1.Kidneys with bad ends.
Journal of the Korean Society of Pediatric Nephrology 2008;12(1):11-22
Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end- replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.
Aging
;
Cell Aging
;
Chromosomes, Human
;
DNA
;
DNA Replication
;
Female
;
Genome
;
Genomic Instability
;
Humans
;
Kidney
;
Kidney Neoplasms
;
Molecular Medicine
;
Nuclear Family
;
Parents
;
RNA
;
Sensitivity and Specificity
;
Telomere
;
Telomere Shortening
;
Transplantation, Homologous
2.Back to the Ends: Chromosomal DNA.
Journal of the Korean Society of Pediatric Nephrology 2008;12(1):1-10
Nucleic scids transfer the genetic information for serving a central biological purpose. The nucleic acids are polymers of nucleotides and they are mainly ribonucleic acid(RNA) and deoxyribonucleic acid(DNA). The nucleotides are stoichiometrically composed of five-carbon sugars, nitrogeneous bases, and phosphoric acids. The chemistry of nucleic acids and characteristics of different genomes are decribed for further study. Most of DNA genomes tend to be circular including bacterial genomes and eukaryotic mitochondrial DNA. Eukaryotic chromosomes in cells, in contrast, are generally linear. The ends of linear chromosomes are called telomeres. The genomes of different species, such as mammals, plants, invertebrates can be compared with the chromosome ends. The telomeric complex allows cells to distinguish the random DNA breaks and natural chromosomal ends. The very ends of chromosomes cannot be replicated by any ordinary mechanisms. The shortening of telomeric DNA templates in semiconservative replication is occurred with each cell division. The short telomere length is critically related to aging, tumors and dieases.
Aging
;
Carbohydrates
;
Cell Division
;
DNA
;
DNA Breaks
;
DNA, Mitochondrial
;
Genome
;
Genome, Bacterial
;
Genome, Mitochondrial
;
Invertebrates
;
Mammals
;
Nitrogen
;
Nucleic Acids
;
Nucleotides
;
Phosphoric Acids
;
Polymers
;
Telomere
3.Cooperative binding interaction of ethidium with allosteric DNA.
Experimental & Molecular Medicine 1999;31(3):151-158
The specific association of drugs with deoxyoligonucleotides, containing a B-Z junction between left-handed Z-DNA and right-handed B-DNA, was examined by fluorescence and circular dichroism (CD) technique. Ethidium was chosen for a simple DNA binding compound because it binds to right-handed DNA and hybrid B-Z forms containing a B-Z junction in a highly cooperative manner. The binding isotherms were analyzed by an allosteric model in order to describe the cooperativity of association. Binding of ethidium to the DNA that are initially in the hybrid B-Z forms showed over an order of magnitude higher affinity than other DNA which were entirely in the B-form. The conformational transitions of deoxyoligonucleotides containing a B-Z junction as a result of ethidium binding were monitored by CD and the influence of NaCl on the complex formation was also determined by the CD spectra. The singular value decomposition (SVD) analysis was used to characterize a family of CD spectra of the species in binding equilibria. The results of SVD analysis showed a strikingly complex thermodynamic equilibria of cooperative binding of drugs to the allosterically converted DNA forms. The results also showed that these DNA forms in low- and high-salt were different in the absence or presence of drug. These results demonstrate that DNA-binding-drugs can preferentially interact with specific DNA structures and that these interactions are accompanied by allosteric changes of DNA conformations.
Allosteric Regulation/genetics
;
Circular Dichroism
;
DNA/chemistry*
;
Ethidium/chemistry*
;
Fluorescent Dyes/chemistry
;
Nucleic Acid Conformation
;
Oligodeoxyribonucleotides/chemistry
;
Sodium Chloride/pharmacology
;
Thermodynamics
4.A Rare Case of Subcutaneous Emphysema following Lateral Pharyngoplasty for Obstructive Sleep Apnea.
Dongchul CHA ; Young woo LEE ; Hyung Ju CHO
Journal of Rhinology 2018;25(2):99-102
Lateral pharyngoplasty is a surgical option for treatment of obstructive sleep apnea (OSA). Here, we present a case involving a 40-year-old healthy man who underwent surgery, including lateral pharyngoplasty and robotic tongue base resection, for OSA. There were no intraoperative or immediate postoperative complications. However, on postoperative day 3, the patient presented with swelling in the temporal and buccal areas and was diagnosed with subcutaneous emphysema, later confirmed by computed tomography. The patient was carefully monitored under conservative care and discharged without complications. Although subcutaneous emphysema following tonsillectomy is a rare complication and usually resolves with conservative management, in certain cases, it might require surgical intervention. Lateral pharyngoplasty involves tonsillectomy and additional incision along the tonsillar fossa, which makes it susceptible to pharyngeal wall defects and, consequently, subcutaneous emphysema. Additionally, lateral pharyngoplasty and robotic tongue base resection cause pain and might thus contribute to the increase in intrapharyngeal pressure, which might aggravate subcutaneous emphysema. Lateral pharyngoplasty should be performed with meticulous dissection of the superior pharyngeal constrictor muscle. Healthcare providers should be aware of these complications and, upon suspicion of the same, place the patient under close observation to prevent life-threatening situations.
Adult
;
Emphysema
;
Health Personnel
;
Humans
;
Sleep Apnea Syndromes
;
Sleep Apnea, Obstructive*
;
Subcutaneous Emphysema*
;
Tongue
;
Tonsillectomy
5.Association of UCP1 Genetic Polymorphisms with Blood Pressure among Korean Female Subjects.
Min Ho CHA ; Byoung Kab KANG ; Dongchul SUH ; Kil Soo KIM ; Young YANG ; Yoosik YOON
Journal of Korean Medical Science 2008;23(5):776-780
Recent studies have provided some clues with regard to the relationship existing between uncoupling protein 1 (UCP1) and blood pressure in animal experiments. In an attempt to determine the genetic polymorphisms that are associated with blood pressure in humans, we have analyzed genetic polymorphisms in UCP1 gene. In this study, we assessed the association between UCP1 genotypes and systolic blood pressure (SBP) and diastolic blood pressure (DBP), in a population comprised of 832 Korean female subjects, using a general linear model, which was adjusted for age and body mass index (BMI). Among 4 genetic polymorphisms and the haplotypes constructed from them, haplotype3 of UCP1, UCP1-ht3[GAGA], evidenced significant associations with SBP (p=0.005) and DBP (p=0.013). However, this haplotype was not significantly associated with obesity phenotypes, including BMI or fat mass (p>0.05), thereby suggesting that its association with blood pressure was independent of obesity phenotypes.
Adult
;
Alleles
;
Blood Pressure
;
Body Mass Index
;
Female
;
Genotype
;
Haplotypes
;
Humans
;
Ion Channels/*genetics
;
Korea
;
Mitochondrial Proteins/*genetics
;
Models, Genetic
;
Obesity/genetics
;
Phenotype
;
*Polymorphism, Genetic
6.Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence.
Dongchul SUH ; Yu Kyoung OH ; Byung Chan AHN ; Man Wook HUR ; Hye Ja KIM ; Mi Hyoung LEE ; Hyo Soon JOO ; Chung Kyoon AUH
Experimental & Molecular Medicine 2002;34(5):326-331
Telomeres are the ends of the linear chromosomes of eukaryotes and consist of tandem GT-rich repeats in telomere sequence i.e. 500-3000 repeats of 5'-TTAGGG-3' in human somatic cells, which are shortened gradually with age. The G-rich overhang of telomere sequence can adopt different intramolecular fold-backs and tetra-stranded DNA structures, in vitro, which inhibit telomerase activity. In this report, DNA binding agents to telomere sequence were studied novel therapeutic possibility to destabilize telomeric DNA sequences. Oligonucleotides containing the guanine repeats in human telomere sequence were synthesized and used for screening potential antitumor drugs. Telomeric DNA sequence was characterized using spectral measurements and CD spectroscopy. CD spectrum indicated that the double-stranded telomeric DNA is in a right-handed conformation. Polyacrylamide gel electrophoresis was performed for binding behaviors of antitumor compounds with telomeric DNA sequence. Drugs interacted with DNA sequence caused changes in the electrophoretic mobility and band intensity of the gels. Depending on the binding mode of the anticancer drugs, telomeric DNA sequence was differently recognized and the efficiency of cleavage of DNA varies in the bleomycin-treated samples under different conditions. DNA cleavage occurred at about 1% by the increments of 1 mM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process.
Antineoplastic Agents/*metabolism
;
Bleomycin/metabolism/pharmacology
;
Circular Dichroism
;
Comparative Study
;
DNA/chemistry/drug effects/*metabolism
;
DNA Damage
;
Dactinomycin/metabolism
;
Doxorubicin/*analogs & derivatives/metabolism
;
Human
;
Nogalamycin/metabolism
;
Nucleic Acid Conformation
;
*Repetitive Sequences, Nucleic Acid
;
Telomere/drug effects/*genetics
7.Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards
Michelle J. SUH ; Jihyun LEE ; Wan-Ho CHO ; In-Ki JIN ; Tae Hoon KONG ; Soo Hee OH ; Hyo-Jeong LEE ; Seong Jun CHOI ; Dongchul CHA ; Kyung-Ho PARK ; Young Jun SEO
Journal of Audiology & Otology 2023;27(4):169-180
This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.
8.Improving Accuracy and Reliability of Hearing Tests: Measurement Standards for Audiometric Devices
Wan-Ho CHO ; Jihyun LEE ; Young Joon SEO ; Tae Hoon KONG ; Michelle J. SUH ; In-Ki JIN ; Soo Hee OH ; Hyo-Jeong LEE ; Seong Jun CHOI ; Kyung-Ho PARK ; Dongchul CHA
Journal of Audiology & Otology 2024;28(3):167-175
Pure-tone audiometry, using an audiometer, is the fundamental hearing test for diagnosing hearing loss. The requirements of the devices and the detailed process for calibrating the related equipment are described in international standards. However, traceable calibration and uncertainty evaluation processes are not widely accepted or applied to the qualification and maintenance of audiometric equipment. Here, we briefly review standard measurement systems for audiometric devices and introduce their calibration procedures. The uncertainty of each calibration process was investigated, and its impact on hearing test results was considered. Our findings show that the traceability of each procedure can be secured, satisfying the uncertainty requirement and being sufficiently smaller than the permissible deviation from the audiometer requirement. To guarantee the objectivity and reliability of hearing tests and maintain low uncertainty, close cooperation and mutual understanding between the metrology field and the medical community are necessary.
9.Improving Accuracy and Reliability of Hearing Tests: Measurement Standards for Audiometric Devices
Wan-Ho CHO ; Jihyun LEE ; Young Joon SEO ; Tae Hoon KONG ; Michelle J. SUH ; In-Ki JIN ; Soo Hee OH ; Hyo-Jeong LEE ; Seong Jun CHOI ; Kyung-Ho PARK ; Dongchul CHA
Journal of Audiology & Otology 2024;28(3):167-175
Pure-tone audiometry, using an audiometer, is the fundamental hearing test for diagnosing hearing loss. The requirements of the devices and the detailed process for calibrating the related equipment are described in international standards. However, traceable calibration and uncertainty evaluation processes are not widely accepted or applied to the qualification and maintenance of audiometric equipment. Here, we briefly review standard measurement systems for audiometric devices and introduce their calibration procedures. The uncertainty of each calibration process was investigated, and its impact on hearing test results was considered. Our findings show that the traceability of each procedure can be secured, satisfying the uncertainty requirement and being sufficiently smaller than the permissible deviation from the audiometer requirement. To guarantee the objectivity and reliability of hearing tests and maintain low uncertainty, close cooperation and mutual understanding between the metrology field and the medical community are necessary.
10.Improving Accuracy and Reliability of Hearing Tests: Measurement Standards for Audiometric Devices
Wan-Ho CHO ; Jihyun LEE ; Young Joon SEO ; Tae Hoon KONG ; Michelle J. SUH ; In-Ki JIN ; Soo Hee OH ; Hyo-Jeong LEE ; Seong Jun CHOI ; Kyung-Ho PARK ; Dongchul CHA
Journal of Audiology & Otology 2024;28(3):167-175
Pure-tone audiometry, using an audiometer, is the fundamental hearing test for diagnosing hearing loss. The requirements of the devices and the detailed process for calibrating the related equipment are described in international standards. However, traceable calibration and uncertainty evaluation processes are not widely accepted or applied to the qualification and maintenance of audiometric equipment. Here, we briefly review standard measurement systems for audiometric devices and introduce their calibration procedures. The uncertainty of each calibration process was investigated, and its impact on hearing test results was considered. Our findings show that the traceability of each procedure can be secured, satisfying the uncertainty requirement and being sufficiently smaller than the permissible deviation from the audiometer requirement. To guarantee the objectivity and reliability of hearing tests and maintain low uncertainty, close cooperation and mutual understanding between the metrology field and the medical community are necessary.