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PubMed2002

Expression of heat shock protein 70 in the cochlea in experimental autoimmune inner ear disease.

To explore whether the immune response of the inner ear could induce heat shock protein 70 (hsp70) in the guinea pig cochlea, we established a model of autoimmune inner ear disease (AIED) by systemically immunizing guinea pigs with homologous crude inner ear antigen (CIEAg). The immunized cochleas and normal control cochleas were examined for the expression of hsp70 by immunohistochemical analysis and in situ hybridization. It was found that 10 of 28 ears showed significant increases in hearing thresholds after the animals had been sensitized with CIEAg, and 67.9% of the ears from the immunized animals had modiolar vasculitis. The hsp70-like proteins were basically expressed in the normal cochleas, but dramatically increased expressions of hsp70 (perhaps also including hsp70-like molecules) and its messenger RNA were observed in the cochleas of the AIED models. The results suggest that the immune response of the inner ear induced the expression of hsp70 in the guinea pig cochleas.

Animals↗
PubMed1999

Discernment of the sensitized inner ear by peripheral immunocompetent lymphocytes.

OBJECTIVE: To investigate the role of peripheral immunocompetent lymphocytes during the immune response in the inner ear. METHODS: Sensitized lymphocytes from peripheral blood, neck lymph nodes and spleen of three groups of donor animals, i.e., group A immunized intradermally with keyhole limpet hemocyanine (KLH) and both inner ears challenged with KLH, group B received only KLH intradermally without inner ear challenge, and group C used as control, were isolated and labelled with 51Cr. The labelled lymphocytes were injected intravenously into the recipients. They were immunized intradermally with right inner ears challenged with KLH. Twenty to 24 h later, the radioactivities in the temporal bones of the recipients were assayed to detect the infiltration of labelled cells. RESULTS: In groups A and B, the radioactivity in the right temporal bones was higher than that in the left temporal bones (P < 0.05). The highest labelling radioactivity was detected in the right temporal bones of group A. The lowest migration of 51Cr-labelled cells to the inner ear was found in group C. The ratio of radioactivity between right (challenged) and left (unchallenged) inner ears was higher in group A than in groups B and C, with the difference being significant (P < 0.05). CONCLUSION: The immune reaction in response to antigenic stimulation in the inner ear is immunologically modulated by the peripheral systemic circulation.

Adjuvants, Immunologic↗
PubMed2004

Fates of mouse embryonic stem cells transplanted into the inner ears of adult mice and embryonic chickens.

The potential of embryonic stem (ES) cells to differentiate into inner ear hair cells was examined in this study. Undifferentiated mouse ES cells transplanted into neomycin-damaged mouse inner ears were evaluated by immunohistochemistry 4 weeks after transplantation. Some ES cells were positive for E-cadherin or NCAM, and most transplanted cells were positive for SSEA3 and Ki67. None were positive for Myosin VIIa or MF20. These results indicate that the damaged inner ear may have some activity inducing ES cells to develop into ectoderm cells, but the effect was insufficient to induce inner ear hair cells. Next, SDIA/BMP-treated ES cells were transplanted into embryonic chicken inner ear rudiments. Embryonic chickens were expected to share the same developmental systems as mice. SDIA/BMP treatment drove ES cells to the population including neural crest cells and probably placode cells ES colonies were found next to or in the otic vesicles but were not a part of vesicle walls, indicating that transplanted ES cells could not be expected to be the same kind of cells as chicken otic vesicle cells Some ES colonies were found at the vestibulo-cochlear ganglions. To induce inner ear hair cells in this system, the competency of ES cells and otic induction signals should be defined further.

Animals↗
PubMed2000

[Expression of heat shock protein 70 in immune response of the guinea pig inner ear].

OBJECTIVE: To explore whether the immune response of the inner ear could induce heat shock protein (hsp) 70 in guinea pig cochlea. METHODS: A model of autoimmune inner ear disease (AIED) was established by systemically immunizing the guinea pig with the homologous crude inner ear antigen (CIEAg). The immunized cochleae and normal control cochleae were examined for the expression of hsp70 with techniques of immunohistochemistry and in situ hybridization. RESULTS: In the control animals, the expression of the hsp70-like protein appeared only in the spiral ganglion, whereas in the cochleae with CIEAg immunization, strong expression of the hsp70-like protein and its mRNA appeared in the spiral ganglion as well as in the stria vascularis and the spiral ligament. The hearing thresholds were significantly increased in 10 out of 28 cochleae (35.7%) with CIEAg immunization. CONCLUSION: The results suggest that the immune response of the inner ear can induce the expression of hsp70 in the guinea pig cochlea.

Animals↗
PubMed1993

Three dimensional MR gradient recalled echo imaging of the inner ear: comparison of FID and echo imaging techniques.

The detailed structures of the inner ear make this region a diagnostic challenge for radiologists. Thin section high resolution CT is the "gold standard" for studies of the fine bony detail of the inner ear. Although CT can delineate bony structures, fine soft tissue details surrounded by CSF/endolymph (such as nerves in the internal auditory canal) are not easily identified. Conventional MR spin-echo T2-weighted images provide good image contrast for such structures, but the current commercially available minimum slice thickness of approximately 2-3 mm is too thick for the inner ear. Volume gradient recalled echo (GRE) MR imaging techniques can be used to achieve thin slices (< 2 mm) while maintaining adequate contrast for detailed examination. In the work reported here a volume GRE sequence that images the echo formed in a steady-state-free-precession (termed "CE-FAST" or "SSFP" on various commercial MRI systems and called SSFP-echo in this work) was used to image inner ear structures. This technique was compared with images generated using conventional volume GRE techniques (GRASS). While small flip angle volume GRE imaging has been used for inner ear imaging previously, the low contrast typical of such density weighting makes it difficult to distinguish soft tissue structures from surrounding CSF/endolymph. In this work, contrast-to-noise ratios (CNR) between CSF/endolymph and brain parenchyma were compared between the sequences at 15 degrees, 30 degrees, 60 degrees, and 90 degrees flip angles. The SSFP-echo sequence produced higher CNR for such structures and consistently outperformed GRASS sequences at flip angles of 30 degrees, 60 degrees, and 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The equality of volume displacements in the inner ear windows.

The equality of volume displacements in the inner ear windows is commonly assumed. In the present work this assumption is experimentally verified. The stapes is given a known displacement. The volume displacement of the round window is determined by measuring the sound pressure set up in a tube cemented to the round window. Inner ears of pigs have been used in the investigation. Supplementary measurements on one human temporal bone have been performed. The equality of the volume flows in the inner ear windows is also supported through an analysis of earlier measurements of the round window displacement for a given sound-pressure level at the eardrum.

Acoustics↗
PubMed2004

Autoimmune inner ear disease.

PURPOSE OF REVIEW: The role of the immune system in mediating inner ear pathology has received considerable attention over the past two decades. The purpose of this paper is to summarize recent basic science research into the pathogenesis of autoimmune inner ear disease (AIED), review the current diagnostic work-up for patients with suspected AIED, and delineate treatment strategies. RECENT FINDINGS: Basic science and clinical studies have been performed to delineate the mechanisms by which autoimmune processes may affect the ear and to develop treatment strategies to reverse this pathology. AIED refers to a rapidly progressive (over a course of weeks to months) sensorineural hearing loss that responds to the administration of corticosteroids. In addition, systemic autoimmune diseases (eg, vasculitides, lupus, Wegener granulomatosis) can secondarily affect the inner ear. Although a number of diagnostic tests for AIED have been advocated, the diagnosis of this entity is still predicated on a positive therapeutic response to corticosteroid administration. Alternate immunosuppressive regimens, designed to be used in patients who cannot be weaned off corticosteroids or whose disease becomes refractory to treatment, have proven to be difficult to develop. Methotrexate, which initially showed promise, has recently been shown to be ineffective in preventing progression of hearing loss. Further research is required to better delineate the pathophysiologic mechanisms involved in AIED and to establish more effective and better tolerated treatment regimens. SUMMARY: The original enthusiasm that was generated by the concept that immune-mediated mechanisms may mediate reversible forms of inner ear pathology has been tempered by the realities conveyed by scientific research. The pathophysiology of AIED is still not well understood. Multiple potential mechanisms have been identified that can result in immune-mediated inner ear pathology. The diagnosis of AIED is based on clinical presentation and response to the administration of corticosteroids. Diagnostic testing may support the diagnosis, and the results of a recent multicenter study should clarify the role of immunologic testing in the diagnosis of this entity. Treatment options are limited, with corticosteroids being the only validated treatment option, and methotrexate offering no significant benefit to patients. The role of cyclophosphamide is restricted to patients willing to endure the attendant risks. With the advent of cochlear implants, the administration of toxic medications to preserve hearing at all costs is a less desirable option.

Adrenal Cortex Hormones↗
PubMed2001

Is the Er:YAG laser damaging to inner ear function?

OBJECTIVE: To assess whether the use of the Er:YAG laser in middle ear surgery has negative effects on inner ear function. STUDY DESIGN: Prospective. PATIENTS: Forty-nine patients with a 4- to 18-month postoperative audiologic follow-up were included in the study (24 stapedotomies, 23 malleostapedotomies, 1 surgery for congenital ear atresia, and 1 tympanoplasty). Twenty patients with conventional stapedotomy formed a control group. RESULTS: No statistically significant differences in preoperative and postoperative bone conduction thresholds and no impairment of postoperative air conduction thresholds were found. There was no significant difference between the results of the laser and the conventional stapedotomy. In addition, no relevant correlation between applied laser energy and postoperative hearing results were found. In summary, the authors were unable to find a negative effect of the Er:YAG laser on inner ear function at the 4- to 18-month audiometric follow-up. CONCLUSION: The clinical use of the Er:YAG laser with the system used in this study poses no risk to inner ear function if the total amount of energy is kept within the limits applied in this study.

Adolescent↗
PubMed2005

Modification of atrial natriuretic peptide receptor expression in the rat inner ear.

HYPOTHESIS: The purpose of this animal study was to confirm the presence of all three atrial natriuretic peptide (ANP) receptor subtypes in the rat inner ear and compare the expression of each receptor after inner ear injection of ANP, phosphate-buffered saline, or a solution containing ANP incubated with anti-ANP antibody (to block upregulation). BACKGROUND: Receptors for ANP and related compounds have been localized in the inner ear of animals and humans. A previous study at this institution demonstrated the ability to up-regulate the expression of the three ANP receptors (ANP-A, ANP-B, ANP-C) in response to round window injection of ANP in the rat inner ear. METHODS: After surgical exposure, the round window of female Lewis rats was injected with various concentrations of ANP, ANP plus anti-ANP antibody, or control. Animals were killed 24 hours after injection, inner ear tissues were harvested and homogenized, and RNA was isolated for reverse-transcription polymerase chain reaction. RESULTS: Electrophoresis showed the presence of all three receptor subtypes with exposure to phosphate-buffered saline. Expression was significantly higher 24 hours after injection with the two concentrations of ANP. This increase was partially blocked with increasing relative concentrations of anti-ANP antibody. CONCLUSIONS: These findings confirm the presence and responsiveness of ANP receptors in the rat inner ear. The ability to block up-regulation with the antibody provides a potential new research tool for manipulating the function of this hormone system in experimental models and, ultimately, in understanding the mechanisms of fluid homeostasis in the inner ear.

Animals↗
PubMed2006

Inner ear and facial nerve complications of acute otitis media with focus on bacteriology and virology.

CONCLUSION: Among 20 patients with inner ear complications and/or peripheral facial palsy secondary to acute otitis media (AOM) a proven or probable bacteriological cause was found in 13 (65%). In seven patients (35%), a proven or probable viral cause was found. Only two of the patients (10%), with a proven bacterial AOM and a clinical picture of a purulent labyrinthitis in both, together with a facial palsy in one, had a substantial degree of dysfunction. Although the number of patients in this study is relatively low our findings show that inner ear complications and facial palsy due to AOM can be of both bacterial and viral origin. Severe sequelae were found only where a bacterial origin was proven. OBJECTIVES: Inner ear complications and/or peripheral facial palsy secondary to AOM are rare. The general understanding is that they are due to bacterial infections. However, in some of these patients there are no clinical or laboratory signs of bacterial infections and they have negative bacterial cultures. During recent years different viruses have been isolated from the middle ear or serologically proven in AOM patients and are thought to play a pathogenetic role. We suggest that in some cases of AOM complications from the inner ear and the facial nerve can be caused by viruses. The purpose of our study was to analyze infectious agents present in patients with inner ear complications and/or facial palsy arising from AOM. PATIENTS AND METHODS: The medical records of 20 patients who had inner ear complications and/or facial palsy following AOM ( unilateral in 18, bilateral in 2) between January 1989 and March 2003 were evaluated. Bacterial cultures were carried out for all patients. Sera from 12 of the patients were stored and tested for a battery of specific viral antibodies. In three patients, investigated between November 2002 and March 2003, viral cultures were also performed on samples from the middle ear and nasopharynx. RESULTS: Nineteen patients had inner ear symptoms. Eight of them had a unilateral sensorineural hearing loss and vertigo, three had vertigo as an isolated symptom and one, with bilateral AOM, had bilateral sensorineural hearing loss. Seven patients had a combination of facial palsy and inner ear symptoms (unilateral sensorineural hearing loss in three, unilateral sensorineural hearing loss and vertigo in two, bilateral sensorineural hearing loss and vertigo in one, with bilateral AOM, and vertigo alone in one). One patient had an isolated facial palsy. Healing was complete in 11 of the 20 patients. In seven patients a minor defect remained at follow-up (a sensorineural hearing loss at higher frequencies in all). Only two patients had obvious defects (a pronounced hearing loss in combination with a moderate to severe facial palsy (House-Brackman grade 4) in one, distinct vestibular symptoms and a total caloric loss in combination with a high-frequency loss in the other. Eight patients had positive bacteriological cultures from middle ear contents: Streptococcus pneumoniae in two, beta-hemolytic Streptococcus group A in two, beta-hemolytic Streptococcus group A together with Staphylococcus aureus in one, Staph. aureus alone in one and coagulase-negative staphylococci (interpreted as pathogens) in two. In the 12 patients with negative cultures, there was a probable bacteriological cause due to the outcome in SR/CRP and leukocyte count in five. In four patients serological testing showed a concomitant viral infection that was interpreted to be the cause (varicella zoster virus in two, herpes simplex virus in one and adenovirus in one.) In three there was a probable viral cause despite negative viral antibody test due to normal outcome in SR/CRP, normal leukocyte count, serous fluid at myringotomy and a relatively short pre-complication antibiotic treatment period.

Adenovirus Infections, Human↗
PubMed1999

Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear.

Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development.

Animals↗
PubMed2004

Genetic disorders of transporters/channels in the inner ear and their relation to the kidney.

Inner ear physiology is reviewed with emphasis on features common to renal physiology. Genetic disorders in transporters/channels for chloride (ClC-K), bicarbonate (Cl(-)/HCO(3)(-) exchanger), protons (H(+)-ATPase), sodium (ENaC, NKKC1, NBC3, NHE3), potassium (KCNQ1/KCNE1, Kcc4), and water (AQP4) in the inner ear and their relation to the kidney are discussed. Based on data from human disorders (with or without mouse counterparts) and mouse models (without human counterparts) this article focuses on the involvement of these transporters/channels in hearing loss.

Animals↗
PubMed1995

Inner ear autoantibodies in patients with sensorineural hearing loss.

In order to identify the inner ear autoantibodies, sera of 195 patients with sensorineural hearing loss and/or vertigo were reached with bovine inner ear antigen by western blotting method. Positive reaction was seen at several molecular weights, in which 33-35 kD, 42 kD and 68 kD were highly reactive. In moderate to severe hearing loss patients, positive reactions with 33-35 kD, 42 kD, 68 kD and others were 25.8%, 26.8%, 26.8% and 71.5% respectively. On the other hand, a positive rate did not clearly correlate with diagnostic entities. Further study to purify inner ear antigen may evaluate inner ear autoimmune disease.

Animals↗
PubMed1994

Distribution of immunoreactive alpha- and beta-subunit isoforms of Na,K-ATPase in the gerbil inner ear.

Biochemical and histochemical studies have demonstrated abundant Na,K-ATPase in the inner ear and provided new information concerning the ion transport capacities of specialized cell types. To extend these earlier observations, we immunostained inner ears from adult gerbils with antibodies specific for the three known alpha- and the two known beta-isoforms of Na,K-ATPase. Different inner ear cell types contained specific and distinct combinations of alpha- and beta-subunit isoforms. Strial marginal cells and vestibular dark cells expressed the alpha 1- and beta 2-isoforms, whereas other positive epithelial cells expressed alpha 1 in combination with beta 1. Ganglion neurons and their peripheral processes showed positive immunostaining for the alpha 3- and beta 1-subunit isoforms. Subpopulations of fibrocytes in the spiral prominence, suprastrial and supralimbal regions, and vestibular system expressed either the alpha 1- or alpha 2-isoform, or both. The differential expression of Na,K-ATPase subunit isoforms presumably reflects different K+ and Na+ transport capacities among inner ear cell types which, working in concert, serve to generate and maintain the unique ionic and electrical environment in the mammalian inner ear.

Animals↗
PubMed1990

Inner ear decompression sickness combined with a fistula of the round window. Case report.

Inner ear barotrauma with rupture of the round or oval window secondary to diving and decompression sickness (DCS) of the inner ear can be a difficult diagnosis to differentiate. The dive profile or associated elements of DCS will often confirm the diagnosis. Occasionally, diagnosis is made during recompression or during operation. The differential diagnosis is important, since immediate recompression is indicated for inner ear DCS, while it is contraindicated in cases of inner ear barotrauma. We have found no cases reported in the world literature in which both diseases have been diagnosed and proven simultaneously. We present a case of a diver who developed DCS with inner ear manifestations complicated by a round window fistula. Treatment and clinical outcome are discussed along with a brief review of the suspected cause.

Audiometry↗