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Proteína Oncogénica v-akt/biosíntesis , Fosfatidilinositol 3-Quinasas/biosíntesis , Adenoma/diagnóstico , Adenoma/genética , Adenoma/patología , Anciano , Cerumen/metabolismo , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Neoplasias del Oído/diagnóstico , Neoplasias del Oído/genética , Neoplasias del Oído/patología , Transportador de Glucosa de Tipo 1/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Proteína Oncogénica v-akt/genética , Fosfatidilinositol 3-Quinasas/genéticaRESUMEN
HYPOTHESIS: The goal of this work is to characterize the morphology and lipid composition of acquired cholesteatoma. We hypothesize that constitutive lipid membranes are present in the cholesteatoma and resemble those found in human skin stratum corneum. METHODS: We performed a comparative noninvasive structural and lipid compositional study of acquired cholesteatoma and control human skin using multiphoton excitation fluorescence microscopy-related techniques and high-performance thin-layer chromatography. RESULTS: The structural arrangement of the cholesteatoma is morphologically invariant along a depth of more than 200 µm and resembles the stratum corneum of hyperorthokeratotic skin. Lipid compositional analyses of the cholesteatoma show the presence of all major lipid classes found in normal skin stratum corneum (ceramides, long chain fatty acids, and cholesterol). Consistent with this, evaluation of Nile red and LAURDAN generalized polarization function images of the cholesteatoma show intercellular regions similar to normal skin stratum corneum in terms of lipid membrane packing and local water content. CONCLUSION: The investigations show the presence of an extremely thickened stratum corneum within the cholesteatoma. The lipid composition and extracellular membranes similar to those of normal skin stratum corneum are present, indicating that a defensive/permeability barrier is present in the cholesteatoma. Finally, it is demonstrated that multiphoton excitation fluorescence microscopy is a suitable noninvasive tool for investigating the morphology and intrinsic physical properties of acquired cholesteatoma.
Asunto(s)
Colesteatoma del Oído Medio/metabolismo , Colesteatoma del Oído Medio/patología , Metabolismo de los Lípidos/fisiología , Fenómenos Fisiológicos de la Piel , Mama/metabolismo , Mama/patología , Cromatografía en Capa Delgada , Conducto Auditivo Externo/metabolismo , Conducto Auditivo Externo/patología , Femenino , Fluorescencia , Colorantes Fluorescentes , Humanos , Lípidos/análisis , Lípidos/aislamiento & purificación , Microscopía de Fluorescencia por Excitación Multifotónica , Oxazinas , Piel/citologíaRESUMEN
OBJECTIVE: The direct activity of antimicrobial peptides against microbes is thought to be an essential first line of defence in the skin; however, little is known about antimicrobial peptide secretion in the skin of the external auditory canal. Evidence suggests that mast cells contribute to the secretion of antimicrobial peptides. This study aimed to examine the distribution of mast cells and antimicrobial peptides, including human ß-defensin-1 and -2 and LL-37, in the external auditory canal skin. METHODS: External auditory canal skin samples from 12 patients undergoing middle-ear surgery with canaloplasty were immunohistochemically stained to detect expression of mast cell markers (tryptase and chymase) and antimicrobial peptides (human ß-defensin-1 and -2 and LL-37). RESULTS: Mast cells and human ß-defensin-1 were present in the ceruminous glands but not in the sebaceous glands. The increased presence of mast cells, human ß-defensin-1 and LL-37 in ceruminous glands suggests that mast cells may participate in the secretion of antimicrobial peptides from ceruminous glands. CONCLUSION: These findings suggest that mast cells contribute to the secretion of antimicrobial peptides in the ceruminous glands of the external auditory canal skin.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/metabolismo , Conducto Auditivo Externo/metabolismo , Mastocitos/fisiología , Fenómenos Fisiológicos de la Piel , Piel/metabolismo , Animales , Glándulas Apocrinas , Quimasas/metabolismo , Conducto Auditivo Externo/citología , Conducto Auditivo Externo/cirugía , Humanos , Inmunohistoquímica , Mastocitos/metabolismo , Procedimientos Quirúrgicos Otológicos , Glándulas Sebáceas , Piel/citología , Triptasas/metabolismoRESUMEN
Although the rectal mucosa remains the traditional site for measuring body temperature in dogs, an increasing number of clinicians have been using auricular temperature to estimate core body temperature. In this study, 88 mature healthy dogs had body temperatures measured with auricular and rectal thermometers. The mean temperature and confidence intervals were similar for each method, but Bland-Altman plots showed high biases and limits of agreement unacceptable for clinical purposes. The results indicate that auricular and rectal temperatures should not be interpreted interchangeably.