Vestibular Aqueduct Morphology Correlates With Endolymphatic Sac Pathologies in Menière's Disease-A Correlative Histology and Computed Tomography Study.

Hypothesis: The vestibular aqueduct (VA) in Menière's disease (MD) exhibits different angular trajectories depending on the presenting endolymphatic sac (ES) pathology, i.e., 1) ES hypoplasia or 2) ES degeneration.

Clinical Imaging Findings of Vestibular Aqueduct Trauma in a Patient With Posttraumatic Meniere's Syndrome.

Posttraumatic Meniere's syndrome is a rare clinical entity. The pathomechanism by which temporal bone trauma leads to fluctuating audiovestibular symptoms, in some cases with a delay of onset many years after trauma, remains elusive. Here, a clinical case and the respective temporal bone imaging data were reviewed to investigate the underlying inner ear pathology.

Mechanical Compression of Coverslipped Tissue Sections During Heat-induced Antigen Retrieval Prevents Section Detachment and Preserves Tissue Morphology.

Heat-induced antigen retrieval (HIAR) is routinely employed on aldehyde-fixed tissue sections to enhance the reactivity of antibodies that exhibit weak or no specific interactions with tissue antigens when applied in conventional immunohistochemical protocols. A major drawback of HIAR protocols is, however, the heat-induced detachment of sections from the microscope slide with resultant impaired tissue morphology or loss of the section. We developed a method in which tissue sections mounted on glass slides are temporally coverslipped, and a clamp is used to compress the sections on the microscope slide during HIAR treatment.

Inner ear pathologies impair sodium-regulated ion transport in Meniere's disease.

Meniere's disease (MD), a syndromal inner ear disease, is commonly associated with a pathological accumulation of endolymphatic fluid in the inner ear, termed "idiopathic" endolymphatic hydrops (iEH). Although numerous precipitating/exacerbating factors have been proposed for MD, its etiology remains elusive. Here, using immunohistochemistry and in situ protein-protein interaction detection assays, we demonstrate mineralocorticoid-controlled sodium transport mechanisms in the epithelium of the extraosseous portion of the endolymphatic sac (eES) in the murine and human inner ears.

An Aminocaprolactam Racemase from Ochrobactrum anthropi with Promiscuous Amino Acid Ester Racemase Activity.

The kinetic resolution of amino acid esters (AAEs) is a useful synthetic strategy for the preparation of single-enantiomer amino acids. The development of an enzymatic dynamic kinetic resolution (DKR) process for AAEs, which would give a theoretical yield of 100 % of the enantiopure product, would require an amino acid ester racemase (AAER); however, no such enzyme has been described. We have identified low AAER activity of 15 U mg in a homologue of a PLP-dependent α-amino ϵ-caprolactam racemase (ACLR) from Ochrobactrum anthropi.

Labyrinthitis Ossificans: On the Mechanism of Perilabyrinthine Bone Remodeling.

Introduction: It has been suggested that remodeling of the otic capsule is highly suppressed by the action of anti-resorptive signals emanating from structures of the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to bacterial meningitis and is characterized by destruction of inner ear structures by the formation of new bone. The aim of this study was to explore the impact of LO on bone remodeling of the otic capsule.

Age as a factor in do not attempt cardiopulmonary resuscitation decisions: a multicentre blinded simulation-based study.

Background: The European Resuscitation Council Guidelines recognise that there is a lack of direct evidence for the effect of age on outcome following cardiopulmonary resuscitation.

Aim: To determine the role that advancing age plays in the decision by clinicians to complete a do not attempt cardiopulmonary resuscitation order based on perceived futility.

Design: A questionnaire-based trial.

Temporal bone histopathology in a case of sensorineural hearing loss caused by superficial siderosis of the central nervous system and treated by cochlear implantation.

Objective: To evaluate the histopathology of the temporal bones of a patient with documented superficial siderosis of the central nervous system who underwent right cochlear implantation six years before death.

Background: Superficial siderosis of the central nervous system is due to chronic or repeated subarachnoid hemorrhage and results in sensorineural deafness in 95% of affected individuals in addition to other neurologic findings. The deposition of hemosiderin in the meninges and around cranial nerves is thought to be causative.

TAK1 expression in the cochlea: a specific marker for adult supporting cells.

Transforming growth factor-β-activated kinase-1 (TAK1) is a mitogen activated protein kinase kinase kinase that is involved in diverse biological roles across species. Functioning downstream of TGF-β and BMP signaling, TAK1 mediates the activation of the c-Jun N-terminal kinase signaling pathway, serves as the target of pro-inflammatory cytokines, such as TNF-α, mediates NF-κβ activation, and plays a role in Wnt/Fz signaling in mesenchymal stem cells. Expression of TAK1 in the cochlea has not been defined.

Extralabyrinthine manifestations of DFNA9.

DFNA9 is an autosomal dominant cause of non-syndromic adult-onset sensorineural hearing loss with associated variable vestibular dysfunction caused by mutations in the COCH gene. DFNA9 has previously been characterized by the presence of unique histopathologic features limited to the cochlear and vestibular labyrinth. This report describes newly discovered extralabyrinthine findings within the middle ear in DFNA9 and discusses their implications.

A method for MS(E) differential proteomic analysis of archival formalin-fixed celloidin-embedded human inner ear tissue.

Proteomic analysis of cadaveric formalin-fixed, celloidin-embedded (FFCE) temporal bone tissue has the potential to provide new insights into inner ear disorders. We have developed a liquid chromatography-mass spectrometry (LC-MS) method for tissue sections embedded with celloidin. Q-TOF (Quadrupole-time of flight mass spectrometry) MS(E) (mass spectrometry where E represents collision energy) and Identity(E)™ were used in conjunction with nano-UPLC (capillary ultrahigh pressure liquid chromatography) for robust identification and quantification of a large number of proteins.

Differences in gene expression between the otic capsule and other bones.

Our long term goal is to understand the molecular pathology of otosclerosis and to develop better forms of therapy. Toward this goal, the current study focused on characterizing the molecular factors responsible for the unique biological features of the otic capsule: its minimal rate of remodeling, and lack of healing capacity when fractured. We compared expression levels of 62 genes involved in bone metabolism between the adult murine otic capsule and the tibia and parietal bones; the latter exemplify bones formed by endochondral and intramembranous ossification, respectively.

Techniques of celloidin removal from temporal bone sections.

Objectives: We sought to determine whether the technique of celloidin removal influences the results of immunostaining in celloidin-embedded cochleae.

Methods: We compared four protocols of celloidin removal, including those using clove oil, acetone, ether-alcohol, and methanol saturated with sodium hydroxide. By optimally fixing our tissue (perfused mice), and keeping constant the fixative type (formalin plus acetic acid), fixation time (25 hours), and decalcification time (ethylenediaminetetraacetic acid for 7 days), we determined whether the technique of celloidin removal influenced the immunostaining results.

Wolfram syndrome: a clinicopathologic correlation.

Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a neurodegenerative disorder characterized by diabetes mellitus and optic atrophy as well as diabetes insipidus and deafness in many cases. We report the post-mortem neuropathologic findings of a patient with Wolfram syndrome and correlate them with his clinical presentation. In the hypothalamus, neurons in the paraventricular and supraoptic nuclei were markedly decreased and minimal neurohypophyseal tissue remained in the pituitary.

Immunocytochemical traits of type IV fibrocytes and their possible relations to cochlear function and pathology.

One of the more consistent and least understood changes in the aging human cochlea is the progressive loss of fibrocytes within the spiral ligament. This report presents an animal model for type IV fibrocyte loss, along with immunocytochemical evidence that noise-induced loss of these cells may account for previously unexplained hearing losses. The remarkably low threshold for noise-induced loss of type IV fibrocytes, approximately 24 dB less than the threshold for adjacent hair cell destruction, may account for the prevalence of missing fibrocytes in humans.

Effects of fixative and embedding medium on morphology and immunostaining of the cochlea.

The localization of proteins by immunostaining is a powerful method to investigate otologic disorders. However, the use of fixatives and embedding media (necessary for the preservation of morphology) can obscure antigens, making it difficult to perform immunoassays. We performed a systematic investigation of the effects of fixative and embedding medium on morphology and immunostaining of the mouse cochlea.

CARMA3 mediates lysophosphatidic acid-stimulated cytokine secretion by bronchial epithelial cells.

NF-kappaB activation in bronchial epithelial cells is important for the development of allergic airway inflammation, and may control the expression of critical mediators of allergic inflammation such as thymic stromal lymphopoietin (TSLP) and the chemokine CCL20. Members of the caspase recruitment domain (CARD) family of proteins are differentially expressed in tissue and help mediate NF-kappaB activity in response to numerous stimuli. Here we demonstrate that CARMA3 (CARD10) is specifically expressed in human airway epithelial cells, and that expression of CARMA3 in these cells leads to activation of NF-kappaB.

Sudden deafness: is it viral?

A number of theories have been proposed to explain the etiopathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL), including viral infection, vascular occlusion, breaks of labyrinthine membranes, immune-mediated mechanisms and abnormal cellular stress responses within the cochlea. In the present paper, we provide a critical review of the viral hypothesis of ISSHL. The evidence reviewed includes published reports of epidemiological and serological studies, clinical observations and results of antiviral therapy, morphological and histopathological studies, as well as results of animal experiments.

Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation.

The T-box transcription factor TBX1 has been identified as the major gene responsible for the etiology of velocardiofacial syndrome/DiGeorge syndrome (VCFS/DGS). Conductive hearing loss occurs in a majority of patients with this syndrome, while sensorineural deafness has also been reported in some cases. Mutations in POU3F4/BRN4, a POU domain transcription factor, cause DFN3, an X-linked nonsyndromic form of deafness characterized by mixed conductive and sensorineural hearing loss.

Studies of otic capsule morphology and gene expression in the Mov13 mouse--an animal model of type I osteogenesis imperfecta.

Type I osteogenesis imperfecta (OI) is a disorder of skeletal bones characterized by bone fragility and blue sclera, which can result from mutations in genes encoding for type I collagen--the COL1A1 and COL1A2 genes. Fifty percent of patients with type I OI develop hearing loss and associated histopathological changes in the otic capsule that are indistinguishable from otosclerosis, a major cause of acquired hearing loss. In an attempt to elucidate molecular and cellular mechanisms of hearing loss in type I OI, we have studied the Mov13 mouse, which has served as an animal model of type I OI by virtue of exhibiting variable transcriptional block of the COL1A1 gene.

3p-- syndrome defines a hearing loss locus in 3p25.3.

Deletions affecting the terminal end of chromosome 3p result in a characteristic set of clinical features termed 3p-- syndrome. Bilateral, sensorineural hearing loss (SNHL) has been found in some but not all cases, suggesting the possibility that it is due to loss of a critical gene in band 3p25. To date, no genetic locus in this region has been shown to cause human hearing loss.

Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis-ichthyosis-deafness syndrome.

Objective: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26).

Study Design: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis.

Methods: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome.

Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear, defective in 22q11DS patients.

Most 22q11.2 deletion syndrome (22q11DS) patients have middle and outer ear anomalies, whereas some have inner ear malformations. Tbx1, a gene hemizygously deleted in 22q11DS patients and required for ear development, is expressed in multiple tissues during embryogenesis.