• Journal of Life Science
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• v.34 no.9
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• pp.609-619
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• 2024

Neurodegenerative diseases are marked by the accumulation of toxic misfolded proteins in neurons. Therefore, strategies for the effective prevention and clearance of aggregates are crucial for therapeutic interventions. Cytoplasmic dynein plays a crucial role in the clearance of aggregates by transporting them to the cell center, where lysosomes are enriched and the aggregates undergo extensive autophagic degradation. Previously, we reported evidence for the activation of dynein by N-acetylglucosamine kinase (NAGK) and Reln. In the present study, we explored the effects of NAGK and Reln upregulation on the clearance of aggregates. To upregulate NAGK and Reln genes in HEK293T cells (a human embryonic kidney cell line), CRISPR/dCas9 activation systems (CASs) were used with specific plasmids encoding target-specific 20 nt guide RNA. The effects of this genetic modulation were analyzed in Huntington's disease cellular models, including HEK293T cells and primary mouse cortical cells, where external mutant huntingtin (mHtt, Q74) aggregates were induced. The results showed that the CAS activation of NAGK or Reln, or their combination, significantly reduced the proportion of cells with Q74 aggregates (aggresomes). This effect was reversed by Ciliobrevin D (a dynein inhibitor) and chloroquine (an autophagy inhibitor), indicating the role of dynein-mediated autophagy in aggregate clearance. These findings provide the basis for therapeutic strategies aimed at enhancing neuronal health through targeted gene activation.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.166-173
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• 2003

Purpose : The cause and pathogenesis of $Henoch-Sch\"{o}nlein$ purpura has been studied for many years but the results are disappointing. Recently the hypothesis that abnormalities involving the glycosylation of the hinge region of immunoglobulin Al(IgAl) may have an important role in the pathogenesis of $Henoch-Sch\"{o}nlein$ purpura is being approved. $Henoch-Sch\"{o}nlein$ purpura is the most common vasculitis Ihat affects children and the prognosis is good. But if kidney invovement occurs, the course may be chronic and troublesome. So we evaluated children with $Henoch-Sch\"{o}nlein$ purpura especially from the point of epidemiology and clinical manifestations. Methods : Investigation of 124 children who were diagnosed with $Henoch-Sch\"{o}nlein$ purpura at Inje University Ilsan Paik Hospital from December 1999 to July 2003 was performed retrospectively through chart review. Efforts were made to get informations about the profile, epidemiology, clinical manifestations, progress of the disease and recurrence rate of patients. Results : The patients were 69 boys and 55 girls, with a mean age of $6.1{\pm}2.7$ years at the time of data collection. The male to female ratio was 1.25 : 1. The occurrence rate was much higher in autumn(from September to November, 31.5%) and winter(from December to February, 28.2%) than in spring and summer, with a peak in November. Joint involvement was shown in 66.9% of patients mostly on the foot/ankle(75.9%), knee(39.8%). Seventy(56.5%) out of 124 patients had abdominal pain and 10 patients(8.1%) showed bloody stools. Renal involvement was observed in 24 patients(19.4%) after 21.1 days on the average. IgA was elevated in 10 of 21 patients(47.6%). $C_3$ and $C_4$ levels were normal in 40 of 49 patients (81.7%) and 47 of 48 patients(97.9%), respectively Antistreptolysin-O(ASO) titer was elevated over 250 Todd units in 29 of 62 Patients(46.8%). Mycoplasma antibody titer was elevated in 21 of 49 patients(42.9%) equal or greater than 1:80. Radiologic studies were peformed in 23 patients. Seven patients(30.4%) showed bowel wall thickening and one of them received intestinal resection and anastomosis operation due to terminal ileum necrosis. Eighty four patients took steroid 1.4 mg/kg/day in average. Recurrence rate was 2.5 in 37 patients(29.8%). Conclusion : $Henoch-Sch\"{o}nlein$ purpura in childhood appears most in about 6 years of age. The occurrence rate is much higher in autumn and winter relatively. Diagnosis can be made through the perspective history taking and the inspection of clinical manifestations, but the laboratory findings are not of great help. A small portion of the patients might show abdominal pain or arthritis before purpura develops, therfore various diagnosis can be made. Radiologic evaluation should be performed to avoid surgical complications in cases accompanying abdominal pain, and long term follow up should be needed especially in patients suffering from kidney involvement. In about 30% of the patients $Henoch-Sch\"{o}nlein$ purpura would recur. Steroid can be used safely without side effects.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.222-230
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• 2005

Purpose : ARC syndrome refers to an association of arthrogryposis, renal tubular dysfunction, and cholestasis. The VPS33B gene was recently identified as the causative gene. So far, 41 cases of ARC syndrome have been reported worldwide, and it has rarely been reported in Korea. This study was conducted to report the clinical findings of seven ARC syndrome cases in Korean children, focusing especially on renal tubular dysfunction. Methods : The hospital records of 7 cases diagnosed as ARC syndrome at Severance Hospital between Mar. 1995 and Aug. 2005 were reviewed and analyzed. Results : Of the 7 cases, 4 were boys and 3 were girls. Six patients(85$\%$) were born with normal birth weight at term, and one was born at preterm. All cases presented with cholestasis and severe jaundice. According to the type of arthrogryposis described by Brown et al, type 3 and 4 were found in 2 patients and type,6, 7, and the undistributed type in one patient respectively. Other associated clinical findings were as follows : failure to thrive in 6(85$\%$), lax skin in 5(71$\%$), and gray platelet syndrome in 4(57$\%$). Urine analysis revealed 6 cases(85$\%$) with proteinuria, 3(43$\%$) with hematuria, 5(71$\%$) with glycosuria, 2(29$\%$) with phosphaturia and 2(29$\%$) with calciuria. Serum electrolytes showed 4 cases(57$\%$) with hyponatremia, 3(43$\%$) with hypokalemia, and 1(14$\%$) with creatinine elevation. Renal tubular dysfunctions were diagnosed as renal tubular acidosis in 6 cases(85$\%$), nephrogenic diabetes insipidus in 2(29$\%$), and Fanconi syndrome in 2(29$\%$). During the follow-up period, 2(29$\%$) had no treatment, 5(85$\%$) had continuous supplementation to correct the electrolyte imbalance and acidosis, and 1(14$\%$) had dialysis. Only one patient had a family history of ARE syndrome in a sibling. Four cases(57$\%$) were diagnosed at the mean age of 8.2 months, and one case was lost during follow-up. Ages of the survived 2 cases were 13 and 25 months, respectively. Conclusion : The rare disease of ARC syndrome Is associated with severe renal dysfunction. However, this study revealed that the renal manifestation of ARC syndrome in Korean children is relatively mild and survival rate is higher than that of previous studies. Contrary to previous reports, this study showed that familial cases are rare and sporadic occurence is possible in Korea. Thus, the diagnosis of this syndrome requires a careful evaluation of the venal function in cases of congenital arthrogryposis, and a mandatory genetic counseling of affected family for prevention of familial occurance. (J Korean Soc Pediatr Nephrol 2005;9:222-230)

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.215-221
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• 2010

Purpose : Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (${\leq}4$ and >$4mg/m^2/h$, ${\leq}40$ and >$40mg/m^2/h$, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>$4mg/m^2/h$) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-.66, P <0.001; dominant model OR 0.35, 95% CI 0.17-.69 P =0.002; recessive model OR 0.12, 95% CI 0.01-.06 P =0.025). Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.421-425
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• 2012

Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on the economic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of the extent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put in place effective cancer control policies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.104-108
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• 2002

Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidized low density lipoproteins (LDL). We studied the effect of Korean wheat on the oxidizability of LDL and the development of experimental atherosclerosis in rabbits on cholesterol diet. For the approach of the aim, antioxidative activity of wheat extracts against oxidation of LDL was investigated. The antiatherogenic effect of wheat was studied against Newzealand whithe (NZW) rabbits fed containing the wheat powder for 12 weeks. PBS extracts of Korean and imported wheats decreased LDL oxidation induced by copper ion by 62.3%, 52.6% respectively in comparison with control. Liver thiobarbituric acid reactive substance (TBARS ) levels of rabbits were significantly lowered in Korean wheat fed group (0.397$\pm$ 0.029 nmol MDA/mg protein, p<0.05) compared to control (0.496$\pm$0.021 nmol MDA/mg protein) and imported wheat group (0.478$\pm$0.019 nmol MDA/mg protein). TBARS levels of kidney showed no significant difference among treatment groups. The aorta of cholesterol-fed rabbits showed typical atherosclerotic lesions when compared with the controls, but the microscopic differences between groups was not clear. The present study suggests that Korean wheat may have higher antioxidative capacity than imported wheat and have more beneficial effects for the treatment of disease by inhibiting the oxidation of LDL.

• Journal of Environmental Policy
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• v.12 no.1
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• pp.75-100
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• 2013

Health damages such as pneumoconiosis and kidney damage, caused by environmental hazardous factors are being reported in health impact assessment conducted on environmentally vulnerable areas, including cement factories and refineries. Current legal system for relieving the environmental victims is not effective enough because the environmental health act does not specify the environmental hazardous factors to be considered for the relief. The aim of this study is to examine the problems of the existing system by making empirical analysis on health damages and afflicted people as well as on cases when afflicted people were able to be covered by remedy system. The results show that, insufficiencies of the relief system are due to the following reasons: First, current Environmental Health Act does not act well as a remedy system. Second, due to its unique nature of environmental health damage, it is hard to identify and prove the cause of health damage and unlawful actions of violators in the process of environmental dispute conciliation and lawsuits against polluters. This paper suggests following solutions on above mentioned problems. First, in defining the range and definition of environmental diseases, negative system should be used alongside with the current positive system. Second, we suggest adding the nature of public law to relief system, in order to ease the legal burden of proof. Third, in case when it is hard to identify the polluters and one cannot expect reliefs for their damage, it is possible to elevate the effectiveness of the relief measure by expanding scope of the search for possible environmental hazardous factors that caused the health damage. It is urgent to improve the relief system so as to secure the environmental rights of Koreans.

• The Korean Journal of Nuclear Medicine
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• v.25 no.2
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• pp.227-236
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• 1991

Background: The evaluation of individual renal function is important to diagnosis and follow-up of various diseases. Ureteral catheterization of each kidney has been widely used for this purpose, but this method had some technical difficulty, frequent complications and much restriction in reapplication. Therefore we tried to applicate radiopharmaceuticals for the evaluation of individual renal function. Methods: We measured 2 hour, 4 hour and 24 hour relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ with 59 patients with various renal diseases to determine their usefulness for assessment of individual renal function and to compare correlations between every renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate. Results: The correlations between 2 hour-, 4 hour- and 24 hour- relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ were R=0.9190 (p < 0.001), R: 0.9229 (p<0.001) and R=0.9917 (p<0.001). In acute obstructive uropathy, the correlations at 2 hour and 4 houre were poor as R=0.1812 (p<0.05) and R=0.4923 (p < 0.05), but the correlation at 24 hour was good as R=0.9942 (p<0.001). Conclusions: We concluded that relative renal uptake at 2 hour and 4 hour had good correlation with relative DTPA uptake ratio in the cases without chronic renal failure and obstructive uropathy. Delayed image with 24 hour relative renal uptake $^{99m}Tc-DTPA$ had the best correlation with relative glomerular filteration rate of $^{99m}Tc-DTPA$ and that might be useful in evaluation of chronic renal disease in which showed increased beckground activity or acute obstructive uropathy.

• Journal of Veterinary Clinics
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• v.29 no.6
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• pp.435-440
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• 2012

This study was designed to evaluate the clinical efficacy and safety of Rhubarb extracts ($Rubenal^{(R)}$) in dogs with chronic renal failure (CRF). Client-owned 40 dogs with CRF graded International renal interest Society (IRIS) II-III were enrolled in this study. The dogs were equally allocated and blindly administered with $Rubenal^{(R)}$ or placebo. The following items were evaluated at day 0, 30, 90 and 180: body condition score (BCS), clinical score (appetite, polydipsia/polyuria, quality of life score), hemogram (WBC, RBC, PCV), serum biochemistry (ALT/AST, ALP, Creatinine/BUN, total protein, albumin), serum electrolyte (Na, K, Cl, Ca, P), systolic blood pressure, urinalysis (UPC, USG) and IRIS stage. In this study, we found that the $Rubenal^{(R)}$ preparation was well tolerated by dogs and induced no adverse effects. Statistically significant improvements were observed in clinical score (quality of life score by vet and clients), serum BUN and creatinine levels, serum phosphorus concentration, level of proteinuria, and the IRIS score of CRF in dogs after 6 month of treatment of $Rubenal^{(R)}$. Those findings suggested that the Rhubarb extracts can improve the clinical signs of CRF (i.e. azotemia, hypertension, proteinuria, hyperphosphoremia) and the quality of life (i.e. BCS, clinical score) and can retard the progression of CRF in dogs. Therefore the Rhubarb extracts can be a good supplementary drug for treating dogs with subclinical and clinical renal diseases. However, care should be taken for interpreting our result, because this study is not double-blinded controlled study but pilot study.

• Journal of Nutrition and Health
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• v.34 no.1
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• pp.48-53
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• 2001

As the severity of environmental pollution increases, the foodstuffs are contaminated more the ever. There are 40 kinds of heavy metals that we are able to consume through the heavy metal contaminated-foodstuffs. Arsenic, lead, cadmium, and chromium out or them have been know to be a potential cause for a alzheimers disease, kidney diseases, and cancer. However, research data on the daily intakes of such heavy metals are limited. This study was performed to evaluate the daily intakes of nutrients and the dietary heavy metals of the college women living in Choongchung-NamDo Area, where had been reported to have high contents of heavy metals for the seafoods. We also investigated the blood levels of the heavy metals. The mean age, height, weight, BMI and percent ideal body weight(PIBW) of the subjects were 20$\pm$1.0yr, 158.4$\pm$0.7cm, 55.1$\pm$1.4kg, 22.4$\pm$.04, and 103.3$\pm$2.5 %, resp-ectivly. The mean of daily energy intake was 1,717.03$\pm$55.99kacl/day(86% of RDA for women). The ratio to energy from carbohydrate, fat and protein was 60: 24: 16. Daily intakes of Vit A, Vit B$_2$, CA, and Fe were under the RDA for those nutrients. The mean adequate ratio of the subjects was 0.92 . The daily intakes of heavy metal, such as As, Pb, Co, Cr and Mn , were 1.80$\pm$0.27mg, 75.21$\pm$4.12$\mu\textrm{g}$, 21.12$\pm$12.34$\mu\textrm{g}$, 60.07$\pm$6.24$\mu\textrm{g}$ and 6.23 $\pm$0.12mg respectively. the blood levels of As, Pb, Co, Cr and Mn were 16.10$\pm$2.10$\mu\textrm{g}$/dl, 4.32$\pm$0.58$\mu\textrm{g}$/dl, 0.02$\pm$0.01$\mu\textrm{g}$/dl, 4.23$\pm$0.41$\mu\textrm{g}$/dl, and 4.40$\pm$0.21$\mu\textrm{g}$/dl, respectively. In conclusion, daily intake of heavy metals for the college women living in Choongchung-NamDo area was lower than that of WHOs re-commendation, however, the blood levels of each heavy metals were higher than those of Japanese, american, and italian, There were no correlations between the dietary intakes and blood levels of each heavy metals. (Korean J Nutrition 34(1):48-53, 2001)