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PubMed1993

[Testing of related antibodies against inner ear tissues and clinical observation on autoimmune inner ear disease].

Forty-one patients of autoimmune inner ear disease were examined with the clinical audiometry and immunocytochemical method. The results showed that there were sensorineural hearing loss in all patients. Serum immunoglobulins (IgG, IgA, IgM) elevation in 14 of 41 patients and antibodies against inner ear tissue in 4 of 41 patients were observed. It suggests that there is specific antibody against inner ear in the serum of patients with autoimmune inner ear disease, and this disease may be originated from the cochlea or the retrocochlea. The method of clinical analyses, the standards of diagnosis and the principles of treatment were discussed.

Adolescent↗
PubMedDate not supplied

Antibodies against inner-ear proteins in the sera of patients with inner-ear diseases.

Sera from patients with various inner-ear diseases, especially Ménière's disease, were investigated by Western blot against guinea pig inner-ear proteins. Of 45 patients, 24 (53%) with various inner-ear diseases had antibodies against inner-ear proteins, compared with 0 of 10 (0%) in control subjects without inner-ear diseases. Of the 10 proteins that showed a positive reaction with patient sera, the 28-kD band was unique in that it appeared only in the membranous fraction of the inner ear and was highly positive (28%) in reaction with Ménière's disease patient sera. The results in the present study with proteins extracted from guinea pig inner ear were consistent with our previous study using proteins from human inner ear, suggesting that the 28-kD protein may be a candidate for detecting autoimmune inner-ear disease.

Animals↗
PubMedDate not supplied

Effect of human fibrin adhesive on the ear. An electrophysiological study of auditory function in the guinea pig correlated to light and electron microscopy of middle ear mucosa and inner ear structures.

The effect of human fibrin adhesive applied to the middle ear has been studied in guinea pig. Auditory function was measured using acoustically evoked brainstem responses. Middle and inner ear structures were studied with light, transmission and scanning electron microscopy. A transitory conductive hearing loss was observed, but after 8 weeks the auditory function appeared normal. Microscopy of the middle and inner ear failed to show any tissue damage.

Animals↗
PubMed1993

Hydrostatic pressure in the inner ear fluid compartments and its effects on inner ear function.

The present study summarizes the experimental findings obtained on the pressure in the inner ear fluids and on the effects of pressure changes on cochlear function in the guinea pig. Two types of pressures have to be distinguished in the inner ear fluid compartments: (i) hydrostatic fluid pressure and (ii) superimposed hydrodynamic high frequency (> 100 Hz) sound pressure oscillations. Hydrostatic pressure in the inner ear fluids in guinea pigs is in the order of 200 Pa (2 cm H2O) and shows slow (< 5 Hz) respiratory and pulsatory oscillations as well as considerable physiological variations in the range of -100 to +700 Pa. In normal ears, hydrostatic pressure in the perilymph equals pressure in the endolymph, and pressure changes applied to one compartment are immediately transmitted to the other one. A high compliance of Reissner's membrane seems to be the cause of this endolymphatic-perilymphatic pressure equalization. In experimental endolymphatic hydrops, a unique animal model for Meniere's disease, endolymphatic pressure is higher (100 Pa and above) than perilymphatic pressure. These pressure gradients occur only in late stages of hydrops, probably when Reissner's membrane has lost its high compliance after long standing distension. Positive endolymphatic-perilymphatic pressure gradients are secondary to and not the primary cause of hydrops formation. Changes of hydrostatic pressure do not affect auditory function as long as they stay in the physiological range. This includes the sudden loss of positive inner ear pressure that occurs in perilymph fistulas. The rationale for surgical repair of perilymph fistulas in patients in order to restore the hearing function thus becomes questionable. Other aspects of surgical repair, however, as e.g. prevention of labyrinthitis due to permanently open fistula, could not be investigated in this model, because in guinea pigs even large fistulas heal spontaneously within a few days. In experimental endolymphatic hydrops, deterioration of auditory thresholds was partially correlated to the presence of positive endolymphatic-perilymphatic pressure gradients. A change in pressure, however, occurred later than the first deterioration in auditory function. Therefore positive endo-perilymphatic pressure gradients may contribute to, but are not the only cause of hearing impairment.

Animals↗
PubMed2001

Development of the vertebrate inner ear.

The inner ear, also called the membranous labyrinth, contains the cochlea, which is responsible for the sense of hearing, and the vestibular apparatus, which is necessary for the sense of balance and gravity. The inner ear arises in the embryo from placodes, which are epithelial thickenings of the cranial ectoderm symmetrically located on either side of hindbrain rhombomeres 5 and 6. Placode formation in mice is first visible at the 12-somite stage and is controlled by surrounding tissues, the paraxial mesoderm and neural ectoderm. Diffusible molecules such as growth factors play an important role in this process. The activity of several genes confers the identity to the placodal cells. Subsequent cellular proliferation processes under influences from the adjacent hindbrain cause the inner ear epithelium to invaginate and form a vesicle called the otocyst. Combinatorial expression of several genes and diffusible factors secreted from the vesicle epithelium and hindbrain control specification of distinct inner ear compartments. Transplantation studies and inner ear in vitro cultures show that each of these compartments is already committed to develop unique inner ear structures. Later developmental periods are principally characterized by intrinsic differentiation processes. In particular, sensory patches differentiate into fully functional sensory epithelia, and the semicircular canals along with the cochlear duct are elaborated and ossified.

Animals↗
PubMed2000

High resolution imaging of the mouse inner ear by microtomography: a new tool in inner ear research.

A newly developed desktop microtomograph was used to evaluate whether it is suitable for visualizing the three-dimensional (3D) morphology of the mouse inner ear (at a micrometer level) and whether it is applicable as a fast screening tool to detect hereditary abnormalities in this organ. To this end, the epistatic circler, a mutant mouse showing abnormal circling behaviour, was used as a model. The inner ears were dissected out, formaldehyde-fixed, and scanned at maximal resolution along the longitudinal axis. After segmentation, stacks of tomographic images were used for 3D reconstruction of the bony labyrinth. Finally, the obtained data were correlated with subsequent conventional histological examination. The spatial resolution (8 microm) achieved by this instrument, was found to be far superior to that obtained by conventional computer tomography (CT) and magnetic resonance (MR)-imaging equipment. The technique provides detailed tomographic images of the bony labyrinths and enables an adequate 3D reconstruction of the inner ear structures in this small mammal. In addition, it allows a screening for pathologic specimens prior to the more time- and labour-consuming histological techniques, which are still essential to gather information at a (sub)cellular level. This imaging technique can be regarded as a valuable tool in future research on hereditary inner ear abnormalities.

Animals↗
PubMed2003

The homeobox gene Emx2 underlies middle ear and inner ear defects in the deaf mouse mutant pardon.

The semi-dominantly inherited mouse mutation pardon (Pdo) was isolated due to the lack of a Preyer reflex (ear flick) in response to sound from a large-scale N -ethyl- N -nitrosourea (ENU) mutagenesis programme. Dissection of the middle ear revealed malformations in all three ossicles, rendering the ossicular chain incomplete. Hair cell counts in the apical turn of the organ of Corti revealed a significant 22.7% increase in the number of outer hair cells. Raised compound action potential thresholds in Pdo/+ mutants suggested a combined sensorineural/conductive hearing loss. We show that a missense mutation in the homeobox gene Emx2 is responsible for these defects, identifying a new function for this gene in the development of specific structures in the ear.

Action Potentials↗
PubMed1995

[A study on serum autoantibodies against inner ear tissue in the blood of patients with inner ear disorders of unknown etiology].

Membranous labyrinth antigen of guinea pigs was prepared. The sera of 33 patients with inner ear disorders of unknown etiology were examined by immunoblotting assay. The autoantibodies against inner ear antigen were found in patient's sera (30.3%). This indicated that the autoimmune activity may play a role in the development of some cases of these diseases. The detection of autoantibodies to inner ear antigen will be of great value to further study on the action of autoimmunological factor contributing to inner ear disorders of unknown etiology.

Adolescent↗
PubMed1996

Guinea pig inner ear antigens: extraction and application to the study of human autoimmune inner ear disease.

In this study, the authors attempted to develop a method of extracting guinea pig inner ear antigens for otoimmunological research, and to investigate the distribution of the antigens in the various structures of the inner ear. The antigens were extracted either from the entire or from various parts of the guinea pig inner ear. These antigens were separated on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Western blot techniques were used to test sera from patients with inner ear disease against guinea pig inner ear protein extracts. It found that the various molecular weight antigens in the inner ear were associated with the different structures of the inner ear. The sera of 37.5% (N = 80) of patients reacted with two bands (30 and 58 kd) of the guinea pig inner ear immunoblots. The 58 kd band was not specific to the inner ear, but instead was also found in the immunoblots of other guinea pig tissues (brain, lung, and liver). This study suggests that the various antigens of interest could be further extracted and purified from the corresponding locations of the inner ear.

Animals↗
PubMed1990

Role of middle ear endotoxin in inner ear inflammatory response and hydrops: long-term study.

The permeability of the round window membrane for Salmonella typhimurium-derived endotoxin was examined with use of a total of 33 chinchillas. One milligram of each endotoxin was instilled into the tympanic cavities via the superior bullae. The endotoxin activities in middle ear effusions (MEEs), perilymph, and sera were determined by limulus amebocyte lysate assay. Endotoxin was detected in perilymph on the inoculated side by 12 hours after endotoxin instillation and persisted for up to 3 weeks. Endotoxin level peaked at 24 to 48 hours postinstillation, and it steadily declined afterward. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic evidence demonstrated remarkable pathologic changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (eg, scalae tympani, scalae vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. This result suggests that endotoxin present in the middle ear can permeate the round window membrane, causing inner ear tissue damage in this animal model.

Animals↗
PubMed2000

[An observation on long-term influence of middle ear bacterial infection on inner ear function and systemic immune reaction].

OBJECTIVE: To understand whether long-term inner ear heat shock response related to heat shock protein(HSP70) caused by middle ear bacterial infection and the potential influence on inner ear function. METHODS: Sixty BALB/c mice were randomly classified into 6 groups including Klebsiella pneumoniae (KP), Staphylococcus aureus, Bacillus pyocyaneus, Bacillus coli, Bacillus proteus and physiological saline control groups. On 135 days after injection, distortion product otoacoustic emissions(DPOAE) was tested and all the samples were collected, which were examined with light and electronic microscopes. HSP70 related molecule expression in inner ear, nuclear factor (NF) kappa Bp65 characterization in mononuclear cell, anti-KP antibody and anti-membranous labyrinth proteins (MLP) were examined. RESULTS: No nuclear transfer of NF kappa Bp65 was observed in any animal. Anti-KP antibody was detected in 30% (3/10) of Staphylococcus aureus group, 29% (2/7) of KP group, 33% (3/9) of Bacillus pyocyaneus group and 10% (1/10) of control group. Anti-MLP antibody was created in 20% (2/10) of Staphylococcus aureus group, 20% (2/10) of KP group, one each in Bacillus pyocyaneus group and control group respectively. Double positive antibody against KP and MLP were found in Staphylococcus aureus group and KP group. When analyzed with Western blot, all the positive bands were small molecules including strongest 26,000-30,000, medium degree 38,000-41,000 and weak 46,000-50,000 except for 68,000 in one case. There was only one significant DPOAE amplification decrease at 1,625 Hz (2f1-f2) in left ear of Bacillus pyocyaneus group and right ear of Bacillus proteus group. No abnormal phenomenon was found in inner ear both under light microscope and electronic microscope. No significant expression of HSP70 was observed in inner ears. CONCLUSION: No long-term heat shock response related to HSP70 existed in the inner ear and the immune inner ear damage may be caused by multiplefactors.

Animals↗
PubMed2006

Serotonin-induced plasma extravasation in the murine inner ear: possible mechanism of migraine-associated inner ear dysfunction.

Sensitivity to sound and vertigo are often components of migraine. Recent studies suggest that plasma extravasation from intradural blood vessels may contribute to migraine pain. This study documented plasma extravasation in the mouse inner ear after intravenous administration of serotonin (5-HT). Horseradish peroxidase (HRP) was injected intravenously to trace protein extravasation in mice, followed 15 min later by intravenous 5-HT or saline. Forty-five minutes later, mice were euthanized. HRP extravasation was visualized immunohistochemically and quantified densitometrically. Baseline and evoked extravasation in stria vascularis and tectorial membrane were indistinguishable from skin, dura mater and tympanic membrane. Brain parenchyma, Scarpa's ganglion, basal spiral ganglion and modiolus, and the central vestibular nerve segment showed no significant 5-HT-induced extravasation. In contrast, 5-HT produced extravasation in the apical spiral ganglion, modiolus, and intralabyrinthine superior and inferior vestibular nerve. Thus, inner ear plasma extravasation is a potential mechanism for migraine-associated vertigo and sound sensitivity.

Animals↗
PubMed1985

Inner ear barotrauma.

Inner ear barotrauma was observed by compressing or decompressing guinea pigs. The barotrauma in compression was greatly influenced by auditory tube function, and, in the animals deprived of this function, we could observe far more severe damage of inner ear hair cells and far more frequent round window rupture than in animals not thus deprived. Barotrauma in decompression was brought about in guinea pigs not deprived of auditory tube function with a decompression speed of 0.1 kg/cm2/sec, which is so severe that even a healthy auditory tube could not endure it. It can be said that the middle and inner ear are more apt to be damaged in decompression than in compression.

Animals↗
PubMed2001

Inner ear autoantibodies and their targets in patients with autoimmune inner ear diseases.

Immunological mechanisms are thought to play an important role in the pathogenesis of some cochleo-vestibular diseases. This study attempts to present further evidence of autoantibodies reactive against guinea pig inner ear proteins found in patients with autoimmune inner ear diseases (AIED) and specifically identifies the main target antigens of these antibodies. Sera from 110 patients with a clinical diagnosis of either rapidly progressive sensorineural hearing loss (n = 32). Ménière's disease (n = 41), sudden deafness (n = 6) or other aetiologies of hearing loss (n = 11) were screened by the Western blot technique. Forty-four percent of the patients' sera had antibodies to several inner ear proteins, of which the 30, 42 and 68 kDa proteins were found to be the most reactive. These highly reactive proteins were identified by gas-phase micro sequencing after digestion with trypsin and separation of peptide fragments by high-performance liquid chromatography. A partial sequence of each protein was determined. These data, together with those obtained from 2-dimensional gel electrophoresis followed by Western blotting, demonstrated that the 30 and 42 kDa inner ear proteins are the major peripheral myelin protein P0 and the beta-actin protein, respectively, while sequence analysis indicated that the 68 kDa protein is novel. These findings further support the hypothesis that several populations of antibodies may contribute to the enhanced immunological activity of AIED patients. They also add a new dimension to our knowledge of AIED and may open new avenues in the development of simple serological assays, which are easier to perform and more rapid than Western blotting.

Animals↗
PubMed1985

[Inner ear hearing loss--predisposing factor in acute disorders of inner ear function (sudden deafness and vestibular loss)?].

49% of 111 patients with sudden hearing loss had pre-existing inner ear damage to a greater extent than would be expected in a population of the same age. The same age-independent hearing loss of inner ear type was seen in 44% of 72 patients with a sudden unilateral isolated vestibular loss. The accumulated occurrence of diseases of the cardial-vascular system, metabolism, and cervical spine is suggested as the reason for the greater extent of inner ear damage with respect of age and the acute disorders in this area. The high proportion of a pre-existing noise deafness in patients (in 38% of men) with sudden hearing loss suggests an increased vulnerability of the inner ear in pre-existing hearing loss.

Adult↗