Chondrosarcoma of the nasal septum: A case report.

Chondrosarcoma make up only 10-20% of malignant primary bone tumors, with 5-10% located in the head and neck (Downey TJ, Clark SK, Moore DW. Chondrosarcoma of the nasal septum. Otolaryngol Head Neck Surg 2001;125:98-100), and nasal septal chondrosarcoma is extremely rare. Surgical excision is the only curative treatment and radiation and chemotherapy have a limited role for palliation. We used a navigation system in endoscopic surgery without complications for a case of chondrosarcoma of the nasal septum by means of a midfacial degloving approach at primary operation and an external incision approach at salvage operation for local recurrence. To our knowledge, this is the first report of the use of such a system for this surgical approach along with a salvage operation. We discuss the clinical presentation, diagnosis, and treatment of this case as well as present a review of the literature.

Differences in the expression of genes between normal tissue and squamous cell carcinomas of head and neck using cancer-related gene cDNA microarray.

CONCLUSION: This study clearly showed the molecular characteristics of head and neck squamous cell carcinoma (HNSCC) on the basis of gene expression patterns. OBJECTIVE: cDNA microarray has recently been shown to have the ability to represent the expression patterns of large numbers of genes from a small amount of tissue, potentially enabling definition of groups of patients with similar biological behavior of cancer. Although gene expression profiling using this technique has proven helpful for predicting the prognosis in various cancers, little is known regarding HNSCC. The aim of this study was to investigate the differences in the expression of various genes between normal tissue and cancers of patients with HNSCC by cDNA microarray. PATIENTS AND METHODS: We extracted mRNA from 17 HNSCC patients and used cDNA microarray analysis to investigate the gene expression patterns. The present study was not designed to perform an inclusive search for genes but rather to focus on cancer-related genes. RESULTS: Seven independent genes were found to be up-regulated in cancer tissues: matrix metalloproteinase-1, -3, and -10, interleukin-8, cadherin 3, hexabrachion, and interferon gamma-inducible protein 10. Hyaluronic acid-binding protein 2, keratin 4, and keratin 13 were categorized as down-regulated. The hierarchical clustering and dendrogram for 17 cancer samples and 425 genes could be grouped into three clusters.

Mutation analysis of COL9A3, a gene highly expressed in the cochlea, in hearing loss patients.

cDNA microarray analysis indicated that COL9A3 is one of the highly expressed genes in the cochlea. This suggests that collagen type IX has a crucial functional role in the inner ear and may be a candidate gene for hearing loss. Mutation analysis was carried out to find possible disease-causing mutations in this gene. The direct-sequencing method was applied to the COL9A3 gene in 159 non-syndromic sensorineural deafness patients and 150 normal controls. Two possible disease-causing mutations were identified: an in-frame deletion of three amino acid residues (G181-P183 del) and a missense mutation (D617E). The patients with the mutations showed a moderate progressive bilateral sensorineural hearing impairment in all frequencies. The present data indicate that mutations of COL9A3 may cause non-syndromic hearing impairment.

Genetic features, clinical phenotypes, and prevalence of sensorineural hearing loss associated with the 961delT mitochondrial mutation.

To examine the frequency of the 961delT mitochondrial point mutation, considered to be associated with aminoglycoside-induced hearing loss, restriction fragment length polymorphism (RFLP) analysis was performed in (1) 334 unrelated sensorineural hearing loss (SNHL) patients and (2) 56 patients with aminoglycoside antibiotic injection history. Approximately 2% of the SNHL patients had the 961delT mutation, raising the possibility of a relatively high prevalence of this mutation among hearing impaired populations. However, the following findings cast doubt on whether this mutation is truly associated with hearing loss: (1) a similar frequency found in the control subjects, (2) hearing loss that was not segregated within the families, (3) rates of heteroplasmy and aging that were not correlated with the severity of hearing loss, and (4) a low prevalence among the aminoglycoside-induced hearing loss patients (1/56=1.8%). The present analysis did not agree with the concept that the 961delT mutation causes aminoglycoside-induced hearing loss.

Type IX collagen knock-out mouse shows progressive hearing loss.

Type IX collagen is one of the important components, together with type II, V, and XI collagens, in the tectorial membrane of the organ of Corti. To confirm the significance of type IX collagen for normal hearing, we assessed the detailed morphological and electrophysiological features of type IX collagen knock-out mice, which have recently been reported as a deafness model. Through assessment by auditory brainstem response (ABR), knock-out mice were shown to have progressive hearing loss. At the light microscopic level, the tectorial membrane of knock-out mice was found to be abnormal in shape. These morphological changes started in the basal turn and were progressive toward the apical turn. Electron microscopy confirmed disturbance of organization of the collagen fibrils. These results suggest that mutations in type IX collagen genes may lead to abnormal integrity of collagen fibers in the tectorial membrane.

Identification of differentially expressed genes in salivary gland tumors with cDNA microarray.

OBJECTIVE: The final goal of this study is to develop a pre-operative fine needle aspiration biopsy (FNA) diagnostic system based on gene expression profiles. As the first step to that end, the present study was performed to determine whether the cDNA microarray system is applicable for histological evaluation of parotid gland tumors. METHODS: We investigated molecular characteristics on the basis of gene expression patterns of the two most common types of salivary gland tumors (pleomorphic adenomas and Warthin tumors) and normal salivary gland tissues, using the cDNA microarray system. RESULTS: Pleomorphic adenomas and Warthin tumors can be classified by cDNA microarray. In pleomorphic adenomas, 11 independent genes were found to be up-regulated and 2 genes were down-regulated. In Warthin tumors, five independent genes were found to be up-regulated, and six genes were down-regulated. In hierarchical clustering analysis, cases were further grouped into two clusters according to the histological type. Furthermore, cDNA microarray enabled pleomorphic adenomas to be subclassified into three clusters according to the histological subtypes. CONCLUSIONS: This study suggested that cDNA microarray may be useful and applicable for the pre-operative diagnosis (such as FNA) of the salivary gland tumor.

Deafness due to A1555G mitochondrial mutation without use of aminoglycoside.

OBJECTIVES/HYPOTHESIS: The objective was to clarify the characteristics of deafness associated with the A1555G mutation within mitochondrial 12S ribosomal RNA gene in the absence of aminoglycoside exposure. STUDY DESIGN: Clinical and genetic studies in family members with the A1555G mitochondrial mutation were performed. METHODS: The subjects were 123 maternally related members of a large Japanese family with the A1555G mutation. All subjects had no previous history of exposure to aminoglycosides. Hearing disability and handicap, tinnitus, and medical histories were analyzed by interviews in all of the subjects, genetic testing was performed in 41 subjects, and pure-tone audiometry was conducted in 26 subjects with hearing disability and handicap. RESULTS: The A1555G mutation was detected in a homoplasmic form (meaning that all the mitochondrial DNA carries the mutation) in all 41 subjects who were screened. The risk for developing postlingual hearing loss was likely to be much higher in the present subjects than in the general population. Both the severity and age at onset of the phenotype were similar in affected subjects within the same sibling group. Pure-tone averages were significantly worse in subjects who developed hearing loss before age 10 years than in those who developed hearing loss later. CONCLUSION: The present study demonstrated that the prevalence of deafness in individuals with the A1555G mitochondrial mutation was likely to be high even in the absence of aminoglycoside exposure and clearly showed the association of severe to profound hearing loss with the onset of hearing loss before age 10 years.

[Overexpression of thymosin beta4 in the cochlea of senescence-accelerated mouse].

OBJECTIVE: To develop gene expression profiles of young and old senescence-accelerated mouse (SAM) cochlea and identify genes responsible for aging-related hearing loss. METHODS: Gene micro-array slides containing 1101 mouse genes were hybridized to cDNA micro-arrays (Atlas Glass Array Mouse 1.0) that were synthesized using total RNAs from the cochlea of 2 mounts and 12 mounts mouse. Hybridization signals were visualized with cyanine-3 fluorescent reporter molecules, and the fluorescence intensities of the images were analyzed. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to validate the micro-array results. Immunofluorescence was used to identify the located region of the protein encoding by the candidate gene in the cochlea. RESULTS: Expression of a majority of the 1101 genes represented on the micro-array slides was not altered during aging; nonetheless, changes in the expression of 3 genes were detected between young and old mouse cochlea. RT-PCR results confirmed the changes in expression of thymosin beta4 of 3 genes examined. Through the using of immunofluorescence, it was shown that thymosin beta4 was primarily located in the tectorial membrane and the supporting cells of outer hair cell. CONCLUSIONS: Using commercially available slide micro-arrays, the results show that aging of the mouse cochlea is associated with changes in patterns of gene expression. This analysis suggests that thymosin beta4 may play a role in aging-related hearing loss. These studies lay the foundation for future studies defining the genetic basis of aging-related hearing loss.

Molecular diagnosis of deafness: impact of gene identification.

Recent progress in identifying genes responsible for hearing loss enables the ENT clinician to apply molecular diagnosis by genetic testing. This article focuses on three genes, which are prevalent and therefore commonly encountered in the clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene responsible for congenital hearing loss in many countries. A series of reports revealed that different combinations of GJB2 mutations exist in different ethnic populations, indicating that ethnic background should be considered when performing genetic testing. GJB2 mutations will be of particular interest in combination with universal infant hearing screening programs, because it has been shown that early identification of hearing loss and early intervention are crucial for language development. Progress in genetic analysis has changed the concept of diseases. The present review introduces the example of two historically distinct categories of disease, Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, which are currently considered to be a continuum of diseases caused by the same gene, PDS. This review also emphasizes that some hearing impairment can be prevented. The 1555A-->G mitochondrial mutation, the most prevalent mitochondrial mutation found in the hearing-impaired population, was found in approximately 3% of the outpatients. The 1555A-->G mutation is known to be associated with a susceptibility to aminoglycoside antibiotics. There may be a considerably large high-risk population and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended.