1.Two cases of pseudohypoparathyroidism in sibling.
Sun Whan KWON ; Hye Jin LEE ; Seon Young CHOI ; Un Ki YOON
Journal of the Korean Pediatric Society 1993;36(6):882-887
Pseudohypoparathyroidism is a medical disorder characterized by a complex disorder of renal resistance to parathyroid hormone and the mechanism underlying the disease is still unclear. The authors described two cases of pseudohypoparathyroidism in sibling,who had metabolic anomalies(hypocalcemia and hyperphosphatemia, high circulatin immunoreactive PTH)and basal ganglia calcification. Bilateral basal ganglia calcifications, which was not visible on plain skull film, was detected by CT scan of brain MRI. We report these cases with a review of related literatures.
Basal Ganglia
;
Brain
;
Humans
;
Hyperphosphatemia
;
Magnetic Resonance Imaging
;
Parathyroid Hormone
;
Pseudohypoparathyroidism*
;
Siblings*
;
Skull
;
Tomography, X-Ray Computed
2.Anti-cancer Effect of Luminacin, a Marine Microbial Extract, in Head and Neck Squamous Cell Carcinoma Progression via Autophagic Cell Death.
Yoo Seob SHIN ; Hyun Young CHA ; Bok Soon LEE ; Sung Un KANG ; Hye Sook HWANG ; Hak Cheol KWON ; Chul Ho KIM ; Eun Chang CHOI
Cancer Research and Treatment 2016;48(2):738-752
PURPOSE: The purpose of this study is to determine whether luminacin, a marine microbial extract from the Streptomyces species, has anti-tumor effects on head and neck squamous cell carcinoma (HNSCC) cell lines via autophagic cell death. MATERIALS AND METHODS: Inhibition of cell survival and increased cell death was measured using cell viability, colony forming, and apoptosis assays. Migration and invasion abilities of head and cancer cells were evaluated using wound healing, scattering, and invasion assays. Changes in the signal pathway related to autophagic cell death were investigated. Drug toxicity of luminacin was examined in in vitro HaCaT cells and an in vivo zebrafish model. RESULTS: Luminacin showed potent cytotoxicity in HNSCC cells in cell viability, colony forming, and fluorescence-activated cell sorting analysis. In vitro migration and invasion of HNSCC cells were attenuated by luminacin treatment. Combined with Beclin-1 and LC3B, Luminacin induced autophagic cell death in head and neck cancer cells. In addition, in a zebrafish model and human keratinocyte cell line used for toxicity testing, luminacin treatment with a cytotoxic concentration to HNSCC cells did not cause toxicity. CONCLUSION: Taken together, these results demonstrate that luminacin induces the inhibition of growth and cancer progression via autophagic cell death in HNSCC cell lines, indicating a possible alternative chemotherapeutic approach for treatment of HNSCC.
Apoptosis
;
Autophagy*
;
Carcinoma, Squamous Cell*
;
Cell Death
;
Cell Line
;
Cell Survival
;
Drug-Related Side Effects and Adverse Reactions
;
Flow Cytometry
;
Head and Neck Neoplasms
;
Head*
;
Humans
;
Keratinocytes
;
Neck*
;
Signal Transduction
;
Streptomyces
;
Toxicity Tests
;
Wound Healing
;
Zebrafish
3.Detection of Mutations in Chronic Hepatitis B Virus under Lamivudine Treatment: Direct Sequencing and CLIP Sequencing.
Hyunwoong PARK ; Hye Lin KWON ; Sang Hoon SONG ; Kyoung Un PARK ; Junghan SONG ; Sung Sup PARK ; Eui Chong KIM
Journal of Laboratory Medicine and Quality Assurance 2008;30(2):285-290
BACKGROUND: Hepatitis B Virus (HBV) is a major risk factor for hepatocellular carcinoma, and about five to six percents of people are infected with HBV in Korea. Lamivudine is a first-line drug having good control against HBV replication, but long-term treatment by lamivudine induces drug resistance. We analyzed the rate of HBV resistance mutation for lamivudine by direct sequencing and CLIP sequencing. METHODS: HBV DNA was isolated from 371 patients who were in treatment, or were planning to be treated with lamivudine. The direct sequencing for lamivudine resistance mutation was performed in 371 patients and CLIP sequencing in 138 patients. We analyzed the mutation rate and the type of mutations for lamivudine resistance. RESULTS: The mutation was detected in 203 patients (54.7%) and (CTG) L180M (ATG) was most common (36.1%) followed by (ATG) M204I (ATT) (29.9%) and (ATG) M204V (GTG) (18.6%). According to the duration of treatment, mutation rates were as follows: 45.3% for less than one year, 71.7% for one to two years, 66.7% for two to three years, and 87.9% for more than three years. The results of the direct sequencing and CLIP sequencing agreed in 134 out of 138 patients, in whom both tests were performed. CONCLUSIONS: We confirmed that HBV mutation rates for lamivudine resistance increased as the lamivudine treatment period increased. The lamivudine resistance mutations detected were similar to the previous studies. CLIP sequencing showed good correlation with the direct sequencing and gave additional mutation information. CLIP sequencing is a promising tool for the detection of lamivudine resistance mutation in HBV that can assist treatment plans.
Carcinoma, Hepatocellular
;
DNA
;
Drug Resistance
;
Hepatitis B virus
;
Hepatitis B, Chronic
;
Hepatitis, Chronic
;
Humans
;
Korea
;
Lamivudine
;
Mutation Rate
;
Risk Factors
4.Mesenchymanl Stem Cell Based Intradiscal Gene Therapy: Therapeutic Implication in Degenerative Disc Disease.
Hyang KIM ; Un Hye KWON ; Kwang Il LEE ; Ki Hong SONG ; Sung Yeop SHIN ; Si Young PARK ; Jin Oh PARK ; Hwan Mo LEE ; Seong Hwan MOON
Journal of Korean Society of Spine Surgery 2004;11(2):67-76
STUDY DESIGN: In-vitro experiments using human mesenchymal stem cells (MSCs), intervertebral disc (IVD) cells and type 5 adenovirus/transforming growth factor-beta1 construct (Ad/TGF-beta1). OBJECTIVES: To determine the effect of MSC-based gene therapy for matrix regeneration of IVD cells. SUMMARY OF LITERATURE REVIEW: MSCs are known to be multipotent in tissue regeneration. In degeneration of IVD, cellular replacement with genetic modification other than that of IVD cells may prove an enhanced mechanism for the regeneration of MATERIALS AND METHODS: MSCs and IVD cells were cultured and an adenovirus construct containing TGF-beta1 cDNA (Ad/TGF-beta1) was also produced. In the first step, the MSCs were transduced with Ad/TGF-beta1, then mixed with IVD cells in various proportions and three dimensionally cultured. [methyl-(3)H]Thymidine and [(35)S]Sulfur incorporation for DNA and proteoglycan synthesis, respectively, were measured. RT-PCR was performed to assess the aggrecan and collagen types I and II mRNA RESULTS: Mixed cultures of MSC and IVD cells showed relatively similar amounts of newly synthesized proteoglycan compared with cultures of IVD cells only. In mixed cultures transduced with Ad/TGF-beta1, there were significant decreases in newly synthesized proteoglycan with increasing the proportions of MSCs, which was also found with the aggrecan and collagen type II mRNA expressions. However, the collagen type I mRNA expression increased with increased proportions of MSCs transduced with Ad/TGF-beta1. CONCLUSION: Cell therapy with MSCs and IVD cells provided a mechanism for cellular augmentation. However, MSC-based gene therapy coupled with IVD cells did not maintain a chondrogenic phenotype.
Adenoviridae
;
Aggrecans
;
Cell- and Tissue-Based Therapy
;
Collagen
;
Collagen Type I
;
Collagen Type II
;
DNA
;
DNA, Complementary
;
Genetic Therapy*
;
Humans
;
Intervertebral Disc
;
Mesenchymal Stromal Cells
;
Phenotype
;
Proteoglycans
;
Regeneration
;
RNA, Messenger
;
Stem Cells*
;
Transforming Growth Factor beta1
5.Pulsed Electromagnetic Field Stimulates Cellular Proliferation in Human Intervertebral Disc Cells.
Hwan Mo LEE ; Un Hye KWON ; Hyang KIM ; Ho Joong KIM ; Boram KIM ; Jin Oh PARK ; Eun Soo MOON ; Seong Hwan MOON
Yonsei Medical Journal 2010;51(6):954-959
PURPOSE: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. MATERIALS AND METHODS: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Omega, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). RESULTS: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05). CONCLUSION: EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
Adult
;
Aspirin/pharmacology
;
Cell Proliferation/*radiation effects
;
Collagen/metabolism
;
Dinoprostone/metabolism
;
*Electromagnetic Fields
;
Enzyme Inhibitors/pharmacology
;
Female
;
Humans
;
Intervertebral Disk/*pathology/radiation effects
;
Male
;
Middle Aged
;
Nitric Oxide/metabolism
;
Tetrazolium Salts/pharmacology
;
Thiazoles/pharmacology
;
omega-N-Methylarginine/pharmacology
6.Diagnostic Significance of Fractional Excretion of Unmeasured Anion(FEua)in Metabolic Acidosis.
Hye Young KIM ; Jin Suk HAN ; Seo Jin LEE ; Un Sil JEON ; Kwon wook JOO ; Jae Ho EARM ; Gheun Ho KIM ; Curie AHN ; Suhnggwon KIM ; Jung Sang LEE
Korean Journal of Nephrology 1999;18(1):112-119
Alcohol can cause rhabdomyolysis by either direct toxicity or associated metabolic abnormality such as hypophosphatemia and hypokalemia. It can also predispose to or cause trauma, seizures, or coma- induced ischemic pressure necrosis. In order to investigate the clinical features of acute renal failure caused by alcohol induced rhabdomyolysis, we reviewed the medical records of the 12 patients. All patients had been drinking much amounts of alcohol for several years. All patients showed elevation of muscle enzyme such as creatine phosphokinase, lactic dehydrogenase, aspartate transaminase and blood urea nitrogen and serum creatinine. Predisposing factors of rhabdomyolysis were ischemic compression due to unconsciousness and dehydration(2 cases), and hypophosphatemia and dehydration(1 case), seizure and dehydration(1 case), and only severe dehydration(3 cases). Initial symptoms were painful swelling at lesion site(5 cases), abdominal pain(2 cases), general ache(2 cases), leg pain without swelling(1 case), dyspnea(1case), and lethargy(1 case). Seven patients developed delirium tremens during recovery stage. Eight patients showed oliguric acute renal failure and 8 patients were treated with hemodialysis. Complications were disseminated intravascular coagulation(DIC)(3 cases), compartment syndrome(2 cases), capillary leak syndrome and DIC(1 case). One of 12 patients died of disseminated intravascular coagulation and other patients showed complete recovery of renal function.
Acidosis*
;
Acute Kidney Injury
;
Alcohol Withdrawal Delirium
;
Aspartate Aminotransferases
;
Blood Urea Nitrogen
;
Capillary Leak Syndrome
;
Causality
;
Creatine Kinase
;
Creatinine
;
Disseminated Intravascular Coagulation
;
Drinking
;
Humans
;
Hypokalemia
;
Hypophosphatemia
;
Leg
;
Medical Records
;
Necrosis
;
Oxidoreductases
;
Renal Dialysis
;
Rhabdomyolysis
;
Seizures
;
Unconsciousness
7.Immunosuppression by T regulatory cells in cows infected with Staphylococcal superantigen.
Byoung Sun CHANG ; Gregory A BOHACH ; Sang Un LEE ; William C DAVIS ; Lawrence K FOX ; Witold A FERENS ; Keun Seok SEO ; Hye Cheong KOO ; Nam Hoon KWON ; Yong Ho PARK
Journal of Veterinary Science 2005;6(3):247-250
Our recent study has provided that the in vitro SEC-induced proliferation of bovine T cells is preceded by a period of a non-proliferative immunoregulation of T cells that may be associated with cytokine production regulated by type 1 or type 2 T cells. Inversion of CD4+:CD8+ T cell ratio and induction of CD8+T cells with immunoregulatory activity could increase the probability of intracellular survival of Staphylococcus aureus (S. aureus). The increase of activated CD8+(ACT2+ BoCD8+) T cells in cows with mastitis caused by S. aureus may be associated with immune-regulatory function in the bovine mammary gland. The difference and similarity between bovine activated CD8+ T cells (CD8+ CD26+)and well-established human CD4+ CD25+ T regulatory (Tr)cells may help to reveal their unique immune regulatory system in the host infected with S. aureus.
Animals
;
Cattle
;
Cell Proliferation
;
Female
;
Lymphocyte Activation/immunology
;
Mastitis, Bovine/*immunology/microbiology
;
Staphylococcal Infections/immunology/*veterinary
;
Staphylococcus/*immunology
;
*Superantigens
;
T-Lymphocytes/*immunology
8.A Case of ABO*Ael02/O04 Genotype with Typical Phenotype O.
Shin Young JOO ; Yeong Sook SHIM ; Mi Jung KIM ; Hye Lin KWON ; Kyung LEE ; Ho Eun CHANG ; Sang Hoon SONG ; Kyoung Un PARK ; Junghan SONG ; Kyou Sup HAN
The Korean Journal of Laboratory Medicine 2008;28(4):319-324
Ael is a rare blood type which has the least amount of A antigen among A subgroups. It can be detected by special tests performed to resolve the discrepancy between red cell and serum typing in routine serological typing. The presence of A antigen on Ael red cell is demonstrable only by adsorption and elution tests. An Ael individual does not secret A substance in the saliva and may have anti-A antibody in the serum which is usually less reactive with the reagent red cells than anti-B antibody. In Korea, Ael02 has been reported more frequently than other Ael alleles. We report a case of Ael02/O04 who presented as typical phenotype O with strong anti-A and anti-B antibodies and no A antigen detected even by adsorption and elution tests. The case has been proved to be Ael02/O04 by direct sequencing analysis. In individuals with history of discrepancies in the results of ABO phenotyping, ABO genotyping is needed for an accurate evaluation of their blood type.
ABO Blood-Group System/classification/*genetics
;
Alleles
;
Child
;
Genotype
;
Heterozygote
;
Humans
;
Male
;
Pedigree
;
Phenotype
;
Sequence Analysis, DNA
9.Dual Roles of Ligamentum Flavum for Spinal Fusion: As an Osteoinductive Agent and Carrier for Ex-vivo Gene Transfer.
Seong Hwan MOON ; Hyang KIM ; Un Hye KWON ; Keong Hee KIM ; Hong Ki YOUN ; Hak Sun KIM ; Soo Bong HAHN ; Hwan Mo LEE
Journal of Korean Society of Spine Surgery 2003;10(1):1-7
STUDY DESIGN: An in-vitro experiment using human ligamentum flavum (LF) and the adnovirus-BMP-2 construct, Ad/BMP-2. OBJECTIVES: To determine the dual roles of LF as an osteoinductive agent and carrier for ex-vivo gene transfer. SUMMARY OF LITERATURE REVIEW: LF is known to have osteogenic potential. Pathologically, ossified LF may cause myelopathy and radiculopathy. BMP-2 is known as an important factor in the differentiation, and maintenance, of osteoblast phenotypes. Ex-vivo gene transfer, using human LF for spinal fusion, has never been attempted before. MATERIALS AND METHODS: The LF cells were cultured from the degenerated LF of spinal stenosis patients. An adenovirus construct, containing BMP-2 cDNA (Ad/BMP-2), was also produced. The LF cell cultures were exposed to the adenoviral construct. The Osteocalcin expression was analysed by Western blot analysis. The osteocalcin and BMP-2 mRNA expressions were analysed by RT-PCR. Bone formation was assessed by alkaline phosphatase and Von Kossa stains. RESULTS: The LF cell cultures, with Ad/BMP-2, showed transgene expression in the Western blot analysis. Also, the cultures exhibited the mRNA expressions of both osteocalcin and BMP-2, in a dose-dependent manner. The LF cultures, with Ad/BMP-2, demonstrated alkaline phosphatase expression and bone nodule formations from the Von Kossa staining. CONCLUSION: The genetically modified LF strongly induced osteogenesis, which can be used during a spinal fusion, as an osteoinductive agent and carrier, for ex-vivo gene transfer.
Adenoviridae
;
Alkaline Phosphatase
;
Blotting, Western
;
Cell Culture Techniques
;
Coloring Agents
;
DNA, Complementary
;
Humans
;
Ligamentum Flavum*
;
Osteoblasts
;
Osteocalcin
;
Osteogenesis
;
Phenotype
;
Radiculopathy
;
RNA, Messenger
;
Spinal Cord Diseases
;
Spinal Fusion*
;
Spinal Stenosis
;
Transgenes
10.The Role of Oxytocin and Vasopressin in Abnormal Water Retention in Generalized Edematous Patients.
Un Sil JEON ; Jin Suk HAN ; Seo Jin LEE ; Kwon Wook JOO ; Hye Young KIM ; Woo Weong HUH ; Gheun Ho KIM ; Jong Ho LEE ; Curie AHN ; Suhnggwon KIM ; Jung Sang LEE
Korean Journal of Nephrology 1998;17(4):559-566
Antidiuretic action of oxytocin is confirmed by in vitro study using with rat IMCD. Vasopressin is elevated in edematous disorders and may play a pathogenetic role in the formation of edema. If oxytocin plays a sirnilar role to vasopressin in water disturbances in human, oxytocin may change as the same way as vasopressin. To verify a role of oxytocin in the regulation of water balance in human, we measured plasma and urine oxytocin with vasopressin by radioimmunoassay in thirteen patients with generalized edema (8 nephrotic syndrome, 3 liver cirrhosis, 2 acute renal failure) before and after control of edema. And they were compared them with those of seven normal controls. Plasma oxytocin level correlated with plasma vasopressin level (r=0.543: P<0.05) and urinary oxytocin level correlated linearly with urinary vaso-pressin (r=0.983, P<0.01). After control of edema, body weight of patients decreased from 65+/- 2 to 58+/-2kg and fractional excretion of sodium decreased from 3.3+/-1.1 to 1.2+/-0.696 (P<0.05). There were no significant changes in serum and urine Na, osmolality, free water clearance, plasma renin activity, aldosterone and norepinephrine. In conclusion, oxytocin was elevated in edematous disorders, and may participate in formation of edema similar to vasopressin.
Aldosterone
;
Animals
;
Body Weight
;
Edema
;
Humans
;
Liver Cirrhosis
;
Nephrotic Syndrome
;
Norepinephrine
;
Osmolar Concentration
;
Oxytocin*
;
Plasma
;
Radioimmunoassay
;
Rats
;
Renin
;
Sodium
;
Vasopressins*
;
Water*