Cytoskeletal organization of the human inner ear.
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Actins↗
Biomedical subjects
M Anniko
Publications and source records attributed to M Anniko.
Reversible changes in inner ear function following hyaluronan application in the middle ear.
A safety study regarding the potential ototoxicity of 1.9% hyaluronan was performed in 20 rats. In all animals the middle ear was completely filled with hyaluronan three times at 2-day intervals between the administrations. Inner ear function was evaluated by computerized auditory brainstem response (ABR) measurements. ABR recordings were performed prior to exposure, after myringotomy (but prior to administration of hyaluronan), 5 days after the last administration (n = 15; these animals were then sacrificed for analysis of the middle ear), one month and 3 months later (n = 5). The hearing thresholds were improved in animals 5 days after the last administration of hyaluronan at 6-8 kHz, whereas the hearing thresholds were impaired at 12 and 20 kHz. After one month, ABR thresholds were even better than precontrol levels at 2, 4 and 6 kHz, whereas at all other frequencies the ABR threshold was normal. Three months after hyaluronan exposure, all ABR thresholds were normal, but viscous material was present in the middle ear in 3 of 5 animals. It is concluded that hyaluronan causes reversible changes in inner ear function but lacks ototoxic adverse effects.
Animals↗
Expression of intermediate filaments and actin in the embryonic human inner ear.
The immunoreactivity for intermediate filaments (IF) and F-actin was documented in serially cryosectioned human inner ears aged 14-19 gestational weeks. An individual immunoreactivity for IF was documented for different cell types in both the cochlear and vestibular parts of the labyrinth. All secretory epithelia showed a similar expression of the cytoskeleton. In outer hair cells, immunoreactivity for vimentin was documented, but not for other IF types. The cytoskeletal composition is similar in the tectorial membrane and in supporting cells of the great epithelial ridge. Strong immunoreactivity for F-actin occurs close to the surface of all vestibular organs and Kölliker's organ, but not to the same extent in other epithelia lining the endolymphatic space.
Actins↗
Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study.
In this open, controlled, randomized multi-clinic trial, monotherapy with imipenem/cilastatin was compared to amikacin plus piperacillin as empiric antibacterial therapy in 210 neutropenic cancer patients. Of patients randomized, 53 (25%) had bacteriologically documented infections and of those 30 had septicemia. A further 80 patients (38%) were evaluable for clinical efficacy but did not have documented infections. Seventy-seven patients (37%) were non-evaluable due to effective antibiotic treatment before the trial, early institution of other antibiotics during the trial, verified non-bacterial infections, no neutropenia or other reasons. There were no significant differences in terms of efficacy between imipenem/cilastatin and amikacin plus piperacillin but a consistent trend towards higher rates of clinical cure or improvement and of elimination of causative pathogens was noted in the imipenem/cilastatin group. In patients who were severely neutropenic (less than 0.1 x 10(9) granulocytes/l), similar cure rates were obtained in the two treatment groups--again with a tendency towards better results in the imipenem/cilastatin group. Among evaluable patients with septicemia, one patient in the imipenem/cilastatin group had persistent Staphylococcus aureus bacteremia during treatment. Five patients in the amikacin plus piperacillin group had persistent bacteremia during treatment; all but one (a Pseudomonas aeruginosa) caused by strains resistant to amikacin or piperacillin. Clinical and laboratory adverse effects were mild in the imipenem/cilastatin group although nausea was significantly more common than in the amikacin plus piperacillin group. Among patients on amikacin plus piperacillin, one died in renal failure, possibly related to treatment. Drug-related serious adverse events were reported in two additional amikacin plus piperacillin patients; one with drug fever and one with hearing loss. Microbiological adverse effects occurred in similar frequencies in the two groups. It is concluded that imipenem/cilastatin is a promising candidate for monotherapy of bacterial infections in neutropenic cancer patients.
Adolescent↗
Glucocorticoid incubation of human ACTH-producing pituitary tumours in vitro. A study on ACTH secretion and cell morphology.
ACTH-producing pituitary adenomas obtained from two patients with Cushing's disease were maintained in organ culture for 2 weeks. After 4-6 days of incubation, hydrocortisone (0.1, 1, and 5 mg/ml) was added to the culture medium. Addition of cortisol to the media in concentrations which generally inhibit the ACTH secretion in vivo in patients with Cushing's disease (1 mg/ml) failed to affect the ACTH secretion in vitro. A decrease of ACTH secretion occurred only with 5 mg/ml after 5 days of incubation. A similar effect on growth hormone (GH) release was seen when cortisol (10 mg/ml) was added to cultures from GH-producing pituitary adenoma. No ultrastructural changes were found in cultured cells that could be attributed to the addition of 0.1 mg/ml cortisol in the culture medium. With higher concentrations, (1 mg/ml and 5 mg/ml) minor ultrastructural changes were suspected. Our present findings implicate the hypothalamus as the target area for the feedback control of ACTH in Cushing's disease but could not reveal whether or not the primary lesion (i.e. the tumor) was of pituitary or hypothalamic origin. Our organ culture system appears to be a suitable model for investigating possible ACTH-regulating factors.
Adenoma↗
Ionic environment of cochlear hair cells.
The scala media of the adult cochlea in mammals comprises a morphologically closed compartment sealed with tight junctions of the intermediate to tight types. The unique ionic composition of endolymph is maintained by the stria vascularis through active reabsorption of sodium and active secretion of potassium against ionic gradients. The subtectorial space is only a partially closed compartment which communicates with the endolymph via holes in the tectorial membrane at its outer insertion to the organ of Corti. Hardesty's membrane divides the subtectorial space into two compartments: one facing the surfaces of inner hair cells and one facing the surfaces of outer hair cells. In the study of comparative anatomy, hair cells, e.g. in the lizard, basilar papilla are of two types: those covered with a tectorial membrane and those being free-standing lacking the tectorial membrane. The ionic environment of the hair cell surface seems to be the same, independent of whether covered with a tectorial membrane or not. The tectorial membrane itself is semipermeable to ions in the endolymphatic space. Only the surface structures of the hair cell with the sensory hairs facing the subtectorial space are exposed to the high concentration of potassium, whereas the remaining parts of the hair cell are surrounded by a fluid having a more normal extracellular type of ionic composition (cortilymph/perilymph). During embryonic development the ionic composition of endolymph develops in parallel with the morphologic maturation of the stria vascularis. A completely mature composition of endolymph is reached before any electrophysiological potentials in the cochlea can be elicited. The sensory hair surface of hair cells has reached a mature morphology prior to the maturation of endolymph. In several species the tectorial membrane is morphologically only partially mature when the increase of the potassium concentration of endolymph starts. Drugs primarily affecting the stria vascularis causing a transient change of the ionic composition of endolymph result in a transient dysfunction of inner ear potentials. If the ionic changes persist for longer time, morphological changes can occur in both the stria vascularis and the hair cells of the organ of Corti. Whether such changes are primarily caused by the ototoxic drug itself or by changes in the ionic composition of endolymph has to be explored further.
Animals↗
Junctional complexes of the in vitro developed inner ear. A freeze fracture study.
The freeze fracture technique was used to study intercellular junctions of inner ear anlages developed in vitro. The 16th gestational day inner ear from the CBA/CBA mouse was cultured for 5 days whereafter the specimens were analyzed. Inner ears developed in vivo were used as controls. A considerable variation in the maturation of the tight junctional complexes occurred in both the vestibular and cochlear parts of the labyrinth. The sequential maturation of tight junctions and gap junctions showed the same structural features in the in vivo and the in vitro developed inner ears, although it seemed that the in vivo developed inner ears showed a slightly more overall mature morphology of tight junctions.
Animals↗
Intermediate filaments in the newborn inner ear of the mouse.
The presence of intermediate filaments in the inner ear of the newborn mouse was analyzed with immunofluorescence techniques using antibodies against the five classes of intermediate filaments: cytokeratins, vimentin, desmin, neurofilaments and glial fibrillary acid protein (GFA). Neurofilaments were found in all nerve fibers from the ganglion cell to the hair cell. In the vestibular ganglion two subpopulations of ganglion cells were identified: a minor part staining intensively with neurofilament and the major part of cells lacking this immunofluorescence. Vimentin occurred in a number of supporting structures in the membranous labyrinth, but not in vestibular or cochlear ganglion cells. Cytokeratins, desmin or GFA were not identified in the inner ear.
Animals↗
Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.
True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.
Adolescent↗
Antibiotics and sensorineural interactions. In vitro studies.
Organ culture of the embryonic inner ear of the mouse results, under normal conditions, in a good morphological morphogenesis and cytodifferentiation of individual cells and tissues. Organ culture is performed during a period corresponding to the embryonic development in vivo. Continuing the culture period causes a deterioration of the organ culture explant. Only a minor portion of the total innervation of vestibular and cochlear parts of the labyrinth occurs prior to birth. Low dose exposure (1-10 micrograms/ml) of ototoxic antibiotics in the culture medium causes a primary morphologic damage of vestibular and cochlear hair cells and a markedly reduced number of nerve fibers and statoacoustic ganglion cells. Likewise the ingrowing nerve fibers are even more vulnerable to aminoglycoside antibiotics than the hair cells. Such a drug exposure in the in vitro system confirms (by a chemical deprivation of nerve fiber ingrowth to developing hair cells) that hair cell differentiation occurs at least initially independent of morphologic contact with ingrowing nerve fibers as was earlier shown using a mechanical excision of the statoacoustic ganglion.
Aminoglycosides↗
Otoconial pathology in a strain of the waltzing guinea pig.
The waltzing guinea pig is born with a clinically apparent vestibular dysfunction. In the present study otoconia in the maculae utriculi were studied with scanning electron microscopy in animals aged from newborn to six months old. Malformed otoconia, dumbbell-shaped and asymmetrically shaped otoconia occurred together with otoconia showing various degrees of morphologic degeneration. It is suggested that the otoconial pathologic condition starts prenatally and that an abnormal composition of endolymph may further contribute to the vestibular dysfunction.
Animals↗
Principles in cochlear toxicity.
The hair cells of the cochlea (neuroepithelium) represent the primary target in most drug-induced ototoxic adverse effects on hearing (e.g. aminoglycoside antibiotics). To what extent an exogenically-induced morphologic damage to hair cells is reversible is not known. In aging structurally altered hair cells can persist for years likewisely not any longer participating in sensory transduction as the hair cells degenerate, secondary changes occur in the spiral ganglion cells and the neuronal pathways. Following heavy metal poisoning an adverse effect is observed on both central and peripheral innervation of the cochlea and only minor primary changes occur in the receptor cells. The link between function and morphology in the cochlea is very obvious regarding the high and middle frequencies with a distinct tonotopic localisation whereas for low frequencies (below 1 khz) such a specific morphologic correlation is lacking. Ototoxic effects primarily affecting the source for the production of endolymph, i.e. the stria vascularis, become manifest at all frequencies and at a rather early stage. Independent of type of substance penetrating into the inner ear, the substance has a considerably slower elimination rate as compared with all other compartments in the body. The toxicity of the drugs seems to be more related to its tissue binding capacity and saturation of receptor sites than related to the concentration of the drug in endo-or perilymph.
Age Factors↗
Hair cell differentiation following tissue interactions for induction of otocyst morphogenesis.
The 12th-12.5th gestational day inner ear otocyst from the CBA/CBA mouse was explanted to organ culture with and without surrounding mesenchyme. One group of otocysts from which the mesenchyme had been removed was cultured in conditioned medium (i.e., medium in which mesenchyme alone had been cultured but had been removed prior to explantation of the "stripped" otocyst, without adjacent mesenchyme). Morphogenesis was good in organ cultures with preserved mesenchyme, acceptable in "stripped" otocysts cultured in conditioned medium, but very poor (or even lacking) in specimens deprived of mesenchyme and cultured in normal medium. In the two latter groups, only a small number of hair cells were identified. Although morphogenesis can be induced in specimens initially deprived of adjacent mesenchyme, a normal tissue relationship seems essential for cytodifferentiation of a normal number of hair cells.
Animals↗
Clinical and histopathologic findings in a patient with Gorlin's syndrome.
An 18-year-old patient with Gorlin's syndrome is described, and the clinical findings associated with the syndrome are discussed. The management of keratocysts occurring in patients with the syndrome requires a follow-up period of more than 5 years.
Adolescent↗
Energy dispersive X-ray microanalysis of individual vestibular hair cells.
Microprobe analysis was performed at the cellular and subcellular levels of type I and type II vestibular hair cells. In principle the same types of elemental histograms were found in the two types of hair cells studied. High concentrations of Cl and K were detected in stereocilia, whereas calcium was found when analyzing stereocilia and the supranuclear cytoplasm.
Animals↗
Formation and maturation of the vestibular ganglion.
The morphologic development of the vestibular ganglia with their peripheral neuronal connections was followed from terminal mitosis until the adult stage (CBA/CBA mouse). Schwann cells enclose vestibular ganglion cells and their peripheral nerve fibres already on the 15th-16th gestational days. The morphological basis for at least some physiological activity is present already before birth. As compared with the spiral ganglion, the vestibular ganglion and its peripheral pathways become mature as much as 5-7 days earlier. An adult morphology is reached during the first postnatal week.
Animals↗
Histochemical, microchemical (microprobe) and organ culture approaches to the study of auditory development.
Cochlear development has been studied by means of biochemistry/histochemistry (Na+/K+-ATPase, adenylate cyclase, 2-deoxy-D-glucose and phospholipids), the energy dispersive X-ray microanalysis technique and organ culture of the mammalian inner ear. A high level of Na+/K+-ATPase and adenylate cyclase occurs in the stria vascularis and has been cytochemically demonstrated at the contraluminal side of marginal cell membranes. An increase in the adenylate cyclase content occurs approximately one day before and in parallel with the rise of the potassium content in endolymph. These processes are preceded by an ultrastructural differentiation of the stria vascularis but appear prior to the rapid increase of the endolymphatic potential. The functional activity of the developing/differentiating cochlea is reflected by increased levels of 2-deoxy-D-glucose first during the postnatal morphologic maturation of the organ of Corti and the stria vascularis approximately 1 week after birth, and, later during the maturation of cochlear potentials 10-14 days after birth. Organ culture of the embryonic inner ear is a suitable tool for studies on early (embryonic) morphologic development, neural induction, fate-mapping, epithelio-mesenchymal interactions and neurotrophic interactions. Concerning postnatal inner ear structures, organ culture has focused on development of afferent nerve fibres. The isolated organ is deprived of efferent fibres of central origin.
Adenosine Triphosphatases↗
Structure and function of the adult cochlea following prenatal irradiation.
The structure and function of the cochlea of the CBA/CBA mouse were analysed after exposure to single doses of gamma irradiation during embryonic development. Pregnant mice were exposed to 0.5, 1 and 2 Gy, respectively, on either the 12th, 13th, or 16th gestational day. Morphological analyses were performed using light microscopy, scanning electron microscopy and transmission electron microscopy while the function was measured with the auditory brainstem response (ABR) technique. The inner and outer hair cells showed pathological changes of sensory hairs and their anchoring in the cuticular plate. Cytocochleogram counting was performed classifying the morphological changes into three different severity degrees of pathology. A dose dependent pattern of irradiation induced pathology was documented. A threshold shift of about 20 dB was found after irradiation with 2 Gy. A flat loss of ABR curves occurred in animals irradiated on the 12th or 16th gestational days. If the fetuses were exposed on the 13th gestational day the high frequencies resulted in more pronounced damage than the middle and low frequencies.
Animals↗