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Biomedical subjects

Takeshi Kubo

Publications and source records attributed to Takeshi Kubo.

At least 19 recordsLinked to original sources

Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia.

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.

Adult↗

Needleless intranasal administration of HVJ-E containing allergen attenuates experimental allergic rhinitis.

Allergic rhinitis (AR) is one of the most common chronic diseases. Although current medications are highly effective in controlling its symptoms, they do not reverse the allergen-specific hypersensitivities that underlie the disease. Immunoglobulin E is a key mediator of AR, and preventing its production is clinically important. In this study, we developed an efficient needleless intranasal protein delivery system using the hemagglutinating virus of Japan envelope vector (HVJ-E). Intranasal delivery of ovalbumin (OVA) once a week for 3 weeks using this system enhanced OVA-induced interferon-gamma production by murine splenocytes. This treatment also attenuated the OVA-induced release interleukin-4 (IL-4) and IL-5 from splenocytes and the production of plasma OVA-specific immunoglobulin E in OVA-sensitive AR model mice. Thus, allergen-containing HVJ-E may be useful for noninvasive treatment of AR.

Administration, Intranasal↗

Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck region.

Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.

Carcinoma, Squamous Cell↗

Mapping of notch activation during cochlear development in mice: implications for determination of prosensory domain and cell fate diversification.

Recent chick experiments have shown that Notch signaling plays context-dependent distinct roles in inner ear development: initially, Notch activity confers a prosensory character on groups of cells by "lateral induction"; subsequently, it is involved in the establishment of fine-graded patterns of hair cells and supporting cells by "lateral inhibition." However, the spatiotemporal pattern of Notch activation in situ during mammalian inner ear development has not been investigated. In this study, we detected the expression patterns of the activated form of Notch1 (actN1) as well as those of endogenous Notch1, Jagged1 (Jag1), and Math1. ActN1 was detected by immunohistochemistry using an antibody that specifically recognizes the processed form of the intracellular domain of Notch1 cleaved by presenilin/gamma-secretase activity. Between embryonic days (E)12.5 and E14.5, actN1 was weakly detected mainly in the medial region of cochlear epithelium, where Jag1-immunoreactivivty (IR) was also observed. Jag1-IR gradually became stronger in a more sharply defined area, finally becoming localized in supporting cells, while actN1 was detected in an overlapping area. Thus, a positive feedback loop was assumed to exist between the expression of Jag1 and actN1. In addition, actN1 started to be strongly expressed in the cells surrounding Math1-positive hair cell progenitors between E14.5 and E15.5. Strong actN1-IR continued in both a supporting cell lineage and in the greater epithelial ridge during the perinatal stage but ended by P7, suggesting that Notch1 activation may initially demarcate a prosensory region in the cochlear epithelium and then inhibit progenitor cells from becoming hair cells via classical "lateral inhibition."

Animals↗

Coronal reformations of the chest on 64-row multi-detector row CT: evaluation of image quality in comparison with 16-, 8- and 4-row multi-detector row CT.

PURPOSE: To evaluate image quality of coronal reformations of chest performed on 64-row MDCT in comparison with 16-, 8- and 4-row MDCT. MATERIALS AND METHODS: Consecutive patients who underwent pulmonary CT angiography using four different MDCT scanners were retrospectively studied with IRB approval: (1) n=30, 64-row MDCT; (2) n=30, 16-row MDCT; (3) n=30, 8-row MDCT; (4) n=30, 4-row MDCT. Coronal reformatted images (2 mm thickness and 2mm intervals for 64-row MDCT; 5 mm thickness and 5 mm intervals for 16-, 8- and 4-row MDCT) were evaluated by consensus reading of two board-certified radiologists who were blinded to scanner type. The image quality of overall chest appearance and individual thoracic structures including heart, aorta and pulmonary arteries was graded using five-point scale. Grades from four different scanners were compared using Kruskal-Wallis test. A second evaluation was performed in 48 randomly selected patients (12 patients for each scanner). Reproducibility was assessed using weighted-kappa analysis. RESULT: Significant reproducibility was observed between the first and second evaluations in 48 patients both for image quality of overall chest (weighted kappa=0.826) and each thoracic structure (mean weighted kappa=0.803; range, 0.729-0.858). Image quality of overall chest and individual thoracic structures differed significantly among four different MDCT groups, with 64-row MDCT having the highest grades, followed by 16-, 8- and 4-row MDCT (mean grades for overall chest in each scanner: 3.9, 3.0, 2.4 and 1.9, respectively) (P<0.0001 for overall chest and each thoracic structure). CONCLUSION: When comparing coronal reformations of chest using four different MDCT scanners, the 64-row MDCT had the highest image quality for overall chest appearance and individual thoracic structures, followed by 16-, 8- and finally 4-row MDCT.

Adult↗

Progressive hearing loss in mice carrying a mutation in the p75 gene.

The neurotrophin receptor p75 (p75NTR) is expressed in the developmental stage of the cochlea. However, the role of the p75NTR in the inner ear remains to be established. In this study, we conducted electrophysiological and morphological analyses of the auditory function of mice carrying a mutation in the p75 gene at different longitudinal stages. The mice carrying a mutation in the p75 gene showed an age-related progressive hearing loss. At 1 month, there was no obvious morphological change in the cochlea of the mice carrying a mutation in the p75 gene compared to wild-type mice, except for a slight loss of spiral ganglion neurons (SGNs). Auditory function was not significantly different between both genotypes from 1 to up to 4 months of age. The mice carrying a mutation in the p75 gene started to show progressive hearing loss at 4 months, when both SGN degeneration and hair cell (HC) loss were observed at the basal turn. These results suggest that the neurotrophin receptor p75 may play a significant role in the maintenance of cochlear function, and that mice carrying a mutation in the p75 gene could be a good animal model of early onset progressive hearing loss.

Acoustic Stimulation↗

Benign paroxysmal positional vertigo due to a simultaneous involvement of both horizontal and posterior semicircular canals.

From April 2001 to November 2003, we investigated 8 patients with benign paroxysmal positional vertigo (BPPV) that was suspected to simultaneously affect both the horizontal and posterior semicircular canals (HSCC and PSCC). These cases showed typical vertical-torsional nystagmus induced by the Dix-Hallpike maneuver, followed by a horizontal nystagmus. They also showed a direction-changing geotropic or apogeotropic positional nystagmus triggered by lateral head rotations in the supine position. Using the three-dimensional analysis of the positional nystagmus, the rotation axis of the positional nystagmus had a component perpendicular to the plane of PSCC and another component perpendicular to the plane of HSCC. All these findings suggest that BPPV in these patients was a combination of posterior and horizontal canal BPPV. The observation of a vertical-torsional positional nystagmus should prompt the specialist to perform not only the canalith repositioning procedure, but also to execute lateral head turns in the supine position.

Adult↗

Neuromagnetic changes of brain rhythm evoked by intravenous olfactory stimulation in humans.

To identify the changes in the respective frequency band and brain areas related to olfactory perception, we measured magnetoencephalographic (MEG) signals before and after instilling intravenously thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide monohydrochloride (TTFD), which evoked a strong and weak sensation of odor, respectively. For the frequency analysis of MEG, a beamformer program, synthetic aperture magnetometry (SAM), was employed and event-related desynchronization (ERD) or synchronization (ERS) was statistically determined. Both strong and weak odors induced ERD in (1) beta band (13-30 Hz) in the right precentral gyrus, and the superior and middle frontal gyri in both hemispheres, (2) low gamma band (30-60 Hz) in the left superior frontal gyrus and superior parietal lobule, and the middle frontal gyrus in both hemispheres, and (3) high gamma band 2 (100-200 Hz) in the right inferior frontal gyrus. TPD induced ERD in the left temporal, parietal and occipital lobes, while TTFD induced ERD in the right temporal, parietal and occipital lobes. The results indicate that physiological functions in several regions in the frontal lobe may change and the strength of the odor may play a different role in each hemisphere during olfactory perception in humans.

Adult↗

Evaluation of thoracic abnormalities on 64-row multi-detector row CT: comparison between axial images versus coronal reformations.

PURPOSE: To evaluate the capability of coronal reformations of chest on 64-row MDCT in demonstrating thoracic abnormalities in comparison with axial images. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent pulmonary CTA on 64-row MDCT were retrospectively studied with institutional review board (IRB) approval. Contiguous 2 mm axial and coronal images were reviewed independently with a 1-week interval, by consensus reading of two board-certified radiologists. Overall image quality was graded using a five-point scale. Abnormalities in mediastinum, hilum, pulmonary vessels, aorta, heart, esophagus, pleura, chest wall, and lung parenchyma were scored: 1 = definitely absent, 2 = probably absent, 3 = equivocal, 4 = probably present, 5 = definitely present. Scores on axial and coronal images were compared using weighted kappa analysis. RESULTS: Overall image quality was not different with statistical relevance between axial and coronal images (mean/median scores; 3.7/4; 3.6/4, respectively, P = 0.286, Wilcoxon signed-rank test). Significant agreement was observed between axial and coronal scores (mean weighted kappa, 0.661; range, 0.362-1). Agreement was almost perfect for pneumothorax, lung and pleural mass, effusion and consolidation (weighted kappa=0.833-1); substantial for pulmonary embolism, trachea, mediastinal lymphadenopathy and non-skeletal chest wall lesion, heart, esophagus, and emphysema (weighted kappa, 0.618-0.799); moderate for atelectasis, mediastinum, hilar nodes, aorta, other lung lesions, skeletal chest wall lesions, linear scarring, nodules > 1 cm, pulmonary artery abnormalities and pleural thickening (weighted kappa, 0.405-0.592); and fair for nodules < 1 cm (weighted kappa = 0.362). CONCLUSION: Coronal reformations on 64-row MDCT had substantial agreement with axial images for evaluation of the majority of thoracic abnormalities.

Adult↗

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↗

Correlation between image noise and body weight in coronary CTA with 16-row MDCT.

RATIONALE AND OBJECTIVES: To evaluate the correlation between image noise and body weight (BW) or body mass index (BMI) in coronary computed tomography angiography (CTA) as a potential parameter for reducing radiation dose in coronary CTA. MATERIALS AND METHODS: Thirty-six patients who underwent electrocardiogram-gated cardiac CT were analyzed in this study. The patients included 26 men and 10 women with a mean age of 60 years (range 43-79 years). All patients were imaged on a 16-row multidetector CT scanner. Mean value of BW and BMI was 83.5 kg and 28.1, respectively. Image noise was defined as standard deviation (SD) of the attenuation values measured by using 1 cm2 circular region of interest in the ascending aorta at the level of the right main pulmonary artery. The SD values were plotted against BW and BMI. The correlations were examined using a linear regression method. A P value of less than .05 was considered significant. RESULTS: The r value of linear regression between noise and BW was 0.90 (P < .001). The r value of linear regression between noise and BMI was 0.74 (P = .015). CONCLUSIONS: Excellent correlation was observed between noise and BW in coronary CTA. These data may be used as potential parameters for customized radiation dose modification to reduce radiation dose in coronary CT examinations.

Adult↗

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↗

Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

Acute Disease↗

A secreted type of beta1,6 N-acetylglucosaminyltransferase V (GnT-V), a novel angiogenesis inducer, is regulated by gamma-secretase.

Glycosyltransferases are present in the Golgi apparatus in a membrane-bound form and are released from cells after cleavage by certain proteases. Beta1,6-N-acetylglucosaminyltransferase V (GnT-V), which is cleaved and secreted from the cells, is involved in the biosynthesis of beta1-6GlcNAc branching on N-glycans and has been implicated in tumor progression and metastasis. We recently reported that a secreted type of GnT-V (soluble GnT-V) itself could promote angiogenesis, which is completely different from its original function as a glycosyltransferase, and this might play a role in tumor invasion. In this study, to explore the molecular basis for this functional glycosyltransferase secretion, its cleavage site was examined and the protease(s) involved in that cleavage were identified. The NH2-terminal protein sequence of purified soluble GnT-V (approximately 100 kDa) from GnT-V-overexpressed cells revealed that its terminus started at His31, located at the boundary position between the transmembrane and stem regions. This secretion was not inhibited by a single amino acid mutation at the cleavage site (Leu29, Leu30 to Asp, His31 to Ala), but specifically inhibited by addition of DFK-167, a gamma-secretase inhibitor, suggesting that gamma-secretase is a plausible protease for secretion processing. In addition, transfection of the gene of familial Alzheimer's disease (FAD)[corrected]-linked presenilin-1, a component of gamma-secretase, increased the secretion rate of endogenous GnT-V; the secretion of soluble GnT-V (approximately 100 kDa) was completely inhibited in presenilin-1/2 double-deficient cells, which have no gamma-secretase activity. Collectively, these results demonstrate that Golgi-resident GnT-V is cleaved at the transmembrane region by gamma-secretase, and this might control tumor angiogenesis through a novel pathway.

Amino Acid Sequence↗

Three-dimensional analysis of benign paroxysmal positional nystagmus in a patient with anterior semicircular canal variant.

OBJECTIVE: To show the positional nystagmus in a patient who had suffered from benign paroxysmal positional vertigo (BPPV) that was thought to be caused by involvement of the anterior semicircular canal (ASCC) (A-BPPV). STUDY DESIGN: Retrospective case report. SETTING: City hospital. PATIENT: The present study reports a rare case of A-BPPV in a 41-year-old woman. CASE REPORT: The patient is 41-year-old woman who developed a positional vertigo after playing volleyball on March 22, 2005 and consulted our hospital the next day. When left Dix-Hallpike maneuver was performed, she showed a positional nystagmus of which fast phase direction of the torsional component was clockwise while that of the vertical component was downward. We plotted the slow phase eye velocity of the positional nystagmus during the left Dix-Hallpike maneuver on three-dimensional coordinates that showed the axis of the positional nystagmus to be perpendicular to the plane of the right ASCC. CONCLUSION: These results suggested that the patient was suffering from A-BPPV.

Adult↗

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↗

Outcome of percutaneous transhepatic venoplasty for hepatic venous outflow obstruction after living donor liver transplantation.

PURPOSE: To evaluate retrospectively the outcome of percutaneous transhepatic venoplasty of hepatic venous outflow obstruction after living donor liver transplantation (LDLT). MATERIALS AND METHODS: The institutional Human Subjects Research Review Board approved the interventional protocol and the retrospective study, for which informed consent was not required. Before treatment, informed consent was obtained from the patient or the patient's parents in all cases. Of 26 consecutive patients (nine male, 17 female; median age, 9 years) suspected of having hepatic venous outflow obstruction after LDLT, 20 patients confirmed to have anastomotic outflow stenosis at percutaneous hepatic venography and manometry underwent venoplasty. Pressure gradients before and after venoplasty were evaluated by using a paired t test. Patients in whom obstruction recurred during follow-up were re-treated with venoplasty with or without expandable metallic stents. Patency was analyzed by using Kaplan-Meier analysis. RESULTS: The initial balloon venoplasty was technically successful in all 20 patients, all of whom had improved clinical findings. The pressure gradient +/- standard deviation was reduced from 14.6 mg Hg +/- 8.6 to 2.2 mg Hg +/- 2.4 (P < .001). Eleven patients had recurrent obstruction and were treated with balloon venoplasty; one of them underwent stent placement, as well as venoplasty. The primary (event-free) patency and 95% confidence interval (CI) at 3, 12, and 60 months after venoplasty were 0.80 (95% CI: 0.62, 0.98), 0.60 (95% CI: 0.38, 0.81), and 0.60 (95% CI: 0.38, 0.81), respectively. The primary assisted patency, maintained with repeated venoplasty and expandable metallic stents, was 1.00 at 60 months. CONCLUSION: Percutaneous venoplasty is an effective treatment for hepatic venous outflow obstruction after LDLT.

Adult↗

[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↗