Developmental and functional analyses of CD8(+) NK1.1(+) T cells in class-I-restricted TCR transgenic mice.

Using a class-I-restricted T cell receptor (TCR) transgenic mice (Tgm), 2C (Valpha3.1/Vbeta 8.2, specific for L(d) + LSPFPFDL), the development and cytokine production of tg-TCR(+) NKT cells were analyzed. We found that CD8(+) or double negative (DN) NKT cells constituted a major population of NKT cells in the H-2(b/b) 2C Tgm (positive selecting background) or the H-2(b/d) 2C Tgm (negative selecting background), respectively. Virtually no NKT cells were generated in the H-2(k/k) 2C Tgm (neutral selecting background). CD8(+) NKT cells in the H-2(b/b) 2C Tgm expressed CD8alphabeta heterodimers, whereas those in the H-2(b/d) 2C Tgm expressed CD8alphaalpha homodimers. These findings suggest that development of a subpopulation of NKT cells is influenced by the H-2 molecules. Upon stimulation with anti-CD3 mAb, tg-TCR(+) NKT cells generated in the H-2(b/b) and H-2(b/d) backgrounds produced IFN-gamma, but not IL-4.

Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener's granulomatosis and relapsing polychondritis.

Novel biological activities of macrophage migration inhibitory factor (MIF) have been rediscovered. In addition, elevation of the serum MIF level has been reported in different types of disorders, including various inflammatory and autoimmune diseases. In the present study, serum MIF levels were analyzed in patients with Wegener's granulomatosis (WG) and relapsing polychondritis. It was shown that the serum MIF levels in these patients were significantly higher than those of normal healthy controls. In a WG patient, the MIF level showed a good correlation with clinical symptoms and C-ANCA titers. Thus, serum MIF levels will be a useful laboratory parameter for following the clinical course of WG patients and determining medical treatment. The immunopathologic roles of MIF in these diseases are discussed.

Relapsing polychondritis: a report of eight cases.

OBJECTIVE: To investigate clinical manifestations of relapsing polychondritis and to clarify the significance of type II collagen antibody in the disease. METHODS: Clinical manifestations and antibody titers were examined in eight cases of relapsing polychondritis which had been treated at Otolaryngology Department, Hokkaido University during the eight years from 1991 to 1998. Anti-type II collagen antibody titer was measured by ELISA method. RESULTS: The most frequent symptom was auricular chondritis; it was seen in 88% (7/8) of the cases. Ocular symptom, nasal chondritis, arthritis, respiratory tract chondritis, and audio-vestibular symptom were also common in the cases. Compared with previous reports, no difference was recognized in the manifestation frequency. Considering none of the samples from the controls was positive for anti-type II collagen antibody, two samples from the disease group were positive. The antibody positive rate was 25% (2/8). CONCLUSION: Though the measurement of type II collagen antibody titer is not a decisive factor for detection of relapsing polychondritis, it is useful as one of the complementary factors for the diagnosis, since there is no specific test for this disease.

Sensorineural hearing loss induced by radiation as a late effect: five cases followed by audiogram.

OBJECTIVE: We studied the progression of the late radiation-induced sensorineural hearing loss (SNHL) to discuss the pathological mechanism responsible for the progression with referring to past reports. METHODS: Five cases were selected among the SNHL cases diagnosed at the Department of Otolaryngology. Hokkaido University. All the cases were followed up with audiograms. RESULTS: All of the five cases showed gradual progression of SNHL, which developed mostly 1 2 years after irradiation for brain tumors. Two of them showed rapid progression from time to time with sudden onset in their clinical courses. All the patients were resistant to any medication such as steroid, vitamin B12 or cerebral circulation activators. CONCLUSION: Two patterns of progressions of radiation-induced hearing loss were observed. Both of them were considered to be explainable by ischemic changes of the vessels as reported earlier. Since there is no effective treatment for radiation-induced SNHL, it is most important to enlighten clinicians in general on this disease.

Preserved otoacoustic emission in a child with a profound unilateral sensorineural hearing loss.

We report a case of profound unilateral sensorineural hearing loss with good response of otoacoustic emission. The patient was a 5-year-old boy. who was diagnosed to have unilateral hearing impairment on pure tone audiometry at the first visit. The affected ear showed the absence of auditory brainstem response; however, its transiently evoked otoacoutic emission and distortion product otoacoustic emission were considered to be normal. These findings indicated that the outer hair cell of cochlea was not impaired and that the impairment should be localized between inner hair cells, primary afferent fiber or its synapses, spiral ganglion of the cochlea and acoustic fiber, or at a combination of these areas. That is, evaluation of otoacoustic emission was useful in determining the region of impairment in sensorineural hearing loss. Further follow-up will be necessary to differentiate the present case from auditory neuropathy.

Churg-Strauss syndrome with pachymeningitis refractory to steroid therapy atone--a case report.

Churg-Strauss syndrome (CSS) is a rare syndrome of unknown cause, which is characterized by bronchial asthma and hypereosinophilia followed by systemic symptoms of angiitis. In 1951, Churg and Strauss first distinguished this disease from periarteritis nodosa. Our patient in particular was also complicated with otorhinological symptoms, which have less frequently been reported in CSS cases. We have detailed her clinical symptoms.

A rare case of carcinosarcoma of the maxillary sinus with osteosarcomatous differentiation.

A unique case of carcinosarcoma in the maxillary sinus is reported. A 47-year-old man visited our hospital with complaints of right nasal obstruction and bloody rhinorrhea. Examination revealed a hemorrhagic mass with necrosis in the maxillary sinus that infiltrated the right nasal cavity. Histologically, the tumor was composed of both carcinomatous and sarcomatous elements. Nests of squamous cell carcinoma and adenocarcinoma were scattered in the sarcomatous element with osteosarcomatous differentiation. No distinct demarcation between the two elements was observed and some spindle-shaped cells in the sarcomatous component were immunoreactive to epithelial markers by immunohistochemical staining. Although the histogenesis of carcinosarcoma remains unclear, the histologic pattern of the present case indicates the possibility that a multipotential cell, capable of both epithelial and mesenchymal differentiation, was the origin of the rare tumor.

Herpes simplex virus type 1 reactivation and antiviral therapy in patients with acute peripheral facial palsy.

OBJECTIVE: Recent studies provide compelling data for the hypothesis that herpes simplex virus type I (HSV-1) is implicated in the pathogenesis of idiopathic peripheral facial palsy (Bell's palsy). The present study analyzed the severity of facial palsy in patients with HSV-1 reactivation and sought to determine the efficacy of acyclovir-prednisone therapy for these patients. MATERIALS AND METHODS: In total, 176 patients, clinically diagnosed with Bell's palsy. were divided into three groups by polymerase chain reaction (PCR) and serological tests--31 patients with HSV-1 reactivation, 45 patients with VZV reactivation (zoster sine herpete) and 100 patients without HSV-1 or VZV reactivation (Bell's palsy). RESULTS: The difference in the worst grade of facial palsy between patients with zoster sine herpete and Bell's palsy was significant (P = 0.01 10, Mann-Whitney U-test). In contrast, no difference in the severity of palsy was observed between patients with HSV-1 reactivation and Bell's palsy. Twelve patients received acyclovir-prednisone treatment within 7 days of onset based on positive PCR results and ten of the 12 (83%) recovered completely. In contrast, 14 patients with HSV-1 reactivation received prednisone treatment because their PCR tests were performed at a later date; ten of these 14 (71%) recovered completely. The difference in the cure rate between the two treatment groups was not significant (P > 0.05, Fisher exact test). CONCLUSIONS: The results indicate that the severity of palsy in patients with HSV-1 reactivation is similar to that in patients with Bell's palsy and suggest that early diagnosis of HSV-1 reactivation by PCR and subsequent acyclovir-prednisone therapy do not improve recovery from facial palsy.

A rare aneurysmal bone cyst of the maxillary sinus: a case report.

Aneurysmal bone cyst (ABC) is a non-neoplastic expansile bone lesion that is common in the long bones; only 2% occurs in the head and neck. We present a case of ABC in a 23-year-old male and describe the clinical and radiological features, histopathology and treatment. Magnetic resonance imaging (MRI) demonstrated multiple internal septations, cysts with fluid-fluid levels of varying intensity, and an intact rim of low-intensity signal completely surrounding the lesion. The tumor was removed by enucleation with resection of the lateral nasal cavity. Histopathologic diagnosis was ABC and fibrous dysplasia. We suggest that MRI is very useful for the diagnosis of ABC. ABC is thought to follow other lesions, and thus when treating ABC, it is important to determine whether any pre-existing lesion has preceded or not; in particular, if the lesion site is in the head and neck region.

Herpes virus reactivation and serum tumor necrosis factor-alpha levels in patients with acute peripheral facial palsy.

Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) plays an important regulatory role in several inflammatory and infectious diseases. In the present study, we evaluated serum TNF-alpha levels of patients with acute peripheral facial palsy using an ELISA method. We examined sera from each group (n = 25 per group) of patients with herpes simplex virus type 1 reactivation (HSV-1). varicella-zoster virus (VZV) reactivation, and with no HSV or VZV reactivation. We also tested the sera of 25 normal controls. No significant difference was found between the serum TNF-alpha levels in facial palsy and controls. No correlation was found between serum TNF-alpha levels in cases with HSV-1 or VZV reactivation and with no HSV-1 or VZV reactivation. These results indicate that serum TNF-alpha levels are not affected by HSV-1 or VZV reactivation in patients with facial palsy.

Optimal stimulus level conditions for measurements of distortion product otoacoustic emissions.

OBJECTIVE: Distortion product otoacoustic emission (DPOAE) is a tool for an objective examination of the cochlea function. While the clinical application of DPOEA test is in progress, the measurements vary depending on the stimulus conditions. We aimed to determine the most appropriate stimulus level in the clinical application of DPOAE test. METHODS: Ninety-seven normal hearing ears and 80 hearing-impaired ears (total 177) were subjected to this study. Two levels of stimulations (L1 and L2) were applied as follows: L1 = L2 = 70 dB; L1 = L2 = 60 dB and L1 = 60/L2 = 50 dB, and DP level was measured at each stimulation, and compared with hearing level. RESULTS: DP level was highest at L1 = L2 = 70 dB. Normal hearing ears and hearing-impaired ears were well differentiated at L1 = L2 = 60 dB. CONCLUSION: In clinical application of DPOAE test, DP levels should be measured at the stimulus level most appropriate for the purposes.

A study of piriform sinus fistula cases.

We have experienced five cases of piriform sinus fistula for the last 10 years. It is a relatively rare disease, and partly because of poor understanding of the disease, in one case infection had repeatedly recurred without being adequately treated for over 20 years, and in most cases there was a long time lapse before the diagnosis. In another case, it was difficult to image the fistula with contrast medium and fistulectomy was performed without identifying it on imaging. We have applied various devices to those cases where imaging of fistula was difficult, and achieved complete resection of fistula and have not observed recurrences of infection after resection.

Hearing loss and growth rate of acoustic neuromas in follow-up observation policy.

OBJECTIVE: It is important to know the growth rate of acoustic neuroma in setting up its observation policy. One aimed to evaluate the significance of growth rate and hearing loss speed from a retrospective study of 31 patients. METHODS: Thirty-one patients with acoustic neuroma (mean age, 57.1 years; range, 9-81 years) who had undergone MRI and audiometry were retrospectively examined. Changes in tumor size and hearing level during follow-up periods were analyzed. RESULTS: The mean annual growth rate was 2.4 mm/year (maximum, 17 mm/year), and the average annual hearing loss speed was 2.3 dB/year (-15.0 - 19.2 dB/year) in the follow-up, and a correlation was recognized between them. Whereas significant difference was noted in annual growth rate and hearing loss speed between the sexes, no correlation was recognized between the annual growth rate or hearing loss speed and the age, tumor size and pure tone average (PTA) at the initial diagnosis. CONCLUSION: Attention must be paid to the acoustic neuroma cases where tumor growth rate is markedly high and those where hearing level rapidly declines during follow-ups. It is difficult, however, to estimate tumor diameter in relation with the changes in hearing level because the natural course of an acoustic neuroma varies in each individual.

Therapy for otitis-prone children in Tenshi hospital.

With the recent emergence and increases of multiple-drugs-resistant Streptococcus pneumoniae, we have been seeing an increasing number of infants with intractable recurrent otitis media which is resistant to the general conservative out-patient treatments such as oral administration of medicines or tympanotomy. In this study, we investigated the inflammation-causing bacteria in the infants with otitis media which were treated in our hospital from January to December in 1997, and in six serious cases among them, we measured IgG subclass and specific IgG2 antibody to S. pneumoniae to examine them. As a result, S. pneumoniae was found to be the cause in 45% of the cases of initial development of otitis media, and in 88% of them the S. pneumoniae was penicillin-resistant. The level of specific IgG2 antibody to S. pneumoniae was low in all the cases, whereas IgG2 subclass was deficient only in one out of the six cases; from these findings, the selectively low level of immune status was thought to be the cause of the recurrences of otitis media. In two cases, clinical condition was markedly improved by immunoglobulin substitute therapy, which demonstrates that immunoglobulin is effective for the intractable recurrent otitis media in infants.

An anti-mumps IgM antibody level in the serum of idiopathic sudden sensorineural hearing loss.

PURPOSE: Measurement of anti-IgM antibody for mumps enables us to diagnose silent mumps infection. From the viewpoint of prophylactic medicine, we examined the incidence of silent mumps infection in idiopathic sudden sensorineural hearing loss (ISSNHL) by measurement of anti-mumps IgM antibody. MATERIALS AND METHODS: Serum level of anti-mumps IgM antibody was evaluated by EIA method in 69 ISSNHL cases. RESULTS: Of the 69 serum samples examined, five samples were positive, two samples were regarded as quasi-positive and other samples were negative for anti-mumps IgM antibody. The positive rate was 7.2% (5/69). The relationship of anti-mumps IgM and IgG antibody was also described. CONCLUSIONS: From the measurement of anti-IgM antibody for mumps, it was possible to diagnose silent mumps infection in ISSNHL. The positive rate of anti-IgM antibody in ISSNHL was 7.2% suggesting that the silent mumps infection could be considered as one of the causative factors of ISSNHL even though its incidence is not so high. Since mumps often occurs without clinical symptoms, it is still considered to be one of the important causes of profound hearing loss. From the viewpoint of prophylaxis of profound hearing loss and deafness, we should understand the situation of virus epidemiology and vaccination.

Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas.

OBJECTIVE: To study the utility of VEMP (vestibular-evoked myogenic potential) in the diagnosis of acoustic neuromas. METHODS: Eighteen patients with unilateral acoustic neuromas were subjected to this study. Myogenic potential responding to loud click stimuli was recorded at ipsilateral sternocleidomastoid muscle. A normal range of VEMP was obtained from 20 controls. VEMP responses were compared with both, clinical symptoms and results of caloric tests. RESULT: Thirteen out of 18 patients showed decreased responses of VEMP at the affected side. VEMP responses seemed to have little relation with dysequilibrium, spontaneous nystagmus, canal paresis and pure-tone hearing. CONCLUSION: VEMP is useful for detecting dysfunction of inferior vestibular nerve in patients with acoustic neuromas.

Effects of spontaneous otoacoustic emissions on distortion product otoacoustic emission.

OBJECTIVE: It has been reported that spontaneous otoacoustic emission (SOAE) can prolong the responses or increase the echo power of transiently evoked otoacoustic emission (TEOAE), yet the effects of SOAE on distortion product otoacoustic emission (DPOAE) have been studied less thoroughly. As most of the previous studies have not paid attention to the patient's age, sex and hearing level, they have not reflected possible effects of those factors. We studied the effects of SOAE specifically on DPOAE in the following subjects. SUBJECTS AND METHODS: The subjects were all females ranging in age from 19 to 24 (average: 21.4) and the 78 ears had a hearing threshold under 15 dB for 1.2, and 4 kHz on pure-tone hearing test. IL088 (Otodynamics) was used for measurement of SOAE and IL092 (Otodynamics) for DPOAE. SOAEs were measured by time-averaging over 100 of the responses, of which those showing a clear peak 3 dB above the noise floor and being reproducible were considered as SOAE-positive. In all the ears. DPOAE responses were measured at L1 = L2 = 70 dB, and in 42 ears also at L1 = L2 = 60 dB and L1/L2 = 60/50 dB. The subjected ears were grouped into two by the presence or the absence of SOAE, and DPOAE amplitudes of 1, 2, and 4 kHz were compared. respectively. RESULTS: Of the total, 39 ears were SOAE-positive and 39 SOAE-negative. Statistically no significant difference was observed in the average hearing level between the SOAE-positive and SOAE-negative groups. The hearing levels did not significantly differ in the frequencies of 1, 2. and 4 kHz, respectively, indicating that influence of the hearing level on DPOAE could be excludable. DPOAE amplitudes at L1 = L2 = 70 dB in the frequencies of 1, 2, and 4 kHz were higher in the SOAE-positive group than in the SOAE-negative group. And DPOAE amplitudes were also higher in SOAE-positive group at L1 = L2 = 60 dB and L1/L2 = 60/50 dB in the frequency of 1.2, and 4 kHz, but significant differences were observed only in the frequencies of 4 kHz. By grouping the ears by the number of SOAE. we revealed the tendency that the larger the number of SOAE, the higher the DPOAE amplitudes. CONCLUSIONS: We evidenced that SOAE has significant effects on DPOAE responses. In clinical application of DPOAE measurement, therefore, the effects should be seriously taken into account.

Identification of the opener and closer of the pharyngoesophagus in laryngectomees.

BACKGROUND: In esophageal and tracheoesophageal speakers, the neoglottis acts not only as the orifice of the digestive tract but also as the airway and the voice source. The opening and closing mechanism is thought to be essential for these functions. It is not known, however, whether there is any active muscular control of neoglottal opening and closing. Examinations have been carried out to find the physiological background of the opening and closing of the neoglottis. In this paper, we present our findings of the opening and closing mechanism of the neoglottis and discuss them with reviewing the previous studies. SUBJECTS AND METHODS: Subjects were volunteer esophageal speakers. Neoglottal width, EMG of the inferior pharyngeal constrictor (IPC) and that of the geniohyoid muscle (GH) were recorded simultaneously during swallowing and air intake for esophageal speech. RESULTS: At rest, the neoglottis was closed by the mucosal protrusion in the posterior wall of the pharyngoesophagus. During swallowing, the neoglottis was widely opened. Traction of the anterior pharyngeal wall anteriorly by the GH and reciprocal suppression of the IPC activity was thought to be the mechanism of the neoglottal opening in this case. However, such simple reciprocity was not observed during air intake, although transient opening of the neoglottis was commonly observed. The GH showed increased activity at neoglottal opening as it did during swallowing. The IPC was. on the other hand, continuously activated, and no significant suppression was observed. During air intake, the muscle is assumed to play a role in maintaining the shape and tension of the posterior mucosal protrusion which acts as a voice source in subsequent phonation. CONCLUSIONS: The GH and the IPC were found to open and close the neoglottis, respectively. Their activities were not always clearly reciprocal in the various functions of the neoglottis.

Correlation between the levels of circulating adhesion molecules and PR3-ANCA in Wegener's granulomatosis.

OBJECTIVE: The adhesion of neutrophils to the vascular endothelial cells appears to be important for the pathogenesis of vasculitis in Wegener's granulomatosis (WG). To determine the pathological significance of the neutrophil adhesion, we have examined and evaluated the relationships between the levels of adhesion molecules and proteinase-3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA), and between the levels of TNF-alpha and disease activities in WG. METHODS: sELAM-1 and sICAM-1 in sera from WG and healthy donors were detected by ELISA. SLex and LFA-1 on neutrophils were detected by flow cytometry. RESULTS: The level of sICAM-1 was significantly higher in active WG than in inactive WG, tending to reflect individual disease activities. There was no difference in the level of sELAM-1 between WG patients and healthy donors. CONCLUSION: Our study suggests that the adhesion of neutrophils to the vascular endothelium is significant for the pathogenesis of the vasculitis in WG.

A family affected by branchio-oto syndrome with EYA1 mutations.

Branchio-oto (BO) syndrome is complicated with congenital preauricular fistulae, branchial fistulae (cysts), and hearing loss (sensorineural, conductive or mixed). As well as branchio-oto-renal (BOR) syndrome. it is known to be an autosomal dominant hereditary disorder. Since mutations in the EYA1 gene have been identified in both BO and BOR syndromes, mutation screening of this gene has been drawing attention as a genetic test to diagnose BOR/BO syndromes. In this study, we genetically investigated the presence of EYA1 mutations in a BO syndrome family in which we observed congenital preauricular fistulae, branchial fistulae (cysts) and hearing loss in four generations. Whereas there was a variety of phenotype expressions in this family, all subjects tested had a nonsense mutation (R264X) in exon 8 of the EYA1 gene. The present report adds further examples to support the usefulness of molecular genetic testing for the diagnosis of patients with BO syndrome.