MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis

Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets.

Reactive oxygen species regulate context-dependent inhibition of NFAT5 target genes

The activation of nuclear factor of activated T cells 5 (NFAT5), a well-known osmoprotective factor, can be induced by isotonic stimuli, such as activated Toll-like receptors (TLRs). It is unclear, however, how NFAT5 discriminates between isotonic and hypertonic stimuli. In this study we identified a novel context-dependent suppression of NFAT5 target gene expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) or a high salt (NaCl) concentration. Although LPS and NaCl both used NFAT5 as a core transcription factor, these stimuli mutually inhibited distinct sets of NFAT5 targets within the cells. Although reactive oxygen species (ROS) are essential for this inhibition, the source of ROS differed depending on the context: mitochondria for high salt and xanthine oxidase for TLRs. Specifically, the high salt-induced suppression of interleukin-6 (IL-6) production was mediated through the ROS-induced inhibition of NFAT5 binding to the IL-6 promoter. The context-dependent inhibition of NFAT5 target gene expression was also confirmed in mouse spleen and kidney tissues that were cotreated with LPS and high salt. Taken together, our data suggest that ROS function as molecular sensors to discriminate between TLR ligation and osmotic stimuli in RAW 264.7 macrophages, directing NFAT5 activity toward proinflammatory or hypertonic responses in a context-dependent manner.

An Epidemiologic & Audiometric Study of Noise-Induced Hearing Loss in Subway Workers / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There is no effective treatment for noise-induced hearing loss (NIHL), and for this reason, prevention is very important. The purpose of this study is to investigate the epidemiologic and audiometric properties of NIHL in subway workers. MATERIALS AND METHODS: This study included 10,792 employees who have worked in the subway. Their hearing acuity was screened out by pure tone audiometry for 1 K & 4 KHz. Of the employees, those whose hearing loss was not caused by noise were excluded from the study and the remaining 665 employees were investigated. The epidemiologic and audiometric properties were investigated on the basis of their ages and working durations. RESULTS: Among the 10,792 employees, 665 (6.2%) showed NIHL. The risk of NIHL increased significantly in individuals who had worked more than 5 years. At 4 KHz, the hearing threshold shift occured within 5 years, then reached a plateau. But below 2 KHz, it progressed gradually, becoming prominent after 10 years of noise exposure. CONCLUSION: We suggest that prevention from exposure to noise is necessary for individuals whose working duration is more than 5 years.

Facial Nerve Function after Anterior Transposition of Facial Nerve / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The transposition of the facial nerve is an essential procedure to obtain optimal surgical field and to remove the lesion completely when the tumor is located medial to the facial nerve. However, we frequently encounter postoperative facial palsy after transposition. The aim of the study is to find out how to treat the facial nerve in order to reduce the incidence and the degrees of postoperative facial palsy after anterior transposition of the facial nerve. MATERIAL AND METHODS: Facial nerve function after anterior transposition of the facial nerve were analyzed retrospectively in 10 cases with skull base tumor using the House-BracKJCann grading system. The minimum follow-up period was 12 months. RESULTS: Favorable outcome was noted when the fallopian canal was exposed as widely as possible, and soft tissues were preserved at stylomastoid foramen. Postoperative facial palsy was recovered completely when the facial nerve was not involved by disease. The final House-BracKJCann grades were I, II, III in three cases in which tumor was involved with the facial nerve. The immediate postoperative function of the facial nerve is influenced by surgical procedure and surgeon's skill, and the final status of the facial nerve function depends on the involvement of tumor in the nerve. CONCLUSION: In order to obtain favorable postoperative facial nerve function, no attempt was made to dissect the facial nerve, and all the soft tissue that were attached to the facial nerve through the stylomastoid foramen were sharply elevated and traspositioned together with the facial nerve.

Olfactory Changes in Patients of Dementia / 대한이비인후과학회지

BACKGROUND: Dementia has emerged as a major healthy challenge, not only for clinicians but for society as a whole. So, there is a growing need for study of dementia. Evaulating the patients with dementia, examination of the sense of smell is not routinely performed. However, one of several neurologic changes include alterations in olfaction. OBJECTIVES: The aim of this study was to evaluate the value of olfactory function test in demented patients as diagnostic tool. MATERIALS AND METHOD: We studied the olfactory functions in 35 patients with dementia of the Alzheimer's type(DAT) and 20 patients with vascular dementia(VD) and compared with normal controls(n=30). These subjects were divided according to the Mini-Mental State Examination(MMSE). We used the T & T olfactometer for the olfactory function test. RESULTS: In the group of questionable DAT, the detection and recognition threshold were 0.25+/-0.95, 2.38+/-1.87, in the group of definitive DAT, 1.51+/-1.52, 3.91+/-1.55 and in the group of definitive vascular dementia, 2.03+/-1.48, 4.53+/-1.45. But, in the normal controls, the detection and recognition threshold was 0.66+/-0.90, 1.55+/-0.81 respectively. CONCLUSION: These findings suggest that olfactory function test are valuable in demented patients as diagnostic tool, but not specific in DAT group and that early detection of DAT is possible by olfactory function test.

Audiometric Changes after Ventilating Tube Insertion in Middle Ear Effusion / 대한이비인후과학회지

Audiometric and clinical findings of 90 patients(146 ears) who were suffered from otitis media with effusion and were treated by tympanostomy tube placement at KangNam General Hospital from Apr. 1994 to Jun. 1996 were analyzed. The results were follows; 1) Sex distribution shows 52 males and 38 females. Age distribution is 4 to 81, and fifty-one percent of them are younger than 9-year-old. 2) Pre-operative pure tone average was 27.1dB in air conduction and 20.6dB in air-bone gap. Post-operative pure tone average of air conduction and air-bone gap was average 12.6dB and 7.5dB at 13th day and 9.3dB and 5.6dB at 44th day after v-tube insertion, respectively. 3) For patients younger than 9-year-old, pre-operative average air conduction threshold was lower and air-bone gap was smaller than that of older age groups. But there are no significant difference of post-operative changes between younger than age of 9 and age between 10-19. 4) There are no significant differences among the groups with different nature of effusion in pre-operative hearing threshold. However the hearing threshold changes in air conduction and air-bone gap were larger in mucoid group than serous one. 5) There are no differences in the pre-operative hearing among the groups with different amount of effusion, but changes of post-operative hearing threshold was bigger in large amount group. 6) The incidence of post-operative otorrhea was 15%(22 ears) and its incidence was higher in mucoid group than serous one.