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Biomedical subjects

M Anniko

Publications and source records attributed to M Anniko.

At least 271 records · Page 15Linked to original sources

Morphological changes in bromocriptine-treated pituitary tumours.

Eight cases of pituitary tumours (3 prolactinomas, 3 tumours secreting GH and 2 tumours with a concomitant secretion of GH and PRL) were treated prior to open surgery with bromocriptine. These cases emanated from a series of totally 128 operated cases with pituitary tumours. The tumour tissue was analysed by light and electron microscopy. In 4 cases severe morphological changes had occurred; minor changes were found in 4 cases. Specific morphological changes indicating a dysfunction effect had occurred in one case. It has not been possible to document any consistent finding with regard to tumour susceptibility to bromocriptine. In the present limited material, the extent of morphological damage could not be correlated to dose, duration of treatment period, or endocrinological type of tumour. Our 8 patients with tumours treated with bromocriptine prior to surgery were cases demonstrating no or unsatisfactory clinical/radiological effects of drug therapy.

Adult↗

Vestibular hair cell pathology following low-dose irradiation during embryonic development.

Pregnant CBA/CBA mice (total gestational age 20-21 days) were whole-body irradiated on the 12th, 13th and 16th gestational days with single doses of 1 and 2 Gy using a 60Co source. Litters were taken for morphological analysis 14-21 days after birth. Irradiation on the 12th and 13th gestational days was thus performed prior to morphologic inner ear organogenesis and cytodifferentiation. In approximately 20% of the total postnatal vestibular hair cell population cytological alterations were evident: giant cytoplasmic protrusions, sensory hair fusion and disintegration of the cuticular plate. The other parts of the hair cells remained intact, including nerve endings. Morphometry was not performed. Hair cells type I are more vulnerable to ionizing irradiation during cytodifferentiation than hair cells of type II. All investigated animals showed clinically a normal balance and a normal righting reflex.

Animals↗

Elemental composition of individual cells and tissues in the cochlea.

Localization of elements at the cellular and sub-cellular levels was performed with the energy dispersive X-ray microanalysis technique, using shock-frozen, freeze-dried and araldite-embedded mouse (CBA/CBA) cochleae sectioned dry. Anatomical identification occurred in the STEM (scanning transmission electron microscopy) mode. In inner hair cell stereocilia the K/Na ratio was 70:1 but only 20:1 in the cytoplasm. In outer hair cell cytoplasm the K/Na ratio was 11:1 while the ratio in stereocilia was similar to that in inner hair cells. Ca was identified in stereocilia and the upper part of the cytoplasm of both outer and inner hair cells. The elemental composition in the subtectorial space is endolymph-like and that in the inner tunnel of the organ of Corti is similar to extracellular fluid. Considerable regional differences in elemental composition occur in the tectorial membrane with regard to P, K and Ca. The highest concentration of Ca occurs in the basal part of the tectorial membrane towards the sensory hairs. The highest concentration of K occurs in the basal and outer parts whereas the middle part of the tectorial membrane contains low levels of both K and Ca. The elemental composition changes in two main directions: 1) from the limbal (growing) region to the tip of the tectorial membrane, and, 2) from upper to lower surfaces. The three cell types of the stria vascularis differ considerably in elemental composition. The highest concentration of K occurs in marginal cells. The basal cells contain more K than do the intermediate cells. A significantly higher concentration of Ca, Cl and Na occurs in marginal cell cytoplasm than in any other cell type in the stria vascularis.

Animals↗

Malformations of vestibular organs following low dose gamma irradiation during embryonic development.

Pregnant mice were whole-body irradiated on the 12th, 13th and 16th gestational day with single doses of 0.5, 1, 2, 3, 4, 10 and 20 Gy, using a 60Co source. No surviving litters occurred in groups exposed to more than 2 Gy. Below this dose, irradiation can cause malformation of the cristae ampullares and the maculae. Malformations were more severe and more frequent in fetuses exposed on the 12th than on the 13th gestational day, indicating that, prior to or the earlier during morphogenesis irradiation takes place, the more vulnerable is the developing tissue. Inner ears exposed to irradiation on the 16th gestational day did not reveal severe malformations.

Animals↗

Microprobe analysis of human otoconia.

Utricular and saccular otoconia (N = 510) from 1 fetus (39th gestational week; Trisomy-18), 2 babies (1 1/2 and 2 months) and 3 adults (58, 61 and 77 years) were analysed with an energy dispersive X-ray microprobe. In all otoconia the elemental composition showed an extremely high concentration of Ca but also Na, Mg, P, S, Cl and K were identified. The presence of non-Ca elements was interpreted as being due to a protein nucleus of the otoconia. Non-Ca elements are more prominent during fetal age and early post-natally than later in life. Old age otoconia contained high concentrations of P which indicates that a ' phosphatization ' of aging otoconia occurs, i.e. calcite otoconia are transformed in situ into apatite by reaction with phosphate ions. The elemental composition of otoconia in Trisomy-18 was similar to that in early postnatal inner ears.

Aged↗

Low-dose gamma irradiation effects on labyrinthine development in vitro.

The 13th and 16th gestational day inner ear anlagen, respectively, were exposed after explantation to an organ culture system to low-dose gamma irradiation with a 2 Gy single dose. The explants were thereafter cultured in vitro for 8 vs. 5 days to an age corresponding to birth in vivo. The explants were analysed with regard to gross morphology and at the light and electron microscopic levels. The 13th gestational day inner ear anlage showed malformations of the gross shape. The gross morphology of the 16th gestational day inner ear explant was unaffected. Irradiated specimens showed a delayed development in general as compared with controls. A defective cytodifferentiation of hair cells was observed at the ultrastructural level. Sensory hair fusion occurred, the sensory hair rootlets were poorly developed as also was the cuticle. Nerve terminals were not identified. The observations in the present in vitro study are in agreement with corresponding earlier published in vivo investigations. The organ culture model can thus be used for irradiation induced selective effects on labyrinthine development.

Animals↗

Incomplete maturation of brainstem auditory nuclei in genetically induced early postnatal cochlear degeneration.

In the Shaker-2 mouse mutant, a cochleo-saccular type of genetically induced inner ear degeneration occurs. Morphological signs of degeneration are evident in the 3rd postnatal week and a severe and almost total degeneration has occurred by the age of 6-9 weeks. There are no qualitative differences between the brain of the normal CBA/J mouse and that of the Shaker-2 mouse. The growth of the auditory brainstem nuclei (dorsal cochlear nucleus and ventral cochlear nucleus) in the mutant Sh-2 mouse has stopped by 14 days of age--but not in the normal CBA/J mouse. The brainstem as a whole continues to grow between 14 and 140 days of age in both strains. The early cochlear degeneration coincides with the critical period when a normal input from the peripheral receptor organ is necessary for the maturation of the central auditory pathway.

Animals↗

Synaptogenesis in co-cultured inner ear explants which share a single statoacoustic ganglion.

Co-cultured otic explants which shared a single statoacoustic ganglion were grown 'in vitro' to the equivalent of gestation day 21 and then processed either for light microscopic or ultrastructural study. Only vestibular sensory epithelium was studied. Nerve fibres from the statoacoustic ganglion (SAG) of the (+) SAG otic explant were attracted to the sites of differentiating vestibular sensory epithelium in the (-) SAG otic explant. Synaptic contact between vestibular sensory hair cells and statoacoustic ganglion neurites was observed in both the (-) SAG and (+) SAG otic explants.

Animals↗

X-ray microanalytic studies on developing otoconia.

The onset of otoconial development in the macula utriculi in CBA/CBA mice occurs on the fifteenth and sixteenth gestational days. Our study was concentrated on the early secretion of calcium in the areas of otoconial formation. The epithelial origin of otoconia is documented. Protrusions from supporting cells in the utricular and saccular epithelia contain very large quantities of calcium in addition to the normal cytoplasmic content of elements. The cell protrusions have an elemental composition clearly differing from that of otoconia as well as from neighbouring utricular cells with protrusions. A directed flow of calcium to developing otoconia from the supporting cells of the maculae is suggested.

Animals↗

Formation of junctional complexes in otocysts developed in vitro. A freeze-fracture study.

The thirteenth gestational day inner ear anlage (otocyst) was explanted to an in vitro system and cultured for 8 days, i.e. to a time corresponding to birth. The freeze fracturing technique was used to evaluate morphological differentiation, particularly as regards cell membrane specializations. The epithelial cells were found fully differentiated, e.g. there were regularly arranged stereocilia on the hair cells. The development of tight junctions and gap junctions followed the same pattern as in vivo, but tight junctions did not reach the same degree of regularity and maturation as they did in vivo. There were very few gap junctions in our in vitro specimens. Several tight junctions had an odd appearance, with loss of the normally punctate structure of the strands and areas with considerable thickening. It is possible that this specific morphology can be explained by differentiation in the in vitro system.

Animals↗

Early development of the stato-acoustic and facial ganglia.

The early embryonic development of the stato-acoustic and geniculate ganglia was documented in CBA/CBA mice by light and transmission electron microscopy. The geniculate ganglion was identified at the 12-15 somite stage with its origin from the epibranchial placode as well as the neural crest. The VIII ganglion develops later at the 25-27 somite stage, having its origin both in the otic vesicle and in the neural crest cells.

Animals↗

Microanalytic and light microscopic studies on the developing otic capsule.

The structure of the middle layer of the bone of the otic capsule is histologically unique: it is of endochondral origin, has no Haversian canals and the ossification develops from several centres which fuse to form the hardest bone in the body. Our study has been concentrated on the development of the otic capsule in the CBA/CBA mouse, followed from the 13th gestational day to early postnatal age. In the 14th gestational day inner ear, a condensation of mesenchyme is detected around the membranous labyrinth. A cartilaginous capsule is present on the 15th-16th gestational day. Prior to birth, ossification centres occur close to the stapedial footplate. Serial cryosectioning of the newborn inner ear reveals very few regions containing high levels of calcium (microprobe analysis) although by light microscopy, several ossification centres can be identified.

Animals↗

The ototoxic potential of EMLA. A new local anesthetic for the tympanic membrane.

Instillation of EMLA, a new local anesthetic, into the middle ear of the guinea pig caused severe morphological damage to the organ of Corti in the first 4 mm from the round window. Further up the cochlea, only derangements of the stereocilia were found. The extent of morphological damage was the same, whether the agent was administered once or several times. The ototoxic potential of EMLA was obvious and is probably due to direct damage in areas where present in high concentrations. Over a short distance of approximately 0.1 mm there is a transition from a total destruction of the organ of Corti to a completely normal morphology.

Anesthetics, Local↗

Inner ear effects of exogenous hyaluronan in the middle ear of the rat.

1.9% hyaluronan (HA) (mol. wt. 3 x 10(6] was applied repeatedly into the middle ear of rats through a myringotomy. The function and structure of the cochlea was analysed by auditory brainstem recordings (ABR) at 2-31.5 kHz and by light microscopy. The myringotomy significantly impaired the ABR thresholds at frequencies below 8 kHz. Five days after the last application of HA, the ABR thresholds showed minor improvements at 6-8 kHz but were impaired at 12 and 20 kHz, as compared with control levels. One month after the last administration of HA, ABR thresholds were significantly improved as compared with the initial level at 2-6 kHz but normal at all other frequencies. After 3 months, all ABR thresholds had returned to the pre-treatment (normal) level. Five days after the last application of HA, the latencies for almost all frequencies were significantly prolonged for waves II and IV at the ABR threshold. After 3 months all latencies had returned to their pre-treatment (normal) values. Highly concentrated hyaluronan (1.9%) is free from ototoxicity but does have transient functional effects on the inner ear.

Animals↗

Aberrant elemental composition of otoconia in the dancer mouse mutant with a semidominant gene causing a morphogenetic type of inner ear defect.

The elemental composition of otoconia from Jerker and Dancer mouse mutants was analysed in both maculae. A normal elemental content was found in otoconia from Jerker mutants, whereas in the Dancer mutant a large number of otoconia from both maculae contained very high concentrations of phosphorus. In these otoconia, the phosphorus calcium ratio was approximately 1:8, in Jerker (and normal) otoconia approximately 1:150-200. However, otoconia from Dancer mutants occurred with also a normal elemental composition. The increasing content of phosphorus in otoconia may possibly indicate an early onset of aging, i.e. corresponding to a phosphatization process as described in aging human otoconia.

Animals↗

A frequency-specific auditory brainstem response technique exemplified in the determination of age-related auditory thresholds.

Using gated sinusoidal stimuli (tone bursts), frequency-specific auditory brainstem responses (ABR) have been recorded in mice. The gating function represents a filter with a constant narrow bandwidth in the investigated frequency range 2-31.5 kHz. The ABR thresholds found in the CBA/CBA mouse using this technique were in close agreement with those previously reported in the literature concerning mice. The ABR thresholds were analysed in 2-18-month-old animals showing a slight impairment of ABR thresholds with increasing age. The individual variations in ABR thresholds were small.

Aging↗

Developmental stage-dependent pattern of inner ear expression of intermediate filaments.

The expression of vimentin, cytokeratins (CKs) and neurofilament (NF) proteins was analysed (using monoclonal antibodies) in the mouse inner ear at the otocyst stage (13th gestational day), when organogenesis was largely completed (16th gestational day) and at birth (21st gestational day). Co-expression of vimentin and CKs occurred at the otocyst stage. On the 16th gestational day, most epithelial cells lacked immunoreactivity for vimentin and considerable variation in CK positivity was found between different regions of the epithelial lining. At birth, CK positivity was lacking in the developing organ of Corti but was present in other types of epithelium lining the scala media. In the vestibular half of the labyrinth, positivity for CKs was found at the apical surfaces of both sensory cells and supporting cells and in epithelia lining the membranous labyrinth. Vimentin positivity occurred in the greater epithelial ridge of the differentiating organ of Corti. Even at this stage the statoacoustic ganglion comprised two subpopulations of ganglion cells: those staining for NF proteins and those lacking this immunoreactivity. Thus, as the inner ear matures, a pattern of cytoskeletal reorganization occurs that is dependent on developmental stage.

Animals↗

Tissue binding kinetics of tobramycin. An experimental study in the mouse inner ear in vitro.

The tissue-binding capacity of tritiated tobramycin (TM) was analysed in an organ culture system in the embryonic inner ear of the mouse. A rapid and probably irreversible binding of TM occurs within 10 min, showing about 100 micrograms TM per gram protein in the vestibular half and about 75 micrograms TM per gram protein in the cochlear half of the labyrinth. A steady state is reached within 60 min. The TM uptake was then 390 micrograms TM per gram protein in the vestibular part and 270 micrograms in the cochlear part of the inner ear. A minor fraction of TM, of the same magnitude as initially bound, becomes irreversibly bound, whereas the slow accumulation which reaches the steady state level seems reversible.

Animals↗