Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis.

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

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.

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.

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.

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.

[Utility of OAE screener (GSI 70) for the evaluation of distortion product otoacoustic emissions].

The purpose of this study was to investigate the ability of the OAE screener GSI 70 to evaluate of cochlea function in neonates, infants and adults. Distortion product otoacoustic emissions (DPOAEs) were measured using the GSI 70 DPOAE Analyzer and evaluated in 123 human ears between December 1999 and June 2000. We performed the following four general clinical tests to determine the reliability of the GSI 70: 1) comparison of DPOAE levels measured using the ILO 92 and the GSI 70 in 55 adult ears, 2) comparison of DPOAE levels measured using the GSI 70 and hearing levels in 55 adult ears, 3) comparison of DPOAE levels measured using the GSI 70 and ABR levels in 45 neonate and infant ears, and 4) evaluation of the utility of DPOAE measurements obtained using the GSI 70 in functional deafness cases. The following results were obtained: 1) DPOAE levels measured with the ILO 92 and the GSI 70 were closely correlated (correlation coefficient, 0.773 at 2 kHz and 0.813 at 4 kHz). 2) The sensitivity of the GSI 70 in adult ears confirmed to have normal hearing was 80% at 2 kHz and 100% at 4 kHz; the specificity of hearing-impaired ears was 94% at 2 kHz and 94% at 4 kHz. 3) The sensitivity of the GSI 70 in normal neonate and infant ears with normal hearing was 100% at 2 kHz and 100% at 4 kHz; the specificity of hearing-impaired neonate and infant ears was 97% at 2 kHz and 94% at 4 kHz. 4) All of the functionally deaf ears showed excellent DPOAE responses. Examinations using the GSI 70 DPOAE analyzer were very easy and fast. Also, the results were highly reliable, with the exception of one adult who was classified as having normal hearing in an out-of-scale hearing level at 2 kHz. We suggest that specific criteria be established for the clinical usage of the GSI 70 in performing objective hearing evaluations.

[Otoacoustic emissions of full-term and preterm neonates].

Transiently evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and spontaneous otoacoustic emission (SOAE) were measured in 45 full-term neonates (68 ears) and 12 preterm neonates (20 ears) with ILO88 & 92. Measurements were performed in the nursery of the obstetrics ward or NICU (not sound proof room) under natural sleeping condition after nursing. No sedating agent was used. TEOAEs were rated "good response" in 61 (89.7%) of 68 full-term neonate ears. DPOAEs were rated "good response" in 40 (71.4%) of 56 full-term neonate ears. SOAEs were detectable in 25 (62.5%) of 40 full-term neonate ears. Considering the high positive rate of TEOAE in full-term neonates and the easy and noninvasive method of measurement, we concluded that TEOAE is useful for auditory screening in neonates. There was failure to detect TEOAEs in 7 ears and the measurements were all performed within 6 days after birth. Some reports claim that residual amnion in the external auditory canal or the middle ear in the first few days after birth causes slight hearing loss. Thus, we expected that making the measurements more than 7 days after birth might yield higher "good response" rates. We sometimes found that the Total Echo Powers of TEOAEs were reduced by the poor condition of the ear probe. Thus, we must be very careful in regard to this technical problem in order to perform accurate examinations. Because of its lower "good response" rate, DPOAE was not as useful for screening as TEOAE. Because of the movements or respiratory noises of the newborn infants, it was hard to detect reliable DPOAEs, particularly in the low frequency range. On the other hand, because of its frequency specificity, particurally at high frequencies, DPOAE will be useful for detecting the partial hearing impairment such as congenital high-tone hearing impairment. It would be difficult to use SOAE as a clinical test. Because it is not an evoked response, its mechanism of generation is not well understood. We expect that following longitudinal changes in SOAE in neonates may yield some information about it. We measured mainly TEOAE in preterm neonates because we had to complete the measurements as soon as possible. High Total Echo Powers of TEOAEs were recorded in most infants over 38 weeks of PCA (post conceptional age). The earliest case showed reliable TEOAE at 35 weeks PCA. In most cases that could be measured twice on different days, the Total Echo Powers of TEOAE, were higher in the second time. We therefore concluded that TEOAE might serve as an examination for monitoring the maturation of preterm neonate hearing.