OBJECTIVE:Phospholipase A2 (PLA2) is a key enzyme in arachidonic acid metabolism, which is involved in the maintenance of biological homeostasis and the onset of various diseases. The immunohistochemical localization of PLA2 in the nasal mucosa has not been reported, even though the presence of messenger RNA of PLA2 has been demonstrated in the human nasal brush sample. The present study was designed to determine the localization of PLA2s in the nasal cavity.METHODS:The immunohistochemichal localization of secretory PLA2 (sPLA2) and cytosolic PLA2 (cPLA2) in the nasal mucosa was studied using adult guinea pig.RESULTS:Both sPLA2 and cPLA2 were localized in the nasal gland as well as the respiratory epithelium, and not in the surrounding vascular endothelial cells, olfactory gland, olfactory epithelium or submucosal tissue.CONCLUSION:Our data provide the first convincing evidence that both sPLA2 and cPLA2 are significantly expressed in the nasal gland and the respiratory epithelium, and are suggested to regulate the function of the nasal mucosa, such as bactericidal, Na secretion, and allergic response.

Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.

We examined the nerve fibers among the cochlear supporting cells (NFSCs) in paraffin- and celloldin-embedded sections stained by the use of sodium retrieval immunoperoxidase technique (SRT) and/or tyramine amplification immunoperoxidase technique (TAT). SRT or TAT showed clear immunostaining of the radial nerve fibers and spiral ganglions, but a combination of the both techniques resulted in a higher density of the immunostained components at an amplification of 300-1,000 fold compared with the conventional immunoperoxidase technique (CIT). The presence of NFSCs was also clear with the combined use. This innervation was seen in the apical turns but not in the basal turns, similar to the location of lipid droplets among the Hensen cells, which are proposed to provide a high-energy source. Although the physiological significance and role of these nerve fibers has not yet been clearly defined, the coexistence of NFSCs and lipid droplets suggests that NFSCs may relate to energy metabolism. Our study also showed that SRT and/or TAT markedly enhanced the signal strength. These methods should allow the detection of very weak immunohistochemical signals under the use of stronger fixation or harder embedding.

We have developed a new interdisciplinary approach for removing large clivus and upper cervical spine tumors. This approach is a combination of the Le Fort I osteotomy, midfacial degloving, and median labiomandibular glossotomy. Our approach gives an excellent, wide surgical field from the nasopharynx, including the base of the skull, to the base of the tongue and permits sufficiently safe extirpation of clivus and upper cervical spine tumors that may not be removed by transoral or transcervical approaches. Our approach not only incorporates the merits of each approach but also creates a larger surgical field that may be modified or expanded to accommodate the removal of more bulky tumors in this region. This novel approach will facilitate more successful resection of tumors arising between the nasopharynx, including the skull base, and the retropharyngeal area.

We describe the successful treatment of a fibromatosis (desmoid tumor) arising from the prevertebral fascia of the neck. Total resection with wide margins is reportedly the best treatment for this kind of tumor. However, the anatomy of the head and neck makes such resection difficult. In this case, we were unable to completely remove the tumor because it was large and located close to the cervical vertebrae, common carotid artery and internal jugular vein. Incomplete resection is known to result in higher tumor recurrence than complete resection. In addition, the recurrence or progression of a tumor in the head or neck region is known to cause mortality by compression of the airway or major blood vessels. On the basis of reports that irradiation is effective treatment for this kind of tumor, we administered 30-Gy irradiation to the affected area. This therapy was very effective and no sign of recurrence was seen for 2 years after irradiation. We found that function-sparing resection plus postoperative radiotherapy is an effective treatment for advanced fibromatosis in the head and neck regions with proximity to or involvement with vital structures.

SUMMARY:We have investigated the expression of chloride channels by examining the cochlea of mice harboring the enhanced green fluorescence protein (EGFP) gene driven by an 11 kbp human CLC-KB gene promoter. CLC-KB was seen not only on the stria vascularis but on spiral ligament and limbal fibrocytes, interdental cells and satellite cells of spiral ganglion neurons that are known to possess both Na,K-ATPase and the Na-K-Cl co-transporter (NKCC). These results suggest that some fibrocytes possessing both the CLC-KB and the NKCC may be involved in the regulation of cell volume, transport and recycling of Cl- such as is seen in the stria vascularis. Moreover, these fibrocytes may recycle Cl- through CLC that accompany Na+ and K+ into the cell via NKCC.

New surgical treatment for the intractable nasal obstruction in patients with nasal allergy by using Argon Plasma Coagulator (APC) was introduced. Of patients with allergic rhinitis treated at our institute, 28 patients complaining nasal obstruction were treated APC surgery. Epithelization of the mucosa of inferior turbinate was almost completely accomplished at 4 weeks after surgery, at which time mucosal swelling was reduced, and nasal obstruction was ameliorated in all cases, though a crust and fibrin membrane adhered to the mucosa between 2 to 4 weeks after surgery, resulting in temporary exacerbation of nasal obstruction. Nasal obstruction was again aggravated in only one patient about 6 months after surgery, but such symptom could be ameliorated by re-coagulation. No bleeding and no smoke occurred in the operation. No morbidity was also noticed after operation. APC is easy to perform safely and effectively compared with another laser surgeries, and is useful for intractable nasal obstruction occurring in patients with allergic rhinitis.

The purpose of this study was to define the histopathological changes in the temporal bone of a fetus with trisomy 18 syndrome, a stillborn due to perosplanchnia. Several anomalies were found including malformation of the auditory ossicles, residual mesenchyme in the middle ear, aberrant tensor tympani muscle, absence of stapedial tendon, aberrant lateral ampullary nerve and wide endolymphatic sinus. The incus body was deformed and separated from the long process by connective tissue and monocrural stapes was noted in the right ear. Three-dimensional reconstruction images provided a clear view of the auditory ossicle malformation. The abnormal findings in our case indicate that ear anomalies in this syndrome might be derived from the component around the first and second branchial arches.

Objectives – To clarify the localization of cyclooxygenase (COX)-1 and -2 in the nasal cavity of guinea pigs and ascertain their physiological roles.Material and Methods – The distribution of the enzymes was investigated using immunohistochemistry.Results – Immunoreactivities for COX-1 and -2 were limited to the nasal glands, and no expression was noted in the surrounding vascular endothelial cells, olfactory glands, respiratory epithelium, olfactory epithelium, submucosal tissue or nerves. To confirm the specificity of the reaction, the kidneys of the same animals were prepared as positive controls. The results demonstrated localization of COX-1 and -2 in uriniferous tubules.Conclusion – Our findings suggest that COX is involved in the secretion of nasal discharge from the nasal glands and that prostaglandins in the nasal discharge are probably secreted directly from the nasal glands.

We immunohistochemically examined the distribution of nerve fibers among supporting cells of the cochlea by using the bloc-surface preparation. The existence of these nerve fibers was not very clear in the standard avidin-biotin complex (ABC) method. However, the standard ABC method complemented with silver intensification procedure provided very fine details of the nerve fibers. The nerves started to appear at low density about 55% of the distance from the apex, and their density gradually increased toward the upper turn. In each portion, the nerve fibers increased in thickness and length as well as the number of synapses made with the nuclei. Moreover, the distribution of these nerves in the fetal cochlea was similar to that in the adult. However, the functional significance and importance of these nerves remains to be determined. Our study also indicates that the silver intensification procedure combined with the standard ABC method is useful for the detailed observation of stereoscopic innervation in thick tissue preparations like such as the cochlea.

近年エアバッグの普及に伴い, 交通事故時の安全性は向上したものの, 一方で副傷害の報告もなされている。 今回われわれは, エアバッグ作動に伴う強大音により, 音響外傷をきたしたと考えられる急性感音難聴例を経験した。 症例は64歳男性で左難聴, 耳鳴を主訴に当科を受診した。 純音聴力検査では, 谷型の中等度感音難聴を示した。 ABLBテスト, 歪成分耳音響放射, 蝸電図, ABRを施行し, 聴覚障害部位は蝸牛と考えられた。 突発性難聴に準じ, 副腎皮質ホルモンを中心の薬物療法を行ったが, 受傷半年後も左聴力低下は不変であった。 交通外傷時の聴力障害の原因として, エアバッグの作動時の強大音により音響外傷が生じうることを念頭に置く必要がある。

Hearing thresholds in elderly humans without a history of noise exposure commonly show a profile of a flat loss at low frequencies coupled with a loss that increases with frequency above approximately 2 kHz. This profile and the relatively robust distortion product otoacoustic emissions that are found in elderly subjects challenge the common belief that age-related hearing loss (presbyacusis) is based primarily on sensory-cell disorders. Here, we examine a model of presbyacusis wherein the endocochlear potential (EP) is reduced by means of furosemide applied chronically to one cochlea of a young gerbil. The model results in an EP that is reduced from 90 to approximately 60 mV, a value often seen in quiet-aged gerbils, with no concomitant loss of hair cells. Resulting measures of cochlear and neural function are quantitatively similar to those seen in aging gerbils and humans, e.g., a flat threshold loss at low frequencies with a high-frequency roll-off of approximately -8.4 dB/octave. The effect of the EP on neural thresholds can be parsimoniously explained by the known gain characteristics of the cochlear amplifier as a function of cochlear location: in the apex, amplification is limited to approximately 20 dB, whereas in the base, the gain can be as high as 60 dB. At high frequencies, amplification is directly proportional to the EP on an approximately 1 dB/mV basis. This model suggests that the primary factor in true age-related hearing loss is an energy-starved cochlear amplifier that results in a specific audiogram profile.

We report 2 cases of carotid artery rupture after irradiation that was performed 1 year and 17 years before the ruptures. When irradiation-induced arterial rupture occurs, it usually does so within a few months following irradiation. However, the histopathological sections obtained in the present cases revealed carotid artery necrosis that was presumably induced by irradiation. Carotid artery rupture is sudden, massive hemorrhage that ranks among the most dreaded complications in the head and neck. However, several patients have been saved by hospital personnel who discovered the rupture in time to take appropriate measures such as cleaning of the wound and protection with myocutaneous or myofascial flaps. Therefore, it is important to be aware of the possibility of rupture or perforation of major vessels after irradiation, even when the radiation therapy was performed a long time ago.

The expression of H+-monocarboxylate cotransporters (MCTs) that facilitate cell uptake of lactate, pyruvate and other monocarboxylates was investigated in the adult and postnatally developing gerbil inner ear. In the mature cochlea, immunoreactive MCT1 was present in marginal cells of the stria vascularis and in type II, suprastrial and limbal fibrocytes. In the adult vestibular system, dark cells and a subpopulation of fibrocytes immediately underlying maculae and cristae stained strongly for MCT1. Satellite cells surrounding mature spiral and vestibular ganglia neurons also expressed MCT1. MCT1 immunoreactivity was present at birth in marginal and dark cells, at 8 days after birth in fibrocytes and at 12 days after birth in satellite cells, and coincided precisely with the developmental expression of Na,K-ATPase in these sites. The coexpression of MCT1 and Na,K-ATPase in these cell types points to MCT1 as an important source of energy to drive inner ear Na,K-ATPase activity. In the adult inner ear, MCT2 was detectable only in tectal cells of the cochlea and supporting cells of the crista ampullaris. Immunostaining was first observed at 16 days after birth in tectal and at 20 days after birth in supporting cells, and at the same time immunoreactive aquaporin 4 appeared in these cells. The coexpression of MCT2 and aquaporin 4 suggests a possible role for MCT2 in regulating transcellular water movement. Because MCT2 facilitates the transport of acidic intermediates, its biological significance also could relate to modulation of cell pH and volume. Maintenance of the inner ear's unique ion and fluid gradients is essential to normal hearing and balance and requires the expenditure of large amounts of energy. The cellular distribution of MCT1 and MCT2 points to their participation in generating these electrochemical gradients and their potential involvement in sensory deficits associated with various inner ear disorders.