Structural basis for an isometric contraction of human outer hair cells.
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Biomedical subjects
Publications and source records attributed to M Anniko.
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The supporting elements of the human organ of Corti express a number of cytokeratins, and it is obvious that the presence of cytokeratins provides mechanical stability to the framework of the entire organ of Corti. In the basal part of the outer hair cells and in the apical part of the Deiters cells, there is a significant expression of actin. In the human outer hair cells, the system of subsurface cisterns is not only restricted to the lateral cell wall but is also continuous to the basal region where the hair cells are closely attached to the supporting Deiters cells. In contrast to the well-known organization of the subsurface cisterns and pillar structures at the lateral outer hair cell wall of rodents, the pillars at the base of human outer hair cells can form channels. These channels allow a direct communication between the lumen of the subsurface cisterns and the intercellular space which separates outer hair cells and Deiters cells. At the apical part of the Deiters cells, a condensation of microfilaments is present which displays morphological similarities to actin fibers. These well-organized structural configurations between outer hair cells and Deiters cells imply that this region has special contractile properties. The human outer hair cells are therefore firmly stabilized not merely apically but also at the cell base, a situation which would permit a mainly isometric contraction under in vivo physiological conditions.
In the present study the literature on the round window membrane (RWM) structure was reviewed and the rat used as an animal model to elucidate structural alterations of the RWM occurring during serous (SOM) and purulent (POM) otitis media. In SOM the RWM was about the same thickness as that of the control, whereas in POM it increased about 5-fold. The structural changes in POM were mainly confined to the epithelium facing the middle ear cavity. The normal flat epithelium was transformed into a pseudostratified epithelium with both ciliated and goblet cells. Light microscopy revealed only minor changes in the RWM structure during SOM. However, ultrastructurally, the connective tissue layer exhibited dense accumulations of collagen and elastic fibres which were not observed in either normal or the POM ears. The study showed that different inflammatory conditions of the middle ear cause different structural alterations of the RWM. To what extent these changes also influence differently the permeability of the RWM remains to be elucidated. Obviously ultrastructural studies are needed to be able to characterize the structural changes which appear in the RWM in a diseased ear.
The effects on inner ear of Xylocain, EMLA, phenol, endotoxin and hydrocortisone were analysed before treatment and 24 h-6 months after instillation of each drug into the round window (RW) niche, where the substance was left. Inner ear function was determined by repeated auditory brainstem recordings (ABR). All cochleae were analysed morphologically at the light microscopic level. Hydrocortisone, Xylocain and endotoxin caused functional changes without morphological correlates, even at long-term follow-up. In contrast, phenol and EMLA caused both functional impairment and graded morphological damage to the organ of Corti in the basal coil. Outer hair cells (OHC) were more vulnerable than inner hair cells (IHC).
Two side effects which limit the use of cisplatin in cancer chemotherapy are severe nephrotoxicity and ototoxicity. The concurrent administration of sodium thiosulfate with cisplatin reportedly protects from cisplatin nephrotoxicity, however, protection from ototoxicity has not been documented. The purpose of this study was to examine the efficacy of using thiosulfate to ameliorate the ototoxic effects of cisplatin. Toward this end, the effects of cisplatin alone, cisplatin administered concurrently with sodium thiosulfate (CIS/THIO), and sodium thiosulfate alone on the auditory brainstem response (ABR) of guinea pigs were compared. ABR waveforms, comparing latencies, amplitudes and response thresholds, were monitored before, immediately after, and 30 days post treatment. Sodium thiosulfate administered with cisplatin (CIS/THIO) consistently protected animals from hearing loss and surprisingly yielded significant increases in amplitude when compared to baseline and saline controls. However, ABRs of CIS/THIO animals returned toward baseline values after 30 days.
A eutectic mixture of two anesthetic solutions is that of lidocaine and prilocaine, which is available commercially as Emla (eutectic mixture of local anesthetics). This solution is commonly used in clinics in superficial skin surgery and when inserting intravenous catheters, and we also wanted to determine its surface effects when applied onto the tympanic membranes (TM) of rats and guinea pigs as animal models. The animals were observed by otomicroscopy for 2 weeks up to 5 months after administrations of the anesthetic solution. Tissue specimens were then obtained for light microscopy and fine structural analysis. The application of Emla caused minor structural changes to the rat TM, but hardly any alterations to that of the guinea pig. The changes displayed were an overall increased thickness, with typical submucosal edema but only slight epithelial reaction. In comparison with previous results with lidocaine, phenol and Bonain's solution, Emla seemed to be harmless to the structure of the TM. However, the efficacy of Emla as a topical TM anesthetic remains to be proved in future clinical trials.
The topographical and cytological features of the pigmented mouse (CBA/CBA) cochlear nerve were analyzed. The cochlear nerve is very short and is approximately 0.2-0.3 mm in its length. The entire cochlear nerve and a portion of the ventral cochlear nucleus are located within the internal acoustic meatus, and are closely surrounded by bone. Approximately 10,000 nerve fibers are present, of which only about 3% are unmyelinated. The distribution of the axon diameters in the myelinated nerves is close to unimodal.
Using the microprobe for energy dispersive X-ray microanalysis, the elemental compositions of both the individual cells of the stria vascularis and of the endolymph were followed simultaneously under normal conditions and after the administration of 120 mg/kg ethacrynic acid (EA). Marginal cells and intermediate cells showed reversible increases in potassium and decreases in sodium concentrations. Shifts in the ionic composition of endolymph occurred later than after elemental changes in the strial cells. The present results indicate that the marginal and the intermediate cells are the primary target for EA-induced ototoxicity. However, generalized toxic effects of EA are also indicated, with a general leakage of different elements occurring during the 30-60 min period after EA administration.
Serum levels of three glycoprotein tumour antigens (carcino-embryonic antigen, CEA; cancer-associated antigen 50, CA-50; gastrointestinal cancer-associated antigen, CA 19-9) were determined on 125 consecutive patients with tumours of the head and neck region. Elevated CEA values (greater than 5 units/ml) were found in 13/70 squamous cell carcinomas, 3/21 benign and 4/18 malignant salivary gland neoplasms. Elevated CA-50 values (greater than 17 units/ml) were found in 19/70 squamous cell carcinomas, 6/18 malignant and 1/21 benign salivary neoplasms. CA 19-9 displayed higher values (greater than 37 units/ml) in 9/68 squamous cell carcinomas, 4/18 malignant and none of 21 benign salivary gland tumours. Combination of CEA and CA-50 analyses increased the proportion of elevated values to 30/70 in squamous cell carcinomas and 10/18 in salivary gland malignancies. In squamous cell carcinomas no correlation between staging or grading and serum levels was detected for any of the markers. Among malignant salivary gland tumours, CA-50 displayed enhanced serum values in 4/6 mucoepidermoid carcinomas. The mean values for CA-50 and CA 19-9 serum levels were significantly higher for malignant salivary gland neoplasms compared to benign tumours. There was a close correlation between CA-50 and CA 19-9 serum levels. Although, the results suggest that at present none of the tumour markers tested have a place alone in the routine examination of patients with tumours affecting the head and neck region, further studies on salivary gland neoplasms and combinations of the tumour markers are justified.
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Morphometric analyses of the cross-sectional areas were performed on spiral ganglion and vestibular gaglion cells in the CBA/CBA mouse from the 16th gestational day up to the age of 1 month. Vestibular ganglion cells undergo a period of rapid growth between the 4th and 12th postnatal day. Spiral ganglion cells revealed a rapid increase in cross-sectional area during the latter part of the 2nd postnatal week. Increases in cell volume could not be correlated to changes in individual morphological or electrophysiological events, but probably reflect adaptation to function. In 1-month-old animals, the cross-sectional area of both vestibular and spiral ganglion cells had decreased as compared with the 2nd postnatal week.
The effect of cortisone on the inner ear function was investigated. A suspension of 2% hydrocortisone in sterile water was instilled into the middle ear in the round window niche area of healthy rats. The hearing for eight frequencies was determined by auditory brainstem response (ABR) measurements. After 5 days of daily local application, ABR thresholds impaired in the high-frequency range 12 to 31.5 kHz. The impaired ABR thresholds remained unchanged throughout 3 weeks of observation, indicating irreversible damage to the inner ear. It is also noteworthy that hydrocortisone delayed healing of the perforated tympanic membrane.
Specimens from the organ of Corti were taken from regions which appeared normal in the cytocochleogram as evaluated with the Nomarski optics. Ultrastructural, qualitative analyses of aging cochlear hair cells in the guinea pig showed, however, principally five distinct types of pathological changes: (1) disintegration of the cuticle; (2) increased amounts of intracellular lamellar structures and submembrane cisternae; (3) aggregations of electron optically dense particles; (4) lysosome-like structures; and (5) vesiculation of cytoplasm. Stereocilia remained intact also in cells where the cuticular plate showed severe degeneration. Outer hair cells showed more extensive cytological changes than inner hair cells. The ultrastructural pathology in aging cochlear hair cells is specific and is a sign of dysdifferentiation of their specific morphology although the hair cells survive for a long time in a more or less dysdifferentiated state. Hair cell changes were primary, leaving afferent and efferent nerve terminals initially morphologically intact.
The freeze-fracture technique was used to study the spiral ganglion cell population in the adult mouse. The majority of the ganglion cells (type I) had a smooth cell surface. Interspersed among these first ganglion cells, a small number of other ganglion cells (type II) showed considerable membrane specializations and were morphologically reminiscent of nerve terminals previously described only in human temporal bones. Calculations of the number of the two types of spiral ganglion cells in sectioned material showed that the adult mouse spiral ganglion comprises of 3%-4% unmyelinated type II ganglion cells.
The catecholamine content in cochlear and facial nerves was determined using high-performance liquid chromatography coupled with electro-chemical detection. Minute amounts of norepinephrine were detected in both nerves in normal CBA/CBA mice and homozygotic jerker mouse mutants, whereas norepinephrine was found only in the facial nerve in the dancer heterozygotic mouse mutant. Dopamine and epinephrine were not detected in any of the mouse strains.
The effect of acoustic stimulation on the postnatal development of deoxyglucose uptake into the mouse cochlea and the inferior colliculus was evaluated. Animals between postnatal day 4 and 20 were separated into four different groups depending on their age. Tritiated deoxyglucose was injected intraperitoneally into each animal and tracer uptake was quantitated by microdissection of the tissues and scintillation counting. Acoustic stimulation at a noise level of 100 dB (A) resulted in supra-normal levels of deoxyglucose uptake for all auditory tissues during postnatal days 13, 14, and 15. The lateral wall tissues, which are non-sensory and non-neuronal, also increased deoxyglucose uptake following acoustic stimulation in a manner that paralleled the uptake by the sensory structures. Serum radioactivity and glucose levels remained unchanged during postnatal development, with these parameters remaining stable with acoustic stimulation.
Pregnant CBA/CBA mice were whole body irradiated with 2 Gy on the 13th or 16th day of gestation, respectively. The exposed fetuses were raised to an age of 21 postnatal days. Auditory brainstem recordings of threshold levels showed a considerable elevation independent of if irradiation had been performed on either the 13th gestational day or the 16th gestational day. In exposed animals a latency difference occurs in the peaks that increases from peak 1 to peak 5, measuring in peak 5 up to 1.16 ms. Also the peak-to-peak length of waves 1-5 increases in irradiated animals. Scanning electron microscopy of the cochleae showed varying degrees of stereociliary derangement of both outer and inner hair cells, particularly in cochleae where irradiation had been performed on the 13th gestational day, but not loss of hair cells. Light microscopic analysis of auditory brainstem nuclei revealed normal conditions except that in inner ears exposed on the 16th gestational day the flocculus was fused to the lateral surface of the anterior ventral cochlear nucleus. It is concluded that the elevated threshold levels in irradiated animals are most likely due to pathological changes in the peripheral receptor organ whereas the increased latencies and the increased peak-to-peak length likewise reflect functional changes in the brainstem auditory nuclei.
Salivary gland neoplasms in childhood and adolescence are rare, especially in the minor salivary glands. Vasoformative tumours and pleomorphic adenomas appear to be the most common benign neoplastic salivary gland lesions in the pediatric age group. The distribution of various malignant histological types is not always consistent with that in the adult population, and they appear more often in girls than in boys. Only 17 cases have previously been documented. The clinical and histological picture of a case of palatal mucoepidermoid carcinoma in a 13-year-old girl is presented as well as a review of the literature on malignant salivary gland tumours in childhood.