Biomedical subjects

Naohito Hato

Publications and source records attributed to Naohito Hato.

17 recordsLinked to original sources

PubMed2006

Induction of myasthenia by immunization against muscle-specific kinase.

Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.

Agrin↗

PubMed2006

A new tool for testing ossicular mobility during middle ear surgery: preliminary report of four cases.

OBJECTIVE: We developed an ossicular vibration tester for the objective and quantitative assessment of ossicular mobility, which is one of the most critical factors affecting postoperative hearing after tympanoplasty. METHODS: Our device consists of three components: a probe shaft with a curved tip to be attached to the target ossicle, a vibration exciter to activate the probe, and a piezoelectric sensor to detect vibrations of the probe. These components are encased in a stainless steel holder, allowing easy hand manipulation during ear surgery. The probe is activated with an electric signal at around 1,600 Hz. The system is controlled with a laptop computer, and the results are presented as the ratio of the ossicular resistance (ROR) to a reference value as a percentage. One measurement takes 10 ms. The device was applied in four selected patients during ear surgery. RESULTS: Several measurements in two of the cochlear implantees showed a greater difference in the RORs of the stapes (15-20% in Case 1 and 35-45% in Case 2), whereas the RORs of the malleus and incus were within the same range. This was thought to correspond to the partial cochlear calcification noted in Case 2. In Case 3, who underwent surgery because of otosclerosis, the ROR of the stapes was high, ranging from 70 to 80%. When measured for the malleus-incus fixation anomaly (Case 4), the ROR of the malleus and incus was in the range of 60 to 70%. Owing to the limited surgical view, the ROR of the stapes could not be measured. No problems related to the measurements with this device were noted. CONCLUSION: The design, principles, measuring procedures, and preliminary results of our new tool for testing ossicular mobility are reported. Measuring the ossicular mobility during surgery may provide important information for deciding the surgical procedures.

Adolescent↗

PubMed2005

Experimental study of an adjustable-length prosthesis in a temporal bone model.

CONCLUSIONS: This prosthesis has the advantage of rapid adjustment at the time of insertion in order to achieve optimal tension and, as a result, optimal sound transmission. OBJECTIVE: To test the acoustic performance of a new, adjustable incus replacement prosthesis in a human temporal bone model. MATERIAL AND METHODS: Experiments were performed in seven human temporal bones, before and after removal of the incus and insertion of the prosthesis. The input comprised 406 pure tones ranging in frequency between 0.1 and 10 kHz at an intensity of 80 dB SPL at the tympanic membrane. The output measurement was stapes footplate displacement, determined by means of a laser Doppler vibrometer. Three lengths of the prosthesis were investigated: optimal, optimal +0.2 mm and optimal +0.4 mm. RESULTS: The optimal-length prosthesis produced similar results to those of an intact middle ear. The slightly longer prostheses decreased middle ear sound transmission at all test frequencies, except those near 1.5 kHz.

Aged↗

PubMed2005

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1.

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.

Animals↗

PubMed2004

Round window membrane motion with air conduction and bone conduction stimulation.

The vibration patterns of the round window (RW) membrane in human cadaver temporal bone specimens were assessed by measurements of the velocity of reflective targets placed on the RW membrane with an approximate spacing of 0.2 mm. The velocity was measured in the frequency range 0.1-10 kHz by a laser Doppler vibrometer in four specimens with air conduction (AC) stimulation and in four specimens with bone conduction (BC) stimulation. The response pattern was investigated by analyzing the velocity response of all targets on the RW membrane, by making iso-amplitude and iso-phase contour plots of the membrane surface, and by creating animations of the surface vibration at several frequencies. Similar response pattern was found with AC and BC stimulations. At frequencies below 1.5 kHz, the RW membrane vibrates nearly as a whole in an in-and-out motion and above 1.5 kHz, the membrane moves primarily in two sections that vibrate with approximately 180 degrees difference. Indication of some traveling wave motion of the RW membrane at those frequencies was also found. At higher frequencies, above 3 kHz, the membrane motion is complex with a mixture of modal and traveling wave motion. An increase of the stimulation level did not alter the vibration pattern; it only gave an increase of the RW membrane vibration amplitude corresponding to the increase in stimulation. When the mode of stimulation at the oval window was altered, by the insertion of a 0.6 mm piston, the vibration pattern of the RW membrane changed.

Acoustic Stimulation↗

PubMed2004

Fluid volume displacement at the oval and round windows with air and bone conduction stimulation.

The fluids in the cochlea are normally considered incompressible, and the fluid volume displacement of the oval window (OW) and the round window (RW) should be equal and of opposite phase. However, other channels, such as the cochlear and vestibular aqueducts, may affect the fluid flow. To test if the OW and RW fluid flows are equal and of opposite phase, the volume displacement was assessed by multiple point measurement at the windows with a laser Doppler vibrometer. This was done during air conduction (AC) stimulation in seven fresh human temporal bones, and with bone conduction (BC) stimulation in eight temporal bones and one human cadaver head. With AC stimulation, the average volume displacement of the two windows is within 3 dB, and the phase difference is close to 180 degrees for the frequency range 0.1 to 10 kHz. With BC stimulation, the average volume displacement difference between the two windows is greater: below 2 kHz, the volume displacement at the RW is 5 to 15 dB greater than at the OW and above 2 kHz more fluid is displaced at the OW. With BC stimulation, lesions at the OW caused only minor changes of the fluid flow at the RW.

Acoustic Stimulation↗

PubMed2003

Basilar membrane and osseous spiral lamina motion in human cadavers with air and bone conduction stimuli.

It is generally accepted that bone conduction (BC) stimuli yield a traveling wave on the basilar membrane (BM) and hence stimulate the cochlea by the same mechanisms as normal air conduction (AC). The basis for this is the ability to cancel or mask a BC tone with an AC tone and the ability to generate two tone distortion products with a BC tone and an AC tone. The hypothesis is proposed that BC stimulates the BM not only through the hydrodynamics of the scala vestibuli and scala tympani, but also through osseous spiral lamina (OSL) vibrations. To test this hypothesis the BM and OSL response with AC as well as BC stimulation was measured with a laser Doppler vibrometer. Human temporal bones mounted on a shaker were used to record the velocities of the bone per se, the BM and the OSL. The measurements were then converted to relative BM and OSL velocities. The results from the basal turn of the cochlea show similar behavior with AC and BC stimulation. The motion of the OSL at the edge where it connects to the BM is in phase and is typically 6 dB lower than the BM motion. With BC stimulation, there is less phase accumulation in the OSL after the cochlea is drained; the OSL moves due to inertial forces and resonates at approximately 7 kHz. Inertial vibration of the OSL may partially contribute to the total response of BC sound, especially at the high frequencies, although current models of the cochlea assume a rigid OSL. The measurements reported here can be used to include a flexible OSL in cochlear models.

Acoustic Stimulation↗

PubMed2003

Effects of acyclovir on facial nerve paralysis induced by herpes simplex virus type 1 in mice.

OBJECTIVES: Bell's palsy has recently been claimed to be caused by herpes simplex virus type 1 (HSV-1) infection. The anti-viral agent acyclovir is a specific inhibitor of herpesvirus replication, and the most effective agent for the treatment herpesvirus infection. The purpose of this experiment was to assess the effect of acyclovir on the facial nerve paralysis included by HSV-1 infection. METHODS: We succeeded in producing an animal model of acute and transient facial nerve paralysis induced with HSV-1 neuritis simulating human Bell's palsy. In this study, acyclovir administration was performed before and after facial nerve paralysis, and continued for 5 days. Controls were given phosphate-buffer saline (PBS) instead of acyclovir, and the incidence and duration of facial nerve paralysis was compared in the acyclovir groups and controls. RESULTS: The incidence of facial nerve paralysis was significantly lower in the group given acyclovir before the paralysis than in the controls, and the duration of facial nerve paralysis was shorter. CONCLUSIONS: Administration of acyclovir before the paralysis reduced the incidence and duration of facial nerve paralysis. Administration of acyclovir after the paralysis improved the duration of facial nerve paralysis.

Acyclovir↗

PubMed2003

Lateralization of the tympanic membrane as a complication of canal wall down tympanoplasty: a report of four cases.

OBJECTIVE: To describe the pathophysiology and treatment of the lateralized tympanic membrane that occurs after canal wall down tympanoplasty. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Four patients in whom lateralization of the tympanic membrane developed as a complication of canal wall down tympanoplasty. RESULTS: The patients had undergone middle ear surgery 20 to 34 years before their first visit to the authors. A Bondy operation with soft-wall reconstruction of the ear canal had been performed in three patients and a modified radical mastoidectomy in one patient. They all had severe conductive hearing loss. Common findings were anterior canal sulcus blunting, good tubal function, normal middle ear mucosa, and mobile stapes. At revision surgery, the lateralized tympanic membrane was removed, and the temporalis fascia was grafted medial to the malleus manubrium. The exposed bony surface in the ear canal was covered with a split-thickness skin graft, and the ear canal and the mastoid cavity were tightly packed to secure the graft. All the patients regained good hearing after the revision. Although deterioration of the anterior tympanic ring was presumed to be the primary cause of the graft lateralization, the lack of a posterior bony ear canal might have facilitated this condition. CONCLUSION: Lateralization of the tympanic membrane can occur even in an ear with a radicalized mastoid cavity, especially when the anterior tympanic ring is torn and the posterior ear canal is reconstructed with soft tissue.

Bone Conduction↗

PubMed2003

Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone.

OBJECTIVE: To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bell's palsy. STUDY DESIGN: This was a retrospective study of 480 Bell's palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases). PATIENTS: Patients met the after criteria: (1) severe or complete Bell's palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60-40 mg/day) with or without oral acyclovir (2,000 mg/day). MAIN OUTCOME MEASURE: Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis. RESULTS: The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent. CONCLUSION: These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bell's palsy.

Acyclovir↗

PubMed2003

Factors contributing to bone conduction: the outer ear.

The ear canal sound pressure and the malleus umbo velocity with bone conduction (BC) stimulation were measured in nine ears from five cadaver heads in the frequency range 0.1 to 10 kHz. The measurements were conducted with both open and occluded ear canals, before and after resection of the lower jaw, in a canal with the cartilage and soft tissues removed, and with the tympanic membrane (TM) removed. The sound pressure was about 10 dB greater in an intact ear canal than when the cartilage part of the canal had been removed. The occlusion effect was close to 20 dB for the low frequencies in an intact ear canal; this effect diminished with sectioning of the canal. At higher frequencies, the resonance properties of the ear canal determined the effect of occluding the ear canal. Sectioning of the lower jaw did not significantly alter the sound pressure in the ear canal. The sound radiated from the TM into the ear canal was investigated in four temporal bone specimens; this sound is significantly lower than the sound pressure in an intact ear canal with BC stimulation. The malleus umbo velocity with air conduction stimulation was investigated in nine temporal bone specimens and compared with the umbo velocity obtained with BC stimulation in the cadaver heads. The results show that for a normal open ear canal, the sound pressure in the ear canal with BC stimulation is not significant for BC hearing. At threshold levels and for frequencies below 2 kHz, the sound in the ear canal caused by BC stimulation is about 10 dB lower than air conduction hearing thresholds; this difference increases at higher frequencies. However, with the ear canal occluded, BC hearing is dominated by the sound pressure in the outer ear canal for frequencies between 0.4 and 1.2 kHz.

Auditory Threshold↗

PubMed2002

Demyelination associated with HSV-1-induced facial paralysis.

In 1995, we developed an animal model of transient homolateral facial nerve paralysis by inoculating Herpes simplex virus type 1 (HSV-1) into the auricle of mice. This study examined the mechanism of facial nerve paralysis in this model histopathologically. Using the immunofluorescence technique with anti-HSV-1 antibody, the time course of viral spread and the site of viral replication were investigated over the entire course of the facial nerve. Furthermore, viral replication and nerve degeneration at the site of viral replication were observed by electron microscopy. On the 7th day after inoculation, facial paralysis was observed in more than 60% of mice. Immunofluorescence study revealed HSV-1 in the geniculate ganglion, the descending root, and the facial nucleus at this stage. On the 9th day, the descending root in the sections stained with osmium looked pale, because prominent demyelination had occurred in this region; electron micrographs showed many degenerated oligodendrocytes and large naked axons. In contrast, the facial nucleus neurons showed no remarkable degeneration, despite HSV-1 particles in their cytoplasm. From these findings, we concluded that facial nerve paralysis in this model is caused mainly by facial nerve demyelination in the descending root.

Animals↗

PubMed2002

Swelling of the intratemporal facial nerve in Ramsay Hunt syndrome.

Although Ramsay Hunt syndrome is one of the most important diseases causing peripheral facial palsy, the detailed pathology of the disease in the intratemporal facial nerve remains unclear. The purpose of this study was to increase knowledge of the pathogenesis of the syndrome by means of surgical findings. Between April 1976 and March 1997 we performed subtotal decompression of the facial nerve in 74 patients with severe Ramsay Hunt syndrome. The grade of nerve swelling was assessed using a microscope and recorded in a standardized form. The relationships between nerve swelling, the timing of surgery and the swelling of each segment were analyzed. Pronounced neural swelling, involving the geniculate ganglion and the horizontal segment, was consistent finding in the acute phase. Although the incidence of pronounced swelling of the horizontal segment gradually declined with time after onset, in most cases nerve swelling persisted even beyond the 16th week after onset. These data suggest that diffuse viral neuritis occurs throughout the intratemporal facial nerve. We assume that the viral inflammatory swelling involving the geniculate ganglion and horizontal segment is mostly responsible for the acute facial palsy in the acute phase.

Adult↗

PubMed2002

Factors contributing to bone conduction: the middle ear.

Measurement of the motion of the malleus umbo and stapes footplate during bone conduction (BC) stimulation was conducted in vitro in 26 temporal bones using a laser Doppler vibrometer over the frequency range 0.1 to 10 kHz. For lower frequencies, both ossicular sites followed the motion of the temporal bone. The differential motion between the malleus and the surrounding bone was greater than the differential motion of the stapes footplate; both resonated near 1.5 kHz. Different lesions were shown to affect the response: (1) a mass attached to the umbo lowered the resonance frequency of the ossicular vibration; (2) fixation of either the malleus or stapes increased the stiffness and shifted the resonance frequency upward; and (3) dislocation of the incudo-stapedial joint did not significantly affect the ossicular vibration. The sound radiated from the tympanic membrane was approximately 85 dB SPL at an umbo differential velocity of 1 mm/s for low frequencies in an open ear canal and about 10 dB higher for an occluded one; at higher frequencies (above 2 kHz) resonances of the canal determine the response. It was also found that the motion between the footplate and promontory was within 5 dB when the specimen was stimulated orthogonal to the vibration direction of the ossicles than in line with the same. Measurement of the differential motion of the umbo in one live human skull gave similar response as the average result from the temporal bone specimens.

Bone Conduction↗

PubMed2002

Pathophysiology of facial nerve paralysis induced by herpes simplex virus type 1 infection.

Herpes simplex virus type 1 (HSV-1) has been proven to be a cause of Bell's palsy; however, the underlying pathophysiology of the facial nerve paralysis is not fully understood. We established a mouse model with facial nerve paralysis induced by HSV-1 infection simulating Bell's palsy and investigated the pathophysiology of the facial nerve paralysis. The time course of the R1 latency in the blink reflex tests paralleled the recovery of the facial nerve paralysis well, whereas electroneurographic recovery tended to be delayed, compared to that of the paralysis; these responses are usually seen in Bell's palsy. On histopathologic analysis, intact, demyelinated, and degenerated nerves were intermingled in the facial nerve in the model. The similarity of the time course of facial nerve paralysis and the electrophysiological results in Bell's palsy and the model strongly suggest that the pathophysiological basis of Bell's palsy is a mixed lesion of various nerve injuries.

Animals↗

PubMedDate not supplied

Bilateral spontaneous cerebrospinal fluid otorrhea.

We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months after surgical repair of the left side, right-side CSF leakage occurred. The right side was repaired surgically, and the patient recovered without incident. From our findings and a review of the literature, we postulate that bilateral CSF otorrhea resulted mainly from the thinness of the tegmen because of well-pneumatized mastoid air cells and the weakness of the dura after chronic inflammatory changes. In case of spontaneous CSF otorrhea, the roof of tegmen should be assessed bilaterally with care using radiologic examinations so as not to overlook a subclinical condition on the contralateral side.

Cerebrospinal Fluid Otorrhea↗

PubMedDate not supplied

Three-dimensional stapes footplate motion in human temporal bones.

The literature provides conflicting information on whether the motion of the stapes footplate is piston-like or some other type of motion, such as rotational or rocking. Examination of the three-dimensional (3D) motion of the stapes footplate appears to be an excellent way to understand this complicated motion. Five microsphere reflective targets were placed on the stapes footplate in ten fresh human cadaver temporal bone preparations, and their vibration measured through an extended facial recess approach using a laser Doppler vibrometer. The five target sites on the stapes footplate were center, anterior, posterior, superior and inferior. The stimulus was a sound input of 80-120 dB SPL at the tympanic membrane over a frequency range of 0.1 to 10 kHz. The 3D motion of the stapes footplate was calculated using the velocity amplitude and phase obtained for each target. For frequencies up to 1.0 kHz the vibration of the stapes footplate was primarily piston-like; this motion became complex at higher frequencies, with rotary motion along both the long and short axis of the footplate. When the cochlea was drained, stapes footplate motion became essentially piston-like for all frequencies.

Aged↗