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1.
Acta Otolaryngol ; 136(11): 1154-1158, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27295405

ABSTRACT

CONCLUSION: The 3-year progression-free survival rate of non-invasive salivary duct carcinoma (SDC) or adenocarcinoma not otherwise specified (NOS) was significantly better than that of invasive SDC or adenocarcinoma NOS in Carcinoma ex pleomorphic adenoma (CXPA). The presence of invasion is an important prognostic factor for SDC and adenocarcinoma NOS in CXPA. OBJECTIVES: CXPA is a rare parotid gland malignant tumor for which therapy is not yet standardized. The purpose of this study was to review the characteristics of CXPA patients and to analyze their outcomes in the Northern Japan Head and Neck Cancer Society. METHOD: The medical records of 33 patients who had been provided initial treatment in 12 institutes of northern Japan from 2002-2011 were reviewed as a multi-institutional retrospective study. RESULTS: The 3-year overall and progression-free survival rate of all patients was 79.9% and 76.8%, respectively. Both the 3-year overall and progression-free survival rates were 87.5% for patients with non-invasive SDC or adenocarcinoma NOS. The 3-year overall and progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS were 60.4% and 30.5%, respectively. The progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS was significantly poor (p < 0.05).


Subject(s)
Adenoma, Pleomorphic/pathology , Carcinoma/pathology , Parotid Gland/pathology , Parotid Neoplasms/pathology , Adenoma, Pleomorphic/mortality , Adult , Aged , Aged, 80 and over , Carcinoma/mortality , Female , Humans , Japan/epidemiology , Male , Middle Aged , Parotid Neoplasms/mortality , Retrospective Studies
2.
Case Rep Neurol ; 6(2): 161-5, 2014 May.
Article in English | MEDLINE | ID: mdl-24932177

ABSTRACT

Cerebral venous thrombosis as a manifestation of paraneoplastic angitis and otitis media, revealing non-Hodgkin B-cell lymphoma (NHBL), is extremely rare. A 57-year-old woman presented with headache, auditory disturbance and recalcitrant otitis media. Magnetic resonance imaging showed brain edema in the temporal lobe and transverse sinus thrombosis. External drainage under antibiotic treatment was repeated based on a diagnosis of invasive otitis media and mastoiditis associated with infectious sinus thrombosis, but the condition deteriorated progressively. Open surgery for otitis media was performed 6 years after the initial symptoms and after a tumorous lesion had been detected in the middle ear. Pathological findings revealed NHBL. We report a rare case of NHBL presenting as otitis media and mastoiditis associated with sinus thrombosis, and a literature review.

4.
Pflugers Arch ; 465(7): 1041-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23417602

ABSTRACT

Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by MßCD or water-soluble cholesterol affect the stiffness, capacitance, motility, and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. Membrane capacitance of isolated guinea pig OHCs were assessed using a two-sine voltage stimulus protocol superimposed onto a voltage ramp (200 ms duration) from -150 to +140 mV. One group of OHCs was treated with 100 µM guanosine 5'-O-(3-thiotriphosphate) tetralithium salt (GTPγS), the GTP analog, administrated into individual cells via patch pipettes. Another group of OHCs was internally perfused with 600 µM guanosine 5'-(ß-thio) diphosphate trilithium salt (GDPßS), the GDP analog. A third group was perfused with internal solution only as a control. Application of 1 mM MßCD shifted non-linear capacitance curves to the depolarized direction of the control group with reduction of the peak capacitance (C mpeak). After the 10-min application of MßCD, shifts of voltage at C mpeak (V cmpeak) and reduction of C mpeak were 73.32 ± 11.09 mV and 9.09 ± 2.10 pF, respectively (n = 4). On the other hand, in the GTPγS-treated group, the shift of V cmpeak and reduction of C mpeak were attenuated remarkably. The shift of V cmpeak and reduction of C mpeak in the 10-min application of MßCD were 9.73 ± 10.92 mV and 3.08 ± 1.91 pF, respectively (n = 7). MßCD decreased the cell length by 16.53 ± 4.27 % in the control group and by 6.45 ± 6.22 % in the GTPγS group. In addition, we investigated the effects of GDPßS on cholesterol-treated OHCs. One millimolar cholesterol was externally applied after the 4-min application of 1 mM MßCD because the shift of V-C m function caused by cholesterol alone was small. Application of cholesterol shifted V-C m curves of the control group to the hyperpolarized direction with increase of the C mpeak. After the 10-min application of cholesterol, changes of V cmpeak and C mpeak were -9.19 ± 6.68 mV and 2.14 ± 0.44 pF, respectively (n = 4). On the other hand, in the GDPßS-treated OHCs, the shift of V cmpeak and increase of C mpeak were attenuated markedly. The shift of V cmpeak and increase of C mpeak after 10 min were 5.13 ± 10.46 mV and -0.55 ± 1.39 pF, respectively (n = 6). This study demonstrated that internally perfused GTPγS inhibited the MßCD effects and GDPßS inhibited the cholesterol effects, raising the possibility that G proteins may be involved in outer hair cell homeostasis as well as the possibility that cholesterol response may be G protein mediated. More study is required to clarify the detailed role of G proteins in the relation between cholesterol and the OHC cytoskeleton.


Subject(s)
Cholesterol/metabolism , GTP-Binding Proteins/metabolism , Hair Cells, Auditory, Outer/metabolism , Animals , Cell Membrane/drug effects , Cell Membrane/metabolism , Cholesterol/pharmacology , Guanosine 5'-O-(3-Thiotriphosphate)/analogs & derivatives , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology , Guinea Pigs , Hair Cells, Auditory, Outer/drug effects , Hair Cells, Auditory, Outer/physiology , Membrane Potentials/drug effects , beta-Cyclodextrins/pharmacology
5.
Acta Otolaryngol ; 132(8): 838-44, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22667462

ABSTRACT

CONCLUSION: We investigated the localization of periostin in middle ear specimens from patients with eosinophilic otitis media (EOM) and from a newly constructed animal model for EOM. Periostin-positive immunostaining was observed in the middle ear sections obtained from the EOM patients. Immunoreactivity for periostin was also seen in the animal model. These results suggest that periostin plays an important role in subepithelial fibrosis in the middle ear in EOM. OBJECTIVE: The purpose of the present study was to investigate the role of periostin in the middle ear of EOM patients and an animal model. METHODS: Histological and immunohistochemical analyses for periostin were carried out in the middle ear specimens of six EOM patients with/without asthma. An animal model of EOM was constructed by intraperitoneal and topical sensitization with ovalbumin (OVA). Histological and immunocytochemical analyses for periostin were also performed in this model. RESULTS: Immunoreactivities for periostin were observed in the basement membrane and extracellular matrix of the middle ear sections obtained from all EOM patients with/without asthma. In the animal model, eosinophil infiltration and middle ear mucosa thickness were observed. Moreover, periostin-positive immunostaining was shown in the extracellular matrix of the middle ear mucosa on the side topically boosted by OVA.


Subject(s)
Cell Adhesion Molecules/metabolism , Eosinophilia/metabolism , Eosinophils/metabolism , Otitis Media/metabolism , Adult , Aged , Animals , Basement Membrane/metabolism , Disease Models, Animal , Eosinophilia/pathology , Eosinophils/pathology , Female , Guinea Pigs , Humans , Immunohistochemistry , Male , Middle Aged , Otitis Media/pathology
6.
Acta Otolaryngol ; 132(7): 686-92, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22497451

ABSTRACT

CONCLUSION: The excessive glutamate released from the type I and type II hair cells and the supporting cells injure the bouton-type endings and the nerve chalices in 30 min ischemia, and neuronal damage of glutamate was slight in 10 min ischemia. OBJECTIVE: In the present study, we investigated by means of post-embedding immunoelectron microscopic analysis whether neuronal damage in the vestibular end organs is associated with the change of cellular glutamate concentration during ischemia. METHODS: Transient local anoxia (10 min, 30 min) of guinea pig inner ear was induced by pressing the left labyrinthine artery. The right sides were used as controls. The morphological changes of the vestibular end organs and the areal gold particle densities representing glutamate were compared in the ischemia side and the control side. RESULTS: The areal gold particle densities of the type I and type II hair cells and the supporting cells in the ischemic side were lower than those of the control side. There were no remarkable morphological changes compared to the control side in 10 min ischemia. In 30 min ischemia, the bouton-type endings were swollen and intercellular spaces between the type I hair cells and the nerve chalices were enlarged.


Subject(s)
Glutamic Acid/metabolism , Hair Cells, Auditory, Inner/pathology , Ischemia/metabolism , Presynaptic Terminals/pathology , Vestibule, Labyrinth/metabolism , Vestibule, Labyrinth/pathology , Animals , Disease Models, Animal , Guinea Pigs , Hair Cells, Auditory, Inner/metabolism , Ischemia/etiology , Ischemia/pathology , Microscopy, Immunoelectron , Presynaptic Terminals/metabolism , Risk Factors , Time Factors , Vestibule, Labyrinth/blood supply
7.
Ann Gen Psychiatry ; 10(1): 27, 2011 Oct 01.
Article in English | MEDLINE | ID: mdl-21961439

ABSTRACT

BACKGROUND: Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population. METHODS: A pure-tone average (0.5-2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women). We also administered the Mini-Mental State Examination (MMSE), the Center for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear regression analysis assessed the association between hearing impairment and mental correlates. RESULTS: The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF) and role emotional (RE) scores of the SF-36v2. CONCLUSIONS: Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients.

8.
Audiol Neurootol ; 16(3): 191-7, 2011.
Article in English | MEDLINE | ID: mdl-20962524

ABSTRACT

OBJECTIVE: Intratympanic (IT) steroid therapy has been proposed as an alternative treatment option for patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, the number and frequency of IT treatments and drug delivery methods remain to be determined. The purpose of this study was to evaluate the efficacy of daily short-term IT dexamethasone (DEX) treatment alone in ISSNHL patients using laser-assisted myringotomy (LAM) for the drug delivery route as an initial and/or salvage treatment. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Seventy-six ISSNHL patients receiving IT DEX. Patients with low-tone hearing loss, unilateral or bilateral fluctuating hearing loss or contralateral hearing loss were excluded. INTERVENTION: DEX (4 mg/ml) was injected through a perforation made by LAM. IT DEX administration was performed on 8 sequential days. MAIN OUTCOME MEASURES: Pre- and postprocedure hearing levels. The average hearing level was determined by 5 frequencies (250, 500, 1000, 2000 and 4000 Hz). RESULTS: Nineteen out of 76 patients fit the criteria for initial treatment in the study (group I), while 24 patients, who had failed systemic therapy, received salvage treatment (group S). The mean age of the patients in groups I and S was 56.2 years with a range from 31 to 73 years of age and 46.0 years with a range from 11 to 76 years of age, respectively. The mean number of days from onset of symptoms to IT therapy in groups I and S was 4.8 days with a range of 1-23 days and 15.3 days with a range of 6-28 days, respectively. In group I, 18 of the 19 patients (95%) showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 40 dB. Twelve patients (63%) recovered completely and 16 patients (84%) demonstrated successful results with an improvement of more than 30 dB. In group S, 14 of the 24 patients (58%) showed improvement of more than 10 dB with a mean improvement of 16 dB. Two (8%) of the 7 patients (29%) with successful results recovered completely. CONCLUSIONS: Daily short-term IT DEX administration using LAM for ISSNHL patients without concurrent therapy showed a high response rate and high cure rate and proved to be an alternative therapeutic option to high-dose systemic steroids as a first- and/or second-line treatment.


Subject(s)
Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/drug therapy , Adolescent , Adult , Aged , Audiometry, Pure-Tone , Child , Dexamethasone/administration & dosage , Female , Glucocorticoids/administration & dosage , Humans , Injections , Male , Middle Aged , Retrospective Studies , Salvage Therapy , Treatment Outcome , Tympanic Membrane
9.
BMC Cancer ; 9: 72, 2009 Feb 27.
Article in English | MEDLINE | ID: mdl-19250538

ABSTRACT

BACKGROUND: Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIalpha (topoIIalpha), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication. The purpose of this study was to evaluate the expression of topoIIalpha in various types of salivary gland tumors and its biological significance. METHODS: The protein expression of topoIIalpha was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tissue from 54 salivary gland carcinomas and 20 benign tumors (10 pleomorphic adenomas and 10 Warthin's tumors). The primary salivary gland carcinoma specimens consisted of 17 adenoid cystic carcinomas, 7 adenocarcinomas not otherwise specified, 7 mucoepidermoid carcinomas, 6 salivary duct carcinomas, 3 acinic cell carcinomas, 3 carcinomas ex pleomorphic adenomas, 3 epithelial-myoepithelial carcinomas, 2 carcinosarcomas, 2 lymphoepithelial carcinomas, 2 myoepithelial carcinomas, 1 oncocytic carcinoma, and 1 squamous cell carcinoma. The associations between clinicopathological factors and outcome were analyzed. RESULTS: Of the 54 primary salivary gland carcinomas, 38 (70%) showed positive expression (> or = 10%) of topoIIalpha protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIalpha was more frequently observed in salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, and adenoid cystic carcinoma, solid type, and it was associated with advanced stage and shortened survival. CONCLUSION: The results of the present study suggest that topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.


Subject(s)
Antigens, Neoplasm/biosynthesis , DNA Topoisomerases, Type II/biosynthesis , DNA-Binding Proteins/biosynthesis , Salivary Gland Neoplasms/enzymology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Adenoid Cystic/enzymology , Carcinoma, Adenoid Cystic/pathology , Child , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Salivary Gland Neoplasms/pathology , Survival Rate , Young Adult
10.
Gan To Kagaku Ryoho ; 36(2): 237-40, 2009 Feb.
Article in Japanese | MEDLINE | ID: mdl-19223737

ABSTRACT

A study of chemotherapy treatment with S-1 in patients with head and neck cancer was conducted in 20 patients with residual tumor after primary chemoradiotherapy, or recurrent tumors. Treatment courses consisted of oral administration of S-1 at a dose of 80 to 120 mg/day depending on the body surface area for 14 consecutive day followed by a 7- day rest period. The response rate in patients with residual tumors after primary chemoradiotherapy was 55.6%(5/9). In patients with recurrent tumors, the response rate was 0%(0/11), however, median survival time was 534.5 days. Therefore, S-1 seemed to be useful for the treatment of patients with head and neck cancer from the point of QOL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Combinations , Female , Head and Neck Neoplasms/diagnostic imaging , Humans , Male , Middle Aged , Oxonic Acid/adverse effects , Tegafur/adverse effects , Tomography, X-Ray Computed , Treatment Outcome
11.
BMC Cancer ; 8: 348, 2008 Nov 26.
Article in English | MEDLINE | ID: mdl-19036131

ABSTRACT

BACKGROUND: Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC). METHODS: An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated in vitro. In addition, the in vivo effect of TS siRNA on tumor progression was assessed using a xenograft model. RESULTS: Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model. CONCLUSION: TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.


Subject(s)
Carcinoma, Adenoid Cystic/pathology , RNA Interference , RNA, Small Interfering/pharmacology , Thymidylate Synthase/genetics , Acetyltransferases/metabolism , Animals , Blotting, Western , Carcinoma, Adenoid Cystic/enzymology , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/therapy , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Female , Gene Expression , Humans , Mice , Mice, Nude , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays
12.
Otol Neurotol ; 29(6): 791-5, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18725860

ABSTRACT

OBJECTIVE: Office treatment for chronic tympanic membrane (TM) perforations has limitations, and alternative methods to myringoplasty are sometimes needed. Serum lacks antigenicity and contains a large variety of growth factors known to modulate proliferation of various tissues to promote wound healing effects. Our purpose was to evaluate the feasibility of autologous serum eardrops therapy with a chitin membrane for closing TM perforations. INTERVENTION: In the outpatient clinic, the perforation margin was cauterized with silver nitrate, and the perforation was covered with a chitin membrane. Patients were instructed to apply autologous serum eardrops daily. Patients were examined every 2 weeks, and the procedure was repeated. RESULTS: We treated 19 sequential patients with chronic TM perforation in 1 ear between October 2005 and September 2007. Closure of the TM was achieved in 11 (58%) of 19 ears, and reduction of the perforation size was observed in 2 ears (11%). Closure rates for small, medium, and large perforations were 57 (8 of 14), 0 (0 of 1), and 75% (3 of 4), respectively. Closure rates for perforations attributable to intratympanic dexamethasone treatment, after myringoplasty and chronic otitis media were 67 (2 of 3), 67 (2 of 3), and 54% (7 of 13), respectively. Time for closure took from 15 to 175 days, with an average of 68 days (5.9 clinic visits). During autologous serum eardrop therapy with a chitin membrane, no remarkable side effects in the treated ears were observed. Measurement of the concentration of the epidermal growth factor, transforming growth factor beta1, fibronectin, and interleukin 6 in the serum showed no decrease in 14 days, suggesting activity remained stable in that period. CONCLUSION: Autologous serum eardrops therapy with a chitin membrane, which requires no surgical intervention, was found to be a promising office-based technique for the closure of chronic TM perforations because of its ease, safeness, and feasibility. However, additional studies are needed to independently analyze the specific benefits of the serum drops and the chitin membrane.


Subject(s)
Chitin/therapeutic use , Tympanic Membrane Perforation/therapy , Administration, Topical , Adolescent , Aged , Chitin/administration & dosage , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Epidermal Growth Factor/blood , Female , Fibronectins/blood , Humans , Interleukin-6/blood , Male , Middle Aged , Polymers/administration & dosage , Polymers/therapeutic use , Serum , Transforming Growth Factor beta1/blood , Young Adult
13.
Cancer Sci ; 98(6): 890-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17428261

ABSTRACT

The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, also called statins, are commonly used as lipid-lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell-extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose-dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. The expression of beta1-integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up-regulation of cell cycle regulators and apoptosis-inducing factors and the down-regulation of integrin-associated molecules and cell proliferation markers. Of down-regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells.


Subject(s)
Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Integrin beta1/metabolism , Simvastatin/pharmacology , Anticholesteremic Agents/pharmacology , Carcinoma, Squamous Cell , Caspase 3/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Focal Adhesion Kinase 1/metabolism , G1 Phase/drug effects , Humans , Mevalonic Acid/administration & dosage , Mevalonic Acid/pharmacology , Neoplasm Invasiveness/prevention & control , Phosphorylation , Signal Transduction , Simvastatin/administration & dosage , Tumor Cells, Cultured
14.
J Membr Biol ; 215(1): 49-56, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17415610

ABSTRACT

The development of motor protein activity in the lateral membrane of the mouse outer hair cell (OHC) from postnatal day 5 (P5) to P18 was investigated under whole-cell voltage clamp. Voltage-dependent, nonlinear capacitance (C (v)), which represents the conformational fluctuations of the motor molecule, progressively increased during development. At P12, the onset of hearing in the mouse, C (v) was about 70% of the mature level. C (v) saturated at P18 when hearing shows full maturation. On the other hand, C (lin), which represents the membrane area of the OHC, showed a relatively small increase with development, reaching steady state at P10. This early maturation of linear capacitance is further supported by morphological estimates of surface area during development. These results, in light of recent prestin knockout experiments and our results with quantitative polymerase chain reaction, suggest that, rather than the incorporation of new motors into the lateral membrane after P10, molecular motors mature to augment nonlinear capacitance. Thus, current estimates of motor protein density based on charge movement may be exaggerated. A corresponding indicator of motor maturation, the motor's operating voltage midpoint, V (pkcm), tended to shift to depolarized potentials during postnatal development, although it was unstable prior to P10. However, after P14, V (pkcm) reached a steady-state level near -67 mV, suggesting that intrinsic membrane tension or intracellular chloride, each of which can modulate V (pkcm), may mature at P14. These developmental data significantly alter our understanding of the cellular mechanisms that control cochlear amplification and provide a foundation for future analysis of genetic modifications of mouse auditory development.


Subject(s)
Gene Expression Regulation, Developmental/physiology , Hair Cells, Auditory, Outer/metabolism , Molecular Motor Proteins/biosynthesis , Molecular Motor Proteins/genetics , Proteins/genetics , Proteins/metabolism , Animals , Mice , Mice, Inbred C57BL , Molecular Motor Proteins/chemistry , Molecular Motor Proteins/physiology , Protein Conformation , Proteins/chemistry
15.
Int J Clin Oncol ; 11(5): 403-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17058139

ABSTRACT

Malignant neoplasms of the salivary gland are uncommon entities in which surgical resection of the primary lesion has been accepted as a standard therapeutic option. The efficacy of radiation and systemic chemotherapy has been limited for patients with recurrent, metastatic, or unresectable disease because of unfavorable response rates and the short duration of the response. We treated one patient with recurrent adenoid cystic carcinoma arising from the sublingual gland and one patient with primary adenocarcinoma arising from the parotid gland with transfemoral intraarterial chemotherapy, based on full-dose cisplatin and docetaxel and concurrent external-beam radiotherapy. The doses of cisplatin and docetaxel in the two patients were 80-100 mg/m2 and 10-15 mg/m2, respectively. Docetaxel was infused first, followed by cisplatin. Both patients obtained complete responses. Although complications such as mucositis, anorexia, neutropenia, and ischemic colitis were observed, they were well tolerated and manageable. The concomitant chemoradiotherapy of cisplatin and docetaxel seemed to be a practicable option for patients with recurrent and unresectable salivary gland carcinomas.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Parotid Neoplasms/drug therapy , Parotid Neoplasms/radiotherapy , Sublingual Gland Neoplasms/drug therapy , Sublingual Gland Neoplasms/radiotherapy , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Aged , Carcinoma, Adenoid Cystic/drug therapy , Carcinoma, Adenoid Cystic/radiotherapy , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Docetaxel , Humans , Infusions, Intra-Arterial , Male , Middle Aged , Parotid Neoplasms/diagnosis , Radiotherapy, Adjuvant , Sublingual Gland Neoplasms/diagnosis , Taxoids/administration & dosage , Treatment Outcome
16.
Otol Neurotol ; 27(5): 604-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16788418

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the efficacy of intratympanic administration of dexamethasone (IT-DEX) treatment on sudden sensorineural hearing loss (SSNHL) patients with diabetes by comparing the results with intravenous administration of dexamethasone (IV-DEX) treatment. STUDY DESIGN: Comparative study. SETTING: University hospital and affiliated hospital. PATIENTS: Ten sequential SSNHL patients with diabetes receiving IT-DEX and 21 sequential SSNHL patients with diabetes receiving IV-DEX. Patients with low tone hearing loss were excluded. INTERVENTION: In the IT-DEX group, two methods were applied to deliver DEX (4 mg/ml): injection through a perforation made by laser-assisted myringotomy or through a tympanostomy tube. IT-DEX administration was performed on 8 sequential days. In the IV-DEX group, DEX was administrated intravenously starting from an amount of 8 mg/d followed by taped doses for 10 days. MAIN OUTCOME MEASURES: Preprocedure and postprocedure hearing levels and complications. RESULTS: In the IT-DEX group, the average hearing level before the treatment was 79 dB. Overall, all 10 patients showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 41 dB. Seven patients (70%) demonstrated successful results, and four recovered completely. In the IV-DEX group, 14 (67%) of the 21 patients showed improvement of more than 10 dB with a mean improvement of 25 dB. Thirteen patients (62%) demonstrated successful results. Free blood sugar during and after the IT-DEX treatment remained below the pretreatment levels, whereas four patients in the IV-DEX group demonstrated worsening of the hyperglycemia. CONCLUSION: IT-DEX treatment is at least as effective as IV-DEX treatment for SSNHL patients with diabetes.


Subject(s)
Dexamethasone/administration & dosage , Diabetes Complications/drug therapy , Glucocorticoids/administration & dosage , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/drug therapy , Tympanic Membrane/surgery , Adult , Aged , Aged, 80 and over , Dexamethasone/therapeutic use , Female , Glucocorticoids/therapeutic use , Humans , Injections, Intravenous , Laser Therapy , Male , Middle Aged , Middle Ear Ventilation , Treatment Outcome
17.
Tohoku J Exp Med ; 209(2): 89-97, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16707850

ABSTRACT

Inner ear hair cells play a major role in the auditory pathway that converts sound stimulation into electrical signals, and then into a neural code. However this function is often lost by aminoglycoside ototoxicity. The injury of inner ear hair cells from aminoglycoside treatment is considered apoptosis, and caspase is an important participant in the apoptosis pathway in many organs. It has been reported that calpain, a calcium-dependent protease, is essential for mediation and promotion of cell death. The purpose of the present study was to investigate effects of caspase and calpain inhibitors on the inner ear hair cells after aminoglycoside treatment, and to explore the cell death pathway. Cochlea explant cultures were prepared from mice of postnatal 6 days, cultured with neomycin and/or protease inhibitors, and then stained with phalloidin-fluorescein isothiocyanate (phalloidin-FITC), which was used as a marker to identify surviving hair cells. We demonstrated that neomycin (0.1-1 mM) reduced the number of outer hair cells in a dose-dependent manner. Furthermore, we showed that leupeptin, a calpain inhibitor, significantly protects against the neomycin-induced loss of outer hair cells, whereas a caspase inhibitor was effective only against a lower concentration of neomycin (0.2 mM). Using the TdT-mediated dUTP-biotin nick and labeling method, we also found that a calpain inhibitor, but not a caspase inhibitor, prevents apoptotic DNA fragmentation after treatment with 1 mM neomycin. These results suggest that calpain, rather than caspase, may be responsible for apoptosis induced by aminoglycoside. Thus, leupeptin may prevent hearing loss from aminoglycoside ototoxity.


Subject(s)
Anti-Bacterial Agents/toxicity , Calpain/antagonists & inhibitors , Cochlea/drug effects , Hair Cells, Auditory, Inner/drug effects , Leupeptins/pharmacology , Neomycin/toxicity , Protein Synthesis Inhibitors/toxicity , Animals , Animals, Newborn , Apoptosis/drug effects , Biomarkers/metabolism , Cell Survival/drug effects , Cochlea/metabolism , Cochlea/pathology , Dose-Response Relationship, Drug , Drug Antagonism , Hair Cells, Auditory, Inner/metabolism , Hair Cells, Auditory, Inner/pathology , Mice , Mice, Inbred C57BL , Organ Culture Techniques , Phalloidine/metabolism
18.
Neurosci Lett ; 399(3): 226-9, 2006 May 22.
Article in English | MEDLINE | ID: mdl-16490310

ABSTRACT

Although dopaminergic neurons are thought to exist in the lateral olivocochlear efferent system and modulate the afferent nerve activity, the distribution of dopamine (DA) receptor subtypes is still obscure. In the present study, we investigated the localization of five subtypes of DA receptor (D1-5) by immunocytochemical analysis and the gene expression of D1-5 using RT-PCR procedure in the rat cochlea. Most, but not all, spiral ganglion neurons were immunolabeled with all the anti-DA receptor subunit antibodies and faint punctuate immunoreactivities were observed in inner hair cell regions. Gene expression for all receptors was detected. These results suggest that all DA receptor subtypes are present in spiral ganglion cells, and potentially regulate afferent neurotransmission.


Subject(s)
Gene Expression/physiology , Receptors, Dopamine/classification , Receptors, Dopamine/metabolism , Spiral Ganglion/metabolism , Animals , Blotting, Northern/methods , Immunohistochemistry/methods , Male , Neurons/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Dopamine/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Spiral Ganglion/cytology
19.
Auris Nasus Larynx ; 33(3): 251-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16431060

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics, 5-year survival, and prognostic factors of squamous cell carcinoma (SCC) of the external and middle ear. METHODS: A multi institutional study. Ninety five cases of patients from 10 institutions were reviewed on their age and sex distribution, initial complaints, stages, tumor locations, treatments, and outcomes. Prognostic factors were discussed based on the Pittsburgh staging system. RESULTS: This disease seems to appear in the elderly with a peak age of 50-69 years. Males appear to be more predisposed than females with an odd ratio of 1.7. The initial complaints were not typical, while 12.6% of patients presented a history of recurrent otitis externa or chronic otitis media. Regional metastasis was recognized in 13.7% of patients, while no distant metastasis was confirmed. SCC located in the external ear could be detected in an earlier stage than that in the middle ear. The overall 5-year survival was 66.8% in total, and decreased significantly with stage. SCC in stages I and II was susceptible to each therapeutic strategy with a 5-year survival of 100%. Operation combined with radiotherapy and/or chemotherapy was the major treatment for stages III and IV SCC, while radiotherapy and chemotherapy were applied mainly for those who had been considered inappropriate for operation. The overall survival was 67.2% for stage III and 29.5% for stage IV, and operation with pathologically tumor free margin could improve the survival to 72.7% when combined with radio- and chemotherapy. Stage, completeness of operation with tumor free margin, recurrence, and metastasis have significant influence on survival. CONCLUSION: Local infiltration seems to be the main behavior of SCC in the external and middle ear. Early diagnosis and treatment were important because SCC in the earlier stage is susceptible to be cured. For tumors of advanced stage, operation should be performed with pathologically tumor free margin, and operation combined with radiotherapy and chemotherapy could improve the survival. Tumor stage adds more influence on survival than its location. Recurrence and metastasis mainly occur in advanced stages and result in a poor survival.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Ear Neoplasms/epidemiology , Ear, External , Ear, Middle , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Disease-Free Survival , Ear Neoplasms/mortality , Ear Neoplasms/pathology , Ear, External/pathology , Ear, Middle/pathology , Earache , Facial Paralysis , Female , Hearing Loss , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Survival Analysis , Temporal Bone/pathology
20.
Otol Neurotol ; 27(1): 14-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16371841

ABSTRACT

OBJECTIVE: We describe our initial experience with endoscopic transtympanic tympanoplasty and evaluate whether this approach is adequate and minimally invasive in the treatment of conductive hearing loss. STUDY DESIGN: Prospective trial. SETTING: University hospital. PATIENTS: Nine patients underwent endoscopic transtympanic tympanoplasty, with an average follow-up period of 17 months. Presurgical diagnosis was made by transtympanic endoscopy through a perforation made by OtoScan laser-assisted myringotomy in the outpatient clinic. METHODS: With clean endoscopic visualization, ossiculoplasty was performed by inserting a trimmed tragal cartilage through the myringotomy perforation made by laser-assisted myringotomy. Two types of ossiculoplasty were performed: columella reconstruction and interposition. The tympanic membrane was covered with a chitin membrane or sealed with a small piece of perichondrium from the tragal cartilage. MAIN OUTCOME MEASURES: Perioperative and postoperative complications and preoperative and postoperative hearing. RESULTS: Endoscopic transtympanic tympanoplasty with columella and endoscopic transtympanic tympanoplasty with interposition were performed in seven and two patients, respectively. Insertion of the cartilage was performed without conversion to a conventional otomicroscopic technique. The average hearing level before the operation was 59 dB. After the endoscopic transtympanic tympanoplasty, the average improved to the level of 27 dB, with an average air-bone gap of 11 dB. The myringotomy perforation was closed within 2 to 3 weeks. CONCLUSION: As opposed to conventional methods, this procedure does not require surgical exposure such as otosclerosis drilling and skin incision, and avoids the substantial risk of unnecessary injury to the chorda tympani. Endoscopic transtympanic tympanoplasty for a disrupted ossicular chain is an adequate and minimally invasive procedure and should prove to be a useful surgical procedure in future endoscopic tympanoplasty.


Subject(s)
Endoscopy/methods , Hearing Loss, Conductive/surgery , Laser Therapy , Tympanic Membrane/surgery , Tympanoplasty/methods , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
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