1.The War on Anti-Aging Medicine.
Journal of the Korean Geriatrics Society 2005;9(1):1-14
Anti-aging medicine has become a popular topic, in the lay press, the (semi-) scientific literature and the Internet. In almost all instances, claims of drugs, health supplements and other types of intervention are not based on any evidence supported by sound scientific knowledge. Specifically, the aging process itself, in contrast to age-related diseases, has so far neither been fully understood, nor significantly influenced in higher species, notably humans. In addition to the ill-defined effects, claims of anti-aging medicine also pose a considerable economic burden on the usually poorly informed older segment of the population. The present paper is based on a recent report by the United States General Accounting Office (GAO) on the questionable and even harmful effects of anti-aging health products for seniors
Aging
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Humans
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Internet
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United States
2.Coefficient Variations of Serum Levels of Phenytoin, Carbamazepine, and Valproic Acid in Compliant Epileptics.
Hae Jung YUN ; O Y KWON ; K J PARK ; N G KIM ; T Y KIM ; S C JEON ; J G HONG ; J H KWAK ; Y H LEE ; N C CHOI ; B H LIM
Journal of the Korean Neurological Association 1999;17(1):72-78
Compliance of epileptic patients is one of the most important factors for adequate therapy. Recently, it had been shown that the variability of three serial measurement of the serum levels of antiepileptic drug(AED) may be used as an indication of the degree of compliance. Coefficient variation(CV) of serum drug levels calculated by only one AED had been used to determine the compliance in epileptic patients who took multiple AEDs. We attempted to evaluate the CV of AEDs and then find the objective clue of compliance and the compatible therapeutic planing according to CV. Ninety seven epileptic patients of outpatients department of the Gyengsang National University Hospital were entered to this study. All patients were taking medication at least for 6 months without any changes of drug regimen. Patient's information was acquired by reviewing the chart and interview with questionnaire. With these informations, we determined the compliance of the patients. Antiepileptic serum levels were measured three times at intervals of at least two to four weeks apart, and their CV was calculated. We compared the CV between the compliant and non-compliant group in each AED(phenytoin, carbamazepine , valproic acid) and three drugs in the compliant group. The mean CVs of phenytoin, carbamazepine and valproic acid in the compliant group were 18.3+/-13.0, 15.2+/-10.2 and 23.8+/-8.9, respectively(mean+/-SD). The mean of CV in the compliant and the non-compliant group were 17.9+/-10.9 and 38.8+/-27.2, respectively. The CVs of the compliant group were significantly lower than those of the non-compliant group(p<0.05). However, CVs had no significant difference between three antiepileptic drugs. This study showed that CVs of AEDs were not different between each AEDs, even though they possess different pharmacokinetic properties. Therefore, the CV of one AED can be used in determining the compliance of the epileptics who are taking multiple AEDs.
Anticonvulsants
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Carbamazepine*
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Compliance
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Humans
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Outpatients
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Phenytoin*
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Surveys and Questionnaires
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Valproic Acid*
3.Clinical Application of Nutrigenomics.
Mi Sun KWAK ; Ki Baik HAHM ; H J JOUNG
Journal of the Korean Medical Association 2006;49(2):163-172
Nutritional genomics (nutrigenomics) is the application of high-throughput functional genomics technologies to nutritional science lying in the interface between the nutritional environment and genetic process. It seeks to provide a molecular genetic understanding of how common dietary nutrition affects health by altering the expression or structure of an individual's genetic makeup. On the other hand, nutrigenetics is significantly different from nutrigenomics since nutrigenetics has been used for decades in certain rare monogenic diseases such as phenylketonuria, and has the potential to provide a basis for personalized dietary recommendation based on the individual's specific genetic background in order to prevent common multifactorial disorders decades before their clinical manifestation. The human genome maps and SNP databases, together with the rapid development of tools suitable for investigating genetic and epigenetic changes in small tissue biopsies provide the means to begin the test hypothesis about the mechanisms by which diet influences disease risk including cancer directly in human subjects, could be inevitable flatforms for clinical application to achieve targeted therapy in near future.
Biopsy
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Deception
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Diet
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Epigenomics
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Genetic Processes
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Genome
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Genome, Human
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Genomics
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Hand
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Humans
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Molecular Biology
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Nutrigenomics*
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Nutritional Sciences
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Phenylketonurias
4.The Superiority of M-Technology for the Hospital Information System: III. comparison of system performance between Relational Database Management System and M-Technology (Superiority of M in HIS).
Joyce H JEON ; Yun Sik KWAK ; Hune CHO ; Hyung Soo KIM
Journal of Korean Society of Medical Informatics 1998;4(2):43-48
In 1994, Ajou University Medical Center implemented a hospital information system with a relational database management system(Ingres) and underwent migration using newly improved M technology in 1996. In this paper, a comparison study of database performance between M and RDBMS is presented. Three different types of comparative studies were carried out on the performances of Ingres, Oracle 7.1 (Oracle) and M-Technology(Mumps). Two types of M are adopted to compare with Ingres: Standard M and Open M. The open M was used for DBMS and Standard M was used for writing applications. The system response time was compared by a simple bulk test in a simulated HIS environment. It was found that the performance of Open M was about 100 times faster than that of Ingres. In the live HIS environment, the performance of Open M was found to be 2-8 times faster than Ingres depending on the number of globals involved in the processing of transactions. The performance of Standard M and MSM-SQL was compared with that of Oracle by a simple bulk test in a simulated HIS environment and found that Standard M was more than 100 times faster than Oracle and MSM-SQL was on an average. 1.7 times faster than Oracle. The M was faster than Ingres and Oracle. Despite the cons of RDBMS already discussed, we have found very few pros of RDBMS if M is applied. We have found that conventional RDBMS requires redundant hardware resources which result in slow processing time which HIS manifests in a serious bottleneck during the course of our development and implementation. The performance of M strongly implies that M is most appropriate DB in a HIS environment.
Academic Medical Centers
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Database Management Systems*
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Hospital Information Systems*
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Reaction Time
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Writing
5.Chemical Dissolution of Intrahepatic Stones in Vitro.
Young Goo KIM ; Kun Sang KIM ; Jong Beum LEE ; Hyung Jin SHIM ; Sang Shin JOO ; Kyung H LEE ; Byung Gook KWAK ; Su Kyoung CHAE ; Hymn Mee PARK
Journal of the Korean Radiological Society 1995;33(6):945-948
PURPOSE: The in vitro dissolution of intrahepatic stones was evaluated using the various solvent mixtures. MATERIALS AND METHODS: Sixty four intrahepatic stones from 16 patients were used. Four kinds of solvent mixtures(No. 1 = basic buffer + EDTA, No. 2=1 + Sulfobetain-12, No. 3=2 + N-acetylcysteine, No. 4=3 + urea) were used. Dissolution rates were determined by measuring the weight loss of stones after 6, 12, 24, 48 hours incubation periods, respectively. RESULTS: The highest dissolution rates in dissolving intrahepatic stones were achieved with No. 4 solvent mixture(1% W/V EDTA/80mM, Sulfobetain-12/1 M, urea, pH 9.5). CONCLUSION: lntrahepatic stones could be largely dissolved up to about 70% of their initial weight after 48 hours incubation period in vitro.
Acetylcysteine
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Edetic Acid
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Humans
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Hydrogen-Ion Concentration
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Urea
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Weight Loss
6.The Factors Associated with Typical Pattern of Brain SPECT in Alzheimer's Disease.
Yong Tae KWAK ; Il Woo HAN ; Oh Young BANG ; Chan H PARK ; Min Seong KOO
Journal of Korean Neuropsychiatric Association 2001;40(3):496-502
OBJECTIVES: During the past few years, the development of functional brain imaging techniques has allowed to describe brain impairment in cognitive disorders. Among them, based on the observation of bilateral parietotemporal hypoperfusion in Alzheimer's disease(AD), single photon emission computed tomography(SPECT) is advocated by some as powerful diagnostic tool in the evaluation of demented patients. The aim of this study is to investigate the usefulness of SPECT in the diagnosis of AD and to clarify the associated factors of parietotemporal hypoperfusion, the typical SPECT pattern of Alzheimer's disease(AD). METHODS: We reviewed the SPECT scans of 26 patients fulfilling NINCDS-ADRDA criteria for probable AD, 14 with typical pattern of SPECT and 12 with atypical pattern of SPECT. Dementia severity was assessed by the Mini-Mental State Examination. Image interpretation was done visually by the consensus opinion of 2 experienced nuclear medicine physicians who were blind to clinical information. To estimate the association of typical pattern of SPECT with other variables of interest, discriminant function analysis was done. RESULTS: Though the overall diagnostic sensitivity of SPECT in AD was 53.8%, it was 76.9%, in early-onset AD patients. Typical pattern of SPECT was more frequent in the patients with early onset of the symptoms. Duration of symptoms, duration of education, sex, severity of disease was not associated with this SPECT pattern. CONCLUSION: These findings may be useful in the clinical setting and point to heterogeneity of AD according to age at onset.
Alzheimer Disease*
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Brain*
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Consensus
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Dementia
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Diagnosis
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Functional Neuroimaging
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Humans
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Nuclear Medicine
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Population Characteristics
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Sex Education
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Tomography, Emission-Computed, Single-Photon*
7.Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population
Heejin JIN ; Soo Heon KWAK ; Ji Won YOON ; Sanghun LEE ; Kyong Soo PARK ; Sungho WON ; Nam H. CHO
Diabetes & Metabolism Journal 2023;47(2):255-266
Background:
Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time.
Methods:
We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project.
Results:
A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level.
Conclusion
We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.
8.Nuclear factor of activated T cells negatively regulates expression of the tumor necrosis factor receptor-related 2 gene in T cells.
Woon Ki KIM ; Ok Ju SUL ; Jung Sook KWAK ; Hye Young HUR ; Anne M LATOUR ; Beverly H KOLLER ; Byoung S KWON ; Choon Soo JEONG
Experimental & Molecular Medicine 2010;42(12):805-810
Tumor necrosis factor receptor-related 2 (TR2, HVEM or TNFRSF-14) plays an important role in immune responses, however, the mechanisms regulating its expression are unclear. To understand the control of TR2 gene expression, we studied the upstream region of the gene. Gel supershift assays revealed inducible binding of nuclear factor of activated T cells (NFAT) to a putative NFAT site within the TR2 promoter. Furthermore, cotransfection of a dominant negative NFAT construct, or siRNA for NFAT, resulted in increased expression of a TR2 reporter gene. Our findings demonstrate that NFAT negatively regulates TR2 expression in activated T cells.
Animals
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Base Sequence
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CD4-Positive T-Lymphocytes/metabolism
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Cells, Cultured
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Down-Regulation
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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NFATC Transcription Factors/*physiology
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Receptors, Tumor Necrosis Factor, Member 14/*biosynthesis
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T-Lymphocytes/*metabolism
9.Identification of novel substrates for human checkpoint kinase Chk1 and Chk2 through genome-wide screening using a consensus Chk phosphorylation motif.
Myoung Ae KIM ; Hyun Ju KIM ; Alexandra L BROWN ; Min Young LEE ; Yoe Sik BAE ; Joo In PARK ; Jong Young KWAK ; Jay H CHUNG ; Jeanho YUN
Experimental & Molecular Medicine 2007;39(2):205-212
Checkpoint kinase 1 (Chk1) and Chk2 are effector kinases in the cellular DNA damage response and impairment of their function is closely related to tumorigenesis. Previous studies revealed several substrate proteins of Chk1 and Chk2, but identification of additional targets is still important in order to understand their tumor suppressor functions. In this study, we screened novel substrates for Chk1 and Chk2 using substrate target motifs determined previously by an oriented peptide library approach. The potential candidates were selected by genome-wide peptide database searches and were examined by in vitro kinase assays. ST5, HDAC5, PGC-1alpha, PP2A PR130, FANCG, GATA3, cyclin G, Rad51D and MAD1alpha were newly identified as in vitro substrates for Chk1 and/or Chk2. Among these, HDAC5 and PGC-1alpha were further analyzed to substantiate the screening results. Immunoprecipitation kinase assay of full-length proteins and site-directed mutagenesis analysis of the target motifs demonstrated that HDAC5 and PGC-1alpha were specific targets for Chk1 and/or Chk2 at least in vitro.
Amino Acid Motifs
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Amino Acid Sequence
;
*Consensus Sequence
;
Genome, Human/*genetics
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Heat-Shock Proteins/chemistry/metabolism
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Histone Deacetylases/chemistry/metabolism
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Humans
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Molecular Sequence Data
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Peptide Fragments/chemistry/metabolism
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Phosphorylation
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Phosphoserine/metabolism
;
Protein Kinases/*metabolism
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Protein-Serine-Threonine Kinases/*metabolism
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Substrate Specificity
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Transcription Factors/chemistry/metabolism
10.Biodistribution and Hepatic Metabolism of Galactosylated 111In-Antibody-Chelator Conjugates: Comparison with 111In-Antibody-Chelator Conjugates.
Dong Suk KWAK ; Jaetae LEE ; Kyu Sik JEONG ; Jeoung Hee HA ; Byeong Cheol AHN ; Kyubo LEE ; Chang H PAIK
Korean Journal of Nuclear Medicine 2003;37(6):402-417
PURPOSE: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand, the receptor mediated uptake into liver and subsequent metabolism of (111) In-labeled galactosylated MoAb-chelator conjugates were investigated and compared with those of (111) In labeled MoAb. MATERIALS AND METHODS: T101 MoAb, IgG2 against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-beta-D-galactose and then radiolabeled with (111) In. Biodistribution and metabolism study was performed with two (111) In-conjugates in mice and rats. RESULTS: (111) In-labeled T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiometabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks, the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free 111In at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. In contrast to DTPA conjugate, the small (111) In-DTPA-like metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. CONCLUSION: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.
Animals
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Bile
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Biliary Tract
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Chelating Agents
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Chromatography, High Pressure Liquid
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Feces
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Hepatocytes
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Humans
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Immunoglobulin G
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Liver
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Metabolism*
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Mice
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Pentetic Acid
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Rats