Publications by authors named "Dae-Kwang Kim"

46 Publications

Alzheimer's Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology.

Nanomaterials (Basel) 2020 Dec 29;11(1). Epub 2020 Dec 29.

Department of Medical Genetics, School of Medicine, Keimyung University, Daegu 42601, Korea.

Alzheimer's disease (AD), a progressively fatal neurodegenerative disorder, is the most prominent form of dementia found today. Patients suffering from Alzheimer's begin to show the signs and symptoms, like decline in memory and cognition, long after the cellular damage has been initiated in their brain. There are several hypothesis for the neurodegeneration process; however, the lack of availability of in vivo models makes the recapitulation of AD in humans impossible. Moreover, the drugs currently available in the market serve to alleviate the symptoms and there is no cure for the disease. There have been two major hurdles in the process of finding the same-the inefficiency in cracking the complexity of the disease pathogenesis and the inefficiency in delivery of drugs targeted for AD. This review discusses the different drugs that have been designed over the recent years and the drug delivery options in the field of nanotechnology that have been found most feasible in surpassing the blood-brain barrier (BBB) and reaching the brain.
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http://dx.doi.org/10.3390/nano11010059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823376PMC
December 2020

Alterations in telomere length and mitochondrial DNA copy number in human lymphocytes on short-term exposure to moderate hypoxia.

Toxicol Rep 2020 17;7:1443-1447. Epub 2020 Oct 17.

Department of Medical Genetics, School of Medicine, Keimyung University, Daegu, Republic of Korea.

Hypoxia is related to a variety of diseases, such as cardiovascular and inflammatory diseases and various cancers. Telomere length (TL) may vary according to the hypoxia level and cell types. To the best of our knowledge, no study has investigated the effect of moderate hypoxia on TL and mitochondrial DNA copy number (mtDNAcn) in human lymphocytes. Therefore, in this study, we analyzed the effect of moderate hypoxia on TL in correlation with mtDNAcn. This study included 32 healthy male nonsmoker's subjects; in this cohort, we had previously studied sister chromatid exchange and microsatellite instability. Blood samples from each subject were divided into three groups: a control group and two experimental groups exposed to moderate hypoxia for 12 or 24 h. Relative TL and mtDNAcn were measured by a quantitative real-time polymerase chain reaction. The TL in the control group did not significantly differ from that in the experimental group subjected to hypoxia for 12 h; however, the TL in the 24 h hypoxia-treated experimental group was significantly higher than that in the control group. The correlation between TL and mtDNAcn was not statistically significant in the two hypoxic states. The increase in TL was observed on exposure to hypoxia for 24 h and not for 12 h; thus, the findings suggest that telomere elongation is related to hypoxia exposure duration. The mtDNAcn in the two experimental groups did not significantly differ from that in the control group. These observations suggest that mtDNAcn alterations show more genetic stability than TL alterations. To the best of our knowledge, this is the first study on human lymphocytes reporting an increase in TL and no alteration in mtDNAcn after short-time exposure to moderate hypoxia.
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http://dx.doi.org/10.1016/j.toxrep.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600389PMC
October 2020

Photobiomodulation (660 nm) therapy reduces oxidative stress and induces BDNF expression in the hippocampus.

Sci Rep 2019 07 12;9(1):10114. Epub 2019 Jul 12.

Department of Biomedical Engineering, School of Medicine, Keimyung University, Daegu, 42601, Korea.

Photobiomodulation therapy (PBMT) effects an important role in neural regeneration and function enhancement, such as expression of nerve growth factor and nerve regeneration, in neuronal tissues, and inhibition of cell death by amyloid beta in neurons is inhibited by PBMT. However, there no studies evaluated the effects of PBMT on oxidative stress in the hippocampus. The aim of this study is to evaluate the effects of PBMT on oxidative stress in the hippocampus. This study assessed the anti-oxidative effect, the expression of BDNF and antioxidant enzymes, as well as the activation of cAMP response element binding (CREB) and extracellular signal-regulated kinase (ERK) signal transduction pathways assess using a hippocampal cell line (HT-22) and mouse organotypic hippocampal tissues by PBMT (LED, 660 nm, 20 mW/cm). PBMT inhibited HT-22 cell death by oxidative stress and increased BDNF expression via ERK and CREB signaling pathway activation. In addition, PBMT increased BDNF expression in hippocampal organotypic slices and the levels of phosphorylated ERK and CREB, which were reduced by oxidative stress, as well as the expression of the antioxidant enzyme superoxide dismutase. These data demonstrate that PBMT inhibits hippocampal damage induced by oxidative stress and increases the expression of BDNF, which can be used as an alternative to treat a variety of related disorders that lead to nerve damage. Activation and redox homeostasis in neuronal cells may be a notable mechanism of the 660-nm PBMT-mediated photobioreactivity.
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http://dx.doi.org/10.1038/s41598-019-46490-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625994PMC
July 2019

No Association between Merkel Cell Polymavirus Infection and Keratoacanthoma in Korean Patients

Authors:
Dae-Kwang Kim

Asian Pac J Cancer Prev 2019 May 25;20(5):1299-1301. Epub 2019 May 25.

Department of Medical Genetics, School of Medicine, Keimyung University, 1095, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea. Email:

Objectives: Keratoacanthoma (KA) is a relatively common benign tumor and resembles squamous cell carcinoma (SCC). The definitive cause of KA remains unclear, but trauma, ultraviolet light, chemical carcinogens, human papillomavirus, genetic factors, and immunocompromised status have been implicated as etiologic or triggering factors. Merkel cell polyomavirus (MCPyV) is suspected to cause the majority of cases of Merkel cell carcinoma (MCC). MCPyV-DNA was found significantly more frequently in MCC and only found in about one fourth of KAs. In a recent study, MCPyV was found in Korean patients with MCC. The aim of this study was to determine the presence of MCPyV in Korean patients with KA. Methods: Paraffin-embedded tissue samples were analyzed for the presence of MCPyV-DNA by polymerase chain reaction (PCR). A total of 105 KA samples were analyzed. Results: A study of MCPyV has not been reported about KA in Korean cases. In the present study the MCPyV was not detected with KA in the Korean patients. Conclusions: This supports that KA and MCPyV are not related to each other and MCVyP is not a major factor in the pathogenesis of KA.
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http://dx.doi.org/10.31557/APJCP.2019.20.5.1299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857863PMC
May 2019

Association between internet gaming addiction and leukocyte telomere length in Korean male adolescents.

Soc Sci Med 2019 02 27;222:84-90. Epub 2018 Dec 27.

Department of Medical Genetics, School of Medicine, Keimyung University, Daegu, Republic of Korea. Electronic address:

Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth. In particular, the potential association between IGA and leukocyte telomere length (LTL) has yet to be examined. In this study we compared LTL in Korean male adolescents with and without IGA and examined the association between LTL and autonomic functions. Specifically, plasma catecholamine, serum cortisol, and psychological stress levels were measured as autonomic functions. Data were collected using participant blood samples analyzed for LTL, catecholamine, and cortisol levels and a set of questionnaires to assess IGA and psychological stress levels of the participants. The LTL measurements were made using a qPCR-based technique, and the relative LTL was calculated as the telomere/single copy (T/S) ratio. T/S ratio was significantly shorter in the IGA group than in the non-IGA group (150.43 ± 6.20 and 187.23 ± 6.42, respectively; p < .001) after adjusting for age. In a univariate regression analysis, age, daily Internet gaming time, IGA score, and catecholamine level (epinephrine and norepinephrine) were significantly associated with T/S ratio. However, duration of Internet gaming exposure, dopamine, cortisol, and psychological stress levels were not found to be associated with T/S ratio. In the final multiple linear regression model, age, daily Internet gaming time, and epinephrine level showed statistically significant relationships with T/S ratio. Our results indicate that in addition to age, involvement in excessive Internet gaming may induce LTL shortening in male adolescents, which may be partially attributable to changes in autonomic function such as catecholamine level. These findings further understanding of the health effects of IGA and highlight the need for screening and intervention strategies for male adolescents with IGA.
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http://dx.doi.org/10.1016/j.socscimed.2018.12.026DOI Listing
February 2019

Genetic association of human Corticotropin-Releasing Hormone Receptor 1 (CRHR1) with Internet gaming addiction in Korean male adolescents.

BMC Psychiatry 2018 12 20;18(1):396. Epub 2018 Dec 20.

College of Nursing, Keimyung University, Daegu, Republic of Korea.

Background: The number of people with Internet gaming addiction (IGA) is increasing around the world. IGA is known to be associated with personal characteristics, psychosocial factors, and physiological factors. However, few studies have examined the genetic factors related to IGA. This study aimed to investigate the association between IGA and stress-related genetic variants.

Methods: This cross-sectional study was conducted with 230 male high school students in a South Korean city. We selected five stress-related candidate genes: DAT1, DRD4, NET8, CHRNA4, and CRHR1. The DAT1 and DRD4 genes were genotyped by polymerase chain reaction, and the NET8, CHRNA4, and CRHR1 genes were genotyped by pyrosequencing analysis. We performed a Chi-square test to examine the relationship of these five candidate genes to IGA.

Results: Having the AA genotype and the A allele of the CRHR1 gene (rs28364027) was associated with higher odds of belonging to the IGA participant group (p = .016 and p = .021, respectively) than to the non-IGA group. By contrast, the DAT1, DRD4, NET8, and CHRNA4 gene polymorphisms showed no significant difference between the IGA group and control group.

Conclusions: These results indicate that polymorphism of the CRHR1 gene may play an important role in IGA susceptibility in the Korean adolescent male population. These findings provide a justification and foundation for further investigation of genetic factors related to IGA.
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http://dx.doi.org/10.1186/s12888-018-1974-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302290PMC
December 2018

Thymol exposure mediates pro-oxidant shift by regulating Nrf2 and apoptotic events in zebrafish (Danio rerio) embryos.

Environ Toxicol Pharmacol 2019 Jan 7;65:1-8. Epub 2018 Nov 7.

Department of Biotechnology, College of Engineering, Daegu University Kyoungsan, Kyoungbook 712-714, Republic of Korea. Electronic address:

The biochemical process of oxidative stress is an integral mechanism of chemical toxicity, contributing to complex pathological disorders. Thymol (THY) has a wide range of therapeutic applications for several ailments, although a better understanding of signaling cues regulated by this compound is needed to address the mechanism of its action. To better perceive the mode of action, we investigated the potential impact of THY on zebrafish embryos, with special emphasis on ROS biogenesis. In this study, we exposed the zebrafish embryos to 25, 50 and 100μM of THY for 96 hours post fertilization (hpf). Noticeable teratogenic effects were observed upon assessing the survival rate (LC = 42.35μM), hatching process, morphological exam and cardiac functions, thereby verifying the toxicity of THY on zebrafish embryos. Furthermore, we analyzed the effect of THY on the levels of ROS, mitochondrial membrane potential (ΔΨm) and immunofluorescence by DCFH-DA, JC-1, Casp-3-FITIC staining, respectively. Furthermore, we preformed the expressional analysis of Nrf2, superoxide dismutase-1 (SOD-1), catalase (CAT), Cytochrome P450 (CYP450) and apoptotic marker proteins (AIF, p53, Bax, Bcl-2, Casp-3 and Casp-9) in zebrafish embryos. As expected, we noticed a significant modulatory effect on the above-mentioned activities by THY. Collectively, our findings suggest that ROS might be the prime mediator responsible for THY-induced oxidative damage, thereby affecting the cellular defense mechanism and apoptotic events in zebrafish embryos.
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http://dx.doi.org/10.1016/j.etap.2018.11.001DOI Listing
January 2019

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.

Molecules 2018 Mar 23;23(4). Epub 2018 Mar 23.

Department of Medical Genetics, Hanvit Institutute for Medical Genetics, School of Medicine, Keimyung University, Daegu 42601, Korea.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.
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http://dx.doi.org/10.3390/molecules23040737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017053PMC
March 2018

Study on Strain Compensation for Multiple-Quantum Well in Infrared Light-Emitting Diode Using the InGaP Strain Barrier.

J Nanosci Nanotechnol 2018 Mar;18(3):2014-2017

CF Technology Division, AUK Corporation, Iksan 54630, Jeonbuk, South Korea.

Strain compensation for multiple-quantum wells (MQWs) relative to the efficiency improvement of infrared light-emitting diodes (IR-LEDs) was investigated through the use of an InxGa1-xP strain barrier. The InxGa1-xP barrier, which was inserted between the n-confinement and active regions, developed for the reduction of lattice-mismatched strains in GaAs/AlGaAs and InGaAs/GaAs MQWs. Through photoluminescence, improved intensity was displayed in InGaAs/GaAs MQWs having InxGa1-xP strain barriers, with a significant increase in the intensity observed at the In0.47GaP strain barrier. This result is attributed to strain compensation between the In0.47GaP tensile strain barrier used and the In0.07GaAs compressive strain in MQWs. Through results based on InGaAs/GaAs MQWs, the highest output power of 6 mW was obtained at the In0.47GaP strain barrier, which shows a relative increase of almost 20% as compared to conventional MQWs.
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http://dx.doi.org/10.1166/jnn.2018.14952DOI Listing
March 2018

Induction of Inflammation In Vivo by Electrocardiogram Sensor Operation Using Wireless Power Transmission.

Sensors (Basel) 2017 Dec 14;17(12). Epub 2017 Dec 14.

Department of Biomedical Engineering, School of Medicine, Keimyung University, Daegu 42601, Korea.

Prolonged monitoring by cardiac electrocardiogram (ECG) sensors is useful for patients with emergency heart conditions. However, implant monitoring systems are limited by lack of tissue biocompatibility. Here, we developed an implantable ECG sensor for real-time monitoring of ventricular fibrillation and evaluated its biocompatibility using an animal model. The implantable sensor comprised transplant sensors with two electrodes, a wireless power transmission system, and a monitoring system. The sensor was inserted into the subcutaneous tissue of the abdominal area and operated for 1 h/day for 5 days using a wireless power system. Importantly, the sensor was encapsulated by subcutaneous tissue and induced angiogenesis, inflammation, and phagocytosis. In addition, we observed that the levels of inflammation-related markers increased with wireless-powered transmission via the ECG sensor; in particular, levels of the Th-1 cytokine interleukin-12 were significantly increased. The results showed that induced tissue damage was associated with the use of wireless-powered sensors. We also investigated research strategies for the prevention of adverse effects caused by lack of tissue biocompatibility of a wireless-powered ECG monitoring system and provided information on the clinical applications of inflammatory reactions in implant treatment using the wireless-powered transmission system.
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http://dx.doi.org/10.3390/s17122905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751571PMC
December 2017

Variable alterations of mitochondrial microsatellite instability and DNA copy number in pulmonary hamartomas.

Cancer Biomark 2016 ;17(4):473-478

Department of Medical Genetics, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Korea.

Background: The genetic alteration of mitochondrial DNA has been regarded as an important step in the development of several human tumors.

Objective: The purpose of this study was to identify frequency of mitochondrial microsatellite instability (mtMSI) and alterations in mitochondrial DNA copy number (mtCN) in pulmonary hamartoma.

Methods: DNA was isolated from tumor tissue and matched non-tumor tissue in 30 patients with pulmonary hamartoma. BAT 25 and 26 were used as nucleus MSI (nMSI) markers, and (C)n and (CA)n in D-loop were used as mtMSI markers. MtCNs were quantified using a competitive quantitative real-time polymerase chain reaction.

Results: nMSI was detected in 5 patients (23.8%) and mtMSI was detected in 2 patients (9.5%) of total 21 hamartoma. There were 14 patients (46.7%), 2 patients (6.7%), and a further 14 patients (46.7%) in the decreased, no change, and increased mtCN groups, respectively. The mean relative mtCN were 0.4 ± 0.3 in the decreased and 3.9 ± 5.1 in the increased mtCN groups, respectively.

Conclusions: nMSI was more frequently appeared than mtMSI in hamartomas, and we also found measurements of mtCNs in patients with pulmonary hamartoma to be extremely variable without any characteristic pattern.
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http://dx.doi.org/10.3233/CBM-160664DOI Listing
March 2017

A Pedigree with c.179 Cytosine to Threonine Missense Mutation of SLC12A3 Gene Presenting Gitelman's Syndrome.

Electrolyte Blood Press 2016 Jun 30;14(1):16-9. Epub 2016 Jun 30.

Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.; Keimyung University Kidney Institute, Daegu, Korea.

A 42-year-old man came to the hospital presenting chest discomfort and general weakness. He had come to the hospital with the same symptoms 3 months ago and 12 years prior. His laboratory test showed hypokalemia, hypomagnesemia and hypocalciuria. The arterial blood gas analysis showed hypochloremic metabolic alkalosis. He had an ultrasonography guided renal biopsy, the result was normal at light microscopy and immunofluorescence microscopy. However, a special stain for Na-Cl cotransporter was weakly expressed compared with the control. The patient and his family underwent genetic sequencing about the SLC12A3 gene. He had a homozygous mutation in the 179(th) nucleotide of Exon 1 on the SLC12A3 gene (p.Thr60Met) and his parents and sisters were diagnosed as carrier state of Gitelman's syndrome (GS). GS is an inherited tubular disorder which presents mild hypokalemia, hypomagnesemia and hypocalciuria. Since the symptoms and laboratory results are not severe, it can go unnoticed by physicians. Herein we present a family with GS, diagnosed by genetic sequencing.
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http://dx.doi.org/10.5049/EBP.2016.14.1.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949203PMC
June 2016

No Association of the rs17822931 Polymorphism in ABCC11 with Breast Cancer Risk in Koreans.

Asian Pac J Cancer Prev 2016 ;17(5):2625-8

Department of Medical Genetics, Hanvit Institution for Medical Genetics, Keimyung University, Daegu, Republic of Korea E-mail :

ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (Δ27) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and Δ27 was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans.
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February 2017

Nuclear and mitochondrial DNAs microsatellite instability and mitochondrial DNA copy number in adenocarcinoma and squamous cell carcinoma of lung: a pilot study.

APMIS 2015 Dec;123(12):1048-54

Department of Thoracic and Cardiovascular Surgery, School of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea.

Mitochondrial genetic changes are considered as a key molecular step of mutations in various cancers. To clarify the role of genetic instability in lung cancer, we analyzed clinicopathological characteristics and frequencies of nuclear and mitochondrial microsatellite instability (nMSI and mtMSI), and alteration of mitochondrial DNA copy number (mtCN) in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of lung. DNA was isolated from 48 patients with ADC and 42 with SCC. Markers for nMSI, BAT 25 and 26, and markers for mtMSI, (C)n and (CA)n in mitochondrial D-loop region, were utilized. The mtCN were measured by real-time polymerase chain reaction. The nMSI was found in two patients (4.2%) of ADC and 6 (14.3%) of SCC. The mtMSI was detected in 10 patients (20.8%) of ADC and 8 (19.0%) of SCC. Mean mtCN was 5.05 ± 8.17 and 3.34 ± 5.14 in ADC and SCC respectively. The mtCN was increased in 35 patients (72.9%) of ADC and 30 (71.4%) of SCC. The mtMSI more frequently appeared in more advanced pathologic T stage in ADC (p = 0.003). Alterations of mtCN and a high frequency of mtMSI in our patient samples indicate that mitochondrial DNA is a potential molecular marker in lung cancers (ADC and SCC) correlating with their histological classification.
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http://dx.doi.org/10.1111/apm.12471DOI Listing
December 2015

In vitro and in vivo effects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia.

Drug Chem Toxicol 2016 26;39(2):153-6. Epub 2015 Jun 26.

e Department of Medical Genetics , College of Medicine, Keimyung University , Daegu , Republic of Korea , and.

Objective: Many studies have shown that melatonin (MLT) has an anti-genotoxic effect in various tissues and cell lines. The aim of this study was to investigate the anti-genotoxic effect of MLT on normal human peripheral lymphocytes by assessing sister chromatid exchange (SCE) in vitro and in vivo.

Materials And Methods: Cells were treated with 50 and 200 μM of MLT. The human volunteers (n = 20) for the in vivo study were administered a single dose of 3 mg MLT daily for 2 weeks. After sufficient time for its clearance, 1.5 mg of MLT daily was then administered to the same volunteers at same the period.

Results: Our results demonstrated the anti-genotoxic effect of MLT in human blood lymphocyte in vitro and in vivo. In vitro, hypoxia increased the SCE frequency compared to the control and both doses of MLT significantly decreased the SCE frequency in the hypoxic cells (p < 0.001). In vivo, oral administration of 3 mg MLT significantly increased the frequency of SCE, yet a small increase of SCE by hypoxia was found. Oral administration of 1.5 mg MLT showed no DNA damage but it had an anti-genotoxic effect.

Discussion And Conclusion: MLT may prove useful for reducing the genotoxic effects of hypoxia in peripheral lymphocytes and suggest its possible role for ischemic diseases.
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http://dx.doi.org/10.3109/01480545.2015.1058393DOI Listing
December 2016

PIK3CA Amplification Is Common in Left Side-Tubular Adenomas but Uncommon Sessile Serrated Adenomas Exclusively with KRAS Mutation.

Int J Med Sci 2015 27;12(4):349-53. Epub 2015 Apr 27.

5. Department of Immunology, Keimyung University School of Medicine, 2800, Dalgubeoldaero, Dalseo-Gu, Daegu, Republic of Korea.

Colorectal cancer is a heterogeneous disorder than arises via multiple distinct pathways, from tubular adenomas (TAs) and sessile serrated adenomas (SSAs), which are clinically, morphologically, and molecularly different. We examined PIK3CA amplification in colorectal precancerous legions, including TAs and SSAs. DNA was isolated from paired normal and tumoral tissues in 64 TAs and 32 SSAs. PIK3CA amplification, KRAS mutation, and BRAF mutation were analyzed by real-time PCR and pyrosequencing. PIK3CA amplification was found in 25% of TAs and 9.4% of SSAs, respectively. KRAS and BRAF mutations were mutually exclusive in both TAs and SSAs. In TAs, PIK3CA amplification was associated with left side and it was mutually exclusive with KRAS mutation. These results suggest that PIK3CA amplification may be early and important event in colorectal carcinogenesis and may drive the development of left-side TAs independently with KRAS mutation.
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http://dx.doi.org/10.7150/ijms.11281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445015PMC
April 2016

Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis.

PLoS One 2015 3;10(3):e0118612. Epub 2015 Mar 3.

Department of Medical Genetics, Keimyung University School of Medicine, Daegu, Republic of Korea; Hanvit Institute for Medical Genetics, City Women's Clinic, Buk-gu, Daegu, Republic of Korea.

Clinical value of mitochondrial DNA has been described in colorectal cancer (CRC). To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI) and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. DNA was isolated from paired normal and tumoral tissues in 78 tubular adenomas (TAs), 34 serrated polyps (SPs), and 100 CRCs. mtMSI, nucleus microsatellite instability (nMSI), KRAS mutation, and BRAF mutation were investigated in these tumors and their statistical analysis was performed. mtMSI was found in 30% of CRCs and 21.4% of precancerous lesions. Mitochondrial copy number was higher in SPs than TAs and it was associated with mtMSI in low grade TAs. KRAS and BRAF mutations were mutually exclusive in TAs and SPs. CRCs with mtMSI showed shorter overall survival times than the patients without mtMSI. In CRCs without nMSI or BRAF mutation, mtMSI was a more accurate marker for predicting prognosis. The genetic change of mitochondrial DNA is an early and independent event in colorectal precancerous lesions and mtMSI and mitochondrial contents are associated with the tubular adenoma-carcinoma sequence, resulting in poor prognosis. This result suggested that the genetic change in mitochondrial DNA appears to be a possible prognosis marker in CRC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118612PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348484PMC
January 2016

Microsatellite instability of nuclear and mitochondrial DNAs in gastric carcinogenesis.

Asian Pac J Cancer Prev 2014 ;15(19):8029-32

Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea E-mail :

Genetic instability contributes to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Microsatellite instability (MSI) has been hypothesized to be involved in carcinogenesis, althgough its mechanisms and exact roles in gastric cancer remain largely unknown. Our aim was to identify associated clinicopathological characteristics and prognostic value of MSI in gastric cancer and precancerous lesions including gastritis, metaplasia, dysplasia, and adenoma. Because mitochondrial DNA has a different genetic system from nuclear DNA, the results of both nuclear MSI and mitochondrial MSI in gastric cancer were reviewed. This review provides evidence that genetic instability of nuclear and mitochondrial DNAs contributes to early stages of gastric carcinogenesis and suggests possible roles in predicting prognosis.
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June 2015

No microsatellite instability using Bethesda panel and revised markers in uterine leiomyomas.

APMIS 2014 Jan;122(1):1-4

Department of Biological Sciences, Dartmouth College, Hanover, NH, USA.

Uterine leiomyomas are benign tumors of the uterus that arise clonally from smooth muscle cells of the myometrium and are very common reason for hysterectomy. The aim of this study was to evaluate microsatellite instability (MSI) in uterine leiomyomas using a set of MSI markers by Promega Corporation (Madison, WI, USA) and the Bethesda guideline. DNA was isolated from paired normal and tumoral tissues in 50 patients with uterine leiomyomas and MSI was analyzed by using seven microsatellite markers. Our result showed that microsatellite stability was found in all uterine leiomyomas. These data confirm the genetic status of uterine leiomyomas for the first time in Korean populations, and suggest that uterine leiomyomas have genetic stability in Korean.
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http://dx.doi.org/10.1111/apm.12232DOI Listing
January 2014

The double retro-aortic left renal vein.

Anat Cell Biol 2012 Dec 14;45(4):282-4. Epub 2012 Dec 14.

Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea.

The renal veins drain the kidney into the inferior vena cava and unite in a variable fashion to form the renal vein. The left renal vein is normally located in front of the aorta. However, the retro-aortic renal vein may course posterior to the aorta due to embryological developmental anomalies. During educational dissection, a rare variation of the left renal vein was found in a 66-year old male cadaver. The double retro-aortic renal veins coursed behind the aorta to drain into the inferior vena cava. The superior retro-aortic renal vein drained into the inferior vena cava at the lower border of the L2 vertebra, and the inferior retro-aortic renal vein drained into the inferior vena cava at the upper border of the L4 vertebra. Such a variant is rare, and is a clinically important observation which should be noted by vascular surgeons, oncologists, and traumatologists.
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http://dx.doi.org/10.5115/acb.2012.45.4.282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531592PMC
December 2012

The lateral thoracic artery passing through duplicated axillary vein: a case report.

Clin Anat 2013 Nov 23;26(8):1014-6. Epub 2012 May 23.

Department of Anatomy, School of Medicine, Keimyung University, Daegu, Republic of Korea.

The axillary vein is a large-blood vessel that lies on the medial side to the axillary artery. The veins of the axilla are more abundant than the arteries and their variations were extremely common. During educational dissection, a rare form of the axillary vein accompanying arterial variation was founded in left arm of 70-year-old female cadaver. The axillary vein was divided into two large veins, anterior and posterior axillary veins according to their anatomical position. The lateral-thoracic artery arose from the second part of the axillary artery and passed through the gap of duplicated axillary vein. Before the lateral-thoracic artery passed through the gap of duplicated axillary vein, the lateral-thoracic artery gave-off an additional branch, which descended superficial to the anterior axillary vein. It surrounded the anterior axillary vein as annular form and the diameter of surrounded part of the anterior axillary vein became narrow. This novel case was reported and its clinical implications of such a variant were discussed.
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http://dx.doi.org/10.1002/ca.22084DOI Listing
November 2013

Different frequency of the absence of the palmaris longus according to assessment methods in a Korean population.

Anat Cell Biol 2012 Mar 31;45(1):53-6. Epub 2012 Mar 31.

Medical Course, Keimyung University School of Medicine, Daegu, Korea.

The palmaris longus (PL) is a slender, spindle-shaped weak flexor of the wrist. Congenital absence of the PL is estimated to occur in 15% among individuals worldwide. However, the frequency of its absence varies considerably among different population groups and with different detection techniques. In the present study, the presence of the PL tendon was examined in a Korean population (n=269) using three clinical tests, namely the Traditional Test, Mishra's Test II, and the Gangata Test. We classified subjects into six types based on whether inspection or palpation was required to determine the presence of the PL and flexor carpi radialis. The most reliable test was determined using Kendall's coefficient of concordance. Our results showed that the PL tendon was absent in 4.1% of the subjects in our study, and bilateral and unilateral absences were 2.2% and 1.8%, respectively. Statistical analysis revealed that these tests had similar reliability for assessing the PL tendon, and the Traditional Test showed the highest effectiveness, at 93%. Therefore the Traditional Test was found to be the most effective for revealing the PL in this Korean population.
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http://dx.doi.org/10.5115/acb.2012.45.1.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328741PMC
March 2012

Bilateral variations of the head of the digastric muscle in Korean: a case report.

Anat Cell Biol 2011 Sep 29;44(3):241-3. Epub 2011 Sep 29.

Medical Course, Keimyung University School of Medicine, Daegu, Korea.

The digastric muscle, as the landmark in head and neck surgery, has two bellies, of which various variations have been reported. In the submental region of a 72-year-old Korean male cadaver, bilateral variations were found in the anterior belly of the digastric muscle. Two accessory bellies, medial to the two normal anterior bellies of the digastric muscle, ran posterior and medially, merging and attaching at the mylohyoid raphe of the mylohyoid muscle. The 3rd accessory belly originated from the right intermediate tendon and ran horizontally, merging the right lower bundle of the right accessory belly and inserted together. These accessory bellies had no connection with the left anterior belly. This unique variation has not been reported in the literature previously, and this presentation will guide clinicians during surgical interventions and radiological diagnoses.
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http://dx.doi.org/10.5115/acb.2011.44.3.241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195829PMC
September 2011

Insertional anatomy and clinical relevance of the distal biceps tendon.

Knee Surg Sports Traumatol Arthrosc 2011 Nov 23;19(11):1930-5. Epub 2011 Jun 23.

Department of Orthopedic Surgery, Dongsan Medical Center, School of Medicine, Keimyung University, 194 Dongsan-dong, Joong-gu, Daegu 700-712, Korea.

Purpose: This study was undertaken to evaluate the incidence of bifurcated distal biceps tendons and the tendon's insertional footprint on the radial tuberosity.

Methods: Twenty-five embalmed cadaveric specimens were dissected. The relationships and orientation of the muscle bellies and distal biceps tendon were examined. The insertional length, width, and footprint area of the distal biceps tendon on the radial tuberosity were evaluated.

Results: In 12 specimens (48%), the distal biceps tendon was in 2 distinct, easily separated parts. The average footprint length, width, and area of the tendon's insertion on the radial tuberosity were 20.5 mm ± 2.0 mm, 9.7 mm ± 1.3 mm, and 156.3 mm(2) ± 29.4 mm(2), respectively. We calculated that the tendon's insertion occupied approximately 35.9% of the area of the radial tuberosity. In the specimens with a bifurcated distal biceps tendon, the long head of the tendon inserted at the posterosuperior portion of the radial tuberosity, and the average area was 71.4 mm(2) ± 11.3 mm(2). The short head of the distal biceps tendon inserted at the anteroinferior portion, and the average area was 88.3 mm(2) ± 24.1 mm(2).

Conclusion: This study confirmed that bifurcated distal biceps tendon insertion is not a rare anatomical variation, showed by recent investigations, and found that the short head of the distal biceps tendon was inserted more anteriorly than the long head on the radial tuberosity. These findings may allow functional independence and isolated rupture of each portion. It can make correct diagnosis possible and allow for a more anatomical orientation of the tendon during surgical repair.
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http://dx.doi.org/10.1007/s00167-011-1586-xDOI Listing
November 2011

Haddad syndrome with PHOX2B gene mutation in a Korean infant.

J Korean Med Sci 2011 Feb 24;26(2):312-5. Epub 2011 Jan 24.

Institute for Medical Genetics, Keimyung University College of Medicine, Daegu, Korea.

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.
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http://dx.doi.org/10.3346/jkms.2011.26.2.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031022PMC
February 2011

Different characteristics of mitochondrial microsatellite instability between uterine leiomyomas and leiomyosarcomas.

Pathol Oncol Res 2011 Jun 18;17(2):201-5. Epub 2010 Sep 18.

Department of Anatomy, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Republic of Korea.

Uterine leiomyomas are benign tumors of the uterus that arise clonally from smooth muscle cells of the myometrium and are the most common reason for hysterectomies. The aim of this study was to evaluate mitochondrial microsatellite instability (mtMSI) in uterine leiomyomas and leiomyosarcomas to clarify the molecular pathogenetic distinction between these tumors. DNA was isolated from paired normal and tumoral tissues in 50 patients with uterine leiomyomas and 14 patients with leiomyosarcomas. mtMSI was analyzed by using eight microsatellite markers. Our result showed that mitochondrial microsatellite instability was not found in all uterine leiomyomas. However, 3 (21.4%) of 14 patients with leiomyosarcomas had mtMSI and the frequencies of mtMSI in these tumors were significantly different (p < 0.01). Distinctive characteristics of mitochondrial genetic instability in uterine leiomyomas and leiomyosarcomas suggested the potential of mtMSI as a marker for differential diagnosis between them.
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http://dx.doi.org/10.1007/s12253-010-9297-zDOI Listing
June 2011

Glucagon-like peptide-1 protects NSC-34 motor neurons against glucosamine through Epac-mediated glucose uptake enhancement.

Neurosci Lett 2010 Jul 13;479(1):13-7. Epub 2010 May 13.

Institute for Medical Genetics, Keimyung University School of Medicine, Dalseo-Gu, Daegu, Republic of Korea.

Bioenergetic deficits are considered a common cause of neurodegenerative diseases. Although creatine supplementation has been shown to be effective in certain neurodegenerative disorders, it is less effective in amyotrophic lateral sclerosis, a disease that primarily affects motor neurons. These neurons are particularly vulnerable to a cellular energy deficit. Using the ATP-depleting drug glucosamine, we evaluated whether the incretin hormone glucagon-like peptide (GLP)-1 protects motor neurons against glucosamine-induced cytotoxicity. Undifferentiated NSC-34 cells were differentiated into glutamate-sensitive motor neurons by a modified serum deprivation technique. Glucosamine inhibited the viability of differentiated NSC-34 cells in a time- and dose-dependent manner. Glucosamine also acutely reduced cellular glucose uptake, glucokinase activity and intracellular ATP levels. As a result, the activity of AMP-activated protein kinase as well as endoplasmic reticulum stress increased. Pretreatment with GLP-1 significantly alleviated glucosamine-mediated neurotoxicity by restoring cellular glucose uptake, glucokinase activity and intracellular ATP levels. The protective effect of GLP-1 was replicated by Exendin-4 but not Exendin-9, and not blocked by inhibitors of phosphoinositide-3 kinase, protein kinase A, cSrc, or epidermal growth factor receptor, but it was blocked by an adenylate cyclase inhibitor. A selective activator for exchange proteins directly activated by cAMP (Epac), but not a selective activator for protein kinase A, mimicked the GLP-1 effect. Therefore GLP-1 may exert its effect mainly through cAMP-dependent, Epac-mediated restoration of glucose uptake that is typically impaired by glucosamine. These findings indicate that GLP-1 could be employed therapeutically to protect motor neurons that are susceptible to bioenergetic deficits.
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http://dx.doi.org/10.1016/j.neulet.2010.05.017DOI Listing
July 2010

Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion.

Cancer Epidemiol 2010 Jun 20;34(3):323-7. Epub 2010 Apr 20.

Department of Surgery, Keimyung University College of Medicine, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, Republic of Korea.

Background: Genetic instability in gastric cancer represents a key molecular step that occurs early in the carcinogenesis process. To clarify the role of genetic instability in the progression from gastric dysplasia to gastric cancer, mitochondrial microsatellite instability (mtMSI) was studied in gastric cancer and gastric dysplasia.

Methods: DNA was isolated from paired normal and tumoral tissues in 24 patients with gastric dysplasia (low grade) and 49 patients with gastric cancer. mtMSI was analyzed using eight microsatellite markers. mtMSI in gastric dysplasia was studied prospectively to elucidate the relation between mtMSI and gastric carcinogenesis.

Results: mtMSI was found in 5 (10.2%) of 49 gastric cancer patients. The mtMSI phenotype was not associated with age, gender, and Helicobacter pylori infection. However, all of the mtMSI was found in intestinal-type gastric cancer (20.8%, p=0.02). In gastric dysplasia, mtMSI was detected in 3 (12.5%) of 24 patients with gastric dysplasia. mtMSI-positive gastric dysplasia showed a poor prognosis statistically compared to mtMSI negative through progression to high-grade dysplasia or gastric cancer.

Conclusions: These data suggest that mtMSI may be an early and important event in the progression of gastric carcinogenesis, especially in intestinal-type gastric cancer.
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http://dx.doi.org/10.1016/j.canep.2010.03.015DOI Listing
June 2010