Synthesis of Psoralen Derivatives and Their Blocking Effect of hKv1.5 Channel

Eun, Jae-Soon,Kim, Kwang-Sik,Kim, Han-Na,Park, Seon-Ah,Ma, Tian-Ze,Lee, Kyung-A,Kim, Dae-Keun,Kim, Hyung-Kyo,Kim, In-Su,Jung, Young-Hoon,Zee, Ok-Pyo,Yoo, Dong-Jin,Kwak, Yong-Geun 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1 ]benzopyran-7-one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects or hKv1.5 stably expressed in Ltk cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5,9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent In blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 27.4 ${\pm}$ 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open charnel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studios were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

Neurodevelopmental Disorders of Children Screened by The Infantile Health Promotion System

김성우,Ha Ra Jeon,Zee-A Han,최자영,Hee Jung Chung,Young Key Kim,Yeo Hoon Yoon 대한재활의학회 2011 Annals of Rehabilitation Medicine Vol.35 No.6

Objective To perform an in depth evaluation of children, and thus provide a systematic method of managing children, who after infantile health screening, were categorized as suspected developmental delay. Method 78 children referred to the Developmental Delay Clinic of Ilsan Hospital after suspected development delay on infantile health examinations were enrolled. A team comprised of a physiatrist, pediatrician and pediatric psychiatrist examined the patients. Neurological examination, speech and cognitive evaluation were done. Hearing tests and chromosome studies were performed when needed clinically. All referred children completed K-ASQ questionnaires. Final diagnoses were categorized into specific language impairment (SLI),global developmental delay (GDD), intellectual disability (ID), cerebral palsy (CP), motor developmental delay (MD) or autism spectrum disorder (ASD). Results 72 of the 78 patients were abnormal in the final diagnosis, with a positive predictive value of 92.3%. Thirty (38.4%) of the 78 subjects were diagnosed as GDD, 28 (35.8%) as SLI, 5 (6.4%) as ASD, 9 (12.5%) as MD, and 6(7.6%) as normal. Forty five of the 78 patients had risk factors related to development, and 18 had a positive family history for developmental delay and/or autistic disorders. The mean number of abnormal domains on the K-ASQ questionnaires were 3.6 for ASD, 2.7 for GDD, 1.8 for SLI and 0.6 for MD. Differences between these numbers were statistically significant (p<0.05). Conclusion Because of the high predictive value of the K-ASQ, a detailed evaluation is necessary for children suspected of developmental delay in an infantile health promotion system.

Factors Related to the Occurrence of Urinary Tract Infection Following a Urodynamic Study in Patients With Spinal Cord Injury

황성일,Bum-Suk Lee,Zee-A Han,Hye-Jin Lee,Sang-Hoon Han,Myeong-Ok Kim 대한재활의학회 2016 Annals of Rehabilitation Medicine Vol.40 No.4

Objective To analyze the factors related to urinary tract infection (UTI) occurrence after an urodynamic study (UDS) in patients with spinal cord injury (SCI).Methods We retrospectively investigated the medical records of 387 patients with SCI who underwent UDS with prophylactic antibiotic therapy between January 2012 and December 2012. Among them, 140 patients met the inclusion criteria and were divided into two groups, UTI and non-UTI. We statistically analyzed the following factors between the two groups: age, sex, level of injury, SCI duration, spinal cord independence measure, non-steroidal anti-inflammatory drug use, diabetes mellitus, the American Spinal Injury Association impairment scale (AIS), lower extremity spasticity, a history of UTI within the past 4 weeks prior to the UDS, symptoms and signs of neurogenic bladder, urination methods, symptoms during the UDS and UDS results. Results Among the 140 study participants, the UTI group comprised 12 patients and the non-UTI group comprised 128 patients. On univariate analysis, a history of UTI within the past 4 weeks prior to the UDS was significant and previous autonomic dysreflexia before the UDS showed a greater tendency to influence the UTI group. Multivariable logistic regression analysis using these two variables showed that the former variable was significantly associated with UTI and the latter variable was not significantly associated with UTI.Conclusion In patients with SCI, a history of UTI within the past 4 weeks prior to the UDS was a risk factor for UTI after the UDS accompanied by prophylactic antibiotic therapy. Therefore, more careful pre-treatment should be considered when these patients undergo a UDS.

Clinical Characteristics of Children with Rett Syndrome

Zee-A Han,Ha Ra Jeon,김성우,박진영,Hee Jung Chung 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.3

Objective To identify the clinical characteristics and investigate function related aspects of Korean children with Rett syndrome. Method A total of 26 patients diagnosed as Rett syndrome were clinically observed until the age of fi ve or over. We surveyed past history, developmental history, and presence of typical clinical features of Rett syndrome. Furthermore, we investigated diff erences in clinical characteristics according to functional status and changes in clinical features related to growth. Results There were no problems related to gestational, perinatal or neonatal history. Only 12 patients had an ultimate head circumference of less than 3 percentile. Developmental regression was definite in all patients. At final assessment, only 14 patients were able to walk. Twenty patients had an epileptic history requiring medication. Sixteen patients with scoliosis showed progression during serial follow-up. Th e percentage of patients who were able to walk before 16 months was higher in the high function group than the low function group. Th e age of regression was 5.4 and 4.0 years in the high and low function group respectively, but the diff erence was not statistically signifi cant. Scoliosis was more severe and seizure onset age was younger in the low function group. Conclusion We investigated 26 clinical characteristics in Korean children with Rett syndrome. Their clinical features change according to age, and we believe such knowledge could be utilized in rehabilitation to minimize their disabilities.

A bioorthogonal approach for imaging the binding between Dasatinib and its target proteins inside living cells

Kim, Young-Rang,Kim, Young Hye,Kim, Sung Woo,Lee, Yong Ju,Chae, Dong-Eon,Kim, Kyung-A,Lee, Zee-Won,Kim, Nam Doo,Choi, Jong-Soon,Choi, Insung S.,Lee, Kyung-Bok The Royal Society of Chemistry 2016 Chemical communications Vol.52 No.79

<P>Herein, we present a simple readout of the binding between a chemical drug and its target proteins in the cytoplasm by using a two-step bioorthogonal labeling method combined with spatially-localized expression of proteins. Dasatinib was modified with transcyclooctene (TCO), and its cytoplasmic target kinases were expressed in intracellular compartments, such as endosomes and F-actins. After bioorthogonal labeling, the colocalization between Dasatinib and its target proteins was observed in intracellular compartments.</P>

Protective Role of Tissue Transglutaminase in the Cell Death Induced by TNF-α in SH-SY5Y Neuroblastoma Cells

Kweon, Soo-Mi,Lee, Zee-Won,Yi, Sun-Ju,Kim, Young-Myeong,Han, Jeong-A,Paik, Sang-Gi,Ha, Kwon-Soo Korean Society for Biochemistry and Molecular Biol 2004 Journal of biochemistry and molecular biology Vol.37 No.2

Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor $\alpha$ (TNF-$\alpha$) and ceramide, a product of the TNF-$\alpha$ signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis showed the tTGase expression by RA treatment. TNF-$\alpha$ or $C_2$ ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-$\alpha$ or $C_2$-ceramide. In addition, the co-treatment of TNF-$\alpha$ and cycloheximide ecreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-$\alpha$ and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-$\alpha$ and ceramide.

Protective Role of Tissue Transglutaminase in the Cell Death Induced by TNF-α in SH-SY5Y Neuroblastoma Cells

( Soo Mi Kweon ),( Zee Won Lee ),( Sun Ju Yi ),( Young Myeong Kim ),( Jeong A Han ),( Sang Gi Paik ),( Kwon Soo Ha ) 생화학분자생물학회 2004 BMB Reports Vol.37 No.2

Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor a(TNF-α) and ceramide, a product of the TNF-αsignaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis tTGase expression by RA treatment. TNF-αor C, ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, mono-dansylcadaverline and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-α or C_(2)-ceramide, In addition, the co-treatment of TNF-α and cycloheximide decreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-α and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-α and ceramide.

Stacking Structures of Few-Layer Graphene Revealed by Phase-Sensitive Infrared Nanoscopy

Kim, Deok-Soo,Kwon, Hyuksang,Nikitin, Alexey Yu.,Ahn, Seongjin,Martí,n-Moreno, Luis,Garcí,a-Vidal, Francisco J.,Ryu, Sunmin,Min, Hongki,Kim, Zee Hwan American Chemical Society 2015 ACS NANO Vol.9 No.7

<P>The stacking orders in few-layer graphene (FLG) strongly influences the electronic properties of the material. To explore the stacking-specific properties of FLG in detail, one needs powerful microscopy techniques that visualize stacking domains with sufficient spatial resolution. We demonstrate that infrared (IR) scattering scanning near-field optical microscopy (sSNOM) directly maps out the stacking domains of FLG with a nanometric resolution, based on the stacking-specific IR conductivities of FLG. The intensity and phase contrasts of sSNOM are compared with the sSNOM contrast model, which is based on the dipolar tip–sample coupling and the theoretical conductivity spectra of FLG, allowing a clear assignment of each FLG domain as Bernal, rhombohedral, or intermediate stacks for tri-, tetra-, and pentalayer graphene. The method offers 10–100 times better spatial resolution than the far-field Raman and infrared spectroscopic methods, yet it allows far more experimental flexibility than the scanning tunneling microscopy and electron microscopy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-7/acsnano.5b02813/production/images/medium/nn-2015-02813x_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5b02813'>ACS Electronic Supporting Info</A></P>

Prevalence and Characteristics of Neuropathic Pain in Patients With Spinal Cord Injury Referred to a Rehabilitation Center

Hae Young Kim,Hye Jin Lee,Tae-lim Kim,EunYoung Kim,Daehoon Ham,Jaejoon Lee,Tayeun Kim,Ji Won Shin,Minkyoung Son,Jun Hun Sung,Zee-A Han 대한재활의학회 2020 Annals of Rehabilitation Medicine Vol.44 No.6

Objective To identify the prevalence and characteristics of neuropathic pain (NP) in patients with spinal cord injury (SCI) and to investigate associations between NP and demographic or disease-related variables. Methods We retrospectively reviewed medical records of patients with SCI whose pain was classified according to the International Spinal Cord Injury Pain classifications at a single hospital. Multiple statistical analyses were employed. Patients aged <19 years, and patients with other neurological disorders and congenital conditions were excluded. Results Of 366 patients, 253 patients (69.1%) with SCI had NP. Patients who were married or had traumatic injury or depressive mood had a higher prevalence rate. When other variables were controlled, marital status and depressive mood were found to be predictors of NP. There was no association between the prevalence of NP and other demographic or clinical variables. The mean Numeric Rating Scale (NRS) of NP was 4.52, and patients mainly described pain as tingling, squeezing, and painful cold. Females and those with below-level NP reported more intense pain. An NRS cut-off value of 4.5 was determined as the most appropriate value to discriminate between patients taking pain medication and those who did not. Conclusion In total, 69.1% of patients with SCI complained of NP, indicating that NP was a major complication. Treatment planning for patients with SCI and NP should consider that marital status, mood, sex, and pain subtype may affect NP, which should be actively managed in patients with an NRS ≥4.5.

Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca ²⁺ -ATPase in Heart Failure

Gorski, Przemek A.,Jang, Seung Pil,Jeong, Dongtak,Lee, Ahyoung,Lee, Philyoung,Oh, Jae Gyun,Chepurko, Vadim,Yang, Dong Kwon,Kwak, Tae Hwan,Eom, Soo Hyun,Park, Zee-Yong,Yoo, Yung Joon,Kim, Do Han,Kook, Grune & Stratton 2019 Circulation research Vol.124 No.9