Metallothioneins (MT), small molecular weight metal binding proteins are known to play an important protective role against heavy metal toxicity, either as antioxidants or pre-oxidants. However, the mode of metabolic fate of MTs in various metal complexes is not clearly understood. This study was carried out to better understand the mode of selective turnover rate of various form of MT in complexes with different metals. The degradation of in vitro translated mouse 35S-cysteine-MT was examined in lysosomal or cytosolic fractions from mouse liver by gel electrophoresis and autoradiography. Overnight incubations of MT showed extensive proteolysis in the lysosomal fraction but not in cytosolic fractions. However, Cu2+-MT was found to be stable under the same experimental condition. In contrast, Zn did not interfere with MT degradation. These results suggest that lysosomes are chiefly responsible for MT removal and appears to be selective on the metals involved in the MT complex. In vitro, translated, radiolabeled MT provides a suitable substrate for investigating the characteristics of MT degradation.
Animal ; Copper/*metabolism/pharmacology ; Ions ; Liver/drug effects/*metabolism ; Lysosomes/metabolism ; Metallothionein/drug effects/*metabolism ; Mice ; Sulfur Radioisotopes ; Support, Non-U.S. Gov't ; Zinc/*metabolism/pharmacology

The simultaneous occurrence of renovascular hypertension and an aldosterone-producing adrenal adenoma is a rare entity. Here, we report the case of a 52-year-old female who had a coexisting aldosterone-producing adrenal adenoma and ipsilateral renal artery stenosis. She was diagnosed with the aldosterone-producing adrenal adenoma and then underwent a laparoscopic left adrenalectomy. Her blood pressure was uncontrolled after the adrenalectomy. Selective renal angiography showed left renal artery stenosis; thus, she underwent balloon angioplasty at the same sitting. Subsequently, her blood pressure returned to normal after administration of a single antihypertensive drug. This case suggests that it is important to recognize the possible coexistence of renal artery stenosis in a patient with an aldosterone-producing adrenal adenoma.
Adenoma* ; Adrenalectomy ; Adrenocortical Adenoma ; Angiography ; Angioplasty, Balloon ; Blood Pressure ; Female ; Humans ; Hyperaldosteronism ; Hypertension, Renovascular ; Middle Aged ; Renal Artery Obstruction*

Vascular ectasia is a well-known cause of lower gastrointestinal bleeding in the elderly. Endoscopically, it usually appears as a flat or elevated bright red lesion. We report on an extremely rare case of a large, pedunculated, polypoid vascular ectasia in an asymptomatic patient. A large pedunculated polypoid mass in the sigmoid colon was observed on colonoscopy during a regular health check-up, and a polypectomy was performed using a detachable snare. In histology, vessels with massive dilation were found mainly in the submucosa, which was consistent with vascular ectasia.
Aged ; Colon, Sigmoid ; Colonoscopy ; Dilatation, Pathologic ; Hemorrhage ; Humans ; SNARE Proteins

PURPOSE: We evaluated allele frequencies and distribution of surfactant protein A2(SP-A2) in Korean neonates in order to estimate the prevalence of RDS, to find out new SP-A alleles, and to establish new steroid therapy. METHODS: Genomic DNA was extracted from 71 neonates and served as a template in PCR for genotype analysis. SP-A gene-specific amplications and gene-specific allele determinations were performed using PCR-cRFLP methods. RESULTS: The distribution for the alleles of the SP-A2 gene in the study population was 1A, 1A0, 1A1, 1A2, 1A3, 1A5, 1A6, 1A7, 1A8, 1A9, 1A11, 1A12. The specific frequencies for the alleles of the SP- A2 gene in the study population were : 1A=11.3%, 1A0=38%, 1A1=12.7%, 1A2=9.2%, 1A5=15.5%, 1A7= 2.9%, 1A8=4.9%, 1A9=2.2%, others=3.3%. CONCLUSION: The frequency of 1A0 was higher than the other SP-A2 alleles in Korean neonates. This finding suggests that the prevalence of RDS in Korea may be low compared with other countries. However, this finding also suggests that Korean neonates have a high risk of infection.
Alleles* ; DNA ; Gene Frequency ; Genotype ; Humans* ; Infant, Newborn* ; Korea ; Polymerase Chain Reaction ; Prevalence

BACKGROUND: Recently, much attention has been focused on the role of protease inhibitors such as acid stable trypsin inhibitor (ASTI) in the invasive growth of malignant tumors. However, there are no report on expression of ASTI from premalignant and/or malignant skin tumors. OBJECTIVES: In the present study the expression of ASTI was investigated in the different type of premalignant and/or, malignant skin tumors in attempt to clarify the relation between the expression of the ASTI and malignancy. METHODS: For the detection of ASTI in the tumor tissue, the immunoperoxidase techniques that used mouse antibody raised against highly purified ASTI. The degree of ASTI immunoreactivity was semiquantitatively assessed for staining intensity as the percentage of ASTI-positive cells. RESULTS: ASTI immunoreactivity was detected in most of the premalignant and malignant skin tissues. Especially, ASTI expression was present widespread in squamous cell carcinoma(SCC) with strong cytoplasmic membrane, where as in normal epidermis they were primarily present in the horny layer. The strong staining was the SCC, keratoacanthoma, Bowen's disease, actinic keratosis, basal cell epithelioma, Paget's disease in decreasing order. The significant difference in the staining intensity was observed between SCC and other groups. CONCLUSION: Results of immunohistochemical studies suggest that the tumor cells themselves could produce ASTI. Considering the suggestion that ASTI is a self protector, inhibitor to proteolytic protease as well as growth-stimulating factor. The present findings may indicate that ASTI expressed in malignant cells may play a role possibly closely associated with tumor development.
Animals ; Bowen's Disease ; Carcinoma, Basal Cell ; Cell Membrane ; Epidermis ; Immunoenzyme Techniques ; Keratoacanthoma ; Keratosis, Actinic ; Mice ; Protease Inhibitors ; Skin* ; Trypsin*

PURPOSE: We evaluated allele frequencies and distribution of surfactant protein A1(SP-A1) in Korean neonates in order to estimate prevalence of RDS to find out new SP-A alleles, and to establish new steroid therapy. METHODS: Genomic DNA was extracted from 100 neonates and served as a template in PCR for genotype analysis. SP-A gene-specific amplications and gene-specific allele determinations were performed using PCR-RFLP methods. RESULTS: The distribution for the alleles of the SP-A1 gene in the study population were 6A, 6A(2), 6A(3), 6A(4), 6A(8), 6A(9), 6A(10), 6A(11), 6A(12), 6A(13), 6A(14), 6A(15), 6A(16), 6A(17), 6A(18), 6A(20). The specific frequencies for the alleles of the SP-A1 gene in the study population were: 6A(2)=21%, 6A(3)=45%, 6A(4)=11%, 6A(8)=9%, 6A(14)=8%. CONCLUSIONS: The frequency of 6A3 was higher than the other SP-A1 alleles in Korean neonates. This finding suggests that the prevalence of RDS in Korea may be low compared with other countries. However, this finding also suggests that Korean neonates have a high risk of infection.
Alleles* ; DNA ; Gene Frequency ; Genotype ; Humans* ; Infant, Newborn* ; Korea ; Polymerase Chain Reaction ; Prevalence

Background and Objectives: Globus pharyngeus is one of the most common symptoms of patients visiting otorhinolaryngology out-patient clinic, and usually long-lasting, difficult to treat, and frequently recurrent. Mucomyst®, N-acetyl cysteine is an inhalation agent mainly used for mucolysis and reducing inflammation in airway via antioxidative effect. The purpose of this study was to evaluate the efficacy of inhaled Mucomyst® treatment in patients with globus pharyngeus refractory to proton pump inhibitor (PPI).Materials and Method We prospectively evaluated the efficacy of Mucomyst® in relieving symptoms of globus pharyngeus refractory to PPI in nine medical centers. Three hundred and three patients enrolled and finally 229 patients finished the inhaled Mucomyst® therapy for 8 weeks. We analyzed the change of Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Visual Analogue Scale (VAS) for globus, and Globus Pharyngeus Symptom Scale (GPS) after use of Mucomyst® for 4 and 8 weeks. Results: The GPS, RSI, RFS, and VAS score significantly decreased serially in patients who finished 8 week-inhalation treatment. The GPS improvement gap was significantly correlated with initial GPS (p<0.001) in multiple regression analysis. Conclusion Inhaled Mucomyst® therapy was effective for the reduction of both subjective and objective findings in refractory globus patients. This study might suggest new treatment option for patients with globus. However, further thorough studies would be needed to assess the real effect of inhaled Mucomyst® treatment as a standard treatment for globus.

By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8⁺ cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells. This finding indicated that immunoproteasome induction was impaired at the translational or posttranslational level by HCV infection. Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by the silencing of PKR expression. In conclusion, our data point to a novel mechanism of immune regulation by HCV that affects the antigen-processing machinery through the PKR-mediated suppression of immunoproteasome induction in infected cells.
Cell Culture Techniques ; Epitopes, T-Lymphocyte ; Gene Silencing ; Hepacivirus ; Hepatitis C* ; Hepatitis* ; In Vitro Techniques ; Interferons ; Lymphocytes ; Peptides ; Protein Kinases* ; RNA, Messenger

Objectives: . Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). Methods: . We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. Results: . Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780). Conclusion . A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Objectives: . Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). Methods: . We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. Results: . Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780). Conclusion . A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.