BACKGROUND AND OBJECTIVES: There are several evidences of reduced cochlea blood flow after noise exposure in the cochlea. However, the pathophysiology of blood flow change is still obscure, and endothelins, proteins that constrict blood vessels and play a key role in vascular homeostasis using its receptors may have importance in this respect. In this study, we investigated the expression changes of endothelin-1 (ET-1), endothelin receptor A (ETAR) and B (ETBR) according to auditory threshold change after noise exposure. MATERIALS AND METHOD: Mice were exposed to different noise to generate transient (group 2) and permanent threshold shift (group 3), respectively. Auditory threshold shifts were evaluated with auditory brainstem response and expression changes of ET-1, ETAR and ETBR after noise exposure were evaluated by immunohistochemistry and real time RT-PCR. RESULTS: After noise exposure, the increased ET-1, ETAR and ETBR immunoreactivities were observe in stria vascularis, spiral ligament and spiral ganglion neuron. ET-1 mRNA expressions increased after noise exposure in both group 2 and group 3 compared to those of the control group. At 2 weeks after noise exposure, however, the ET-1 mRNA expressions in group 3 increased compared to that of the control but decreased compared to that of group 2. On the other hand, ETAR mRNA expression increased at 2 weeks after noise exposure in both groups, just after noise exposure in group 2 and at 2 weeks after noise exposure in group 3. CONCLUSION: These results suggest that expression changes of ET-1, ETAR and ETBR might be associated with hearing threshold shift and recovery after noise exposure in the cochlea.
Animals ; Auditory Threshold ; Blood Vessels ; Cochlea ; Endothelin-1 ; Endothelins ; Evoked Potentials, Auditory, Brain Stem ; Hand ; Hearing ; Homeostasis ; Immunohistochemistry ; Mice ; Neurons ; Noise ; Proteins ; Receptors, Endothelin ; RNA, Messenger ; Spiral Ganglion ; Spiral Ligament of Cochlea ; Stria Vascularis

OBJECTIVE: To compare a high acceleration three-dimensional (3D) T1-weighted gradient-recalled-echo (GRE) sequence using the combined compressed sensing (CS)-sensitivity encoding (SENSE) method with a conventional 3D GRE sequence using SENSE, with respect to image quality and detectability of solid focal liver lesions (FLLs) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced liver MRI. MATERIALS AND METHODS: A total of 217 patients with gadoxetic acid-enhanced liver MRI at 3T (54 in the preliminary study and 163 in the main study) were retrospectively included. In the main study, HBP imaging was done twice using the standard mDixon-3D-GRE technique with SENSE (acceleration factor [AF]: 2.8, standard mDixon-GRE) and the high acceleration mDixon-3D GRE technique using the combined CS-SENSE technique (CS-SENSE mDixon-GRE). Two abdominal radiologists assessed the two MRI data sets for image quality in consensus. Three other abdominal radiologists independently assessed the diagnostic performance of each data set and its ability to detect solid FLLs in 117 patients with 193 solid nodules and compared them using jackknife alternative free-response receiver operating characteristics (JAFROC). RESULTS: There was no significant difference in the overall image quality. CS-SENSE mDixon-GRE showed higher image noise, but lesser motion artifact levels compared with the standard mDixon-GRE (all p < 0.05). In terms of lesion detection, reader-averaged figures-of-merit estimated with JAFROC was 0.918 for standard mDixon-GRE, and 0.953 for CS-SENSE mDixon-GRE (p = 0.142). The non-inferiority of CS-SENSE mDixon-GRE over standard mDixon-GRE was confirmed (difference: 0.064 [−0.012, 0.081]). CONCLUSION: The CS-SENSE mDixon-GRE HBP sequence provided comparable overall image quality and non-inferior solid FFL detectability compared with the standard mDixon-GRE sequence, with reduced acquisition time.
Acceleration ; Artifacts ; Consensus ; Dataset ; Humans ; Liver ; Magnetic Resonance Imaging ; Methods ; Noise ; Retrospective Studies ; ROC Curve

PURPOSE: Aim of this study was to assess effects of InsureGraf® (SK-Bioland Co., Korea), an artificial dermis developed by using tissue engineering technology in severe burn patients. METHODS: To examine the clinical effectiveness of InsureGraf®, we transplanted them in patients with severe burns. A total of 14 joint regions in 8 patients received InsureGraf® graft selectively from July to December, 2014. The graft results were determined after confirming the take rate of the transplanted skin graft on top of the InsureGraf®. Take rates were examined twice, at 7 and 14 days after grafting. Photographs of the skin grafts were evaluated individually by two burn surgeon specialists, and the mean values were recorded. RESULTS: The take rate was 99% after day 7 and 100% after day 14 respectively. CONCLUSION: InsureGraf® can be used successfully as an artificial dermis that allows one-stage operation in severe burn patients, exhibiting a successful early-stage graft take rate that is close to 100%.
Burns ; Collagen* ; Dermis ; Humans ; Joints ; Skin ; Specialization ; Tissue Engineering ; Transplants ; Treatment Outcome*

The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-kappaB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-kappaB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-kappaB binding activity, even though these could enhance NF-kappaB signaling in the absence of other stimuli. Moreover this suppressed NF-kappaB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-kappaB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent.
Animals ; Antibiotics, Antineoplastic/therapeutic use ; *Apoptosis ; Caspases/metabolism ; Cell Line ; Colchicine/pharmacology ; DNA/metabolism ; *DNA Damage ; Doxorubicin/therapeutic use ; Humans ; Mice ; Microtubules/chemistry/*drug effects/metabolism ; NF-kappa B/antagonists & inhibitors/*metabolism ; Neoplasms/drug therapy ; Nocodazole/pharmacology ; Protein Binding ; Signal Transduction ; Tubulin Modulators/*pharmacology ; Vinblastine/pharmacology

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.
Adult ; Aged ; Biomarkers, Tumor/*genetics ; Female ; Genetic Markers/genetics ; Genetic Predisposition to Disease/epidemiology/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Peptides/*genetics ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Assessment/methods ; Sensitivity and Specificity ; Stomach Neoplasms/*epidemiology/*genetics ; Tumor Suppressor Proteins/*genetics

To gain insight on the role of pro-inflammatory cytokines in the pathogenesis and treatment of rheumatoid arthritis (RA), the phorbol 12-myristate 13-acetate (PMA) -induced IL-6 gene expression and the effect of caffeic acid phenethyl ester (CAPE) on the PMA-induced IL-6 gene expression were investigated in human fibroblast-like synoviocytes (FLSs). Synovial tissue samples were obtained from rheumatoid arthritis patients, and FLSs were isolated. The cells were stimulated with PMA (100 nM) for 6 hrs to induce IL-6 gene. The cells were pretreated with CAPE (20, 50, 100 microM) prior to PMA treatment. PMA increased IL-6 RNA expression, binding activities of transcription factors (NF-kappaB, AP-1) to IL-6 promoter, and IL-6 promoter activity. However, CAPE inhibited PMA-induced IL-6 mRNA expression in dose-dependent manner, and also inhibited the increased binding activities of transcription factors to IL-6 promoter and IL-6 promoter activity. These results suggest that CAPE might regulate PKC-mediated IL-6 expression and inflammatory reactions in RA.
Arthritis, Rheumatoid* ; Cytokines ; Gene Expression* ; Humans ; Interleukin-6* ; RNA ; RNA, Messenger ; Transcription Factors

To investigate the properties of ryanodine binding sites of the bird skeletal SR vesicles, SDS PAGE, purification of RyR, and (3H)ryanodine binding study were carried out in the SR vesicles prepared from the chicken pectoral muscle. The chicken SR vesicles have two high molecular weight (HMW) protein bands as in eel SR vesicles on SDS PAGE. The HMW bands on SDS PAGE were found in the (3H) ryanodine peak fraction (Fr3-5) obtained from the purification step of the ryanodine receptor protein. Bmax and KD of the chicken (3H)ryanodine binding sites were 12.52 pmol/mg protein and 14.53 nM, respectively. Specific (3H)ryanodine binding was almost maximal at 50~100 micrometer Ca2+, but was not increased by 5 mM AMP and not inhibited by high Ca2+. Binding was significantly inhibited by 20~100 micrometer ruthenium red and 1 mM tetracaine, but slightly inhibited by Mg2+. From the above results, it is suggested that chicken SR vesicles have the ryanodine binding sites to which the binding of ryanodine is almost maximal at 50~10 micrometer Ca2+, is significantly inhibited by ruthenium red and tetracaine, slightly inhibited by Mg2+, but not affected by AMP and not inhibited by high Ca2+.
Binding Sites* ; Birds ; Chickens* ; Eels ; Electrophoresis, Polyacrylamide Gel ; Molecular Weight ; Ruthenium Red ; Ryanodine ; Ryanodine Receptor Calcium Release Channel ; Sarcoplasmic Reticulum ; Tetracaine

In this study, we investigated whether TNF-alpha, IL-1beta, CTMA (carboxymethyl trimethylammonium) and LPD (Lup-20[29]-ene-3beta, 28-diol) affect mucin release from airway goblet cells and compared the activities of these agents with the inhibitory action of PLL and the stimulatory action of ATP on mucin release. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on 3H-mucin release. The results were as follows: TNF-alpha, CTMA and LPD increased mucin release at the highest concentration, but IL-1beta did not. We conclude that CTMA and LPD can stimulate mucin release by directly acting on airway mucin-secreting cells, and suggest that these agents should be further investigated for the possible use as mild expectorants during the treatment of chronic airway diseases.
Adenosine Triphosphate ; Animals ; Biological Products* ; Cricetinae* ; Cytokines* ; Epithelial Cells* ; Expectorants ; Goblet Cells ; Mucins* ; Tumor Necrosis Factor-alpha

Poly-L-lysine (PLL) was reported to suppress mucin release from airway goblet cells during 30 min treatment period. In this study, we investigated whether PLL consistently suppresses mucin release from cultured airway goblet cells during 24 h after 30 min treatment and also specifically suppresses the release of mucin without any effects on the other releasable glycoproteins. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of PLL to assess the effects on 3H-mucin release and on the total elution profile of the treated culture medium. The total mucin content during 24 h after 30 min treatment of PLL was assesed to investigate the consistency of effects. PLL did not affect the release of the other releasable glycoproteins whose molecular weights were less than mucin, and decreased the total mucin content during 24 h after 30 min treatment. We conclude that PLL can specifically suppress mucin release from cultured airway goblet cells and the suppression on mucin release is consistent. This finding suggests that PLL might be used as a specific airway mucin-regulating agent by directly acting on airway mucin-secreting cells.
Animals ; Cricetinae* ; Epithelial Cells* ; Equidae ; Glycoproteins ; Goblet Cells ; Molecular Weight ; Mucins*

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
Acetophenones/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Death/*drug effects ; Cell Line, Tumor ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Superoxides/metabolism ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology