PURPOSE: Despite the reduced incidence and mortality of gastric cancer, this illness still remains the second leading cause of cancer death in Korea. Various adjuvant chemotherapies have been proposed for patients with advanced gastric cancer. Randomized trials comparing chemotherapies with best supportive care have consistently shown that cytotoxic treatment is of some benefit. Nevertheless, there has been no major improvement in the overall prognosis of advanced gastric cancer. METHODS: We have examined the chemotherapy sensitivity of advanced gastric cancer specimens by using an ex vivo ATP based chemosensitivity assay (ATP-TCA). A variety of chemotherapeutic agents were tested. The one hundred and forty specimens we tested were from resection specimens. RESULTS: The histological tumor classification, lymphatic invasion, neural invasion and venous invasion affected the chemosensitivity of some drugs. 5-FU was a more potent drug than cisplatin, doxorubicin, iriontecan and methotrexate. The chemosensitivity of differentiated cancer was different compared to that of undifferentiated cancer. Doxorubicin and iriontecan were more effective in poorly differentiated, signet ring cell and diffuse type cancers. The manner of tumor invasion affected the chemosensitivity to some drugs. CONCLUSISON: Further study is necessary to assess the effectiveness of some chemotherapy drugs on advanced gastric cancer, including their effect on tumor recurrence and patient survival.
Adenosine Triphosphate ; Cisplatin ; Doxorubicin ; Fluorouracil ; Humans ; Incidence ; Korea ; Methotrexate ; Prognosis ; Recurrence ; Stomach Neoplasms

PURPOSE: Recently, laparoscopic appendectomy (LA) has been widely performed in developed countries. In addition, minimally invasive surgery such as LA is a challenge to surgical residents. The aim of this study is to evaluate learning curve of residents in comparison to that of experienced surgeons. METHODS: Fifty cases of LA that were performed by experienced surgeons (group A) and forty-seven cases of LA that were performed by 8 residents (group B) were reviewed retrospectively. RESULTS: Operative time was longer in group B (50.8+/-12 vs. 82.8+/-40 min. P<0.001). Hospital days of group B was shorter (4.8+/-2.4 vs. 3.7+/-2.1 days P=0.021). No other parameters were statistically significant. In group A, wound infection developed in 1 case. In group B, wound infection developed in 4 cases, intraabdominal abscess in 1, subcutaneous emphysema in 1. CONCLUSION: Inexperienced surgeons can perform laparoscopic appendectomy easily in the early days of individual laparoscopic training course.
Abscess ; Appendectomy ; Developed Countries ; Learning Curve ; Operative Time ; Retrospective Studies ; Subcutaneous Emphysema ; Wound Infection

This report is a clinical review of 298 cases of early gastric cancer that were treated at Kosin Medical Hospital during 8 years from 1984 to 1992. In 1962, the Japanese Gastroenterological Endoscopy Society defined early gastric cancer as a lesion confined to the mucosa or submucosa and not related to the presence of lymph-node metastasis. The prognosis for early gastric cancer (EGC) is generally excellent, but the proportion of EGC cases progressing to advanced gastric cancer is steadily increasing nowadays. The presence or absence of lymph-node metastasis in EGC is an important prognostic factor; in other words, the survival rate or recurrence rate of node-negative EGC is known to be much better than that of node-positive EGC. The incidence of EGC among resected gastric cancers was 14.7%, and has been increasing annually. The mean age of the EGC patient was 52.4 years, and the most common type was IIc. The size of the lesion was variable, but the most common range was 1~3 cm. Lymph-node metastasis accurred more frequently with the larger sized lesions. In this study, several factors such as age, sex, tumer location, tumer size, depth of invasion, macroscopic and histologic type were evaluated to determine frequency of lymph node metastasis. In the analysis of these eight facters, sex, tumer size, depth of invasion and Lauren type were statistically correlated with lymp node metastasis.
Asian Continental Ancestry Group ; Endoscopy ; Humans ; Incidence ; Lymph Nodes* ; Mucous Membrane ; Neoplasm Metastasis* ; Prognosis ; Recurrence ; Stomach Neoplasms* ; Survival Rate

Purpose: To investigate the baseline characteristics in patients with diabetic macular edema (DME) during 7 years according to the need for additional treatments after intravitreal ranibizumab (RBZ) loading injections. Methods: The medical records of 32 patients treated with intravitreal RBZ loading for DME during 7 years were reviewed. After three-consecutive monthly RBZ injections, additional treatment was decided according to the patient’s response to RBZ loading. Based on whether the patients received treatment with or without additional injections, including intravitreal antivascular endothelial factor or steroid injection, they were divided into the “no add (NA)” or “add” groups, respectively. The baseline best-corrected visual acuity (BCVA), macular volume (MV), central subfoveal thickness, and other clinical factors were analyzed, and their 7-year changes were compared between the two groups. Results: The BCVA of the NA group was better than that of the add group at 2, 3, 5, and 7 years (year 2, 3, and 5; p < 0.01, respectively). Baseline MV was significantly smaller in the NA group than in the add group (10.72 ± 0.88 μm vs. 11.98 ± 1.64 μm, p = 0.008). The DME duration before treatment in the NA group was significantly shorter than in the add group (1.03 ± 0.98 years vs. 1.91 ± 1.33 years, p = 0.042). The proportion of patients with serous retinal detachment or cystic macular edema was significantly lower in the NA group than in the add group (35.3% vs. 73.3%, p = 0.042). The NA group had smaller MV until 2 years than the add group (year 1, p = 0.002; year 2, p = 0.006). Conclusions The DME patients without additional treatments during 7 years after the initial loading treatment had shorter duration of DME and diffuse retinal thickening morphologic type with lower MV at baseline, and better long-term visual prognosis.

Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused by defects in a variety of genes. The goal of our study was to determine the clinical features and to analyze gene mutations in a large cohort of Korean patients with sporadic or familial IH. We recruited 23 patients. They showed a broad range of onset age and various values of biochemical data. Whole exome sequencing was performed on two affected cases and one unaffected individual in a family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA. In one family who underwent the whole exome sequencing analysis, approximately 300 single nucleotide changes emerged as candidates for genetic alteration. Among them, we identified a functional mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous gain-of-function mutations in the CASR gene were found in other subjects; D410E and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro-PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current study represents a variety of biochemical phenotypes in IH patients with the molecular genetic diagnosis of IH.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Cohort Studies ; Heterozygote ; Humans ; Hypoparathyroidism/diagnosis/*genetics/pathology ; Middle Aged ; Nuclear Proteins/*genetics ; Parathyroid Hormone/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Calcium-Sensing/*genetics ; Registries ; Republic of Korea ; Transcription Factors/*genetics ; Young Adult

BACKGROUND: Relationships among portable scanning mobility particle sizer (P-SMPS), condensation particle counter (CPC), and surface area monitor (SAM), which are different metric measurement devices, were investigated, and two widely used research grade (RG)-SMPSs were compared to harmonize the measurement protocols. METHODS: Pearson correlation analysis was performed to compare the relation between P-SMPS, CPC, and SAM and two common RG-SMPS. RESULTS: For laboratory and engineered nanoparticle (ENP) workplaces, correlation among devices showed good relationships. Correlation among devices was fair in unintended nanoparticle (UNP)-emitting workplaces. This is partly explained by the fact that shape of particles was not spherical, although calibration of sampling instruments was performed using spherical particles and the concentration was very high at the UNP workplaces to allow them to aggregate more easily. Chain-like particles were found by scanning electron microscope in UNP workplaces. The CPC or SAM could be used as an alternative instrument instead of SMPS at the ENP-handling workplaces. At the UNP workplaces, where concentration is high, real-time instruments should be used with caution. There are significant differences between the two SMPSs tested. TSI SMPS showed about 20% higher concentration than the Grimm SMPS in all workplaces. CONCLUSIONS: For nanoparticle measurement, CPC and SAM might be useful to find source of emission at laboratory and ENP workplaces instead of P-SMPS in the first stage. An SMPS is required to measure with high accuracy. Caution is necessary when comparing data from different nanoparticle measurement devices and RG-SMPSs.
Calibration ; Nanoparticles*

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.
Animals ; Dimethyl Sulfoxide ; Fibroblasts* ; Gene Expression ; Hepatocytes* ; Methods ; Mice ; Myocytes, Cardiac ; Neurons ; Phenotype ; Pluripotent Stem Cells ; Stem Cells ; Transcription Factors

Transgenic (TG) pigs are important in biomedical research and are used in disease modeling, pharmaceutical toxicity testing, and regenerative medicine. In this study, we constructed two vector systems by using the promoter of the pig glial fibrillary acidic protein (pGFAP) gene, which is an astrocyte cell marker. We established donor TG fibroblasts with pGFAP-CreER(T2)/LCMV-EGFP(LoxP) and evaluated the effect of the transgenes on TG-somatic cell nuclear transfer (SCNT) embryo development. Cleavage rates were not significantly different between control and transgene-donor groups. Embryo transfer was performed thrice just before ovulation of the surrogate sows. One sow delivered 5 TG piglets at 115 days after pregnancy. Polymerase chain reaction (PCR) analysis with genomic DNA isolated from skin tissues of TG pigs revealed that all 5 TG pigs had the transgenes. EGFP expression in all organs tested was confirmed by immunofluorescence staining and PCR. Real-time PCR analysis showed that pGFAP promoter-driven Cre fused to the mutated human ligand-binding domain of the estrogen receptor (CreER(T2)) mRNA was highly expressed in the cerebrum. Semi-nested PCR analysis revealed that CreER(T2)-mediated recombination was induced in cerebrum and cerebellum but not in skin. Thus, we successfully generated a TG pig with a 4-hydroxytamoxifen (TM)-inducible pGFAP-CreER(T2)/EGFP(LoxP) recombination system via SCNT.
Animals, Genetically Modified ; Astrocytes ; Central Nervous System ; Cerebellum ; Cerebrum ; DNA ; Embryo Transfer ; Embryonic Development ; Estrogens ; Female ; Fibroblasts ; Fluorescent Antibody Technique ; Glial Fibrillary Acidic Protein ; Humans ; Nuclear Transfer Techniques ; Ovulation ; Polymerase Chain Reaction ; Pregnancy ; Real-Time Polymerase Chain Reaction ; Recombination, Genetic ; Regenerative Medicine ; RNA, Messenger ; Skin ; Swine ; Tissue Donors ; Toxicity Tests ; Transgenes

Background: Ammonia and hydrogen sulfide are harmful gases generated during aerobic/anaerobic bacterial decomposition of livestock manure. We evaluated ammonia and hydrogen sulfide concentrations generated from workplaces at livestock farms and determined environmental factors influencing the gas concentrations. Methods: Five commercial swine farms and five poultry farms were selected for monitoring. Real-time monitors were used to measure the ammonia and hydrogen sulfide concentrations and environmental conditions during the manure-handling processes. Monitoring was conducted in the manure storage facility and composting facility. Information on the farm conditions was also collected through interview and walk-through survey. Results: The ammonia concentrations were significantly higher at the swine composting facilities (9.5–43.2 ppm) than at other manure-handling facilities at the swine and poultry farms, and high concentrations of hydrogen sulfide were identified during the manure agitation and mixing process at the swine manure storage facilities (6.9–19.5 ppm). At the poultry manure-handling facilities, the ammonia concentration was higher during the manure-handling processes (2.6–57.9 ppm), and very low hydrogen sulfide concentrations (0–3.4 ppm) were detected. The air temperature and relative humidity, volume of the facility, duration of manure storage, and the number of animals influenced the gas concentrations. Conclusion A high level of hazardous gases was generated during manure handling, and some levels increased up to risk levels that can threaten workers' health and safety. Some of the farm operational factors were also found to influence the gas levels. By controlling and improving these factors, it would be possible to protect workers' safety and health from occupational risks.

Purpose: To investigate the oxidative damage and changes of retinas by blue light through zebrafish and to confirm the protective effect of polyphenol on retina cells using grape seed-derived polyphenols. Methods: To induce oxidative damage and changes of the retina by blue light, blue light LED (10,000 Lux, 480 nm) was added to the zebrafish grown in the dark room after pretreating polyphenols derived from grape seed at various concentrations (0, 0.1, 1, 10 μg/mL, respectively) for 4 days. Changes in retinal thickness and numbers of outer nuclear layer nuclei through hematoxylin & eosin staining were evaluated. Results: Photoreceptor layer thickness of blue light exposed group was significantly thinner than the group without blue light (108.1 ± 27.7 μm vs 41.1 ± 17.0 μm). As pretreated polyphenol concentration increased, photoreceptor layer thickness was increased (41.1 ± 17.0, 56.3 ± 18.6, 90.7 ± 23.7, 99.1 ± 23.1 μm, p < 0.05), and damage to outer nuclear layer nuclei was also decreased. Conclusions Exposure to blue light is an important factor for increasing oxidative stress in the retina. Grape seed-derived polyphenols have been shown to protect photoreceptor cells and retinal pigment epithelial cells from oxidative stress. This suggests that the antioxidant effect of polyphenol compounds may help suppress the progression of retinal diseases associated with oxidative stress such as age-related macular degeneration.