Biomedical subjects

Kunihiro Fukushima

Publications and source records attributed to Kunihiro Fukushima.

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

Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancer.

We analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.

Carcinoma, Squamous Cell↗

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↗

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

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

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

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↗

PubMed2005

Fine deletional mapping of chromosome 4q22-35 region in oral cancer.

We analyzed the loss of heterozygosity of the long arm of chromosome 4 in 40 oral cancers, using 16 microsatellite markers based on data from the human genome sequence, and defined the deletional mapping of the region with putative tumor suppressor genes. Our data revealed two distinct commonly deleted regions around the markers, D4S2623 and D4S1644, with an allelic deletion of 44 and 39%, respectively. Additional mapping and use of the markers near one of these hot spots narrowed down the minimally deleted region about 1.5 Mbp around the marker, D4S2623. Caspase 6 is localized 280 kb from the marker, D4S2623. Fine mapping of this region with possible tumor suppressor gene suggests caspase 6 as a putative tumor suppressor gene. Further molecular analysis of caspase 6 should be performed to clarify its role in oral carcinogenesis.

Alleles↗

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↗

PubMed2003

Language development of a multiply handicapped child after cochlear implantation.

The presence of additional handicaps in hearing-impaired children makes the prediction of language ability after cochlear implantation unreliable. Only limited follow-up data on developmental improvement after implantation among multiply handicapped children is available. The present study reports the course of development (audiological and linguistic) after cochlear implantation in one subject with moderate mental retardation. Preoperatively, his language development showed 34 months delay when compared to chronological age. The difference had shortened to 23 months by 2 years post-surgery. The subject's cognitive delay had not changed upon 2-year follow-up. The cochlear implant can be credited to his improvement in language development.

Child↗

PubMed2003

Monosyllable speech perception of Japanese hearing aid users with prelingual hearing loss: implications for surgical indication of cochlear implant.

OBJECTIVE: The monosyllable speech perception ability after years of educational intervention was compared between prelingually deafened pediatric hearing aid users and their cochlear implant counterparts. DESIGN: An open-set monosyllabic speech perception test was conducted on all subjects. The test required subjects to indicate a corresponding Japanese character to that spoken by the examiner. Fifty-two subjects with prelingual hearing impairment (47 hearing aid users and 5 cochlear implant users) were examined. RESULTS: Hearing aid users with average pure-tone thresholds less than 90 dB HL demonstrated generally better monosyllable perception than 70%, which was equivalent or better performance than that of the cochlear implant group. Widely dispersed speech perception was observed within the 90-99 dB HL hearing-aid user group with most subjects demonstrating less than 50% speech perception. In the cluster of >100 dB HL, few cases demonstrated more than 50% in speech perception. The perception ability of the vowel part of each mora within the cochlear implant group was 100% and corresponding to that of hearing aid users with moderate and severe hearing loss. CONCLUSION: Hearing ability among cochlear implant users can be comparable with that of hearing aid users with average unaided pure-tone thresholds of 90 dB HL, after monosyllabic speech perception testing was performed.

Adolescent↗

PubMed2003

Deletion mapping of split hand/split foot malformation with hearing impairment: a case report.

Split hand/split foot malformation (SHFM), which typically appears as lobster-like limb malformation, is a rare clinical condition caused by a partial deletion of chromosome 7q. Hearing impairment sometimes accompanies syndromic SHFM cases; a case of inner and middle ear malformation with SHFM is described in this report. We conducted a genetic evaluation of this patient and found a deleted region that overlaps a previously reported locus of SHFM as well as a DFNB14 locus that can cause nonsyndromic hearing impairment by autosomal recessive inheritance.

Abnormalities, Multiple↗