Biomedical subjects

Tadashi Kitahara

Publications and source records attributed to Tadashi Kitahara.

At least 19 recordsLinked to original sources

PubMed2006

Fos-enkephalin signaling in the rat medial vestibular nucleus facilitates vestibular compensation.

In the present study, we first observed up-regulation in preproenkephalin (PPE)-like immunoreactivity (-LIR), a precursor of Met- and Leu-enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi-MVN) after unilateral labyrinthectomy (UL). By means of double-staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE-LIR neurons were also Fos immunopositive. The time course of decay of these double-stained neurons was quite parallel to that of UL-induced behavioral deficits. This suggests that these double-labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi-MVN by means of a 15-min pre-UL application of antisense oligonucleotide probes against c-fos mRNA into the ipsi-MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP-1 DNA binding activity and PPE expression in the ipsi-MVN after UL. C-fos antisense study also revealed that depression of Fos-PPE signaling in the ipsi-MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi-MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi-MVN neurons could regulate consequent PPE expression via the AP-1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation.

Adaptation, Physiological↗

PubMed2006

Intracranial vertebral artery dissection mimicking acute peripheral vertigo.

When diagnosing and treating patients with acute vertigo, the clinician must differentiate brain lesions from benign peripheral disorders. We here report a rare case of acute vertigo caused by intracranial vertebral artery dissection mimicking peripheral disease. A 67-year-old man presented with spontaneous nystagmus and moderate ataxia preceded by neck pain. No other neurological signs were observed, suggesting acute peripheral vertigo. However, magnetic resonance imaging (MRI) demonstrated a cerebellar infarction. Simultaneous magnetic resonance angiography (MRA) showed no flow void of the left vertebral artery and contrast-enhanced MRA demonstrated a double lumen sign, suggesting that vertebral artery dissection was a cause of infarction. The clinical course was favorable without anticoagulation drugs, which are sometimes contraindicated because of the potential risk of subarachnoid hemorrhage. Vertebral artery dissection can cause cerebellar infarction in patients without vascular risk factors mimicking acute peripheral vertigo. Careful history regarding the neck pain is important and MRA in combination with MRI can replace angiography in diagnosing this disorder.

Aged↗

PubMed2006

Factors relating to the vertigo control and hearing changes following intratympanic gentamicin for intractable Ménière's disease.

OBJECTIVE: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM). STUDY DESIGN: Prospective. SETTING: Tertiary referral medical center. PATIENTS: Twenty-eight patients with intractable Ménière's disease. INTERVENTIONS: Three intratympanic injections of GM (once per day for three consecutive days). MAIN OUTCOME MEASURES: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined. RESULTS: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the 11 patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group. CONCLUSION: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

Adult↗

PubMed2006

[Delayed facial nerve palsy after otologic surgery].

Delayed facial nerve palsy (DFP) is rarely experienced after otologic surgeries that do not directly touch the facial nerves, such as tympano-mastoidectomy, cochlear implants, and stapes surgery, and is troublesome to both surgeons and patients if it happens. Here, we report 7 cases of DFP, including one case that developed DFP after endolymphatic sac surgery. The ratios of occurrence were as follows: 0.7% (2/305) for tympano-mastoidectomy, 0.8% (3/354) for cochlear implant, 0.4% (1/260) for stapes surgery and 1.0% (1/98) for endolymphatic sac surgery. All otologic surgeries, except for endolymphatic sac surgery, exposed the chorda tympani, and all surgeries, except for stapes surgery, underwent drilling for a mastoidectomy. Furthermore, DFP was always observed ipsilaterally to the operated ear after otologic surgeries and was never seen after benign parotid tumor surgery or total laryngectomy. Therefore, there may be a strong relationship between DFP and the procedures, used during otologic surgeries.

Adult↗

PubMed2005

Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3.

Although the bases for both the sporadic and inherited forms of Ménière's disease (MD) remain undefined, it is likely to be multifactorial, one of the factors being a genetic predisposition. Recently, genetic association studies on complex diseases have become very popular and most of them are case-control studies using single nucleotide polymorphisms (SNPs) as markers. Mutations/polymorphisms in KCNE potassium channel genes might play a causative role in MD, because KCNE potassium channels have been suggested to be present and active in transmembrane ion and water transports in the inner ear. In the present study, to identify MD susceptibility genes, we have conducted a genetic association study with optimized sampling, optimized phenotyping/genotyping, and a selection of KCNE genes as the candidate genes. The SNPs analyses identified 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene in 63 definite MD cases as well as 205 and 237 non-MD control subjects. For both KCNE1 and KCNE3 genes, a significant difference in frequency of each SNP was confirmed between MD cases and non-MD control subjects. The result indicates that 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene could determine an increased susceptibility to develop MD.

Adult↗

PubMed2005

Prospective studies on mental status and quality of life in patients with head and neck cancer treated by radiation.

Factors affecting the quality of life (QOL) in patients undergoing radiation therapy for head and neck cancer were determined in a prospective study. Full psychiatric interviews and self-report questionnaires concerning patients' QOL, pain, anxiety, mood, coping style and personality were administered to 35 patients with Stage I or II head and neck cancer before radiation therapy (week 0), and approximately one month (week 4) and two months (week 8) after starting of radiation. Anxiety, depression and pain were more severe at week 4 than at baseline. Anxiety was less at week 8, but depressive symptoms remained remarkable. Stepwise regression analyses revealed that changes in depressed mood and pain partially accounted for changes in disease-specific QOL. General health QOL related to a premorbid personality of openness and an emotional aspect of a coping style. Therapeutic interventions including psychiatric management of depression and physical management of pain appear to be crucial for preserving QOL during radiation treatment of patients with head and neck cancer.

Adaptation, Psychological↗

PubMed2005

Changes in transient receptor potential cation channel superfamily V (TRPV) mRNA expression in the mouse inner ear ganglia after kanamycin challenge.

The transient receptor potential cation channel subfamily V (TRPV) is a non-specific cation ion channel receptor family that is gated by heat, protons, low extracellular osmolarity and arachidonic acid derivatives. Since some of these endogenous agonists of TRPV receptors are reactive oxygen intermediates produced by lipoxygenases, it has been hypothesized that some members of the TRPV family may respond to challenges by reactive oxygen species. This study used real-time PCR to quantitatively track changes in TRPV1-4 mRNA expression in the spiral, vestibular, and trigeminal ganglia and the kidney from kanamycin (KM)-treated mice. TRPV1, TRPV2, TRPV3 and TRPV4 mRNAs were expressed in spiral and vestibular ganglia, and TRPV2 and TRPV1 mRNAs were most predominant in control mice. After KM (700 mg/kg s.c. b.i.d., 14 days), TRPV1 mRNA and protein expression were significantly up-regulated both in the spiral and vestibular ganglia, but expression was unaffected in the trigeminal ganglion and kidney. Real-time PCR also demonstrated a significant down-regulation in TRPV4 mRNA expression in the inner ear ganglia and kidney after KM treatment. All these mRNA and protein expression changes were eliminated by simultaneous administration of dihydroxybenzoate (300 mg/kg s.c. b.i.d., 14 days), an anti-oxidant that blocks KM ototoxicity. It is proposed that up-regulated TRPV1 expression during KM exposure may promote ganglion cell survival by contributing to neuronal depolarization, with KM-induced tinnitus and dizziness as consequences.

Animals↗

PubMed2005

Prognosis of inner ear periphery and central vestibular plasticity in sudden deafness with vertigo.

OBJECTIVES: We sought to elucidate the clinical problems and otopathology of patients with sudden deafness with vertigo (SDV). METHODS: In 24 patients with SDV who had significant canal paresis (CP) at their first visit to our hospital between 1997 and 2001, we examined pure tone audiograms, caloric tests, and several questionnaires twice, at the first visit within 5 days after the onset and around 2 years after steroid therapy. RESULTS: These examinations revealed that improvements of auditory and vestibular function in patients with SDV tended to be correlated with one another. Sixteen of the 24 patients (66.7%) still had CP. This rate in SDV was significantly worse than that reported previously for vestibular neuritis (VN). On the other hand, patients with SDV with long-lasting CP had a faster reduction of head-shaking afternystagmus and of handicaps in their everyday life due to dizziness than did patients with VN and CP. CONCLUSIONS: These findings suggest that SDV may deteriorate the inner ear function more severely but accelerate the central vestibular compensation more effectively than VN after the lesion. It is well known that vestibular neurectomy causes much more severe motion-induced dizziness after surgery than does labyrinthectomy. Taken together, these findings suggest different regions of damage in SDV (mainly the labyrinth, as in labyrinthectomy) and VN (mainly the ganglion, as in vestibular neurectomy).

Adult↗

PubMed2004

Localization of the mitochondrial uncoupling protein family in the rat inner ear.

Uncoupling proteins (UCPs) are a proton transporter family located in the mitochondrial inner membrane. The molecular expression and activity of UCPs in brown adipose tissue and skeletal muscle are regulated by factors as diverse as chronic overeating and cold exposure, suggesting roles in energy expenditure and heat production. Although UCP2, UCP4 and brain mitochondrial carrier protein-1 (BMCP-1, i.e. UCP5) mRNAs are expressed in the central nervous system, their central function is unknown. This study presents the first evidence on localization and quantitative expression of UCPs in the rat inner ear by real-time PCR and immunohistochemistry. Real-time PCR studies revealed that UCP2 mRNA was expressed in the vestibular and spiral ganglia more abundantly than any other UCP. Neocortex, by contrast, contained UCP2 and UCP4 equally. Notably, UCP3 and UCP4 mRNAs were expressed in inner ear ganglia, but brain UCP3 mRNA expression level was undetectable by simple PCR. Immunohistochemical studies confirmed that both UCP2- and UCP3-like immunoreactivities were detected in vestibular and spiral ganglion cells and co-localized with a mitochondrial marker, MitoFluorGreen. According to previous reports, UCP2 and UCP3 are thermogenic in yeast and brain UCP2 has been suggested to modulate pre- and post-synaptic events by axonal thermogenesis. It has also been reported recently that UCP2 and UCP3 responses to superoxide application may be an antioxidant protective mechanism. Therefore, it is suggested that mitochondrial UCPs (UCP2, UCP3, UCP4) may play both a protective role against oxidative damage and a thermal signaling role in the eighth nerve.

Animals↗

PubMed2004

Changes in aquaporin expression in the inner ear of the rat after i.p. injection of steroids.

The aquaporins (AQPs) are a family of small transmembrane water transporters. It has recently been revealed that they play a role in regulating homeostasis in the inner ear fluids. Steroid therapy is usually administered to patients with inner ear disorders; however, the mechanism of steroid effects has not been clearly determined. To elucidate the points of action of steroids in the inner ear, we recently examined the distributions of AQP isoform mRNAs in the rat inner ear and identified AQP1-6 mRNAs in the rat cochlea and AQP1, 3, 4, 5 and 6 mRNAs in the rat endolymphatic sac by means of reverse transcriptase polymerase chain reaction (PCR). In this study, we investigated changes in expression of AQP mRNAs in the rat inner ear after i.p. injections of steroids using real-time quantitative PCR and found that AQP3 mRNA in the endolymphatic sac was significantly upregulated in both dose- and time-dependent manners. This result suggests that steroids may effect water homeostasis in the rat inner ear via AQPs.

Animals↗

PubMed2004

Paroxetine, a selective serotonin reuptake inhibitor, reduces depressive symptoms and subjective handicaps in patients with dizziness.

OBJECTIVE AND STUDY DESIGN: When treating dizzy patients, the psychiatric aspect should be carefully addressed regardless of whether a well-defined organic disease is present. In this prospective study, we aimed to elucidate the role of paroxetine, a selective serotonin reuptake inhibitor, in the treatment of dizziness. SETTING AND PATIENTS: Forty-seven patients who complained of dizziness were treated with 20 mg of paroxetine per day. The depressive state of the patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment outcomes were measured with self-assessment of subjective handicaps in daily life using a dizziness and unsteadiness questionnaire. The questionnaire consisted of five factors related to emotional or bodily dysfunction that could be affected by dizziness. Changes in Self-Rating Depression Scale scores and subjective handicaps were assessed at 4 and 8 weeks after the start of paroxetine. RESULTS: In patients having well-defined organic diseases with high Self-Rating Depression Scale scores, paroxetine improved all five subjective handicap factors as well as Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale scores showed a significant correlation with improvement of subjective handicaps, which was related to emotional problems but not factors related to bodily dysfunction. Paroxetine was also effective for an improvement of factors related to emotional problems and Self-Rating Depression Scale scores in patients not having organic diseases but with high Self-Rating Depression Scale scores. In patients either with or without organic diseases with low Self-Rating Depression Scale scores, paroxetine had no effect on any subjective handicap factors and Self-Rating Depression Scale scores. CONCLUSION: In the treatment of dizzy patients, paroxetine was effective at relieving subjective handicaps caused by dizziness, specifically, in patients with high Self-Rating Depression Scale scores.

Activities of Daily Living↗

PubMed2004

Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation.

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca(2+) pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.

Animals↗

PubMed2004

Surgical management of special cases of intractable Meniere's disease: unilateral cases with intact canals and bilateral cases.

If a clinician seeks to allow patients with vertigo to return to work as soon as possible, it is very important to determine the appearance of vestibular symptoms during convalescence just after treatment, as well as the long-term results. Apprehensive patients with vertigo may undergo severe psychological torment if treatment requires long-term rest in bed before they can return to daily life. In this paper, we observed postoperative vestibular symptoms (subjective sensation and objective nystagmus) in 50 patients with intractable Meniere's disease, including cases from our previous preliminary report, during the period of convalescence just after endolymphatic sac drainage and steroid instillation surgery (EDSS). All symptoms were eliminated within 8 days after EDSS. There was no significant difference in the duration of any vestibular symptoms between bilateral (n = 8) and unilateral cases (n = 42). This result indicates that EDSS could be as safe a treatment for bilateral Meniere's disease as for unilateral disease. In unilateral cases with intact semicircular canal function (n = 17), postoperative evoked vestibular sensation, positional, and positioning (Dix-Hallpike) nystagmus disappeared significantly earlier than in those with canal paresis (n = 25). This result indicates that EDSS could keep the vestibular peripheral function of patients with unilateral Meniere's disease with intact canals quite stable after surgery. Therefore, EDSS could be recommended as an initial, less-invasive surgical treatment for intractable Meniere's disease, especially in unilateral cases with intact canals and in bilateral cases.

Dexamethasone↗

PubMed2004

Management of hemorrhagic high jugular bulb with adhesive otitis media in an only hearing ear: transcatheter endovascular embolization using detachable coils.

A 51-year-old woman had a hemorrhagic high jugular bulb protruding into the posterosuperior part of the tympanic cavity in her left ear. This (only hearing) ear had severe adhesive otitis media resulting in repetitive hemorrhage from the jugular bulb. Therefore, treatment to stop the bleeding was required. Since invasive middle ear surgery in an only hearing ear would involve a high risk of hearing loss and massive bleeding, transcatheter endovascular embolization using detachable coils was selected for this special case; it safely blocked the blood flow and preserved the patient's hearing level. This is the first such report in the otosurgical field, showing that transcatheter endovascular embolization using detachable coils was quite effective in a difficult case of a hemorrhagic high jugular bulb with severe adhesive otitis media in an only hearing ear.

Ear Diseases↗

PubMed2003

Effects of unilateral labyrinthectomy on GAD, GAT1 and GABA receptor gene expression in the rat vestibular nucleus.

To elucidate the role of the GABAergic neuronal system in the recovery from peripheral vestibular damage (unilateral labyrinthectomy), we used a real-time quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression of GAD65, GAD67, the GABAA receptor alpha1 subunit, the GABAB R1 subunit, and the GABA transporter GAT1, in the vestibular nucleus complex of the rat 6 and 50 h following the lesion GAD65 and GAD67 gene expression were also measured in the flocculus. The GABAA alpha 1 subunit mRNA was up-regulated in the ipsilateral vestibular nucleus 6 h post-lesion but decreased in expression thereafter. GAD65 mRNA was up-regulated in the vestibular nuclei bilaterally 50 h after the lesion. In the flocculus, GAD65 mRNA expression was bilaterally up-regulated 50 h post-operatively. GAT1 mRNA expression was initially up-regulated in the ipsilateral vestibular nucleus and then underwent a bilateral increase 50 h post-operatively. These results demonstrate that following unilateral labyrinthectomy, major changes in the expression of GAD, GAT and GABA receptor subunit genes occur in the vestibular nucleus, which are likely to affect the process of behavioural recovery.

Animals↗

PubMed2003

Fos induction in the amygdala by vestibular information during hypergravity stimulation.

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.

Afferent Pathways↗

PubMed2003

A new rotational test for vertical semicircular canal function.

OBJECTIVE: We developed a new rotating chair in order to assess the function of the vertical semicircular canal (VSCC) by analyzing VSCC-induced post-rotatory nystagmus (PRN). METHODS: We examined 14 healthy subjects, wearing goggles equipped with an infrared CCD camera, and sitting on a chair which was designed to stimulate a pair of the VSCCs by tilting the head 60 degrees backward with a 45 degrees rotation to the left or right side from the sagital plane. The time constant (TC) or maximal slow phase eye velocity (MSPEV) of the vertical component of four kinds of PRN were analyzed in four corresponding rotatory conditions, and used as functional index of the corresponding VSCC. RESULTS: The mean values of MSPEV in both anterior semicircular canal (ASCC) and posterior semicircular canal (PSCC)-induced PRN tended to be lower (P<0.10) than those induced by the lateral semicircular canal (LSCC). The result suggests that the threshold to the angular velocity in the VSCC is lower than that in the LSCC. The mean values of TC in both ASCC and PSCC-induced PRN were significantly lower (P<0.05) than those induced by the LSCC. CONCLUSION: The significant reduction of TC in VSCC-induced PRN compared with LSCC-induced PRN indicates that VSCC function is less affected by velocity storage mechanisms than LSCC function. The rotational test with respect to the VSCC can be used as a tool for assessing vertical canal function.

Adult↗

PubMed2003

Steroid effects on vestibular compensation in human.

Vestibular neuritis (VN) rapidly damages unilateral vestibular periphery, inducing severe balance disorders. In most cases, such vestibular imbalance is gradually restored to within the normal level after clinical therapies. This successive clinical recovery occurs due to regeneration of vestibular periphery and/or accomplishment of central vestibular compensation. We experienced 36 patients with VN treated at our hospital, including cases in our previous preliminary report. To elucidate effects of steroid therapy both on the recovery of peripheral function and on the adaptation of central vestibular compensation, we examined caloric test and several questionnaires with two randomly divided groups, 18 steroid-treated and 18 nonsteroid-treated patients, over two years after the onset. These examinations revealed that steroid-treated patients had a tendency of better canal improvements (13/18, 72%) than nonsteroid-treated ones (10/18, 55.6%). However, there was no significant difference between these two groups. In cases with persistent canal paresis, steroid-treated patients (n = 5) reduced handicaps in their everyday life due to the dizziness induced by head and/or body movements and the disturbance of their mood, more effectively than those with nonsteroid therapy (n = 8). These findings suggest that steroid therapy with VN could be effective on not only vestibular periphery but central vestibular system, to restore the balance.

Activities of Daily Living↗