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M Anniko

Publications and source records attributed to M Anniko.

284 records · Page 16Linked to original sources

Age-related auditory brainstem response (ABR) threshold changes in the dancer mouse mutant.

An age-related analysis of auditory brainstem response (ABR) thresholds in 42 heterozygotic dancer mouse mutants (1-13 months old) showed an impairment of ABR thresholds with increasing age, though individual threshold curves could vary considerably. As compared with normal CBA/CBA mice, a progressive deterioration of ABR thresholds occurred from the 2nd postnatal month onwards. The dancer mutant has an inner ear with a morphogenetic type of defect, caused by a semidominant gene which is located in chromosome 19.

Aging↗

Expression of intermediate filament proteins in the inner ear of the dancer mouse mutant.

The expression of intermediate filaments (using well defined monoclonal antibodies to detect neurofilaments, vimentin, and cytokeratins nos. 8 and 18) was analysed in the inner ear of the dancer mouse mutant (with a morphogenetic type of inner ear defect) and compared with that in the normal CBA/CBA mouse. A similar pattern of immunoreactivity was found in the two mouse strains.

Animals↗

Prenatal low-dose gamma irradiation of the inner ear induces changes in the expression of intermediate filaments.

The expression of intermediate filaments (1F) was analysed in the inner ear in normally developed adult CBA/CBA mice and in mice of the same age which had been gamma irradiated in utero with a low dose 1-2 Gy single exposure. Well characterized monoclonal antibodies (mAbs) against all classes of intermediate filament proteins (cytokeratins-Cks, vimentin, neurofilaments, desmin and glial fibrillar acidic protein) were used. With the exception of neurofilament proteins, the expression of intermediate filament proteins was the same in adult normal and irradiated inner ears, irrespective of gestational age at exposure. A complex Ck pattern occurred in the various cell types comprising the membranous labyrinth. In spite of the differences in cell shape and internal organization of organelles, epithelia actively involved in inner ear fluid homeostasis (stria vascularis, dark cell epithelium, endolymphatic duct and sac) revealed, according to our mAbs, the same expression of Cks, except for the mouse counterpart of human Ck 7, which was found exclusively in the stria vascularis and the endolymphatic duct and sac. The pattern of intermediate filament composition in the labyrinth was the same in the mouse as in man. Irradiation on gestational days 12 or 13 (the otocyst stage)--but not at more advanced embryonic age--induced immunoreactivity for neurofilament proteins in vestibular hair cells (HC) and to a minor extent also in cochlear HC. No such positivity was found in the control material.

Abnormalities, Radiation-Induced↗

Cytokeratin diversity in epithelia of the human inner ear.

The expression of cytokeratins (Cks) nos. 5, 7, the combination 5 and 8, 8, 10, 17, 18 and 19 was analysed in the inner ear of 14-24-week-old human fetuses, using 10 different well characterized monoclonal antibodies (mAbs). A complex pattern of Ck immunoreactivity was found. Cks 8 and 18 were identified in both cochlear and vestibular hair cells as well as in all other epithelia. Epithelia involved in fluid regulation (stria vascularis, Reissner's membrane and dark cell epithelium) revealed the same pattern of Ck immunoreactivity in spite of morphological differences in cell configuration. A specific Ck, no. 10 as detected with the mAbs RKSE 60, was found in the endolymphatic duct and sac. The expression of Cks in the human inner ear is in principle similar to that found in the labyrinth of other animal species, for instance in the mouse. However, the human inner ear had a more complex pattern than any inner ear so far known in animal species.

Antibodies, Monoclonal↗

The influence of prenatal gamma irradiation on the ageing of the cochlea.

Pregnant CBA/Ca mice were subjected to whole-body irradiation on the 12th, 13th or 16th day of gestation with 0.5, 1 or 2 Gy, respectively. Auditory brainstem response (ABR) thresholds in the offspring at one month of age were significantly elevated. The irradiated mice were raised to an age of between 25 and 36 months. Before the animals were killed, the ABR thresholds were again determined and compared with those in age-matched controls. The most pronounced ABR threshold loss at a high age occurred in those animals irradiated on gestation day 12. There was a significant (up to p less than 0.001) potentiation of the age-related loss of ABR threshold in the old irradiated mice. In the scanning electron microscope, both inner and outer hair cells were missing in large numbers in exposed animals, irrespective of irradiation dose. Remaining hair cells and also the pillar cells showed signs of degeneration. In particular, damage observed in the mid-cochlear region was significantly more pronounced in the old irradiated mice than in the old control mice. It is concluded 1) that elevation of ABR thresholds in ageing irradiated animals is due to damage to cells and nerve endings in the peripheral receptor organ, and 2) that prenatal irradiation significantly potentiates age-related hearing loss. Exposure to gamma rays seems to function as a sensitizer causing premature ageing.

Aging↗

Inner ear disturbances following inoculation of endotoxin into the middle ear.

Inner ear function was assessed by a frequency-specific (+/-100 Hz) auditory brainstem response (ABR) technique after a single instillation of a suspension of purified E. coli lipopolysaccharide in sterile water into the round window (RW) niche in rats. Instillation of endotoxin caused a transient concentration and tonotopically dependent dysfunction of the inner ear. The largest threshold impairment occurred in the high-frequency region anatomically located close to the RW. At 31.5 kHz the threshold impairment persisted throughout the study. Morphologic damage to the inner ear was not detected at the light microscopic level when using serial sections from decalcified specimens. Our study supports the clinical hypothesis that remnants of non-viable bacteria such as endotoxins, when trapped in the middle ear, can promote middle ear effusion and dysfunction of the inner ear.

Animals↗

Vestibular hair cell pathology in the dancer mouse mutant.

The morphogenetic type of inner ear defect in the dancer (Dc/+) mouse mutant affects primarily the vestibular part of the labyrinth. The animals show a circling-waltzing behaviour. The inner ears from 7-day to 12-month-old Dc/+ mutants have been analysed. Apart from gross malformations, the gene caused changes in fine structure which were found primarily in the cuticular plate and the stereocilia. As the cuticle gradually disintegrated, the sensory hairs became disarrayed and later showed hair fusion. The combination of the gross malformations and the specific ultrastructural changes in the hair cells probably interferes with both posture and behaviour and, probably together with a dysfunction of the central nervous system, is the cause of the animal's behaviour.

Animals↗

Cytoskeletal identification of intermediate filaments in the inner ear of the jerker mouse mutant.

The expression of the five main groups of intermediate filaments (IF) and their subgroups, especially cytokeratins, was analysed in cryosections of the labyrinth of the jerker mouse mutant and compared with normal CBA/CBA controls. Fourteen different well characterized monoclonal antibodies were used. In principle the same pattern of IF was found in the two mouse strains. IF were not found in hair cells of the mouse inner ear, which may reflect a disparity as compared with human fetal hair cells. Chain-specific (epitope-specific) differences were visualized in cytokeratin no. 8 with regard to cells in epithelia involved in the homeostasis of inner ear fluids. Differences in immuno-staining occurred between adjacent cells in the same epithelium, for instance in the semicircular canals.

Animals↗

Intermediate filament proteins in the embryonic inner ear of mice under normal conditions and after exposure to ototoxic drugs.

The expression of the intermediate filament subclasses cytokeratins (CKs), vimentin, and neurofilament triplet proteins (NFs) was analysed in the embryonic inner ear of the CBA/CBA mouse, in vivo and in vitro, using well-defined monoclonal antibodies. Some of the cultured inner ears were exposed to 1-10 micrograms/ml of the ototoxic drugs gentamicin, ethacrynic acid or cisplatin. There was no difference in the expression of IF pattern in the cultured inner ears as compared with the in vivo developed labyrinths. Exposure to the ototoxic drugs did not affect the expression of CKs, vimentin, or NFs. CKs 8 and 18 were identified in all inner ear epithelia. In the mature hair cells, only the apical surfaces showed immunoreactivity to CKs. In addition, CKs 7 and 19 were visualized in the epithelia involved in maintaining endolymph homeostasis. The ganglion cells showed co-expression of CKs, vimentin and NFs, each having a characteristic localization in the cells.

Animals↗

Aberrant frequency tuning and early stereociliary derangement in genetic inner ear disease.

We have developed an auditory brainstem response (ABR) based method for frequency selective forward masking tuning curve technique. Normative data from CBA/CBA mice are compared with tuning curves (TCs) from heterozygote dancer mice which in most cases initially had a normal ABR threshold. The sharpest tuning in normal mice was obtained at 10 kHz (Q10 = 7.6) and 12 kHz (Q10 = 10.9). With increasing age the mutants showed a broadening of the TC tip before ABR threshold impairment occurred. Morphological analysis of the cochleae from dancer mutants revealed an early disarray of hair cell stereocilia which became increasingly more severely affected with advancing age. We conclude that the broadening of the TC tip is an early finding in the genetically induced cochlear susceptibility which can be correlated to stereociliary dysfunction.

Animals↗

Structurally based new functional interpretations of the subsurface cisternal network in human outer hair cells.

The system of subsurface cisterns (SSC) in human outer hair cells (OHC) was studied by high-resolution transmission electron microscopy (TEM). The SSC consist of only a single layer of cisterns, either flattened or tubular. The subsynaptic cisterns of efferent synapses are an integral part of the SSC. The outer leaflet of the SSC facing the cell membrane is connected to the OHC wall by pillars arranged in a highly regular and geometric pattern. The inner leaflet facing the cytoplasm displays an identical pattern of particles arranged in a star-like configuration so that pores are formed centrally. Pores are also identified at the outer leaflet and at the insertion of the pillars into the cell membrane. It is hypothesized that this highly specific organization of SSC, so far described only in the human OHC wall, is controlled by the efferent acetylcholine-mediated innervation.

Cell Membrane↗

Variability in genetically induced age-related impairment of auditory brainstem response thresholds.

In genetically induced hearing impairment or deafness, the recessive mode of inheritance is by far the most common, but it has seldom been feasible to document audiological aberrations. In this study, auditory brainstem response (ABR) thresholds were analysed in groups of 10 heterozygote jerker (je/+) mice each, at ages of 3, 6 and 9 months in the frequency range 2-31.5 kHz. The animals were thereafter regularly tested up to a final age of 12 months. Forty age-related CBA/CBA mice were used as controls. The individual ABR thresholds in 3-, 6-, 9- and 12-month-old CBA/CBA mice were very similar, as also were those in 3- and 6-month-old je/+ mice (mean values within the normal range). In contrast, at 9 months--and even more so at 12 months--all je/+ animals showed large individual variations, with ABR thresholds varying randomly from near-normal to profound impairment. The wide individual spread of ABR thresholds in old je/+ animals was interpreted as reflecting the expression of a random influence of recessive jerker vis-à-vis the wild type of gene.

Aging↗

Cholesteatoma. A clinical and morphological analysis.

A total of 33 consecutively operated aural cholesteatomas were analysed with regard to preoperative findings and correlated with the morphology of the cholesteatoma tissue. Patients were found in all age groups, 9/33 of the patients were operated at an age below 15 years. A persistent ear discharge had occurred in all patients but in 9 cases the patient history was of less than one year. Impaired hearing was found in 29/33. A demineralization of ossicles was observed at X-ray also in cases in which the ossicular chain appeared normal at operation. In only 5/33 cases was there a retraction of the tympanic membrane without a perforation. The morphological features were the same in both very rapidly and very slowly growing cholesteatomas.

Adolescent↗