The molecular biology of vestibular schwannomas and its association with hearing loss: a review.

Hearing loss is the most common symptom in patients with vestibular schwannoma (VS). In the past, compressive mechanisms caused by the tumoral mass and its growth have been regarded as the most likely causes of the hearing loss associated with VS. Interestingly, new evidence proposes molecular mechanisms as an explanation for such hearing loss. Among the molecular mechanisms proposed are methylation of TP73, negative expression of cyclin D1, expression of B7-H1, increased expression of the platelet-derived growth factor A, underexpression of PEX5L, RAD54B, and PSMAL, and overexpression of CEA. Many molecular mechanisms are involved in vestibular schwannoma development; we review some of these mechanisms with special emphasis on hearing loss associated with vestibular schwannoma.

Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in Sertoli cells.

CONTEXT: Although gonadotropins and testosterone are high in the fetal/early postnatal periods, Sertoli cells remain immature and spermatogenesis does not progress. We hypothesized that Sertoli cells do not respond to testosterone because they do not express the androgen receptor. OBJECTIVE: The objective of the study was to describe the precise ontogeny of androgen receptor expression in the human testis from fetal life through adulthood. DESIGN: This was an immunohistochemical study on testicular biopsies from fetal, neonatal, prepubertal, pubertal, and adult human testes. MAIN OUTCOME MEASURES: Quantification of androgen receptor expression in Sertoli cells was measured. Evaluation of androgen receptor expression in peritubular and interstitial cells as well as anti-Müllerian hormone and inhibin-alpha was also performed. RESULTS: Androgen receptor expression was first observed in the nuclei of few Sertoli cells at the age of 5 months. Labeling was weak in 2-15% of Sertoli cells until 4 yr of age and progressively increased thereafter. High levels of androgen receptor expression were observed in more than 90% from the age of 8 yr through adulthood. Androgen receptor was positive in peritubular cells and variable in interstitial cells. Anti-Müllerian hormone immunolabeling was strong in all Sertoli cells from fetal life throughout prepuberty and weakened progressively as spermatogenesis developed. Inhibin-alpha expression was detected in all Sertoli cells from fetal life through adulthood. CONCLUSIONS: A lack of androgen receptor expression could explain a physiological Sertoli cell androgen insensitivity during fetal and early postnatal life, which may serve to protect the testis from precocious Sertoli cell maturation, resulting in proliferation arrest and spermatogenic development.

Retroperitoneal Castleman's disease with colon cancer. A rare association.

Castleman's disease (CD) is a rare disorder of uncertain aetiology characterised by massive proliferation of lymphoid tissue usually localised as mediastinal masses, although abdominal involvement has been reported. Localised forms are usually associated with a good prognosis, but several more aggressive multifocal variants have been observed. Two different histologic subtypes have been described: the hyaline vascular type, more common in unicentric CD and usually asymptomatic, and the plasma cell form. Unicentric CD may be associated with an increased risk of lymphoma, but there was no reported increased risk of other malignancies. A patient with plasma cell subtype unicentric CD localised in retroperitoneum associated with an adenocarcinoma of ileocaecal valve and liver metastasis is reported.

Significado funcional de la expresión del receptor de andrógenos en el hombre normal y en hombres infértiles

La producción de testosterona en los humanos se inicia alrededor de las semanas 8a y 9a de gestación. Este es un evento crucial para el desarrollo sexual primario en un embrión 46,XY (masculinización) y para el normal desarrollo sexual secundario en la pubertad (virilización). La testosterona además es esencial para mantener los caractéres sexuales secundarios en la vida adulta y para iniciar y preservar la espermatogénesis. Las acciones de los andrógenos se cumplen por medio del receptor de andrógenos (RA). La unión de los andrógenos a su receptor induce un cambio estructural en el RA, convirtiéndolo de un estado inactivo a su forma activa. En el testículo humano la inmunoexpresión del RA se ha detectado exclusivamente en el núcleo de células de Sertoli, en las células de Leydig y en las células mioides peritubulares. La función de estas células está estrechamente relacionada a la concentración y expresión del RA. Mutaciones en el RA ocasionan alteraciones en la acción de los andrógenos, afectando la función endocrina a nivel testicular y de otros órganos diana, comprometiendo además la función reproductiva. El significado de la expresión del RA en la patología testicular funcional congénita y adquirida del testículo humano no está aún bien establecido. En la presente revisión se evalúan los diferentes patrones de expresión inmunohistoquímica del RA reportados en el testículo de hombres normales y en pacientes con patología testicular, y se valora el significado funcional de las alteraciones histológicas y moleculares del RA en relación con la disfunción de la fertilidad en estos pacientes.

Testosterone production begins at weeks 8 to 9 of gestation in the human; this a critical event for primary male sexual development in a 46,XY embryo (masculinization), and for normal secondary sexual development at puberty (virilization). Testosterone also is essential to maintain the secondary sexual characters during adulthood, and for the initiation and preservation of spermatogenesis. The androgen actions are mediated by the androgen receptor (AR). Upon binding of androgens to its receptor, the AR undergoes a conformational change that converts it from an inactive state to its active DNA-binding state. In the human testis, the AR immunoexpression has been detected exclusively in the Sertoli cells nuclei, in the Leydig cells, and in the peritubular myoid cells. These cells function have an strong relation with the AR concentration and expression. Mutations of the AR results in alteration of androgens actions, affecting the endocrine function at the testicular level and in other target organs, affecting also the reproductive function. The meaningful of the AR expression in the congenital and acquired functional testicular pathology, has not been established yet. In this review different immunohistochemical expression patterns of the AR, reported in the testis from normal men, and from patients with testicular pathology are evaluated; also the functional significance from the histological and molecular alterations of the AR are evaluated, in relation with the fertility dysfunction of these patients.

Keratinas: biología celular y significado funcional normal y patológico / Keratins: cell biology and it normal and pathological functional significance

Las Keratinas (Ks), son filamentos intermedios que forman parte del citoesqueleto de las células epiteliales. Pueden expresarse en los epitelios simples (Ks. 7, 8, 19 y 20) y en epitelios estratificados (Ks. 1, 2, 5, 9, 10, 11, 16). La diferente expresión de estas proteínas multigénicas del citoesqueleto está ligada a programas de diferenciación celular específicos (OSBORN & WEBER, 1983; NAGLE, 1988); por ello, el estuio de las Ks. tiene singular importancia en el conocimiento de nuevos aspectos de la Histología e Histopatología, como también de la Biología del Desarrollo. Además, la evaluación de las Ks. mediante técnicas de inmunofluorescencia o inmunohistoquímicas es útil en la correcta identificación y caracterización de las células normales, displásicas y neoplásicas (OSBORN & WEBER, NAGLE). Los distintos patrones de expresión de las Ks. se correlacionan con el grado de diferenciación de células epiteliales inmaduras, y, pór ello, con el grado de diferenciación de los tumores malignos. (FUCHS & GREEN, 1980; FRANKE et al. 1981b; MOLL et. al. 1892a; SCHAAFSMA & RAMAEKERS, 1994). Por último, la valoración de los cambios de inmunoexpresión de Ks. es útil para el diagnóstico diferencial entre metaplasias escamosas típicas y atípicas, incluyendo las displasias epiteliales moderadas y severas y las neoplasias intraepiteliales anteriormente denominadas carcinomas in situ (MOLL et. al., 1982a; TSENG et. al., 1982; QUINLAN et. al., 1985; HUSZAR et. al., 1986; GIGI-LEITNER et. al., 1986; HEID et. al., 1988)