Biomedical subjects

Kazunori Nishizaki

Publications and source records attributed to Kazunori Nishizaki.

At least 19 recordsLinked to original sources

PubMed2006

Sudden hearing impairment combined with diabetes mellitus or hyperlipidemia.

The objective of this study was to delineate whether the presence of the risk factors of microvascular disorder (MD) contribute to the prognostic outcome in patients with idiopathic sudden deafness (ISD). Retrospective clinical record review was conducted with 106 patients of ISD. Pure tone hearing thresholds were compared among the groups with or without hyperglycemia and hypercholesterolemia. Significantly better hearing recoveries were observed in cases with hyperglycemia as compared with controls. There was a tendency that the magnitude of hearing recovery in hypercholesterolemia was greater than that of controls although there was no statistical difference. The presence of the risks in MD could be an indicator of better hearing prognosis of ISD if we choose appropriate treatments. Heterogeneity of the ISD makes the establishment of the relationship between the risk factors of MD and etiology of some cases of ISD. We may have to choose the treatments for ISD considering whether the patient has any risk factor of MD.

Adolescent↗

PubMed2006

Longitudinal formant analysis after cochlear implantation in school-aged children.

INTRODUCTION: The purpose of this investigation was to describe the correlation between vocal and hearing development by longitudinal analysis of sound spectrograms, as a basic system for evaluating progress in vocal development. SUBJECTS AND METHODS: Two school-aged children with prelingual deafness were evaluated diachronically to assess speech perception and speech intelligibility after cochlear implantation. One child had non-syndromic hearing impairment without any known neurological deficit except for hearing loss, while the other had hearing impairment accompanied by mild mental retardation and attention deficit disorder. Their voices were recorded for monthly follow-up after cochlear implantation; these were used for formant analysis and compared with their mother's voice, and alteration of the formant data was also compared with monosyllable speech perception. RESULTS: Formant analysis demonstrated high concordance was observed between monosyllable speech perception and speech intelligibility. F1-F2 forms of the patients more closely resembled those of their mothers after 1 year's follow-up. The time point at which speech development altered was very similar in both cases although the final outcomes were different. CONCLUSION: Fair improvement of articulation after cochlear implant was demonstrated by the F1-F2 gram analysis. This procedure can be used for data sharing and cooperation between medical and educational specialists.

Child↗

PubMed2006

Using assessment of higher brain functions of children with GJB2-associated deafness and cochlear implants as a procedure to evaluate language development.

OBJECTIVE: While investigators have reported that patients with GJB2-associated deafness and cochlear implants have preferable language development, the mechanisms of this phenomenon remains unknown. The goal of the present study was to assess higher brain functions of patients with GJB2-related and GJB2-unrelated deafness as a method of evaluating language development. METHODS: Eight children with cochlear implants were subjected to genetic testing for GJB2 and underwent the Raven colored progressive matrices test, Rey's auditory verbal learning test, Rey's complex figure test, the standardized language test for aphasia, the picture vocabulary test, and the standardized comprehension test for abstract words. RESULTS: Three children were diagnosed with GJB2-related deafness, and five children were diagnosed with GJB2-unrelated deafness. All three GJB2-related cases demonstrated normal range higher brain functions and fair language development. By contrast, one GJB2-unrelated case showed a semantic disorder, another demonstrated a visual cognitive disorder with dyslexia, and another had attention deficit-hyperactivity disorder. CONCLUSIONS: Children with GJB2-unrelated deafness showed a high frequency of heterogeneous disorders that can affect proper language development. This difference between children with GJB2-related and GJB2-unrelated deafness may account for the improved language development in children with GJB2-related deafness and cochlear implants. Further, genetic diagnosis of the non-syndromic hearing loss represents a useful tool for the preoperative prediction of outcomes following a cochlear implant procedure.

Audiometry↗

PubMed2006

Expression of Notch1 and Hes5 in the developing olfactory epithelium.

CONCLUSION: Notch signaling pathway may play an important role in the development of the olfactory epithelium (OE). Objectives. To elucidate whether the Notch signaling pathway mediates the developmental processes in the developing OE. MATERIALS AND METHODS: The expression of Notch1 and Hes5 in the developing OE of mice with ages ranging from embryonic day (E) 11 to postnatal day (PN) 14 was examined. RESULTS: As detected by in situ hybridization, Notch1 was expressed in scattered cells located in the basal portion of the embryonic OE and later in the cell layer adjacent to the basal lamina from E11 to PN14. Hes5 was expressed in scattered cells located in the basal portion of the embryonic OE from E11. However, at the late embryonic stage, the number of Hes5-positive cells decreased and after birth distinct Hes5-positive cells were not observed in the OE.

Animals↗

PubMed2006

TH1/TH2 and regulatory cytokines in adults with otitis media with effusion.

OBJECTIVE: Otitis media with effusion is one of the most common and intractable ear diseases. However, the role of Th1, Th2, and immunoregulatory cytokines on the pathogenesis of the disease in adult patients remains to be determined. The aim of this study is to disclose the cytokine expression in middle ear effusions (MEEs) in adults and to compare the profile on the basis of the presence of allergic rhinitis and the type of effusions. STUDY DESIGN: A prospective controlled clinical study. PATIENTS: MEEs were collected from 80 adult subjects. The concentration of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, and interferon (IFN)-gamma in MEEs were determined by using enzyme-linked immunosorbent assay. RESULTS: IL-2, IL-4, IL-5, IL-10, IL-12, and IFN-gamma in MEEs were detected in 60 (75.0%), 33 (41.3%), 42 (52.5%), 14 (17.5%), 80 (100%), and 66 (82.5%) samples, respectively. Among these cytokines, only the concentration of IL-4 in the allergic rhinitis-positive group was significantly higher than that in the allergic rhinitis-negative group. On the other hand, IL-2, IL-12, and IFN-gamma were detected, regardless of the presence of allergic rhinitis, and the concentration of these cytokines correlated with each other. The correlation between the concentration of IL-4 and IL-5 was also detected. In addition, both the incidence rate and the concentration of IL-10 in MEEs were significantly higher in the mucoid type compared with those in the serous type effusions. CONCLUSION: Regardless of allergic status, IL-12 may play a critical role in the pathogenesis of otitis media with effusion by affecting the production of IL-2 and IFN-gamma. In addition, IL-4 may have some impact on the immunologic condition in adults with allergic rhinitis. IL-10 potentially affects the viscosity of MEEs.

Adult↗

PubMed2006

E prostanoid 2 (EP2)/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2.

Prostaglandin E2 (PGE2) is a lipid mediator that displays important immunomodulatory properties, such as polarization of cytokine production by T cells. Recent investigations have revealed that the effect of PGE2 on cytokine production is greatly influenced by external stimuli; however, it is unclear whether PGE2 plays a significant role in major histocompatibility complex-mediated antigen-specific T-cell responses via binding to one of four subtypes of E prostanoid (EP) receptor alone or in combination. In the present study, we sought to determine the effect of PGE2 on antigen-specific CD4+ T-cell responses in humans, especially in terms of receptor specificity. We used purified protein derivative (PPD) and Cry j 1 as T helper type 1 (Th1) and Th2-inducing antigens, respectively. We generated several different Cry j 1- and PPD-specific T-cell lines (TCLs). PGE2 significantly and dose-dependently inhibited the proliferation and subsequent production of interleukin-4 by Cry j 1-specific TCLs and of interferon-gamma by PPD-specific TCLs upon antigen stimulation. Administration of EP2 receptor agonist and EP4 receptor agonist suppressed these responses in an adenylate cyclase-dependent manner, while EP1 and EP3 receptor agonists did not. Messenger RNA for EP2, EP3 and EP4, but not EP1, receptors were detected in Cry j 1- and PPD-specific TCLs, and no differences in EP receptor expression were observed between them. Furthermore, PGE2 and EP2 receptor agonist significantly inhibited interleukin-5 and interferon-gamma production by peripheral blood mononuclear cells in response to Cry j 1 and PPD stimulation, respectively. These results suggest that PGE2 suppresses both Th1- and Th2-polarized antigen-specific human T-cell responses via a cAMP-dependent EP2/EP4-mediated pathway.

Adenylyl Cyclase Inhibitors↗

PubMed2005

Identification of a candidate tumor suppressor gene RHOBTB1 located at a novel allelic loss region 10q21 in head and neck cancer.

PURPOSE: Aims of the study are to narrow-down the hotspot region on 10q21 defined by previous genome-wide loss of heterozygosity (LOH) analysis in head and neck squamous cell carcinomas (HNSCC) and to define candidate tumor suppressor genes (TSG) concerned with 10q21. MATERIALS AND METHODS: LOH analysis was carried out with ten polymorphic microsatellite markers. Expression analysis was performed by semi-quantitative RT-PCR, and mutation analysis by PCR and direct sequencing. RESULTS: LOH analysis on 10q21 in 52 HNSCC indicated distinctive and frequent allelic loss at D10S589 (42%). Among flanking genes, we found the RHOBTB1 gene as a candidate TSG, since an intragenic marker demonstrated the highest LOH (44%). Expression analysis revealed down-regulation of RHOBTB1 mRNA in 37% of tumors. Interestingly, all the five tumors that showed decreased expression of RHOBTB1 were accompanied with LOH, supporting the haploinsufficiency and class 2 TSG characteristics of RHOBTB1. No pathogenic mutation of RHOBTB1 was found. Furthermore, another gene within the region, EGR2, was also taken under scope. LOH frequencies around the EGR2 gene were relatively low (23 and 33%). Albeit semi-quantitative expression analysis of EGR2 demonstrated downregulation in 45% of tumor samples, no relation was found between the expression levels and LOH status. CONCLUSION: Frequent allelic loss and decreased expression of RHOBTB1 suggested that this gene has a role in tumorigenesis of a subset of HNSCC.

Base Sequence↗

PubMed2005

Adenocarcinoma ex pleomorphic adenoma of the head and neck: Report of five cases.

OBJECTIVE: Adenocarcinoma ex pleomorphic adenoma is a rare tumor, and thus the management of the tumor has not been established. METHODS: The retrospective review of the clinical records at Okayama University was performed. RESULTS: We present five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck, including a rare case with nasopharyngeal adenocarcinoma ex pleomorphic adenoma. There was no response to chemotherapy with nedaplatin and 5-FU, but the nasopharyngeal adenocarcinoma ex pleomorphic adenoma showed a remarkable regression after the administration of docetaxel. CONCLUSION: The combination therapy that includes docetaxel may be a promising treatment for adenocarcinoma ex pleomorphic adenoma of the head and neck.

Adenoma, Pleomorphic↗

PubMed2005

Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas.

We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer.

Carcinoma, Squamous Cell↗

PubMed2005

The engraftment of transplanted bone marrow-derived cells into the olfactory epithelium.

To investigate whether bone marrow cells migrate and are engrafted into the olfactory epithelium and differentiate into olfactory neurons, bone marrow cells of green fluorescence protein (GFP) mice were transplanted into lethally irradiated recipient mice. Immunohistochemical staining was performed to evaluate the engraftment of donor bone marrow cells into the olfactory epithelium. Immunostaining for GFP was found initially in the olfactory epithelium 2 weeks after bone marrow reconstruction. The percentage of GFP positive cells increased up to 12 months after bone marrow reconstruction. Double staining for GFP and olfactory marker protein showed that a population of the GFP-positive cells had characteristics of olfactory neurons. These results demonstrate that bone marrow cells can be engrafted in the olfactory epithelium and then differentiate into olfactory neuron cells.

Analysis of Variance↗

PubMed2005

Regeneration of rat auditory ossicles using recombinant human BMP-2/collagen composites.

Tympanoplasty operations to improve hearing impairment require a wide middle ear cavity and reconstruction of columellar formations. There is no specific material for use in the reconstruction of columellar formations. Tissue response to BMP has been employed as regenerative material. To our knowledge, however, there are no reports of the reconstruction of columellar formations using recombinant human bone morphogenetic protein-2/bovine collagen composites in the middle ear. The purpose of this study is to investigate whether recombinant human bone morphogenetic protein-2/bovine collagen composites (rhBMP-2 composites) are appropriate for use as regenerative material for tympanoplasty. In the form of pellets, rhBMP-2 composites were implanted as columellae into the tympanic cavity. At 2, 4, 6, 8, and 12 weeks after surgery, the middle ear of the animals (n = 4 at each week) was stained with hematoxylin-eosin for light microscopic observation. All composites were in the process of ossification or had ossified according to their developmental stages and were covered with a single layer of squamous or cuboidal epithelium. The new bone formed in these composites was persistently stable and displayed some columellar conditions assessed by histological examination. This study led to the conclusion that rhBMP-2 composites make excellent regenerative material for auditory ossicles.

Animals↗

PubMed2005

In vitro and in vivo suppression of GJB2 expression by RNA interference.

Mutations in GJB2 (gap junction protein, beta-2) are the major cause of autosomal recessive non-syndromic hearing loss. A few allele variants of this gene also cause autosomal dominant non-syndromic hearing loss as a dominant-negative consequence of expression of the mutant protein. Allele-specific gene suppression by RNA interference (RNAi) is a potentially attractive strategy to prevent hearing loss caused by this mechanism. In this proof-of-principle study, we identified a potent GJB2-targeting short interfering RNA (siRNA) to post-transcriptionally silence the expression of the R75W allele variant of GJB2 in cultured mammalian cells. In a mouse model, this siRNA duplex selectively suppressed GJB2(R75W) expression by >70% of control levels, thereby preventing hearing loss. The level of endogenous murine Gjb2 expression was not affected. Our data show that RNAi can be used with specificity and efficiency in vivo to protect against hearing loss caused as a dominant-negative consequence of mutant gene expression.

Animals↗

PubMed2005

RT-PCR analysis of Tecta, Coch, Eya4 and Strc in mouse cochlear explants.

Tecta, Coch, Eya4 and Strc are mouse orthologs of four human deafness-associated genes. Their expression is markedly restricted to specific cell types in cochleae. Cochleae were dissected on embryonic day 15 and cultured in vitro. Relative messenger RNA abundance of each gene was quantified by RT-PCR and compared in-vivo cochleae of equivalent embryonic age. After 48 h in culture, in-vivo and explant Strc expression levels were equivalent, Eya4 level reduced in explanted tissues, and expression of Tecta and Coch did not show the expected temporal rise. Expression of these genes was detectable even after 96 h. These results suggest that it is feasible to test the expression of inner ear specific genes in explanted cochleae.

Animals↗

PubMed2005

Immunosuppressive effect of restraint stress on the initiation of allergic rhinitis in mice.

BACKGROUND: Exposure to acute stressors modulates both innate and acquired immune function. However, little is known about whether stress has the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVES: To determine the effects of acute restraint stress on the initiation of allergic rhinitis in a murine model. METHODS: CBA/J mice were repeatedly intranasally sensitized with phospholipase A2 (PLA2) from honeybee venom without adjuvant. Restraint stress was applied using uniform cylinders once a week for a continuous 8-hour period, on five occasions in total. Production of PLA2-specific antibodies and degree of nasal and blood eosinophilia were compared between stressed and control mice. RESULTS: Repeated intranasal sensitization with PLA2 induced PLA2-specific IgE and marked eosinophilia in both the nose and blood in CBA/J mice. Exposure to restraint stress significantly inhibited production of PLA2-specific IgE, IgG1 and IgG2a. Conversely, the stress exerted no significant effect on eosinophilia. CONCLUSIONS: Exposure to acute restraint stress inhibits antigen-specific antibody production, but not local or systemic eosinophilia. The results of this study suggest that acute stress has the potential to modulate the initiation of allergic rhinitis.

Animals↗

PubMed2005

Quantitative study of the vestibular sensory epithelium in cochleosaccular dysplasia.

BACKGROUND: Cochleosaccular dysplasia is the most common pathologic finding seen in children with profound congenital sensorineural hearing loss. There has been no quantitative study on the peripheral vestibular system in cochleosaccular dysplasia. OBJECTIVE: To investigate quantitatively the extent of pathologic changes of the vestibular sensory epithelium in cochleosaccular dysplasia. SUBJECTS AND METHODS: Thirteen temporal bones with congenital deafness from 10 individuals were selected for this study from the temporal bone collection of University of Minnesota that showed suitable pathologic findings for the histopathologic criteria of cochleosaccular dysplasia. Age-matched normal control temporal bones were also selected. The vestibular hair cells including types I and II hair cells were counted separately in the saccular macula, utricular macula, and three cristae of the semicircular canals using Nomarski microscopy. RESULTS: The hair cell densities of types I and II hair cells in the macula of the saccule in cochleosaccular dysplasia were significantly decreased compared with the data of normal subjects. Both types I and II hair cells in the utricular macula and the cristae of the three semicircular canals in cochleosaccular dysplasia were well preserved, and no significant difference was observed between findings of cochleosaccular dysplasia and normal controls in the utricle and the three semicircular canals. CONCLUSIONS: In cases with cochleosaccular dysplasia, the neurosensorial hair cells of the saccule were affected; however, the osseous labyrinth, the membranous utricle, and the semicircular canals were normal. Further studies should be performed to establish the pathogenesis of cochleosaccular dysplasia in humans.

Adolescent↗

PubMed2005

Genetic and epigenetic alterations of BRG1 promote oral cancer development.

Loss of heterozygosity (LOH) analysis is a sensitive method to detect deletions of specific chromosome regions which are considered to harbor of putative tumor suppressor gene (TSG)s. Previous allelotype analyses in various human cancers suggested the presence of at least one TSG in chromosome 19p13 region. Functional analysis of BRG1, a member of SWI/SNF complex proteins, located at 19p13.2, suggested it to be a candidate TSG in different types of human cancers. We examined LOH at 19p13 region in 39 oral cancers by using six microsatellite markers and found allelic deletion in 25 of 39 (64%) samples. A microsatellite marker near BRG1 locus showed the highest LOH in tumor samples. To clarify the role of BRG1 gene in oral carcinogenesis, we checked its mutation status in tumor samples. As mutation of the BRG1 gene was not detected in oral cancers, we examined the mRNA expression level. Quantitative RT-PCR analysis surprisingly demonstrated increased expression of BRG1 mRNA in 62% of primary tumors as compared with that of matched normal samples. Since functions of BRG1 and BRM, another member of SWI/SNF highly homologous to BRG1, may be interrelated, we also examined BRM mRNA expression in the same samples. In most samples, the expressions of BRG1 and BRM changed in the same direction consistent with reported data on human cancer cell lines. An important finding is that expression of an alternative in frame splicing form of BRG1 which includes exon 26 is selectively decreased or lost in most tumor samples. This unique 33 amino-acid sequence of BRG1 protein shows very high homology with heterogeneous nuclear ribonucleoprotein E and may affect the function and level of BRG1 through modifications on post-transcriptional control. All these findings suggest that the genetic and epigenetic alterations of BRG1 may have a role in oral cancer development.

Alternative Splicing↗

PubMed2004

A novel laser-assisted stapedotomy technique for congenital stapes fixation.

OBJECTIVE: To investigate whether a novel laser-assisted stapedotomy technique is effective in treating congenital stapes fixation. METHODS: With this surgical method, the suprastructure of the stapes is vaporized continuously from the superior half of the anterior crus to the inferior part of the posterior crus using a potassium-titanyl-phosphate (KTP) laser. The midmost point of the vaporization is the head of the stapes. This method was used to treat three patients with congenital stapes fixation (total of four ears). RESULTS: The average hearing gain using this method was 32.2 dB, which lasted for at least 1 year. No complications were observed. CONCLUSIONS: This novel laser-assisted stapedotomy technique is an excellent method for the treatment of congenital stapes fixation.

Adolescent↗

PubMed2004

Long-term results of tonsillectomy as a treatment for IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis with IgA deposits present mainly in the mesangial areas. We performed a 10-year retrospective case-control study of 71 patients with IgAN to evaluate the long-term effects and prognostic factors associated with tonsillectomy. Forty-one patients (19 males and 22 females) underwent tonsillectomy (Group A) and 30 patients (13 males and 17 females) did not (Group B). These patients were followed for more than 10 years after renal biopsy. The average age at initial renal biopsy was 29.78 years in Group A and 33.0 years in Group B. The average follow-up period was 13 years and 3 months in Group A, and 12 years and 7 months in Group B. Glomerular damage demonstrated on renal biopsy was more extensive in Group A than in Group B. Prognosis after 10 years of follow-up was compared between the two groups. The clinical remission rate was 24.4% in Group A and 13.3% in Group B, the stable renal function rate was 82.9% in Group A and 70.0% in Group B, and the renal survival rate was 95.1% in Group A and 73.3% in Group B. The renal survival rate in Group A was significantly higher than that in Group B (p <0.05). Although evaluation of renal pathology based on renal biopsy was useful in predicting the long-term effects of tonsillectomy in IgAN patients, the results of tonsillar provocation tests were not.

Adolescent↗