Jun Yeon Won

Clonazepam quiets tinnitus: a randomised crossover study with Ginkgo biloba.

Objective To assess the effect of Ginkgo biloba and clonazepam, a γ-aminobutyric acid (GABA)-receptor agonist, upon tinnitus. Methods This was an open-label, randomised, crossover study. 27 men and 11 women (aged 16–80 (mean 58)) with tinnitus for more than 2 months were enrolled. Participants were randomised to either clonazepam or G biloba for the first 3 weeks. For the next 2 weeks of washout no medication was taken. For the final 3 weeks, subjects were given the other drug. The initial dose of clonazepam and G biloba was one tablet daily (clonazepam 0.5 mg; G biloba 40 mg). Subjects were instructed to increase the dose by one tablet every 3 days to a maximum of four tablets daily until they perceived a satisfactory decrease in tinnitus loudness or intolerable side effects. Tinnitus was assessed with pitch and loudness matching, tinnitus handicap inventory, and visual analogue scales of loudness, duration and annoyance. Results Comparing before and after each drug, clonazepam significantly improved tinnitus loudness (74% of subjects), duration (63%), annoyance (79%), and tinnitus handicap inventory score (61%), whereas the G biloba showed no significant differences on any of these measures. Conclusion Clonazepam is effective in treating tinnitus; G biloba is ineffective.

RNA sequencing identifies novel markers of non-small cell lung cancer.

INTRODUCTION The development of reliable gene expression profiling technology increasingly impacts our understanding of lung cancer biology. Here, we used RNA sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer (NSCLC) and normal lung tissues and to investigate expression in lung cancer tissues. METHODS We enrolled 88 male patients (mean age, 61.2 years) with NSCLC. RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from 54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma. Immunohistochemistry was performed to validate differential candidate gene expression in a different NSCLC group. RESULTS RNA-Seq produced 25.41 × 10(6) (± 8.90 × 10(6)) reads in NSCLC tissues and 24.70×10(6) (± 4.70 × 10(6)) reads in normal lung tissues [mean (± standard deviation)]. Among the genes expressed in both tissues, 335 were upregulated and 728 were downregulated ≥ 2-fold (p < 0.001). Four upregulated genes - CBX3, GJB2, CRABP2, and DSP - not previously reported in lung cancer were studied further. Their altered expression was verified by immunohistochemistry in a different set of NSCLC tissues (n = 154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35 cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p < 0.01). CONCLUSIONS CBX3 and CRABP2 expression was markedly increased in lung cancer tissues and especially CRABP2 may be promising candidate genes in lung adenocarcinoma.

Plasma Osteopontin Is a Useful Diagnostic Biomarker for Advanced Non-Small Cell Lung Cancer

Background Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. Methods Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. Results The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). Conclusion Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

Prevalence and Factors Associated with Neck and Jaw Muscle Modulation of Tinnitus

Forceful contractions of neck and jaw muscles have consistently been shown to modulate tinnitus and can be used to screen patients who are responsive to somatic stimulation and, therefore, optimal candidates for somatosensory-based treatment. To identify the factors associated with somatic modulation of tinnitus, 163 patients underwent 19 neck and jaw maneuvers after an extensive physiological and audiological profile was compiled. Overall, tinnitus was modulated in 57.1% of ears tested. Unilateral tinnitus showed greater prevalence of modulation. Neck maneuvers generally decreased tinnitus loudness, whereas jaw maneuvers increased loudness. Female gender and buzzing tinnitus were associated with a high prevalence of modulation and a decrease in tinnitus loudness. Loud tinnitus and low-pitched tonal tinnitus were associated with exacerbation of the condition as a result of somatic testing. Use of these characteristics to select optimal candidates for somatosensory-based tinnitus therapies may be essential for the development of an effective approach for tinnitus treatment.

Extratympanic electrocochleographic changes on noise-induced temporary threshold shift

OBJECTIVE: Electrocochleography (ECoG) is a sensitive evoked-response test for evaluating changes in cochlear function. We investigated the extratympanic ECoG in a noise-induced temporary threshold shift (TTS) to evaluate the usefulness of ECoG in the early detection of noise-induced hearing loss (NIHL). STUDY DESIGN AND METHODS: In a prospective analysis, 15 healthy ears were exposed to 90.3- to 105.0-dB noise for 3 hours in the same computer-game arcade. Pure-tone audiometry and ECoG were performed before, immediately after, and 24 hours after the exposure. RESULTS: Before the exposure, the average hearing level was 5.8 ± 2.7 dB, which increased significantly to 12.8 ± 2.8 dB immediately after exposure. A marked increment in the SP/AP (summating potential/action potential) ratio was observed with the TTS. The mean ratio was 0.22 ± 0.11 before the exposure, 0.46 ± 0.18 in the TTS phase, and 0.20 ± 0.11 after resolution. CONCLUSION: The results of this study suggest that the SP/AP ratio is useful for the early detection and monitoring of NIHL. (Otolaryngol Head Neck Surg 2004;130:437–42.)

SPARC is involved in the maintenance of mitotically inactivated mouse embryonic fibroblast cells

Mitotically inactivated feeder cells such as mouse embryonic fibroblast (MEFs) cells have been widely applied for physical and physiological support in the pluripotency maintenance of human pluripotent stem cells (hPSCs). However, accurate supporting mechanism or factors of feeder cells are poorly understood. Here, we isolated differentially expressed genes between wild-type MEFs and mitotically inactivated MEFs (miMEFs) by employing annealing control primer-based GeneFishing polymerase chain reaction. We identified a secreted protein acidic cysteine-rich glycoprotein (SPARC) gene that is upregulated in miMEFs. Suppression of SPARC expression in miMEFs using small interference RNA (siRNA) displayed gradual detachment of miMEFs. Furthermore, we found a significant reduction of OCT4- and SSEA3-positive hPS cell population maintained on SPARC siRNA-miMEFs compared to on miMEFs by flow cytometrical analysis. These findings suggest that SPARC plays a critical role in the maintenance of miMEFs without loss of cell number and might be a key component for supporting the culture of hPSCs.