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The fact that in vitro culture of murine organ allografts prior to transplantation enhances graft survival is commonly accepted. In this study, we examined the possibility of thyroid allotransplantation for the therapy of total thyroidectomy in the rat model. Transplanted thyroid function was determined by 125I uptake ratio and evaluated by immunohistochemical and microautoradiographical assessments. Fully allogeneic thyroid glands cultured for 8-24 hr in Hank's balanced salt solution (HBSS) at pH 6.3 or 7.2 were transplanted to rats under the kidney capsule. Five weeks after allotransplantation, thyroid glands cultured for 16 hr in HBSS at pH 6.3 presented prolonged survival. This procedure could be used as an initial therapy not only for total thyroidectomized patients but also for patients with primary hypothyroidism.

It is generally accepted that subacute thyroiditis is a self-limited inflammatory disease of the thyroid gland, characterized by severe pain and tenderness on the thyroid gland, transient thyrotoxicosis, erythrocyte sedimentation rate elevation, systemic manifestations of inflammation such as malaise, fever and fatigue. It recurs in about 10-20% of patients. Some authors have reported cases of subacute thyroiditis with liver dysfunction, such as elevation of transaminase (glutamic oxalacetic transaminase-GOT, glutamic pyruvic transaminase-GPT) and alkaline phosphatase. These abnormalities were all reduced in the course of therapy, and none of patients showed recurrent subacute thyroiditis or liver dysfunction. In this report, we present a case of subacute thyroiditis associated with liver dysfunction which progressed and improved in parallel wite the thyroiditis. The serum antibody titer against Coxsackie A virus was elevated, and Coxsackie A virus was suspected to be the etiological agent.

Extracorporeal shock wave lithotripsy (ESWL) was undertaken on 11 patients with sialolithiasis. In three patients, fragmented calculi were excreted via the duct of the gland. In four patients, though fragmented calculi were excreted from the gland to the duct, complete disappearance was not achieved. It was therefore necessary to remove the fragmented calculi by intraoral ductotomy. However, without ESWL, submandibular glandectomy would have been unavoidable. As for the two patients who had an intraducted stone and the one patient who had a 20 mm stone in his submandibular gland, ESWL was not effective. No severe complications occurred either during or after ESWL. ESWL is beneficial for the treatment of salivary stones, especially of the intraglandular and transitional zone type, and for stones smaller than 10 mm.

We usually use 6 frequencies, 250, 500, 1000, 2000, 4000 and 8000 Hz, in conventional pure tone audiometry. When these 6 points do not show hearing loss, our clinical diagnosis is no hearing loss. If the hearing loss is not located in the clinical 6 frequencies, we cannot detect it.The authors diagnosed 6000 Hz-dip type acute hearing loss in a 43-year-old male with tinnitus. We measured the hearing levels at 6 frequencies and found no hearing loss. The pitch of his tinnitus was 6000 Hz, so we measured the hearing levels at 4 other frequencies (800, 1500, 3000 and 6000 Hz) and detected a 6000 Hz-dip.Steroid treatment cured both the tinnitus and the 6000 Hz-dip hearing loss.When hearing loss occurs at a frequency other than the conventional pure tone audiometric frequencies, a mistaken diagnosis of no hearing loss is made. If the patient complains of tinnitus, the clinician should investigate the pitch and measure the hearing level near the frequency of the tinnitus. This is a useful method of discovering narrow diptype acute hearing loss.

Nasal administration of thallium-201 (201Tl) has previously been shown to be useful for the assessment of olfactory nerve connectivity in vivo. We assessed the biological effects of nasal 201Tl administration in mice to determine its safety before conducting clinical trials on humans. 201Tl uptake was evaluated in normal mice (n = 5) in vivo by using a high-resolution gamma camera and radiography 15 min, 1, 2 and 9 d after administration of 201TlCl to the right side of the nasal cavity (10 μl 201TlCl per nostril, 74 MBq/ml). Murine olfactory epithelial thickness (n = 5) was measured 9 d following nasal administration of 201TlCl. We assessed the odor detection ability of normal mice (n = 8) following nasal administration of 201TlCl to both sides of the nasal cavity, by observing cycloheximide solution avoidance behavior. We subsequently administrated 201TlCl (n = 4) or saline (n = 4) to both nostrils to assess the odor detection ability of mice following bilateral olfactory nerve transection. 201Tl uptake by the nasal cavity decreased immediately following nasal administration of 201Tl in normal mice. Nasal administration of 201Tl did not affect the olfactory epithelial thickness or the odor detection ability of normal mice. Recovery of odor detection ability following olfactory nerve transection was not significantly different between mice nasally administered with 201Tl, and mice administered with saline. Thus, nasal administration of 201Tl for the diagnosis of traumatic olfactory impairment did not produce harmful biological effects in vivo.

A rare case of extramedullary plasmacytoma in the sino-nasal cavity is presented. During a prolonged clinical course, the tumor has recurred several times after irradiation, chemotherapy and surgery, and presented in the clavicular bone as well. Immunohistochemical staining of each tumor showed IgA kappa phenotype, and immunoelectrophoresis of the serum showed overproduction of IgA with kappa light chains. Although an elevation of serum IgA persists, the patient has remained well without evidence of overt multiple myeloma.

Squamous cell carcinoma accounts for approximately 98 per cent of all malignant neoplasms that occur in the nasopharynx. The high incidence of nasopharyngeal carcinoma (NPC) is a characteristic of the Oriental races. Viral and environmental factors appear to have an etiologic impact on this disease. The most common sites are the lateral wall followed by the roof. NPC spreads primarily by local infiltration and regional metastases. Local infiltration of the eustachian tube is evidenced clinically when the patients presents with a unilateral conductive hearing loss secondary to the development of a secretory otitis media. Multiple cranial nerve deficits can develop. The maxillary and mandibular branches of the trigeminal complex (V2 and V3) are the most commonly involved cranial nerves and indicate extension of the tumor through the foramen rotundum and foramen ovale. Lateral rectus deficits cause the patient to complain of diplopia, especially on lateral gaze, indicating tumor involvement along the course of cranial nerve VI. More extensive internal and external ophthalmoplegias suggest orbital or cavernous sinus involvement. Lateral extension or spread into the pterygomaxillary fossa and the infratemporal fossa can easily affect the lower cranial nerves (IX, X, XI, XII), indicating that the tumor has progressed into the area of the jugular foramen. Lack of significant tumor bulk in the nasopharynx or parapharyngeal spaces with paralysis of the lower cranial nerves usually indicates involvement of adjacent lymph nodes surrounding the jugular foramen rather than direct extension from the primary tumor. Lymphatic spread from the nasopharynx may be either unilateral or bilateral. When the tumor has spread into the upper deep cervical lymph nodes, a cervical mass usually first becomes detectable clinically.

The prevalence of MHL in 202, 1 to 6 year-old children with communication disorders who visited our clinic in 1991 was investigated. 1) 31% of the subjects had MHL bilaterally. The prevalence of MHL was 44% at age 1 year, 20% at age 2 years, 36% at age 3 years, 24% at age 4 years, 39% at age 5 years, 33% at age 6 years. 2) 88% of children with MHL had OME, 10% had mild sensorineural hearing loss, and 2% had cerminous plug. 3) The prevalence of MHL in children with mental retardation and autistic disorders was 9%, that with stuttering was 9%, that of OME accompanied by moderate and severe hearing disorders was 6%. 4) The primary causes in 191, except for those with stuttering, were as follows; the prevalence of MHL was 30%, that of mental retardation and autistic disorders was 24%, and that of articulation disorders was 28%. 5) On the other hand, the prevalence of MHL in children with retarded language development and articulation disorders was 30%, which was significantly higher than that of the other communication disorders. Accordingly, the results of this study suggest that MHL in early childhood greatly influences communication disorders.

The distribution of ofloxacin (OFLX) in the palatal tonsil and maxillary sinus mucosa was quantitatively analyzed. OFLX (100mg), lomefloxacin (100mg), and tosufloxacin (75mg) were administered orally 2 hours before surgery. The tissue concentration of OFLX was 1.61±0.46μg/ml on average and was higher than the serum concentration (0.72±0.21μg/ml), the tissue/serum ratio (2.24) was significant. The tissue concentration of OFLX was higher than that of lomefloxacin and tosufloxacin. In addition, clinical and bacteriological trials on patients with otorhinolaryngological infections was carried out. OFLX was administered orally at a dose 600mg for more than three days. The incidence of stains resistant to OFLX (MIC>3.13μg/ml) was 5.8%. The overall clinical efficacy rate was 86.7% and there were no safety problems. It was concluded that OFLX is a useful drug for treating otorhinolaryngological infections.

Novel tricyclic ring systems, irmdazo[3,4-d]pyridazino[4,5-b][1,4]thiazines 3, imidazo[2,1-b]pyridazino[4,5-e][1,3,4]thiadiazines 15 and 18 were prepared by the reaction of 5-amino-4-chloropyridazin-3(2H)-ones 1 and 5(4)-(1-methylhydrazino)-4(5)-chloropyridazin-3(2H)-ones 13 (16) with isothiocyanates 2 and 7.

The reactions of amidinothioureas, imidoylthioureas, thioacylamidines, O-methyl-1-aryl-2-thioisobiurets, and 1-aryl-isodithiobiurets with diethyl azodicarboxylate (DEAD, diethyl diazenedicarboxylate) gave the corresponding thiadiazoles by the oxidative cyclic S−N bond formation. Analogously, the oxidative cyclization of 2-phenyl-5-(1-methylthiosemicarbazido)-3(2H)-pyridazinones with DEAD provided 4-methyl-7-phenyl-4H-pyridazino[4,5-e][1,3,4]thiadiazin-8(7H)-ones

Terminal N-monoacylated triamines 6 were easily obtained by hydrolysis of the acylated fused piperazines 5, which were prepared by the reaction of triamines 1 with benzil 2 followed by acylation.

Chlorocarbonylsulfenyl chloride was allowed to react with 1-alkylidene-4-phenylthiosemicarbazones in the presence of triethylamine to give 1,2,4-triazolines, whereas with 1-arylidene-4-phenylthiosemicarbazones to afford 1,2,4-dithiazolidines. Treatment of diarylidenethiocarbohydrazides and diarylidenaminoguanidines with chlorocarbonylsulfenyl chloride under similar conditions gave 1,2,4-dithiazolidines and 1,2,4-thiadiazolidines, respectively.

5-Hydrazinopyridazin-3(2H)-ones 1 reacted with dimethyl acetylenedicarboxylate 2 to give 4,6-dihydropyridazino[4,5-c] pyridazin-5-(1H)-ones 3 by cyclization with dehydrogenation. On the other hand, the reaction of 4-bromo-5-hydrazino- and 5-bromo-4-hydrazinopyridazin-3(2H)-ones 8 and 10 with diester 2 resulted in the novel cyclization with rearrangement to give compounds 3 and 9 together with the expected cyclization products.

Substituted thiosemicarbazones were allowed to react with α-chloroacetyl chloride to give two types of 1,3-thiazolin-4- ones which arose from the different cyclization depending on the substituents

The reaction of 5-hydrazinopyridazin-3(2H)-ones 1 with α-keto diester 2 in acetic acid afforded the corresponding 4,6-dihydropyridazino[4,5-c]pyridazin-5(1H)-ones 3 and pyrrolo[2,3-d)pyridazin-4(5H)-ones 4. Compounds 3 were also obtained from 4-bromo-5-hydrazinopyridazin-3(2H)-ones 8 and 2 under milder conditions. 5-Bromo-4-hydrazinopyridazin-3(2H)-one 9, the regioisomer of 8b, also reacted readily with 2a to give 4,7-dihydropyridazino[4,5-c]pyridazin-8(1H)-one 10b, the regioisomer of 3b.

Cyclization of the Michael adducts 1 and 6 formed from ene-hydrazines and dimethyl acetylenedicarboxylate (DMAD) in the presence of polyphosphoric acid (PPA) produced the fused 1,2-diazepine rings 2 and 7. However, the adducts when heated in 1,2,3,4-tetrahydronaphthalene (tetralin) preferentially provided the fused pyridone rings 4 and 10 and the fused pyrrole rings 5 and 11.

Hydrazinoethanols 1 were reacted with aldehydes 2 and 6 and glutaraldehyde (14) in aqueous solution to give dioxatetraazaperhydroanthracenes 3, 7, 12, and 13 and -perylenes 15 in yields of 19-88 and 42-72%, respectively. Compounds 3, 7, 12, and 15 were deduced by (13)C-NMR spectra to have two C(2) symmetry axes, while compound 12 was shown to have a symmetry axis by X-ray crystallography. The most favorable stereoisomers were consistent with predictions obtained by the semiempirical molecular orbital method AM1. The structure of compound 15 was confirmed by X-ray crystallography.

The reaction of 5-hydrazinopyridazin-3(2H)-ones 1 with α-keto diester 2 in acetic acid afforded the corresponding 4,6-dihydropyridazino[4,5-c]pyridazin-5(1H)-ones 3 and pyrrolo[2,3-d)pyridazin-4(5H)-ones 4. Compounds 3 were also obtained from 4-bromo-5-hydrazinopyridazin-3(2H)-ones 8 and 2 under milder conditions. 5-Bromo-4-hydrazinopyridazin-3(2H)-one 9, the regioisomer of 8b, also reacted readily with 2a to give 4,7-dihydropyridazino[4,5-c]pyridazin-8(1H)-one 10b, the regioisomer of 3b.

Novel tricyclic ring systems, irmdazo[3,4-d]pyridazino[4,5-b][1,4]thiazines 3, imidazo[2,1-b]pyridazino[4,5-e][1,3,4]thiadiazines 15 and 18 were prepared by the reaction of 5-amino-4-chloropyridazin-3(2H)-ones 1 and 5(4)-(1-methylhydrazino)-4(5)-chloropyridazin-3(2H)-ones 13 (16) with isothiocyanates 2 and 7.

Copolymers having a poly(2-oxazoline) graft chain were prepared by radical polymerization of the macromonomer CH 2 =C(R')CO 2 (CH 2 CH 2 N[COR]) n Me (1) (R= Me, Bu; R'= H, Me) with styrene, methyl methacrylate or acrylamide. The 1 H NMR data in different solvents revealed that the copolymer prepared from 1 and styrene has a strong surfactant activity

A 38-year-old man was referred by his general practitioner to our department on 28 October 1991, with a 2-week history of vertigo. A left aural polyp was identified. The audiogram showed a moderate conductive loss on the left side. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the expanding lesion in the descending portion of the facial nerve. However, there was no seventh nerve paresis. At operation, the neurinoma (Schwannoma) filled the middle ear cleft and extended from the genu to the stylomastoid foramen. The floor of the middle ear had been eroded, exposing the jugular bulb. Facial nerve paresis is the usual presenting feature of a facial neurinoma. The case is presented for the reason that the absence of facial palsy as a presenting feature is rather rare, especially in the cases with large tumor and extensive bone erosion.

0歳から文字音声法に手指法を併用して言語治療を行った重度聴覚障害幼児4例の, 手指から音声言語に移行する段階を検討した結果, 以下の7段階の存在が示唆された.各聴覚障害幼児の個々の発達段階に応じた言語治療が重要であることを強調した。第1段階は手指で受信可能となり, まだ発信手段がない段階.第2段階は, 受信で手指が音声より優勢で, 発信は手指でのみ可能な段階.第3段階は, 受信, 発信ともに手指が音声より優位な段階.第4段階は, 受信で音声が手指より優位となるが, 発信では手指が依然としで優位な段階.第5段階は, 受信で手指より音声が優勢となり, 発信では音声と手指の併用がめだつ段階.第6段階は, 受信, 発信ともに音声が手指より多用される段階.第7段階は受信, 発信ともに音声のみで可能となる段階である.

A 62-year-old woman visited our hospital complaining of abnormal sensation in the pharynx. Physical examination revealed a pulsating mass on the right side of the posterior wall of the mesopharynx. CT and angiography confirmed that the internal carotid artery had an abnormal course and was compressing the pharyngeal wall.The clinical importance and etiology of tortuosity of the internal carotid artery are discussed.

A 57-year old man had a left anterior neck tumor, and another small tumor was found in the laryngeal ventricle by indirect laryngoscopy. A CT scan showed a well-circumscribed tumor growing from the thyroid lamina into the paraglottic space. Under general anesthesia the tumor was dissected with fenestration of the thyroid ala without any complications, such as hoarseness or deformity. In Japan 35 cases of cartilagenous tumors arising in the laryngeal cartilage have been reported, including our case. In six of these 35 cases the tumor was in the thyroid cartilage. Both chondrosarcoma and chondroma are often seen in the thyroid cartilage, whereas chondroma is seen more frequently than chondrosarcoma in the cricoid carilage.

In adult humans, hypothyroidism has been associated with a reduced sense of smell. There are few reports on the effect of hypothyroidism on the sense of smell in adult animals. We examined whether hypothyroidism abolishes the sense of smell in adult mice and examined the changes of the olfactory epithelium. Hypothyroidism was produced in adult mice by addition of thiamazole to their drinking water or intra-peritoneal injection. The olfaction of mice was estimated by successful recording of behavioral task, using cycloheximide, which has been commonly used as a repellent in rodents. The sense of smell was tested before, during, and after thiamazole treatment. Thyroid function was assessed by radioimmunoassay of blood serum for free thyroxine. The mice were killed after treatment and the olfactory epithelium was studied at the light microscopic level to determine the effects of thiamazole treatment.Mice given 0.01% thiamazole in the drinking water for 100 days were not hyposmic. The control mice given tap water to drink for 100 days maintained their sense of smelll. Mice given daily intra-peritoneal injection of 0.5 mg thiamazole for 100 days were not hyposmic. Daily i. p. injection of 1.5mg thiamazole to the mice for 20 days attenuated their sense of smell. By contrast, the control mice, given daily i. p. injection of 0.1ml normal saline were normosmic. In the olfactory epithelium of the hypothyroid and hyposmic mouse, the structures composed of basal cells, olfactory cells, and supporting cells were preserved. However, a marked decrease was observed in the number of olfactory cells. These findings indicate that hypothyroidism produces olfactory disturbance in mice and injures the olfactory receptor neurons.

The surgical management of an infectious and fistulous wound with a pharyngoesophageal tumor is one of the greatest challenges for head and neck and plastic surgeons. The free jejunal transfer has been the standard technique for pharyngoesophageal reconstruction, and the free omental flap has been one of the most reliable methods for reconstructing contaminated wounds. A jejuno-mesenteric flap is suitable for such complicated wounds. Pharyngoesophageal defects are reconstructed by the jejunum, and contaminated and heavily irradiated neck wounds are covered with the mesenteric flaps connected with a revascularized jejunum. The technique described here possesses the advantages of both a free jejunal flap and an omentum flap. Therefore, it is a reliable method for reconstructing the pharyngoesophageal defects of complicated wounds.

Objective: To image olfactory nerve regeneration in vivo using a high-resolution gamma cam- era and radiography after nasal administration of thallium-201 (olfacto-scintigraphy). Methods: Six Wistar rats were trained to avoid the smell of cycloheximide as a test of olfactory function. The olfactory nerve fibers of 3 rats were then carefully transected bilaterally with a Teflon knife, avoiding damage to the olfactory bulbs. The remaining 3 rats underwent sham operations and were used as controls. Steel wires were implanted in the left olfactory bulb of each rat for locating the bulbs with plain X-rays. The rats were assessed 2, 14, 28, and 42 d after the olfactory nerve transection or sham operation for their ability to detect odours and for transport of 201Tl to the olfactory bulb area 8 h after nasal administration of 201Tl. Results: Both transport of 201Tl to the olfactory bulb area (p < 0.04) and ability to detect odours (p < 0.04) significantly increased with a time course after olfactory nerve transection. Conclusion: 201Tl transport to the olfactory bulb may be useful to visually assess olfactory ability in vivo. We plan to test olfacto-scintigraphy clinically by nasal administration of 201Tl in patients with posttraumatic olfactory loss.

The curry odorant of the odor stick identification test for Japanese (OSIT-J) is useful in screening for olfactory impairment in Japanese subjects.The present study was designed to determine the most useful odorant of the OSIT-J in screening for olfactory impairment in Japanese subjects.We studied olfactory impairment screening with the OSIT-J in 83 participants (49 male, 34 female; average age 50 years) in an executive check-up at NTT West Kanazawa Hospital. Olfactory discrimination acuity was evaluated with three odorants of the OSIT-J (rose, curry, and sweaty-smelling clothes), each known to be significantly correlated with the assessment of the Japanese standard olfaction test (TT olfactometer). Those participants who did not score full marks in tests with the three odors were assessed with another nine odorants of the OSIT-J.The positive predictive value was 100% in the screening with the curry odorant. In 38 participants who did not identify all three odors correctly, the identification of the curry odor was significantly correlated with the scores for all 12 odors (p0.005). Identification of the curry odor was not significantly correlated with identification of the menthol odor of OSIT-J.

We conducted a double-blind intergroup comparative study investigating the efficacy, safety and PK-PD analysis of the new oral carbapenem antibacterial drug tebipenem pivoxil (TBPM-PI) for the treatment of otolaryngological infections in adults to establish the recommended clinical dosage. The primary endpoint was the clinical effect of a 7-day oral administration of TBPM-PI to subjects with confirmed cases of infection by any of the 5 major bacterial species causative for otolaryngological infections (Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, and Haemophilus influenzae) assigned to three groups set according to the TBPM-PI dosage, namely, a 450 mg group (150 mg t.i.d), a 500 mg group (250 mg b.i.d), and a 900 mg group (300 mg t.i.d). 1. Clinical efficacy: At the end of administration or at discontinuation, the efficacy rate for the 112 subjects in the efficacy analysis set was 72.1% (31/43 subjects) in the 450 mg group, 88.6% (31/35 subjects) in the 500 mg group, and 85.3% (29/34 subjects) in the 900 mg group. Both the 500 mg and 900 mg groups showed a high efficacy rate of over 80%. 2. Bacteriological efficacy: The disappearance rate of the pre-administration causative bacteria (5 major bacterial species) at the end of administration (at discontinuation), it was 92.2% (47/51 strains) in the 450 mg group, 94.7% (36/38 strains) in the 500 mg group, and 91.7% (33/36 strains) in the 900 mg group. All the groups showed a high disappearance rate, with no large differences among them. All strains of S. pneumoniae, including PRSP, as well as those of S. pyogenes and M. catarrhalis disappeared. The overall disappearance rate of H. influenzae was 78.6%, namely, 76.9% in the 450 mg group, 100% in the 500 mg group, and 66.7% in the 900 mg group, showing differences among the groups. 3. PK-PD: The PK-PD analysis was executed in 124 strains isolated from 111 subjects in which the plasma TBPM concentration and the MIC of causative organism were measured. The target value of the PK-PD parameter was examined from the relation between PK-PD parameter and bacteriological efficacy. The presumed target value of AUCf/MIC was 10-20, Cmaxf/MIC was 4. On the other hand, a clear relation was not found between TMIC and the bacteriological efficacy. 4.The incidence of adverse reactions related to symptoms and signs was 28.8% (21/73 subjects) in the 450 mg group, 35.8% (24/67 subjects) in the 500mg group, and 30.6% (22/72 subjects) in the 900 mg group. The incidence of abnormal changes in laboratory test values was 8.2% (6/73 subjects) in the 450 mg group, 9.2% (6/65 subjects) in the 500 mg group, and 9.9% (7/71 subjects) in the 900 mg group. There were no differences in either of these categories among the groups, and the incidence was considered not to be correlated with dose. Based on the above, we considered that TBPM-PI at doses of 250 mg b.i.d (500 mg/day) promises high clinical usefulness for the treatment of otolaryngological infections in adults.

The Kanazawa Otolaryngological Association has conducted a biennial hearing examination program for the Kanazawa City government since 2000 targeting persons aged 65 to 74 years. Studying results for 15,589 persons seen from 2000 to 2005 including 3247 undergoing more than one annual examination, we found results to be generally similar to those reported thus far. Of subjects, diagnosed with hearing loss, 16.4% were at 35dB or more. Almost 80% ranged from 35 to 50 dB. Aging was the most common cause of hearing impairment, followed by chronic otitis media at 5-8% and obstruction of the auditory tube (or secretory otitis media) at 3-5%. Of examinees with hearing impairment, 6-7% required treatment. High-frequency hearing loss (presbycusis) accounted for 40.0% of those 65-66 years old and 66.8% of those 73-74 years old. Among the 3247 persons undergoing more than one annual examination (mean followup: 6 years), those with obviously impaired hearing accounted for 2.1% with high-frequency hearing loss and 10.5% with no high-frequency hearing loss. Over 70% of those advised to use hearing aids were reluctant to do so. More work is thus needed with hearing-aid manufacturers to make devices more attractive to wear and use if we are to achieve the goals of the hearing examination program. Although we would like to continue the program by underlining the importance of hearing ability to administrative offices and local medical associations, there are limits on what local communities alone can do.

Tumor metastasis is a complex phenomenon that is the culmination of effects of numerous cellular factors. We have shown that the Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is capable of inducing a wide range of such factors in cell culture, expression of which is also elevated in the LMP1-expressing tumor, nasopharyngeal carcinoma (NPC), a highly invasive neoplasm. Recently, the membrane crosslinker protein, ezrin, has been implicated in tumor cell metastasis and malignant progression. In this study, we evaluated the possible role of LMP1 and ezrin in the pathophysiology of NPC. We show that C-terminal phosphorylation of ezrin is increased by the expression of LMP1 in nasopharyngeal (NP) cells through a protein kinase C (PKC) pathway. LMP1 enhances the organization of a ternary complex of CD44, ezrin and F-actin, which is a prerequisite for ezrin phosphorylation. In NPC tissues, the expression of phosphoezrin and LMP1 is directly correlated. Silencing of endogenously expressed ezrin suppresses LMP1-induced cell motility and invasiveness. Moreover, the inhibition of ezrin phosphorylation by PKC inhibitor suppresses migration and invasion of NP cells. These data show that the phosphorylation of ezrin and its recruitment to the cell membrane linked to F-actin and CD44 is a process required for LMP1-stimulated cell motility and invasion of NP cells.