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Park, Jin Kyun,Byun, Joo-Yun,Park, Ji Ah,Kim, Yu-Yon,Lee, Ye Ji,Oh, Jeong In,Jang, Sun Young,Kim, Young Hoon,Song, Yeong Wook,Son, Jeewoong,Suh, Kwee Hyun,Lee, Young-Mi,Lee, Eun Bong BioMed Central 2016 ARTHRITIS RESEARCH AND THERAPY Vol.18 No.-
<P><B>Background</B></P><P>Bruton’s tyrosine kinase (Btk) is critical for activation of B cells and myeloid cells. This study aimed to characterize the effects of HM71224, a novel Btk inhibitor, both <I>in vitro</I> and in a mouse model of experimental arthritis.</P><P><B>Methods</B></P><P>The kinase inhibition profile of HM71224 was analyzed. The in vitro effects of HM71224 on B cells and monocytes were analyzed by examining phosphorylation of Btk and its downstream signaling molecules, along with cytokine production and osteoclast formation. The in vivo effects of HM71224 were investigated in a mouse model of collagen-induced arthritis (CIA).</P><P><B>Results</B></P><P>HM71224 irreversibly bound to and inhibited Btk (IC<SUB>50</SUB> = 1.95 nM). The compound also inhibited the phosphorylation of Btk and its downstream molecules such as PLCγ2, in activated Ramos B lymphoma cells and primary human B cells in a dose-dependent manner. Furthermore, HM71224 effectively inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes. Finally, HM71224 improved experimental arthritis and prevented joint destruction in a murine model of CIA.</P><P><B>Conclusions</B></P><P>HM71224 inhibits Btk in B cells and monocytes and ameliorates experimental arthritis in a mouse model. Thus, HM71224 is a potential novel therapeutic agent for rheumatoid arthritis in humans.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s13075-016-0988-z) contains supplementary material, which is available to authorized users.</P>
Kim, Yong Kyun,Kim, Su-Hyun,Kim, Hyung Wook,Kim, Young Ok,Jin, Dong Chan,Song, Ho Chul,Choi, Euy Jin,Kim, Yong-Lim,Kim, Yon-Su,Kang, Shin-Wook,Kim, Nam-Ho,Yang, Chul Woo SAGE Publications 2014 Peritoneal dialysis international Vol.34 No.4
<B>Background</B><P> Previous studies have demonstrated that increased body mass index (BMI) is associated with decreased mortality in hemodialysis (HD) patients. However, the association between BMI and survival has not been well established in patients undergoing peritoneal dialysis (PD). The aim of the study was to determine the association between BMI and mortality in the PD population using the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD) cohort in Korea. </P><B>Methods</B><P> Prevalent patients with PD were selected from the CRC registry for ESRD, a prospective cohort study on dialysis patients in Korea. Patients were categorized into four groups by quartiles of BMI. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) of mortality with a BMI of quartile 2 (21.4 - 23.5 kg/m<SUP>2</SUP>) as the reference. </P><B>Results</B><P> A total of 900 prevalent patients undergoing PD were included. The median follow-up period was 24 months. The multivariate Cox proportional hazard model showed that the lowest quartile of BMI was associated with higher mortality (HR 3.00,95% confidence interval (CI), 1.26 - 7.15). However, the higher quartiles of BMI were not associated with mortality compared with the reference category of BMI quartile 2 (Quartile 3: HR 1.11, 95% CI, 0.43 - 2.85, Quartile 4: H R 1.64,95% CI, 0.66 - 4.06) after adjustment for clinical variables. </P><B>Conclusions</B><P> Lower BMI was a significant risk factor for death, but increased BMI was not associated with mortality in Korean PD patients. </P>
Impact of Dialysate Calcium Concentration on Clinical Outcomes in Incident Hemodialysis Patients
Kim, Hyung Wook,Kim, Su-Hyun,Kim, Young Ok,Jin, Dong Chan,Song, Ho Chul,Choi, Euy Jin,Kim, Yong-Lim,Kim, Yon-Su,Kang, Shin-Wook,Kim, Nam-Ho,Yang, Chul Woo,Kim, Yong Kyun,Malindretos., Pavlos Williams & Wilkins Co 2015 Medicine Vol.94 No.40
<P><B>Abstract</B></P><P>The association between dialysate calcium (DCa) concentration and mortality in hemodialysis (HD) patients is controversial. In this study, we evaluated the impact of DCa concentration on mortality in incident HD patient.</P><P>Incident HD patients were selected from the Clinical Research Center registry—a prospective cohort study on dialysis patients in Korea. Patients were categorized into 3 groups according to the prescribed DCa concentration at the time of enrollment. High DCa was defined as a concentration of 3.5 mEq/L, mid-DCa as 3.0 mEq/L, and low DCa as 2.5 to 2.6 mEq/L. The primary outcome was all-cause mortality and secondary outcomes were cardiovascular or infection-related hospitalization.</P><P>A total of 1182 patients with incident HD were included. The number of patients in each group was 182 (15.4%) in high DCa group, 701 (59.3%) in the mid-DCa group, and 299 (25.3%) in the low DCa group. The median follow-up period was 16 months. The high DCa group had a significantly higher risk of all-cause mortality compared with the mid-DCa group (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.28–3.90, <I>P</I> = 0.005) and the low DCa group (HR 3.67, 95% CI 1.78–7.55, <I>P</I> < 0.001) after adjustment for clinical variables. The high DCa group was associated with higher risk of cardiovascular and infection-related hospitalization compared with the low DCa group (HR 3.25, 95% CI 1.53–6.89, <I>P</I> = 0.002; and HR 2.77, 95% CI 1.29–5.94, <I>P</I> = 0.009, respectively). Of these 1182 patients, 163 patients from each group were matched by propensity scores. In the propensity score matched analysis, the high DCa group had a significantly higher risk of all-cause mortality compared with the mid-DCa group (HR 2.52, 95% CI 1.04–6.07, <I>P</I> = 0.04) and the low DCa group (HR 4.25, 95% CI 1.64–11.03, <I>P</I> = 0.003) after adjustment for clinical variables.</P><P>Our data showed that HD using a high DCa was a significant risk factor for all-cause mortality and cardiovascular or infection-related hospitalization in incident HD patients.</P>