RESUMEN
Using newly generated transgenic mice in which the coding region of the connexin29 (Cx29) gene was replaced by the lacZ reporter gene, we confirmed previous immunochemical results that Cx29 is expressed in Schwann cells, oligodendrocytes and Bergmann glia cells. In addition, we detected lacZ/Cx29 in Schwann cells of the sciatic nerve and in particular of the spiral ganglion in the inner ear, as well as at low abundance in the stria vascularis. Furthermore, we found lacZ/Cx29 expression in nonmyelinating Schwann cells of the adrenal gland, in chondrocytes of intervertebral discs and the epiphysis of developing bones. Electron microscopic analyses of myelin sheaths in the central and peripheral nervous system of Cx29-deficient mice detected no abnormalities. The nerve conduction in the sciatic nerve of adult Cx29-deficient mice and the auditory brain stem response as well as visually evoked potentials in 4- to 10-week-old Cx29-deficient mice were not different from wild-type littermate controls. Thus, in contrast to connexin32 and connexin47, which are also expressed in myelinating cells, Cx29 does not contribute to the function of myelin in adult mice.
Asunto(s)
Médula Suprarrenal/metabolismo , Huesos/metabolismo , Cartílago/metabolismo , Conexinas/biosíntesis , Conexinas/genética , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Sistema Nervioso/metabolismo , Médula Suprarrenal/citología , Animales , Cartílago/citología , Condrocitos/metabolismo , Epífisis/metabolismo , Potenciales Evocados Auditivos del Tronco Encefálico/genética , Potenciales Evocados Visuales/genética , Femenino , Genes Reporteros , Operón Lac , Masculino , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Vaina de Mielina/metabolismo , Vaina de Mielina/ultraestructura , Sistema Nervioso/citología , Conducción Nerviosa/genética , Células de Schwann/metabolismo , Células de Schwann/ultraestructura , Nervio Ciático/citología , Nervio Ciático/metabolismo , Ganglio Espiral de la Cóclea/citología , Ganglio Espiral de la Cóclea/metabolismoRESUMEN
The prognosis of idiopathic sudden hearing loss depends on its severity; acute complete deafness, for example, has a particularly bad prognosis. The treatment of acute deafness is based on a systemic application of corticosteroids. Corticoid concentrations in the cochlea are higher after transtympanic application in comparison to systemic application. We therefore investigated whether an additional transtympanic corticoid therapy gives an advantage over systemic standard therapy. We report on 27 patients with sudden idiopathic profound hearing loss or deafness who were treated in the Department of Otorhinolaryngology, University of Essen, Germany. Fourteen patients were treated with a rheologic infusion therapy with systemic prednisolone. Thirteen patients were treated additionally with methylprednisolone (Urbason) transtympanically through a ventilation tube. In the first group of patients who were treated with infusion therapy and corticoids systemically, three patients had good recovery of hearing. Another five patients had a partial recovery of hearing. The average hearing gain from 0.5-4 kHz was 15 dB. In the group of patients who were treated additionally with local corticoids, two patients reported a good recovery of hearing and another two patients only had a partial recovery of hearing. The average hearing gain in the above-mentioned frequency range was 11 dB. In our patients the additional transtympanic application of corticoids did not result in a significantly improved recovery of hearing in comparison to the patients treated with the standard therapy alone.
Asunto(s)
Glucocorticoides/administración & dosificación , Pérdida Auditiva Súbita/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificación , Enfermedad Aguda , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana TimpánicaRESUMEN
Pediatric cholesteatoma can be classified as congenital or acquired based on clinical criteria. We studied the expression patterns of five distinctive cytokeratins in both types of cholesteatoma in order to improve understanding of their pathogenesis and origin. A comparable expression pattern for CK10, CK14, CK18, CK19 and 34betaE12 antigens was found in the matrix of congenital and acquired pediatric cholesteatoma. Our results demonstrate that congenital and acquired pediatric cholesteatoma exhibit an identical cytokeratin distribution pattern, suggesting that they share a common origin. Therefore, it seems possible that a portion of the so-called "acquired" cholesteatoma may actually originate from advanced congenital cholesteatoma with secondary destruction of the tympanic membrane in the pediatric patient population.
Asunto(s)
Colesteatoma del Oído Medio/etiología , Colesteatoma del Oído Medio/metabolismo , Oído Medio/metabolismo , Queratinas/metabolismo , Niño , Preescolar , Colesteatoma del Oído Medio/clasificación , Colesteatoma del Oído Medio/congénito , Epidermis/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Membrana Mucosa/metabolismoRESUMEN
The gap junction protein connexin30 (Cx30) is expressed in a variety of tissues that include epithelial and mesenchymal structures of the inner ear. We generated Cx30 (Gjb6) deficient mice by deletion of the Cx30 coding region. Homozygous mutants (Cx30((-/-))) were born at the expected Mendelian frequency, developed normally and were fertile. However, they exhibit a severe constitutive hearing impairment. From the age of hearing onset, these mice lack the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea, i.e. the endocochlear potential, which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium starts to degenerate by cell apoptosis. This degeneration process is likely to account for the concomitant decrease of the endolymphatic potassium concentration and the aggravation of the hearing loss in adult Cx30((-/-)) mice. The Cx30 ((-/-)) phenotype thus reveals the critical role of Cx30 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. The Cx30 deficient mice may represent a valuable model to study the mechanism of the hearing loss in human patients carrying a homozygous deletion of the CX30 gene (del Castillo et al., 2002, New Engl. J. Med., 346, 243-249).
Asunto(s)
Cóclea/fisiología , Conexinas/deficiencia , Pérdida Auditiva/metabolismo , Alelos , Animales , Cóclea/metabolismo , Conexina 30 , Conexinas/genética , Conexinas/metabolismo , Modelos Animales de Enfermedad , Pérdida Auditiva/genética , Inmunohistoquímica , Ratones , Ratones NoqueadosRESUMEN
INTRODUCTION: Gap junction proteins (connexins = Cx) form transmembrane channels and mediate the transfer of small molecules and ions between the cytoplasm of adjacent cells. Most tissues express several Cx isoforms. The precise combination might play an important role in the maintenance of cell differentiation. Human carcinogenesis is accompanied by aberrant expression and function of Cx. While the larynx is a target organ for many tumor promoters, no data on Cx expression in laryngeal mucosa are available. The goal of the study was to observe the expression of different Cx (Cx26, -30, -32 and -43) in the normal mucosa, hyperkeratoses and carcinomas of the human larynx. METHOD: The immunofluorescence method was performed in normal (n = 7) and dysplastic (n = 6) laryngeal mucosa and in squamous cell carcinoma (n = 7) using affinity-purified polyclonal rabbit antibodies against the 4 Cx isoforms and FITC-conjugated secondary antibodies. RESULTS: The immunofluorescence staining of the normal human vocal fold's epithelium showed the expression of Cx26 and Cx30 in the parabasal and intermediate layers, whereas Cx43 was localized in the basal, parabasal and lower intermediate layers. Cx epitopes could not be found in the upper layers. The precanceroses showed a similar expression of the Cx compared to normal laryngeal epithelium. Due to the higher degree of staining observed in dysplastic specimens, a hyperexpression of Cx26, -30 and -43 could be assumed. The squamous cell carcinomas were characterized by inhomogeneous staining for Cx26, -30 and -43. Regions of intensive expression alternated with regions of no expression. Cx32 could not be observed by immunofluorescence staining in laryngeal tissue. CONCLUSION: In immunohistochemical terms, there was no alteration of the expression of Cx isoforms during carcinogenesis in the laryngeal epithelium. These results do not exclude a loss of functional intercellular gap junction communication by posttranslational modifications of Cx isoforms or disturbed Cx integration into the gap junction channel. Further studies should investigate potential defective gap junctional intercellular communication in cancer cells based on molecular studies.