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1.  Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal 
AIM: To investigate the effects of Lizhong Tang, an herbal product used in traditional Chinese medicine, on mouse small intestine interstitial cells of Cajal (ICCs).
METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. The ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. All of the experiments were performed at 30-32  °C.
RESULTS: ICCs generated pacemaker potentials, and Lizhong Tang produced membrane depolarization in current-clamp mode. The application of flufenamic acid (a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong Tang. Pretreatment with thapsigargin (a Ca2+-ATPase inhibitor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong Tang. However, pacemaker potentials were completely abolished in the presence of an external Ca2+-free solution, and under this condition, Lizhong Tang induced membrane depolarizations. Furthermore, When GDP-β-S (1 mmol/L) was in the pipette solution, Lizhong Tang still induced membrane depolarizations. In addition, membrane depolarizations were not inhibited by chelerythrine or calphostin C, which are protein kinase C inhibitors, but were inhibited by U-73122, an active phospholipase C inhibitors.
CONCLUSION: These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.
PMCID: PMC3627890  PMID: 23599652
Interstitial cells of Cajal; Lizhong Tang; Motility; Gastrointestinal tract; Whole-cell patch clamp configuration
2.  Utility of digital pulse oximetry in the screening of lower extremity arterial disease 
The aim of this study was to evaluate screening methods in the lower extremities by measurement of the digital pulse oximetry (oxygen percent saturation [SpO2]) of toes for peripheral arterial disease (PAD).
A prospective study was performed among 49 patients (98 limbs) with lower extremity arterial occlusive disease. We attempted to measure the ankle-brachial index (ABI), digital pulse oximetry (SpO2), and computerized tomographic angiography (CTA). Patients were divided into three groups by the traditional Fontaine classification system by symptom and CTA criteria: 1) Critical limb ischemia (Fontaine III and IV), 2) Claudication; (Fontaine II), and 3) asymptomatic limbs (Fontaine I).
The sensitivity, specificity, positive and negative predictive values between active treatment groups (group I and II; endovascular and open surgery) and conservative group (group III) are all statistically significant. ABI; 55.09%, 94%, 96.7%, 39.02% (R = 12.54, P < 0.000) SpO2; 87.06%, 87.8%, 84.3%, 90% (R = 40.11, P < 0.000). Pre-SpO2 and pre-ABI all show statistically significant correlation in group I vs. group II, symptomatic PAD (group I and II) vs. asymptomatic PAD (group III), and the total PAD comparison. The Pearson's correlation coefficient between SpO2 and ABI all show significant correlation in group II. Pre-SpO2 vs. Pre-ABI show strong positive correlation except asymptomatic group (group III).
Digital pulse oximetry can be a useful, simple, noninvasive screening device as well as ABI in PAD.
PMCID: PMC3278641  PMID: 22347711
Peripheral arterial disease; Digital; Pulse oximetry; Ankle-brachial index
3.  Acute Peritonitis Caused by a Fibrosarcoma of the Transverse Colon in an Adult 
Annals of Coloproctology  2014;30(6):280-284.
A fibrosarcoma is a malignant mesenchymal tumor derived from fibrous connective tissue. It usually develops in the deep soft tissues of the extremities, as well as the trunk, head, and neck. In extremely rare cases, a fibrosarcoma may occur in the gastrointestinal tract. Most cases of fibrosarcoma in the gastrointestinal tract have been observed in the pediatric age group while only a few cases have been reported in adults. A 61-year-old male presented with pain in the entire abdominal region. Chest radiography showed free air in the subphrenic space. After an emergency operation, we found a solid mass around the transverse colon and performed a segmental resection with a lymphatic dissection of the transverse colon, including the mass. A pathologic examination showed a fibrosarcoma with a perforation. There was no perioperative complication. The patient was discharged on postoperative day 11 and had follow-ups for 1 year without any recurrence.
PMCID: PMC4286775  PMID: 25580415
Fibrosarcoma; Transverse colon; Adult
4.  Spontaneous intrahepatic portosystemic shunt managed by laparoscopic hepatic vein closure 
Journal of Minimal Access Surgery  2014;10(4):207-209.
Intrahepatic portosystemic shunt (IPSS) is uncommon and usually follows trauma or iatrogenic injury, but spontaneous shunts may also occur, in patients without the evidence of chronic liver disease. Although interventional endovascular management of the shunts is the treatment of choice, a surgical approach can be used when the percutaneous approach fails. We report here a case of symptomatic spontaneous IPSS between the posteroinferior branch of right portal vein and the right inferior hepatic vein, which was successfully managed with laparoscopic closure of the hepatic vein. To the best of our knowledge, this is the first case report of laparoscopic management of spontaneous IPSS.
PMCID: PMC4204266  PMID: 25336823
Hepatic vein; intrahepatic; laparoscopy; portosystemic shunt; spontaneous
5.  Effect of Dialysis Initiation Timing on Clinical Outcomes: A Propensity-Matched Analysis of a Prospective Cohort Study in Korea 
PLoS ONE  2014;9(8):e105532.
Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR).
We enrolled a total of 1691 adult patients who started dialysis between August 2008 and March 2013 in a multi-center, prospective cohort study at the Clinical Research Center for End Stage Renal Disease in the Republic of Korea. The patients were classified into the early-start group or the late-start group according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The primary outcome was patient survival, and the secondary outcomes were hospitalization, cardiovascular events, vascular access complications, change of dialysis modality, and peritonitis. The two groups were compared before and after matching with propensity scores.
Before propensity score matching, the early-start group had a poor survival rate (P<0.001). Hospitalization, cardiovascular events, vascular access complications, changes in dialysis modality, and peritonitis were not different between the groups. A total of 854 patients (427 in each group) were selected by propensity score matching. After matching, neither patient survival nor any of the other outcomes differed between groups.
There was no clinical benefit after adjustment by propensity scores comparing early versus late initiation of dialysis.
PMCID: PMC4138196  PMID: 25137235
6.  Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy 
PLoS ONE  2014;9(8):e104354.
Idiopathic membranous nephropathy (iMN) is a common cause of nephrotic syndrome in adults. A biomarker to accurately indicate the severity of iMN and predict long-term prognosis is insufficient. Here, we evaluated the clinical significance of circulating tumor necrosis factor receptors (cTNFRs) as prognostic biomarkers of iMN with nephrotic syndrome. A total of 113 patients with biopsy-proven iMN and 43 healthy volunteers were enrolled in this study. Ninety patients with iMN had nephrotic range proteinuria. Levels of cTNFRs were measured by using serum samples collected at the time of initial diagnosis. Levels of cTNFRs were higher in the patients with nephrotic syndrome than in those with subnephrotic range proteinuria or in the healthy volunteers (P for trend <0.001). Estimated glomerular filtration rate and proteinuria tended to worsen as the cTNFRs levels increased. Having a cTNFR1 level within the highest tertile was a significant risk factor for renal progression after adjustment, in comparison with the other tertiles (hazard ratio [HR], 3.39; 95% confidence interval [95% CI], 1.48–7.78; P = 0.004). The cTNFR2 level within the highest tertile also significantly increased the risk of renal progression (HR, 3.29; 95% CI, 1.43–7.54; P = 0.005). Renal tubular TNFRs expression was associated with cTNFRs level. However, the cTNFRs levels were not associated with autoantibody against phospholipase A2 receptor reactivity/levels or treatment response. This study demonstrated that cTNFRs levels at the time of initial diagnosis could predict renal progression in patients with iMN.
PMCID: PMC4123977  PMID: 25098821
7.  Comparison of HER2 expression between primary colorectal cancer and their corresponding metastases 
Cancer Medicine  2014;3(3):674-680.
The aim of this study was to compare human epidermal growth factor 2 (HER2) status in primary colorectal cancer and paired liver or lung metastasis. Gene amplification of HER2 has been intensively evaluated in contemporary oncology, especially in breast and stomach cancer. The knowledge of HER2 status in primary and metastatic sites may be of potential value for therapeutic decision making in metastatic colon cancer. The HER2 status was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 94 colorectal cancer with corresponding liver or lung metastases. HER2 amplification was present in 19 of the 188 (10.1%) of both primary and metastases combined. Four (4.6%) patients showed HER2 amplification in the metastasis and 10 (10.6%) patients showed HER2 amplification in the primary tumor. In 14 cases (14.8%), the HER2 status of the primary lesions was different from that of the associated metastases. The presence of HER2 overexpression in KRAS mutant colon cancer was found in 5.3%. No relationship was found between HER2 expression and KRAS status (P = 0.486). The evidence of HER2 positive metastatic lesion and primary colorectal cancer suggest that HER2 assessment might be considered in selected cases when this may help change the therapeutic decision.
PMCID: PMC4101759  PMID: 24668895
Colon cancer; HER2; KRAS; metastasis
8.  Serum Bilirubin Affects Graft Outcomes through UDP-Glucuronosyltransferase Sequence Variation in Kidney Transplantation 
PLoS ONE  2014;9(4):e93633.
Oxidative stress is a major mediator of adverse outcome after kidney transplantation. Bilirubin is produced by heme oxygenase-1 (HO-1), catalyzed by UDP-glucuronosyltransferase (UGT1A1), and has potential as an antioxidant. In this study, we investigated the effects of HO-1 and UGT1A1 sequence variations on kidney allograft outcomes.
Clinical data were collected from 429 Korean recipients who underwent kidney transplantation from 1990–2008. Genotyping for UGT1A1*28 and HO-1 (A−413T) was performed. Acute rejection and graft survival were monitored as end-points.
Serum levels of total bilirubin were significantly increased after transplantation (0.41±0.19 mg/dL to 0.80±0.33 mg/dL, P<0.001). Post-transplant 1-year bilirubin level was higher in 6/7 or 7/7 carriers compared with 6/6 homozygotes in terms of the UGT1A1*28 polymorphism (6/6 vs. 6/7 vs. 7/7: 0.71±0.27 vs. 1.06±0.36 vs. 1.10±0.45 mg/dL, P<0.001). According to an additive model of genotype analysis, the 7-allele genotype had a protective effect on the development of acute rejection compared with the 6-allele (odds ratio 0.43, 95% CI 0.25–0.73, P for trend = 0.006). Multivariate Cox regression analysis revealed that individuals carrying the 7-allele had a decreased risk of graft loss, by a factor of 0.36 (95% CI 0.15–0.85, P = 0.019). The HO-1 (A−413T) polymorphism had no effect on serum bilirubin levels or graft outcomes.
The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.
PMCID: PMC3972238  PMID: 24690955
9.  Comparison of Task Performance, Hand Power, and Dexterity with and without a Cock-up Splint 
Journal of Physical Therapy Science  2013;25(11):1429-1431.
[Purpose] The purpose of this study was to investigate the difference in task performance, grip and pinch strength, and dexterity with and without cock-up splints, which are widely used in occupational therapy practice. [Methods] Twenty-three participants performed Jebsen-Taylor hand function test and grooved pegboard for task performance and dexterity. The power grip and pinch strength was measured using Jamar hydraulic hand dynamometer and pinch gauge. [Results] In the result of the Jebsen-Taylor hand function test, task performance with the cock-up splint was slower compared to without the splint for all items. Men’s grip power with the cock-up splint was found to be significantly decreased compared to without the splint. Women’s grip and palmar pinch strength with the splint decreased significantly compared to without the splint. In the grooved pegboard test, the dexterity of both men and women with the cock-up splint decreased significantly compared to without the splint. [Conclusion] To assist patients to make wise decisions regarding the use of splints, occupational therapists must have empirical knowledge of the topic as well as an understanding of the theoretical, technical, and related research evidence. The results of this study will be useful in the analysis and understanding of changes in hand function in splint applications for people with hand dysfunction.
PMCID: PMC3881471  PMID: 24396204
Dexterity; Hand power; Splint
10.  Comparison of Muscle Activation while Performing Tasks Similar to Activities of Daily Livings with and without a Cock-up Splint 
Journal of Physical Therapy Science  2013;25(10):1247-1249.
[Purpose] This study investigated changes in the activation of the main elbow muscle while performing tasks similar to activities of daily living (ADL) with and without a cock-up splint. [Methods] Sixteen participants performed a simulated feeding task and picked up light and heavy cans in the Jebsen-Taylor hand function test. The activation of the biceps brachii, the triceps brachii, and the brachioradialis with and without the cock-up splint was measured using a BTS FreeEMG 300 wireless electromyography system (BTS, Inc., Milan, Italy). [Results] The activation of the biceps brachii and the brachioradialis was significantly higher while performing the simulated feeding task with the cock-up splint than without the splint. While picking up the light and heavy cans, the activation of the brachioradialis was significantly decreased by wearing the cock-up splint. In the heavy cans task, the activation of the triceps brachii was significantly higher with the cock-up splint than without the splint. [Conclusion] This study showed that diverse muscles' activation was increased or decreased when wearing the cock-up splint while performing tasks similar to ADL. The results of this study can be used as an educational resource for therapists teaching patients about splint application and splint compliance in ADL.
PMCID: PMC3820189  PMID: 24259768
Cock-up splint; Jebsen-Taylor hand function test; Muscle activation
11.  Suppression of Heme Oxygenase-1 by Prostaglandin E2-Protein Kinase A-A-Kinase Anchoring Protein Signaling Is Central for Augmented Cyclooxygenase-2 Expression in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages 
Prostaglandin (PG) E2 is an immunomodulatory lipid mediator generated mainly via the cyclooxygenase-2 (COX-2) pathway from arachidonic acid at sites of infection and inflammation. A positive feedback loop of PGE2 on COX-2 expression is critical for homeostasis during toll-like receptor (TLR)-mediated inflammatory processes. The mechanism of PGE2-regulated COX-2 expression remains poorly understood. The low-molecular-weight stress protein heme oxygenase-1 (HO-1) contributes to the anti-inflammatory, anti-oxidant and anti-apoptotic response against environmental stress.
We explored the involvement of HO-1 on PGE2 regulation of LPS-induced COX-2 expression in RAW 264.7 macrophages.
LPS-induced COX-2 expression in RAW 264.7 macrophages was enhanced by exogenous PGE2 or cyclic AMP (cAMP) analogue and was suppressed by a COX inhibitor (indomethacin), a protein kinase A (PKA) inhibitor (KT5720), and A kinase anchoring protein (AKAP) disruptors (Ht31 and RIAD). This result suggests that the stimulatory effects of endogenous and exogenous PGE2 on COX-2 expression are mediated by a cAMP-PKA-AKAP-dependent pathway. The induction of HO-1 was observed in LPS-stimulated RAW 264.7 macrophages. This induction was suppressed by exogenous PGE2 and enhanced by blockage of the endogenous PGE2 effect by the PKA inhibitor or AKAP disruptors. In addition, HO-1 induction by the HO activator copper protoporphyrin suppressed LPS-induced COX-2 expression, which was restored by the addition of exogenous PGE2. The induction of HO-1 inhibited LPS-induced NF-κB p-65 nuclear expression and translocation.
AKAP plays an important role in PGE2 regulation of COX-2 expression, and the suppression of HO-1 by PGE2-cAMP-PKA-AKAP signaling helps potentiate the LPS-induced COX-2 expression through a positive feedback loop in RAW 264.7 macrophages.
PMCID: PMC3756181  PMID: 24003391
Cyclooxygenase-2; heme oxygenase-1; lipopolysaccharide; prostaglandin E2; macrophages
12.  What does absence of lymph node in resected specimen mean after neoadjuvant chemoradiation for rectal cancer 
The effect of insufficient node sampling in patients with rectal cancer managed by neoadjuvant chemoradiation followed by surgery has not been clearly determined. We evalulated the impact of insufficient sampling or even abscence of lymph nodes in the specimen on survival in patients at high-risk (T3, T4 or node positive) for rectal cancer.
We conducted a single institution, retrospective analysis of all patients who underwent surgical rectal resection following neoadjuvant chemoradiation for treatment of mid to lower rectal cancer between 1997 and 2009. ypNX was defined as the absence of lymph nodes retrieved in the resected specimen.
A total of 132 patients underwent resection for treatment of rectal cancer following neoadjuvant chemoradiation. Ninety four patients (71.2%) were considered as having node-negative disease, including ypNx and ypN0. In 38 patients (28.8%), the primary tumor was associated with regional lymph node metastases (ypNpos). The mean number of retrieved nodes per specimen was 14.2, respectively. The five-year overall survival from initial operation for the ypNx group was 100%, respectively. The estimated five-year overall survival for ypN0 and ypNpos was 84.0% and 60.3%, respectively (P =0.001). No significant differences in overall survival were observed between the ypNx and ypN0 group (P =0.302).
Absence of recovered LN in resected specimens after neoadjuvant chemoradiation was observed in 7.6% of specimens. Absence of LN should not be regarded as a risk factor for poor survival or as a sign of less radical surgery.
PMCID: PMC3846736  PMID: 23957923
Rectal neoplasm; Surgery; Neoadjuvant chemoradiation
13.  Small Increases in Plasma Sodium Are Associated with Higher Risk of Mortality in a Healthy Population 
Journal of Korean Medical Science  2013;28(7):1034-1040.
Elevated blood pressure (BP) is the most common cause of cardiovascular disease. Salt intake has a strong influence on BP, and plasma sodium (pNa) is increased with progressive increases in salt intake. However, the associations with pNa and BP had been reported inconsistently. We evaluated the association between pNa and BP, and estimated the risks of all-cause-mortality according to pNa levels. On the basis of data collected from health checkups during 1995-2009, 97,009 adult subjects were included. Positive correlations between pNa and systolic BP, diastolic BP, and pulse pressure (PP) were noted in participants with pNa ≥138 mM/L (P<0.001). In participants aged ≥50 yr, SBP, DBP, and PP were positively associated with pNa. In participants with metabolic syndrome components, the differences in SBP and DBP according to pNa were greater (P<0.001). A cumulative incidence of mortality was increased with increasing pNa in women aged ≥50 yr during the median 4.2-yr-follow-up (P<0.001). In women, unadjusted risks for mortality were increased according to sodium levels. After adjustment, pNa ≥145 mM/L was related to mortality. The positive correlation between pNa and BP is stronger in older subjects, women, and subjects with metabolic syndrome components. The incidence and adjusted risks of mortality increase with increasing pNa in women aged ≥50 yr.
PMCID: PMC3708074  PMID: 23853486
Age; Blood Pressure; Mortality; Plasma Sodium; Sex Characteristics
14.  Factors influencing hepatocellular carcinoma prognosis after hepatectomy: a single-center experience 
Recurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection.
This study was of a retrospective cohort design, and 126 patients who underwent hepatic resection for HCC at Gachon University Gil Medical Center between January 2005 and December 2010 were enrolled. Various clinical, laboratory, and pathological data were evaluated to determine the prognostic factors affecting OS and DFS.
Two- and 4-year OS and 2- and 4-year DFS were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis, preoperative α-fetoprotein (> 400 ng/mL), tumor size (≥ 5 cm), multiple tumors (two or more nodules), presence of portal vein invasion, modified Union for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter OS. In the multivariate analysis, presence of microvascular invasion, modified UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a shorter DFS.
The presence of vascular invasion was an independent poor prognostic factor for OS and DFS in patients with HCC after hepatic resection. Thus, close postoperative surveillance for early detection of recurrence and additional treatments are urgently needed in patients with vascular invasion after hepatic resection.
PMCID: PMC3712151  PMID: 23864801
Carcinoma, hepatocellular; Hepatic resection; Prognosis; Vascular invasion
15.  Valproic Acid Regulates α-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes 
Biomolecules & Therapeutics  2013;21(3):222-228.
Although the role of α-synuclein aggregation on Parkinson’s disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of α-synuclein are unclear yet. We recently reported that α-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing α-synuclein in neuron, on α-synuclein expression in rat primary astrocytes. VPA concentrationdependently increased the protein expression level of α-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted α-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in α-synuclein. Whether the increased α-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.
PMCID: PMC3830121  PMID: 24265868
α-synuclein; Valproic acid; Stability; JNK; Neuroprotection; Acetylation
16.  The Occurrence of Warfarin-Related Nephropathy and Effects on Renal and Patient Outcomes in Korean Patients 
PLoS ONE  2013;8(4):e57661.
Warfarin-related nephropathy (WRN) is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR) >3.0) causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors.
During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea.
WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN.
WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.
PMCID: PMC3613349  PMID: 23560034
17.  Severe hyperkalemia requiring hospitalization: predictors of mortality 
Critical Care  2012;16(6):R225.
Severe hyperkalemia, with potassium (K+) levels ≥ 6.5 mEq/L, is a potentially life-threatening electrolyte imbalance. For prompt and effective treatment, it is important to know its risk factors, clinical manifestations, and predictors of mortality.
An observational cohort study was performed at 2 medical centers. A total of 923 consecutive Korean patients were analyzed. All were 19 years of age or older and were hospitalized with severe hyperkalemia between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made either at the time of admission to the hospital or during the period of hospitalization. Demographic and baseline clinical characteristics at the time of hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital mortality were reviewed, using the institutions' electronic medical record systems.
Chronic kidney disease (CKD) was the most common underlying medical condition, and the most common precipitating factor of hyperkalemia was metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7% had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality rate was 30.7%; the rate was strongly correlated with the difference between serum K+ levels at admission and at their highest point, and with severe medical conditions such as malignancy, infection, and bleeding. Furthermore, a higher in-hospital mortality rate was significantly associated with the presence of cardiac arrest and/or MOF at the time of diagnosis, emergent admission, and intensive care unit treatment during hospitalization. More importantly, acute kidney injury (AKI) in patients with normal baseline renal function was a strong predictor of mortality, compared with AKI superimposed on CKD.
Severe hyperkalemia occurs in various medical conditions; the precipitating factors are similarly diverse. The mortality rate is especially high in patients with severe underlying disease, coexisting medical conditions, and those with normal baseline renal function.
PMCID: PMC3672605  PMID: 23171442
18.  Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma 
International Journal of Oncology  2012;41(5):1601-1609.
Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.
PMCID: PMC3583872  PMID: 22971679
dendritic cells; hepatocellular carcinoma; clinical trial
19.  Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study 
BMC Nephrology  2012;13:93.
Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.
A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.
Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.
Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
PMCID: PMC3465238  PMID: 22935351
Autosomal dominant polycystic kidney disease; Biomarkers; Renal function
20.  Influence of Iron Regulation on the Metabolome of Cryptococcus neoformans 
PLoS ONE  2012;7(7):e41654.
Iron is an essential nutrient for virtually all organisms and acts as a cofactor for many key enzymes of major metabolic pathways. Furthermore, iron plays a critical role in pathogen-host interactions. In this study, we analyzed metabolomic changes associated with iron availability and the iron regulatory protein Cir1 in a human fungal pathogen Cryptococcus neoformans. Our metabolite analysis revealed that Cir1 influences the glycolytic pathway, ergosterol biosynthesis and inositol metabolism, which require numerous iron-dependent enzymes and play important roles in pathogenesis and antifungal sensitivity of the fungus. Moreover, we demonstrated that increased cellular iron content and altered gene expression in the cir1 mutant contributed to metabolite changes. Our study provides a new insight into iron regulation and the role of Cir1 in metabolome of C. neoformans.
PMCID: PMC3402442  PMID: 22911836
21.  Induction of Donor-Specific Tolerance: Is This Achievable? 
PMCID: PMC3295979  PMID: 22403511
Donor-specific tolerance; Antigen-presenting cells; Intercellular adhesion molecule 1
22.  Reversible Pulmonary Hypertension in Adolescent with Left Atrial Myxoma 
We report a patient of left atrial huge myxoma presenting with severe pulmonary hypertension in adolescents. A patient was a 14-year-old boy presented with sudden onset dyspnea. Transthoracic echocardiographic study revealed the presence of a nodular, 4.34 × 8.11 cm sized, mobile, hyperechoic mass in the left atrium and severe pulmonary hypertension with tricuspid insufficiency. After surgical therapy, tricuspid regurgitation and pulmonary hypertension was decreased and the patient was stabilized and had an uneventful clinical course.
PMCID: PMC3259550  PMID: 22259669
Cardiac tumour; Pulmonary hypertension; Left atrial myxoma
23.  Acral-type Malignant Acanthosis Nigricans Associated with Gastric Adenocarcinoma 
Annals of Dermatology  2011;23(Suppl 2):S208-S210.
Acanthosis nigricans is a symmetric eruption characterized by the presence of a hyperpigmented, velvety cutaneous thickening, that can develop on any part of the body, but characteristically affects the flexural areas of the body. The velvety hyperkeratotic lesions can be located on the dorsum of the hands and feet in dark-skinned people in the form of a variant of acanthosis nigricans called as acral acanthotic anomaly or acral type acanthosis nigricans. Although acanthosis nigricans is associated with malignant tumors, particularly gastric carcinoma, acral type acanthosis nigricans has never been reported to be associated with gastric adenocarcinoma. In our present study, we describe a case of 58-year-old man with acral type acanthosis nigricans and its association with carcinoma of the stomach; a marked improvement was seen in the skin condition of the patient with chemotherapy.
PMCID: PMC3229067  PMID: 22148052
Acanthosis nigricans; Acral type; Gastric adenocarcinoma
24.  Microbial community and metabolomic comparison of irritable bowel syndrome faeces 
Journal of Medical Microbiology  2011;60(Pt 6):817-827.
Human health relies on the composition of microbiota in an individual’s gut and the synthesized metabolites that may alter the gut environment. Gut microbiota and faecal metabolites are involved in several gastrointestinal diseases. In this study, 16S rRNA-specific denaturing gradient gel electrophoresis and quantitative PCR analysis showed that the mean similarity of total bacteria was significantly different (P<0.001) in faecal samples from patients with irritable bowel syndrome (IBS; n = 11) and from non-IBS (nIBS) patients (n = 8). IBS subjects had a significantly higher diversity of total bacteria, as measured by the Shannon index (H′) (3.360.05). GC/MS-based multivariate analysis delineated the faecal metabolites of IBS from nIBS samples. Elevated levels of amino acids (alanine and pyroglutamic acid) and phenolic compounds (hydroxyphenyl acetate and hydroxyphenyl propionate) were found in IBS. These results were highly correlated with the abundance of lactobacilli and Clostridium, which indicates an altered metabolism rate associated with these gut micro-organisms. A higher diversity of Bacteroidetes and Lactobacillus groups in IBS faecal samples also correlated with the respective total quantity. In addition, these changes altered protein and carbohydrate energy metabolism in the gut.
PMCID: PMC3167923  PMID: 21330412
25.  Aromatic Hydroxylation of Indan by o-Xylene-Degrading Rhodococcus sp. Strain DK17▿  
The metabolically versatile Rhodococcus sp. strain DK17 utilizes indan as a growth substrate via the o-xylene pathway. Metabolite and reverse transcription-PCR analyses indicate that o-xylene dioxygenase hydroxylates indan at the 4,5 position of the aromatic moiety to form cis-indan-4,5-dihydrodiol, which is dehydrogenated to 4,5-indandiol by a dehydrogenase. 4,5-Indandiol undergoes ring cleavage by a meta-cleavage dioxygenase.
PMCID: PMC2798653  PMID: 19880642

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