Robust and Reproducible Generation of Induced Neural Stem Cells from Human Somatic Cells by Defined Factors

Background and Objectives@#Recent studies have described direct reprogramming of mouse and human somatic cells into induced neural stem cells (iNSCs) using various combinations of transcription factors. Although iNSC technology holds a great potential for clinical applications, the low conversion efficiency and limited reproducibility of iNSC generation hinder its further translation into the clinic, strongly suggesting the necessity of highly reproducible method for human iNSCs (hiNSCs). Thus, in orderto develop a highly efficient and reproducible protocol for hiNSC generation, we revisited the reprogramming potentials of previously reported hiNSC reprogramming cocktails by comparing the reprogramming efficiency of distinct factor combinations including ours. @*Methods@#We introduced distinct factor combinations, OSKM (OCT4+SOX2+KLF4+C-MYC), OCT4 alone, SOX2 alone, SOX2+HMGA2, BRN4+SKM+SV40LT (BSKMLT), SKLT, SMLT, and SKMLT and performed comparative analysis of reprogramming potentials of distinct factor combinations in hiNSC generation. @*Results@#Here we show that ectopic expression of five reprogramming factors, BSKMLT leads the robust hiNSC generation (>80 folds enhanced efficiency) from human somatic cells compared with previously described factor combinations. With our combination, we were able to observe hiNSC conversion within 7 days of transduction. Throughout further optimization steps, we found that both BRN4 and KLF4 are not essential for hiNSC conversion. @*Conclusions@#Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

Inhibitory effects of a beta-dunnione compound MB12662 on gastric secretion and ulcers / 한국실험동물학회지

The effects of a beta-dunnione compound MB12662 on the gastric secretion and ulcers were investigated in rats. In order to assess the effects of MB12662 on the gastric secretion and acidity, rats were subjected to pylorus ligation operation, and 6 hours later, gastric fluid was collected. Treatment with MB12662 reduced the gastric fluid volume to 47.3% of control level and increased pH. In an alcohol-induced ulcer model, rats were orally administered 3 mL/kg of ethanol, and 1 hour later, the ulcer lesions ware measured under a stereomicroscope. MB12662 reduced ulcer index in a dose-dependent manner which was much stronger than a proton-pump inhibitor pantoprazole. In a stress-induced ulcer model, rats were subjected to water-immersion restraint stress, and 5 hours later, the ulcer lesions ware examined. MB12662 also attenuated the stress-induced gastric lesions, although the efficacy of MB12662 was lower than that of pantoprazole. Therefore, it is suggested that MB12662 could be a candidate compound for the prevention or treatment of gastric ulcers induced by gastric over-secretion and alcoholic hangover.

A Study of Periodic Health Examination of the First Grade of High School in Seongnam City

BACKGROUND: It is evident that obesity and other associated chronic diseases are increasing. Since 1998, periodic health examination has been taken in the first grade of high school in accordance with the law nationally and will be expanded to other grades. We evaluated the health status of this population and thought the problems and pitfalls of this program. METHODS: We took 983 students of the first grade of high school in Seongnam city from April to June 2002. We used the questionnaire and test results as the first line methods of evaluation. Phone counselling was used as the follow-up method. Chi-square test was the main analytic method. RESULTS: Impaired visual acuity and absence of hepatitis B viral antibody were shown in over 40% of this population. Obesity, anemia, hyperlipidemia, hypertension were followed as the next most popular problems. Though 7.9% of 983 students were to be examined again, only 53.8% of them were re-examined. 52.7% of the student who took re-examination was proved normal. 47% of the test students thought that they were not healthy. Over half of students had the problems of exercise and eating behavior. CONCLUSION: We concluded that many students had the behavioral problems causing the chronic diseases. Medical prevention and education program is needed and medical faculties must participate in these programs. In periodic health examination various follow-up programs and screening-questionnaires on psychologic problems must be invented and applied for students.

A Study of Periodic Health Examination of the First Grade of High School in Seongnam City

BACKGROUND: It is evident that obesity and other associated chronic diseases are increasing. Since 1998, periodic health examination has been taken in the first grade of high school in accordance with the law nationally and will be expanded to other grades. We evaluated the health status of this population and thought the problems and pitfalls of this program. METHODS: We took 983 students of the first grade of high school in Seongnam city from April to June 2002. We used the questionnaire and test results as the first line methods of evaluation. Phone counselling was used as the follow-up method. Chi-square test was the main analytic method. RESULTS: Impaired visual acuity and absence of hepatitis B viral antibody were shown in over 40% of this population. Obesity, anemia, hyperlipidemia, hypertension were followed as the next most popular problems. Though 7.9% of 983 students were to be examined again, only 53.8% of them were re-examined. 52.7% of the student who took re-examination was proved normal. 47% of the test students thought that they were not healthy. Over half of students had the problems of exercise and eating behavior. CONCLUSION: We concluded that many students had the behavioral problems causing the chronic diseases. Medical prevention and education program is needed and medical faculties must participate in these programs. In periodic health examination various follow-up programs and screening-questionnaires on psychologic problems must be invented and applied for students.

The Relationship between Seven Health Habits (Alameda 7) and Health-related Quality of Life

BACKGROUND: The purpose of this study was to investigate the relationship between 7 health habits and health-related quality of life using the SF-36 questionnaires. METHODS: The subjects for this study were 550 workers in Seongnam City, Kyonggi Province, Korea. Data were collected by using constructed questionnaires from 11 September 2004 to 25 September 2004. Statistical analyses were conducted using SPSS. RESULTS: There were positive relationships of favorable health habits as indicated by Alameda 7 to health-related quality of life. After controlling for the effects of confounding cofactors that included age, sex, diseases, and other health habits, multiple regression analysis indicated as follows. 1) The item of 'eating breakfast everyday' were significantly related to the grade of social function (SF) and bodily pain (BP). 2) The item of 'sleeping for 7~8 hours a day' were significantly related to all domains of the SF-36 except physical function (PF). 3) The item of 'normal Body Mass Index' were significantly related to the grade of Role limitations-emotional (RE). 4. The item of 'regular physical exercise' were significantly related to the grade of general health (GH), physical function (PF), Vitality (VT), and mental health (MH). Other health habits like not snacking between meals, never smoking, and low alcohol consumption were not associated with any of the SF-36 profiles. CONCLUSION: There were positive relationships of favorable health habits to health-related quality of life. It is important to have favorable health habits for good health-related quality of life.

A Study of Treatment Realities and Recognition of Male Osteoporosis

BACKGROUND: Osteoporosis has been thought of as a disease of women, but the incidence of male osteoporosis is increasing and is expected to keep rising due to alcohol abuse, smoking and increased life expectancy for men. This study was done to evaluate how many men recognized the significance of osteoporosis and its management. METHODS: There were 138 male subjects who underwent Bone Mineral Density (DEXA) from January 2000 to August 2003 at Sung Nam Central Hospital. We reviewed their BMD results and formed questionnaires which were constructed to evaluate men's recognition and treatment realities of osteoporosis. Telephone interviews and mailing services were utilized. The respondents were 96 (69.6%) and analysis was done. RESULTS: The average age of the 138 men was 55. Among them, there were 55 (39.9%) and 68 (49.3%) men who had been diagnosed with osteopenia and osteoporosis, respectively. Information on osteoporosis was obtained mainly from mass media like TV and newspaper (57.3% of total answers). The reason for undergoing test for osteoporosis was related to the annual screening tests (40.6% of total answers). Most of these people were likely to ignore the significance of osteoporosis, because only 26 percent answered they should receive proper treatment in case of osteoporosis although they did not have any symptoms at the time of the diagnosis. Among these osteoporotic patients, 76.7 percent did not seek any medical care and the most common reason for refusal to treatment was no existing symptoms for osteoporosis. Among the total, 67.4 percent of the patients said there had been no change of life behavior after the diagnosis. CONCLUSION: We found that men had relatively more knowledge of osteoporosis than we expected, but they knew little about the need for treatment and possible severe complications like major fractures that may occur. Also, we found the diagnosis of osteoporosis has little effect on behavioral changes. In conclusion, family physicians should take more interest in the education of patients to increase compliance for its treatment.

Heart Rate Variability in Metabolic Syndrome

BACKGROUND: Metabolic syndrome is a cluster of multiple cardiovascular risk factors. There are many suggestions that decreased Heart Rate Variability (HRV) is associated with cardiovascular disease. The purpose of this study was to find out the association between metabolic syndrome and HRV and to find out the affecting factors to HRV. METHODS: The study subjects were people who visited a health promotion or obesity center of a medical college in Suwon from January to February, 2002. Healthy 149 subjects were divided into two groups of metabolic vs non-metabolic syndrome. Mean Heart Rate (MHR), Standard Deviation of N-N interval (SDNN), The Square Root of the Mean Squared Difference of successive NN intervals (RMSSD), Total Power (TP), Low Frequency (LF), High Frequency (HF), and LF/HF ratio were used as the indices of HRV. T-test was used to compare the HRV of metabolic and non-metabolic syndrome, and multiple regression analysis was used to find out the affecting factors to HRV. RESULTS: HRV indices were significantly lower in metabolic syndrome. The mean+/-SD of SDNN, RMSSD, TP, LF, HF of metabolic vs non-metabolic syndrome was 39.2+/-14.5 vs 32.9+/-10.8 (ms, P=0.015), 30.5+/-14.6 vs 23.3+/-11.6 (ms, P=0.006), 1270.0+/-975.3 vs 893.2+/-652.6 (ms2, P=0.028), 354.4+/-410.8 vs 198.3+/-259.2 (ms2, P=0.008), 273.3+/-292.1 vs 148.9+/-137.2 (ms2, P=0.001), respectively. RMSSD and LF significantly decreased in the hypertensive group. Parameter estimate was 5.52 (ms, P=0.041), and 217.63 (ms2, P=0.002), respectively. TP and LF decreased as HDL cholesterol decreased. Parameter estimate was 24.31 (ms2, P=0.02), 11.12 (ms2, P=0.008), respectively. CONCLUSION: The HRV decreased in metabolic syndrome, and BP and HDL-cholesterol significantly affected HRV.

Clinical observation on balaria in Kang Hwa Hospital

BACKGROUND: In the Republic of Korea, there had been no reports about indigenous malaria cases since 1984 until a vivax malaria case was detected in 1993. Thereafter fram 1993 to 1996, 486 malaria cases were reported. Most of the patients were soldiers in the northern militarized zone. However, since 1997, several patients with malaria were detected in Kang Hwa where there had previously been no report of malaria cases. It is our intent to report the 16 cases diagrnosed in Kang Hwa Community Hospital from January 1, 1997 to August 10, 1998. METHODS: Medical records of the malaria cases from January 1, 1997, to August 10, 1998 in Kang Hwa Community Haspital were reviewed. All of the patients had no histories of traveling abroad, drug abuse or blood transfusion. They were all civilians. Laboratory studies including blood cell count, routine chemistry and platelet-associated IgG(PAIgG) and abdominal sanography were taken. RESULTS: All of the patients were diagnosed with malaria by blood smears. Common symptams were fever(100%), headache(94%), rigors(81%), myaJgia(56%), nausea or vomiting(44%), alternate day fever (25%), left flank pain(19%), diarrhea(13%), and abdominal pain(13%). Splenomegaly was detected in 92% of cases by sonography. Laboratory findings included leukopenia(37.5%), anemia(37.5%) and thrombocytopenia(81.3%). Platelet-associated IgG was elevated in 1 of 5 thrombocytopenic patients who had had the laboratory study performed. All recovered withaut complications. CONCLUSIONS: Cases of indigenous malaria have been progressively increasing in the Republic of Korea. Fortunately, patients responded well to treatment, but continued interest will be required in the future.