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Kim, Min Keun,Kang, Tae Ho,Kim, Sung Kyum,Jeong, Yu Seok,Yun, Han Dae,Kim, Hoon The Korean Society for Applied Biological Chemistr 2012 Applied Biological Chemistry (Appl Biol Chem) Vol.55 No.6
The rsmA gene was cloned from soft-rot bacterium Pectobacterium carotovorum subsp. carotovorum LY34 (Pcc LY34), and its role in pathogenicity was investigated by marker exchange mutagenesis. From a cosmid library of Pcc LY34 genomic DNA, a positive clone carrying the rsmA gene was selected, and the gene was cloned by polymerase chain reaction (PCR) amplification. The gene is 186 bp in size and encodes a protein of 62 amino acids with a predicted molecular mass of 6,839 Da. The calculated pI of the RsmA is 8.16. The phylogenetic tree showed that the RsmA of Pcc LY34 appeared genetically identical to the CsrA of Pectobacterium atrosepticum SCRI1043 (100% identity) and similar to the CsrA of Yersinia pestis KIM10+(98.3%). The gene was disrupted by the $Km^r$ gene, and the cells became mutated (i.e., $RsmA^-$ mutant). The pathogenicity test revealed that the disease rating of the $RsmA^-$ mutant only differed slightly from that of the wild type on a slice of potato tuber and a Chinese cabbage stalk. These results suggest that RsmA is not an essential factor for the pathogenicity of Pcc LY34 and that the rsmA gene of Pcc LY34 is not completely derepressed in the $RsmA^-$ mutant for virulence-related genes, contrary to the results of Erwinia carotovora subsp. carotovora $RsmA^-$ mutant, which proved hypervirulent for celery petioles. These results showed that the microenvironmental conditions of the host and/or strain of pathogen are important for the coordination of virulence gene expression.
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Determination of Insulin Signaling Pathways in Hepatocytes
Sang Kyum Kim 한국독성학회 2005 Toxicological Research Vol.21 No.3
Diabetes is a major cause of morbidity and mortality, and associated with a high risk of atherosclerosis, and liver, kidney, nerve and tissue damage. Defective insulin secretion in pancreas and/or insulin resistance in peripheral tissues is a central component of diabetes. It is well established that, regardless of the degree of muscle insulin resistance, glucose levels in diabetic and non-diabetic individuals are determined by the rate of hepatic glucose production. Moreover recently studies using liver-specific insulin receptor knockout mice show the paramount role of the liver in insulin resistance and diabetes. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. The first major section of this review defines the major insulin-mediated signaling pathways including phosphatidylinositol 3-kinase and mitogen activated protein kinases. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways, including methods for determination of kinase phosphorylation, the use of pharmacological inhibitors of kinase and dominant-negative kinase constructs, and the application of new RNA interference methods.
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Kim, On-Yoo,Shin, Yoon-Kyum,Yoon, Young Kwon,Ko, Eu Jeong,Cho, Sung-Rae Korean Academy of Rehabilitation Medicine 2015 Annals of Rehabilitation Medicine Vol.39 No.1
<P><B>Objective</B></P><P>To investigate the effect of treadmill walking exercise as a treatment method to improve gait efficiency in adults with cerebral palsy (CP) and to determine gait efficiency during overground walking after the treadmill walking exercise.</P><P><B>Methods</B></P><P>Fourteen adults with CP were recruited in the experimental group of treadmill walking exercise. A control group of 7 adults with CP who attended conventional physical therapy were also recruited. The treadmill walking exercise protocol consisted of 3-5 training sessions per week for 1-2 months (total 20 sessions). Gait distance, velocity, VO<SUB>2</SUB>, VCO<SUB>2</SUB>, O<SUB>2</SUB> rate (mL/kg·min), and O<SUB>2</SUB> cost (mL/kg·m) were assessed at the beginning and at the end of the treadmill walking exercise. The parameters were measured by KB1-C oximeter.</P><P><B>Results</B></P><P>After the treadmill walking exercise, gait distance during overground walking up to 6 minutes significantly increased from 151.29±91.79 to 193.93±79.01 m, and gait velocity increased from 28.09±14.29 to 33.49±12.69 m/min (p<0.05). Energy efficiency evaluated by O<SUB>2</SUB> cost during overground walking significantly improved from 0.56±0.36 to 0.41±0.18 mL/kg·m (p<0.05), whereas O<SUB>2</SUB> rate did not improve significantly after the treadmill walking exercise. On the other hand, gait velocity and O<SUB>2</SUB> cost during overground walking were not significantly changed in the control group.</P><P><B>Conclusion</B></P><P>Treadmill walking exercise improved the gait efficiency by decreased energy expenditure during overground walking in adults with CP. Therefore, treadmill walking exercise can be an important method for gait training in adults with CP who have higher energy expenditure.</P>
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Kim, Jee Hung,Park, Hyung Soon,Heo, Su Jin,Kim, Sang Kyum,Han, Jung Woo,Shin, Kyoo-Ho,Kim, Seung Hyun,Hur, Hyuk,Kim, Kyung Sik,Choi, Young Deuk,Kim, Sunghoon,Lee, Young Han,Suh, Jin-Suck,Ahn, Joong-Ba S. Karger AG 2019 Oncology Vol.96 No.2
<P><B><I>Background:</I></B> We retrospectively investigated the treatment outcomes of second-line treatment with pazopanib or gemcitabine/docetaxel in patients with advanced soft tissue sarcoma (STS). <B><I>Methods:</I></B> Ninety-one patients who were treated with pazopanib or gemcitabine/docetaxel for advanced STS between 1995 and 2015 were analyzed. <B><I>Results:</I></B> Forty-six and 45 patients received pazopanib and gemcitabine/docetaxel, respectively. The median progression-free survival for the group treated with pazopanib was 4.5 months compared with 3.0 months for the gemcitabine/docetaxel group (<I>p</I> = 0.593). The median overall survival for the group treated with pazopanib was 12.6 months compared with 14.2 months for the gemcitabine/docetaxel group (<I>p</I> = 0.362). The overall response rates (ORRs) were 6.5 and 26.7% in the pazopanib and gemcitabine/docetaxel groups, respectively. The following parameters had ORRs favoring gemcitabine/docetaxel: age ≥50 years (31.6 vs. 2.9%, <I>p</I> = 0.006), histologic grade 1–2 (40.9 vs. 0%, <I>p</I> = 0.001), and poor first-line treatment response (23.3 vs. 3.0%, <I>p</I> = 0.022). Gemcitabine/docetaxel was associated with better ORRs for the following histologic subtypes: leiomyosarcoma (<I>p</I> = 0.624), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (<I>p</I> = 0.055), and angiosarcoma (<I>p</I> = 0.182). However, the ORR of synovial sarcoma favored pazopanib (<I>p</I> = 0.99). <B><I>Conclusions:</I></B> The efficacies of pazopanib and gemcitabine/docetaxel as second-line treatments after doxorubicin or ifosfamide failure differed among clinical and histologic subgroups and appeared to facilitate a more personalized treatment approach for advanced STS.</P>
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Kim, Jong-Choon,Shin, Dong-Ho,Kim, Sung-Ho,Bae, Chun-Sik,Kim, Joon-Kyum,Cha, Shin-Woo,Han, Jung-Hee,Lee, Hyun-Sook,Chung, Moon-Koo Korean Society of ToxicologyKorea Environmental Mu 2004 Toxicological Research Vol.20 No.1
The present study was carried out to investigate the potential adverse effects of CKD-602 by a 5-day repeated intravenous dose in Sprague-Dawley rats. The test article, CKD-602, was administered intravenously to male and female rats at dose levels of 0.07, 0.22, 0.67, 2.0 and 6.0 mg/kg/day for 5 days consecutively. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period after cessation of the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. There were 2 and 5 treatment related deaths in the 0.67 and 2.0 mg/kg/day dose groups of both genders, respectively. Treatment related clinical signs, including hair loss, skin paleness, decreased locomotor activity, emaciation, and changes in stool were observed in a dose-dependent manner from the third day after initiation of the injection. Decrease or suppression of body weight was also observed dose-dependently in males and females of the treated groups. Gross postmortem examinations revealed a dose-dependent increase in the incidence and severity of atrophy or hypertrophy and white membrane formation in the spleen, atrophy of the thymus, diffuse white spots and paleness of the liver, paleness of the lung, kidney and adrenal gland, and dark red discoloration and dark red contents in the alimentary tract. Based on these results, it was concluded that the 5-repeated intravenous injection of CKD-602 to male and female rats resulted in increased incidence of abnormal clinical signs and death, decreased or suppressed body weight, and increased incidence of abnormal gross findings. In the present experimental conditions, the $LD_{50}$ value was 2.07 (95% confidence limit not specified) mg/kg/day in both genders and the $LD_{10}$ value was 1.72 (95% confidence limit not specified) mg/kg/day in both genders.
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Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice
Sang Kyu Lee,Dong Ju Lee,Tae Won Jeon,Gyu Sub Ko,Se Hyun Yoo,Hyun Woo Ha,Mi Jeong Kang,Wonku Kang,Sang Kyum Kim,Tae Cheon Jeong 한국독성학회 2010 Toxicological Research Vol.26 No.2
Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 ㎎/㎏ in corn oil once for dose response or treated orally with 1-BB at 1500 ㎎/㎏ for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.
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In vitro and vivo assessment of cytochrome P450-mediated herb-drug interaction of Ssang-hwa-tang
( Sang Yoon Lee ),( Ji Yoon Lee ),( Wonku Kang ),( Kwang Il Kwon ),( Soo Jin Oh ),( Jin Yeul Ma ),( Sang Kyum Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
We have evaluated the herb-drug interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P<0.005 or P<0.001, respectively), which raises the possibility that SHT may increase the toxicity of environmental toxicants through the elevation of CYP2E1-mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2 inhibition, but not CYP2E1 induction, suggesting that changes in the chemical composition of SHT through fermentation can affect the inhibition of CYP1A2 activity. ⓒ2012 Elsevier Ltd, All rights reserved.ⓒ2012 Elsevier Ltd. All rights reserved.
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