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PubMed2002

Receptor-regulated and inhibitory Smads are critical in regulating transforming growth factor beta-mediated Meckel's cartilage development.

The proper development of Meckel's cartilage is critical for craniofacial skeletogenesis, because it serves as the primordium for the formation of mandible, malleus, incus, and sphenomandibular ligament. Cranial neural crest (CNC) cells contribute significantly to the formation of Meckel's cartilage. Members of the transforming growth factor beta (TGF-beta) family control the proliferation and differentiation of CNC cells during craniofacial skeletogenesis. TGF-beta signaling is transduced from the cell membrane to the nucleus by means of specific type I and type II receptors and phosphorylated Smad proteins. Here we demonstrate that application of TGF-beta promotes chondrogenesis by specifically increasing proliferation of CNC-derived chondrocytes and production of extracellular matrix. To understand the molecular regulation of TGF-beta signaling, we have examined the biological function of both TGF-beta receptor-regulated and inhibitory Smads during Meckel's cartilage development. The expression patterns of Smad2, 3, and 7 are identical to the ones of endogenous TGF-beta and its cognate receptors during Meckel's cartilage development, establishing the potential that these intracellular signaling Smads may regulate TGF-beta-mediated chondrogenesis. Functional haploinsufficiency of Smad2 delays TGF-beta-mediated Meckel's cartilage development. Overproduction of Smad7 severely inhibits Meckel's cartilage formation, indicating a negative feedback on TGF-beta signaling by inhibitory Smad is critical in orchestrating TGF-beta-mediated gene regulation during embryonic chondrogenesis. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression.

Animals↗
PubMed2003

Malleal processus brevis is dispensable for normal hearing in mice.

The mammalian middle ear cavity contains a chain of three ossicles (the malleus, incus, and stapes), which develop from the mesenchyme of the first two branchial arches. Mice deficient in the Msx1 homeobox gene exhibit craniofacial abnormalities, including the absence of the malleal processus brevis that is normally attached to the upper part of the tympanic membrane. Here, we show that the expression of Msx1 and Msx2 overlaps in the malleal primordium during early embryonic development. A functional redundancy of Msx1 and Msx2 in the development of the middle ear is suggested by the stronger hypomorphism in the malleus of Msx1(-/-)/Msx2(-/-) embryos, including the absence of the malleal manubrium and the malleal processus brevis. The expression of Bmp4, a known downstream target of Msx1 in several developing craniofacial organs, was down-regulated in the malleal primordium, particularly in the region of the developing malleal manubrium, of Msx1 and Msx1(-/-)/Msx2(-/-) embryos. Msx genes, thus, appear to act in a cell autonomous manner, possibly by regulating Bmp4 expression, in the formation of the malleus. Transgenic rescue of the cleft palate of Msx1(-/-) mice overcame the neonatal lethality and allowed Msx1(-/-) mice to grow into adulthood but retain the phenotype of the absence of the malleal processus brevis. The availability of this animal model for the first time allowed us to measure auditory evoked potentials to assess the functional significance of the malleal processus brevis. The results demonstrated unimpaired auditory function in Msx1(-/-) mice. In addition, mutant mice appeared normal in balance behavior and in the vestibular evoked potential screening test. These results indicate that the malleal processus brevis is not necessary for sound transmission and seems dispensable for normal hearing and balance in mammals.

Animals↗
PubMed2003

Further structures in the jaw apparatus of Limnognathia maerski (Micrognathozoa), with notes on the phylogeny of the Gnathifera.

The jaws of Limnognathia maerski, Micrognathozoa, were investigated with light- and scanning electron microscopy. The study yielded several new structures and sclerites, including the ventral part of main jaw, the pharyngeal lamellae, the manus, the dorsal and ventral fibularium teeth, and a reinterpretation of the fibularium compartmentalization. Furthermore, it was shown that several jaw elements are composed of densely packed rods. Comparison with Rotifera and Gnathostomulida suggested that the micrognathozoan main jaw is homologous with the rotifer incus and the gnathostomulid articularium and that the pseudophalangids (the ventral jaws) and their associated sclerites correspond to the rotifer mallei. These results imply that Micrognathozoa is more closely related to Rotifera than to Gnathostomulida.

Animals↗
PubMed1975

Auditory systems of Heteromyidae: functional morphology and evolution of the middle ear.

Middle ears (515) from 26 species of the rodent family Heteromyidae - genera Dipodomys, Microdipodops, Perognathus, and Liomys - were studied both grossly and histologically, for qualitative and quantitative comparisons. Middle ear modifications characteristic of each genus are qualitatively described. Quantitative comparisons are made among the 26 species in the study. Some correlations between middle ear size and other measurements are discussed. The middle ear is an acoustical transformer that for best efficiency must match the impedance of the cochlea to the impedance of the air in the external auditory meatus. It accomplishes this by a pressure increase and a velocity decrease through the combined effects of the lever and areal ratios; however, because the important consideration is a matching of two impedances rather than an absolute pressure increase, the pressure transformer ratio is a less informative measure of the middle ear's efficiency than is the impedance transform ratio. The impedance transformer mechanism is explained (from a morphological point of view), and equations are presented. Dipodomys, Microdipodops, and Perognathus have a theoretical transmission (at the resonant frequency) of 94-100% of the incident acoustical energy; Liomys, 78-80%. The areal ratio of stapes footplate to 2/3 tympanic membrane is remarkably constant among the species, varying only from 0.04 to 0.07: in Dipodomys and Microdipodops this small ratio is due to the very large tympanic membrane; in Perognathus and Liomys it is due to the extremely small stapes footplate. The lever ratio of incus to malleus varies from 0.28 to 0.33 in Dipodpmys and Microdipodops, from 0.37 to 0.46 in Perognathus, and from 0.55 to 0.60 in Liomys. In addition, the middle ear volumes and the morphology of tympanic membrane, ossicles, ligaments, and muscles, all combine to minimize both mass and stiffness. All these data suggest middle ear mechanisms which are very efficient over a broad frequency range. The middle ear modifications found in heteromyids are adaptive in predator avoidance, especially in areas of little natural cover; nevertheless, contrary to expectations, there is no firm relationship between habitat and the extent of these modifications in the 26 species. However, environment did apparently plan an important role in the evolution of the family, and this is discussed.

Acoustics↗
PubMed1975

Evolution of the mammalian middle ear.

The structure and evolution of the mandible, suspensorium, and stapes of mammal-like reptiles and early mammals are examined in an attempt to determine how, why, and when in phylogeny the precursors of the mammalian tympanic bone, malleus, and incus (postdentary jaw elements and quadrate) came to function in the reception of air-borne sound. The following conclusions are reached: It is possible that at no stage in mammalian phylogeny was there a middle ear similar to that of "typical" living reptiles, with a postquadrate tympanic membrane contracted by an extrastapes. The aquamosal sulcus of cynodonts and other therapsids, usually thought to have housed a long external acoustic meatus, possibly held a depressor mandibulae muscle. In therapsids an air-filled chamber (recessus mandibularis of Westoll) extended deep to the reflected lamina and into the depression (external fossa) on the outer aspect of the angular element. A similar chamber was present in sphenacodontids but pterygoideus musculature occupied the small external fossa. The thin tissues superficial to the recessus mandibularis served as eardrum. Primitively, vibrations reached the stapes mainly via the anterior hyoid cornu, but in dicynodonts, therocephalians, and cynodants vibrations passed mainly or exclusively from mandible to quadrate to stapes and the reflected lamina was a component of the eardrum. In the therapsid phase of mammalian phylogeny, auditory adaptation was an important aspect of jaw evolution. Auditory efficiency, and sensitivity to higher sound frequencies were enhanced by diminution and loosening of the postdentary elements and quadrate, along with transference of musculature from postdentary elements to the dentary. These changes were made possible by associated modifications, including posterior expansion of the dentary. Establishment of a dentary-squamosal articulation permitted continuation of these trends, leading to the definitive mammalian condition, with no major change in auditory mechanism except that in most mammals (not monotremes) the angular, as tympanic, eventually bcame a non-vibrating structure.

Animals↗
PubMed1983

Auditory development in the mouse: structural maturation of the middle ear.

The development of middle-ear structures in the mouse was examined in nine groups of pups between 1 and 45 days of age. The area of the tympanic membrane (pars tensa and pars flaccida), the length of the lever arms of the malleus and incus, the surface area of the oval window, and the volume of the bulla all showed systematic changes during neonatal life. The area of the oval window reached maturity first and the lever arms achieved 90% of their adult size on day 11. The tympanic membrane achieved the same criterion on day 18. These data help us further to understand the processes that contribute to the functional ontogeny of the middle ear.

Age Factors↗
PubMed1992

The ear in subterranean insectivora and rodentia in comparison with ground-dwelling representatives. I. Sound conducting system of the middle ear.

Compared to acoustically unspecialized mammals (soricids and murids), the middle ear of subterranean insectivores and rodents (twelve species of six families examined) was clearly distinguished and characterized by many common features: rather round and relatively larger eardrum without a pars flaccida; reduced gonial; loose or no connection between the malleus and the tympanic bone; reduced and straightened transversal part of the malleus; enlarged incus; increased and rather flat incudo-mallear joint; rather parallel position of the mallear manubrium and incudal crus longum in some species (and their fusion in bathyergids); reduced or even missing middle ear muscles. Convergent occurrence of these structural features in taxa of different origin and their generally derived character suggest that they cannot be categorized as degenerative. The form of the stapes can be considered as a non-adaptive trait; it was taxon specific yet remarkably polymorphous in some species and exhibited no convergent features among subterranean mammals. Structural retrogression resulting in a columella-like stapes was observed in some species lacking the stapedial artery. The stapedial base was relatively larger than in unspecialized mammals. The subterranean mammals did not exhibit conspicuously enlarged eardrums as would be required for sensitive tuning to low frequencies. It is, however, argued that while selective pressures in the subterranean ecotope promoted hearing of low frequencies, hearing sensitivity did not have to be enhanced.

Animals↗
PubMed1983

Experimental use of fibrin tissue adhesive in middle ear surgery.

The biocompatibility of a new tissue adhesive was tested. Its major advantages are adhesions, hemostasis, and the promotion of wound healing. In experimental surgery on 43 middle ears of chinchillas, documented by histological evidence obtained 45 days after operation, the validity of the following two hypotheses was established. That fibrin tissue adhesive placed upon the footplate of the stapes is biologically compatible, biodegradable and does not cause toxic, inflammatory or foreign body reactions, or other tissue damage to middle ear structures. That a small piece of bone glued on the long process of the incus with fibrin tissue adhesive shows permanent tissue union. In addition, in cases where the inner ear was accidentally opened by surgically subluxating the stapes and adhesive was free to enter the vestibule, evidence was obtained that there was no damage to inner ear structures. This finding deserves further investigation.

Animals↗
PubMed1983

The fate of an ossicular allograft in tympanoplasty.

Correction of ossicular defects in tympanoplasty most commonly involves the use of commercially available prostheses or preserved allograft ossicles. Incus autografts and tragal cartilage autografts are also used by many surgeons. Presculptured preserved allograft ossicles have not been used widely, but are used almost exclusively by our clinic. The fate of ossicular grafts has been reported by a number of in investigators with evidence obtained at revision surgery. In this paper we will be able to trace the fate of a presculptured preserved autograft ossicle clinically and pathologically. The unique aspect of this study is the demonstration of the ossicular status in post mortem temporal bone dissection followed by histopathological serial section studies.

Aged↗
PubMed1986

Homograft (allograft) tympanoplasty update.

If homograft tympanoplasty is to be of value, specific instances in which homograft tympanic membrane, malleus, and incus (TMMI) provide significant hearing and anatomical advantages over standard techniques should be identified. This author has performed 305 homograft tympanoplasties limited to the reconstruction of the severely damaged middle ear. Indications include: previous failure with standard tympanoplasty techniques; high risk of anatomic or hearing failure with standard techniques (total perforation with absent malleus, slag burns); reconstruction of radical mastoidectomy; congenital aural atresia. The first 125 consecutive homograft tympanoplasties were reported in 1982. One hundred eighty additional homograft tympanoplasties have been performed since then. In the past 3 years the anatomic success rate has risen to 97% (174/180) with refinement of surgical techniques. Eighty-five percent of all patients have maintained an average air-bone gap of 25 dB or better. Formalin preserved homograft tympanic membranes with attached malleus offer significant advantages over standard tympanoplasty techniques in these specific indications.

Ear↗
PubMed1993

Congenital perilymphatic fistula and associated middle ear abnormalities.

To specifically determine the frequency and type of middle ear abnormalities associated with perilymphatic fistula (PLF), a retrospective chart review was performed of 94 patients (117 ears) who underwent exploratory tympanotomy for PLF from 1980 to 1989. Of the 117 ears explored, 80 (68.4%) had a PLF, and in 65 (81.3%) of these ears, a middle ear malformation was associated with the PLF. Of these 65 ears in which a congenital middle ear abnormality was observed, a malformed stapes was the most common abnormality seen (39 ears, 60%), followed by a deformed round window (20 ears, 30.8%), a deformed incus (11 ears, 16.9%), and a deformed promontory (2 ears, 3%). Often these malformations coexisted amongst themselves or with inner ear abnormalities. Sixteen children (25 ears) had an inner ear malformation identified on computed tomography (CT); all of these children had a PLF found at the time of surgery. This study demonstrated that 86.3% of the ears found to have a PLF had a deformity of the middle ear, inner ear, or both. A malformation of the stapes, most frequently identified as a deformity of its superstructure (and presumably also the anterior footplate), was the most common congenital middle ear abnormality found to be associated with PLF in children.

Adolescent↗
PubMed2002

Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the ablation of ossicular tissue using a 1,053 nm Ti:Sapphire chirped pulse amplifier laser system configured to deliver ultrashort pulses of 350 femtoseconds (fs) (3.5x10(-13) seconds) in cadaver temporal bone. STUDY DESIGN/MATERIALS AND METHODS: Ablation of the formalin-fixed incus and stapes was performed using an ultrashort pulse laser (USPL) (0.4 mm beam diameter, pulse fluence of 2.0 J/cm2, and pulse repetition rate of 10 Hz). The ablation rate was measured using optical micrometry, and crater surface morphology examined using scanning electron microscopy. RESULTS: The laser produced precise bone ablation at a rate of 1.26 microm/pulse, with almost no evidence of thermal damage, and very little evidence of photomechanical injury. CONCLUSIONS: Ultrashort pulse lasers may provide a useful clinical tool for otologic and skull base surgery, where precise hard tissue ablation is required adjacent to critical structures.

Cadaver↗
PubMed1981

Fetal ear malformations induced by maternal ingestion of thalidomide in the bonnet monkey (Macaca radiata).

Gross malformations of the external, middle, and internal ear were seen in fetal monkeys following maternal ingestion of thalidomide. Twenty-five pregnant bonnet monkeys (Macaca radiata) were each given a single oral dose of 10 mg/kg of thalidomide on day 24, 25, 26, 27, 28, or 29, or 30 mg/kg on day 25 or 28 of gestation. (Day of mating is assumed to be day zero of pregnancy). The skeletons, processed and stained with Alizarin Red S, were examined for changes in configuration and/or ossification of the ossicles and temporal bones. Bilateral temporal bones of one case, treated on day 24, were sectioned at 10 microns and examined histologically. Twelve fetuses collected at 70 +/- 3 days of gestation showed no gross ear defects, while 10 out of 13 fetuses collected at 100 +/- 3 days of gestation had structural anomalies similar to those observed in humans. All malformations were severe in fetuses treated on day 24 of gestation and lessened in degree of severity with treatments on days 25-28. Fetuses treated on day 29 were normal. External ear anomalies included microtia with meatal atresia or stenosis, and varying degrees of auricular hypoplasia. Defects of the middle ear were predominantly hypoplasia of malleus, incus, and tympanic ring. Fused ossicles and cochlear and vestibular window abnormalities were only seen in animals treated on day 24. The internal ear exhibited petrosal hypoplasia and delayed ossification of the lateral aspect of the lateral and posterior semicircular canals. Cochlear, vestibular, semicircular, and transcapsular canal defects were confirmed histologically in one case.

Abnormalities, Drug-Induced↗
PubMed1997

Retinoic acid disturbs mouse middle ear development in a stage-dependent fashion.

The mammalian middle ear contains a chain of three ossicles, the malleus, incus, and stapes, that transmit into the inner ear the vibrations produced in the tympanic membrane by aerial sound. I show here that retinoic acid interferes with the formation of the middle ear in a stage-specific fashion. The malformations produced are derived from a retinoic acid-induced inhibition of the formation and/or migration of the cranial neural crest that generates the middle ear skeletal elements and not from a respecification of neural crest identity to more posterior fates. I have used these effects of retinoic acid to analyze the temporal sequence of events involved in the morphogenesis of the middle ear. I show that the middle ear bones develop from several primordia that originate in a typical temporal sequence from Day 8 plus 4.5 hr to Day 8 plus 7.5 hr of pregnancy. Moreover, interactions between adjacent bones are not required for their proper formation. My results also suggest a Hoxa-2-mediated patterning of the otic capsule in the region where the oval window is located.

Animals↗
PubMed1997

New growth of axons in the cochlear nucleus of adult chinchillas after acoustic trauma.

This study determined the effect of acoustic overstimulation of the adult cochlea on axons in the cochlear nucleus. Chinchillas were exposed to an octave-band noise centered at 4 kHz at 108 dB sound pressure level for 1.75 h. One chinchilla was never exposed to the noise, and several others had one ear protected by an ear plug or prior removal of the malleus and incus. Exposure of unprotected ears caused loss of inner and outer hair cells and myelinated nerve fibers, mostly in the basal half of the cochlea. Cochlear nerve fiber degeneration, ipsilateral to the exposed ears, was traced to regions of the cochlear nucleus representing the damaged parts of the cochlea. In silver impregnations of a deafferented zone in the posteroventral cochlear nucleus, the concentration of axons decreased by 43% after 1 month and by 54% after 2 months. However, by 8 months, the concentration of thinner axons, with diameters of less than 0.46 microm, increased by 46-90% over that at 2 months. The concentration of axons with larger diameters did not change. Between 2 and 8 months small axonal endings appeared next to neuronal cell bodies. This later increase of thinner axons and endings is consistent with a reactive growth of new axons of relatively small diameter. The emergence of small perisomatic boutons suggests that the new axons formed synaptic endings, which might contribute to an abnormal reorganization of the central auditory system and to the pathological changes that accompany acoustic overstimulation.

Animals↗
PubMed1993

Surgery for congenital anomalies of the middle ear with mobile stapes.

In a series of 104 patients with congenital middle ear anomalies operated on from 1964 to 1986, 27 cases were found in which the stapes footplate was mobile and the conductive deafness was due to an anomaly in the remaining part of the ossicular chain. In 8 cases the middle ear anomaly was caused by discontinuity of the ossicular chain owing to congenital malformation. In the other 19 ears, epitympanic fixation of the ossicular chain was observed, whether or not in combination with malformation of the stapes, incus or malleus. Ossicular chain reconstruction produced an improvement of at least 15 dB in 6 of the first 8 cases with discontinuity of the ossicular chain. The mean gain was 31 dB. Epitympanotomy with exposure of the fixed ossicle and if necessary ossicular chain reconstruction led to an improvement of at least 15 dB in 12 of the 19 ears, with a mean gain of 28 dB.

Adolescent↗
PubMed1983

Mineral and collagen content of human ossicles.

With increased use of human otologic homograft tissue for implantation, different preservation techniques and products are used for storing and preserving the grafts before surgery. Preserved ossicles may, according to some authors, already exhibit signs of decalcification after 2 weeks. Therefore, the mineral (calcium, phosphorus) and collagen content of human ossicles (incus) and mastoid cortex and the influence of different storage techniques was biochemically investigated. No significant mineral or collagen-concentration changes were observed after a 6-week storage in pH-7 formaldehyde or in cialit, in either the ossicles or in the cortical bone. These biochemical findings are in agreement with histologic observations and with similar experiments using the photon absorptiometry technique.

Calcium↗
PubMed1979

[On the elasticity of the ligamentum anulare. Experimental investigations into human temporal bone preparations with the help of an electromagnetic probe (author's transl)].

An electromagnetic probe was used to investigate the elasticity of the ligamentum anulare in human temporal bone preparations. The static measurement showed with preserved auditory ossicles but without tympanic membrane an average displacement of 37--41 micron at a pressure of 10 mN. Five different points of measurement did not lead to any significant differences; we must assume that the elastic properties of the ligamentum anulare are completely equal. After the removal of the malleus and incus, the displacement increased by only 2.2 micron, by another 4.2 micron if the stapes tendon was severed. Under these circumstances, too, a completely even elongation is proved to occur in all sections of the ligamentum anulare. Different pressures lead to a no-load characteristic which is linear in the 5--20 mN range, suggesting excellent elastic properties of the ligamentum anulare. From these data we may assume that the oscillation behavior of the basis stapedis approaches that of a membrane pump, with a linear transmission of great oscillation amplitudes possible.

Elasticity↗