[Show abstract][Hide abstract] ABSTRACT: The immune system senses exogenous threats or endogenous stress through specialized machinery known as pattern recognition receptors (PRRs). These receptors recognize conserved molecular structures and initiate downstream signaling pathways to control immune responses. Although various immunologic pathways mediated by PRRs have been described, recent studies have demonstrated a link between PRRs and autophagy. Autophagy is a specialized biological process involved in maintaining homeostasis through the degradation of long-lived cellular proteins and organelles. In addition to this fundamental function, autophagy plays important roles in various immunologic processes. In this review, we focus on the reciprocal influences of PRRs and autophagy in modulating innate immune responses.
[Show abstract][Hide abstract] ABSTRACT: Blood pressure control is the most established practice for preventing the progression of chronic kidney disease. Evidence addressing blood pressure control status or nocturnal blood pressure dipping in Korean hypertensive patients with chronic kidney disease is scarce. We recruited 1317 hypertensive patients (chronic kidney disease stages 2-4, median age 58) from 21 centers in Korea. These patients underwent office and ambulatory blood pressure monitoring. High office and ambulatory blood pressure were defined as >140/90 mm Hg and >135/85 mm Hg (daytime)/ >120/70 mm Hg (nighttime), respectively. The blood pressure control status was as follows: true controlled (19%), white-coat (4.3%), masked (33.9%) and sustained uncontrolled (42.3%) hypertension. The dipping status was as follows: extreme-dipping (14.9%), dipping (33.3%), non-dipping (34.5%) and reverse-dipping (17.3%). Masked and sustained hypertension as well as non-dipping/reverse-dipping was more apparent in proportion to renal dysfunction and the extent of proteinuria. Ageing (58 years), male gender, obesity, diabetic nephropathy and proteinuria (>300 mg g(-1) Cr or dipstick proteinuria1+) were independently associated with sustained uncontrolled hypertension. Diabetic nephropathy, old age, a history of stable angina/heart failure, advanced renal dysfunction and higher proteinuria levels were also significantly associated with non-dipping and reverse-dipping. Half of Korean chronic kidney disease patients had uncontrolled blood pressure and a non-dipping nocturnal blood pressure pattern. Future studies are warranted to assess the predictive values of ambulatory blood pressure for cardiorenal events in Korean chronic kidney disease patients.Hypertension Research advance online publication, 19 September 2013; doi:10.1038/hr.2013.127.
Hypertension Research 09/2013; · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and safety of propofol and midazolam for sedation during esophagogastroduodenoscopy (EGD) in children.
We retrospectively reviewed the hospital records of 62 children who underwent ambulatory diagnostic EGD during 1-year period. Data were collected from 34 consecutive patients receiving propofol alone. Twenty-eight consecutive patients who received sedation with midazolam served as a comparison group. Outcome variables were length of procedure, time to recovery and need for additional supportive measures.
There were no statistically significant differences between the two groups in age, weight, sex, and the length of endoscopic procedure. The recovery time from sedation was markedly shorter in propofol group (30±16.41 minutes) compared with midazolam group (58.89±17.32 minutes; p<0.0001). During and after the procedure the mean heart rate was increased in midazolam group (133.04±19.92 and 97.82±16.7) compared with propofol group (110.26±20.14 and 83.26±12.33; p<0.0001). There was no localized pain during sedative administration in midazolam group, though six patients had localized pain during administration of propofol (p<0.028). There was no serious major complication associated with any of the 62 procedures.
Intravenous administered propofol provides faster recovery time and similarly safe sedation compared with midazolam in pediatric patients undergoing upper gastrointestinal endoscopy.
[Show abstract][Hide abstract] ABSTRACT: Autophagy is a fundamental cellular process in eukaryotic cells for maintaining homeostasis by degrading cellular proteins and organelles. Recently, the roles of autophagy have been expanded to immune systems, which in turn modulate innate immune responses. More specifically, autophagy acts as a direct effector for protection against pathogens, as well as a modulator of pathogen recognition and downstream signaling in innate immune responses. In addition, autophagy controls autoimmunity and inflammatory disorders by negative regulation of immune signaling. In this review, we focus on recent advances in the role of autophagy in innate immune systems.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular risk factors are considered to also be risk factors for dementia. Recent studies have shown that the prevalence of cognitive dysfunction is high in patients with cardiac diseases. However, few studies have investigated the influence of cardiac function on cognition and brain structural changes in dementia. The aims of this study were to determine the relationship between cardiac and cognitive function, and to characterize any structural changes in the brain that could be caused by cardiac function in patients with dementia.
Dementia patients (n=93) were recruited prospectively with checking for the presence of vascular risk factors such as hypertension. Cognitive function was measured by the Mini-Mental State Examination, modified Mini-Mental State test, and Korean version of the Dementia Rating Scale. Brain magnetic resonance imaging was conducted to evaluate the cerebral white-matter changes (WMC), ventricular dilation, and cortical and hippocampal atrophy. Cardiac function was evaluated using two-dimensional echocardiography. We divided the patients into two groups according to the presence (+) or absence (-) of WMC.
In the entire cohort, the size of the left atrium (LA) was positively correlated with the degree of WMC, irrespective of age (p<0.05). The LA was larger in the WMC (+) group (n=42) than in the WMC (-) group. General cognitive function was significantly lower in the WMC (+) group than in the WMC (-) group. Subjects with an enlarged LA tended to exhibit lower cognitive function and more-severe cerebral WMC.
Cardiac dysfunction represented by LA enlargement could be related to cognitive decline and WMC of the brain resulting from impairment of the cerebral hemodynamic process in dementia.
Journal of Clinical Neurology 06/2012; 8(2):123-9. · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases.
Yonsei medical journal 03/2012; 53(2):241-7. · 0.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primase is the enzyme that synthesizes RNA primers on single-stranded DNA during normal DNA replication. In this study, the catalytic core domain of primase from Streptococcus mutans UA159 was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 1.60 Å resolution using a synchrotron-radiation source. The crystal belonged to space group P4(1) or P4(3), with unit-cell parameters a = b = 52.63, c = 110.31 Å. The asymmetric unit is likely to contain one molecule, with a corresponding V(M) of 1.77 Å(3) Da(-1) and a solvent content of 30.7%.
Acta Crystallographica Section F Structural Biology and Crystallization Communications 01/2012; 68(Pt 1):98-100. · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autophagy is an ancient biological process for maintaining cellular homeostasis by degradation of long-lived cytosolic proteins and organelles. Recent studies demonstrated that autophagy is availed by immune cells to regulate innate immunity. On the one hand, cells exert direct effector function by degrading intracellular pathogens; on the other hand, autophagy modulates pathogen recognition and downstream signaling for innate immune responses. Pathogen recognition via pattern recognition receptors induces autophagy. The function of phagocytic cells is enhanced by recruitment of autophagy-related proteins. Moreover, autophagy acts as a delivery system for viral replication complexes to migrate to the endosomal compartments where virus sensing occurs. In another case, key molecules of the autophagic pathway have been found to negatively regulate immune signaling, thus preventing aberrant activation of cytokine production and consequent immune responses. In this review, we focus on the recent advances in the role of autophagy in pathogen recognition and modulation of innate immune responses.
[Show abstract][Hide abstract] ABSTRACT: As the population ages, endoscopic retrograde cholangiopancreaticography (ERCP) is being used increasingly as a diagnostic and therapeutic tool for elderly patients with pancreatobiliary disease. The aim of this study was to assess the outcomes, safety and complications associated with ERCP performed in the elderly patients.
We retrospectively reviewed the medical record of 596 patients who were 50 years of age or older and underwent ERCP from January 2005 to September 2010. The patients were classified into two groups according to the age: non-elderly, 50-74 years old and elderly, ≥75 years old. Comparisons were made between two groups.
Five hundred and ninety-six patients (132 elderly and 464 non-elderly patients) were enrolled. The success rate of ERCP was 89.4% in the elderly and 91.9% in the non-elderly. The major complications were occurred in 11 patients of the elderly and 16 of the non-elderly, and the complication rate was significantly higher in the elderly compared to the non-elderly (8.3% vs. 3.4%, p=0.011). Pancreatitis occurred in 2 elderly patients and 10 non-elderly patients (1.5% vs. 2.1%, p=1.0). There was a higher rate of bleeding in the elderly patients (4.5% vs. 1.3%, p=0.01).
ERCP is effective and safe even in elderly patients. Outcomes of diagnostic and therapeutic ERCP in the elderly patients were similar to those in non-elderly patients. Elderly patients undergoing ERCP carried similar risk of pancreatitis but a higher risk of bleeding and perforation compared to non-elderly patients.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 12/2011; 58(2):88-92.
[Show abstract][Hide abstract] ABSTRACT: Decreased BMI has been reported that it may be associated with cognitive decline in the elderly. Weight loss is common in patients with PD. However, studies comparing cognitive changes according to BMI changes in PD have not been done yet. We performed this study to know a relationship between BMI changes and the rate of cognitive decline in PD. PD patients were recruited retrospectively. The patients (n=104) were divided into two groups according to BMI changes during initial 6 months of follow-up: decreased (n=52) vs. stable BMI groups (n=52). Cognitive functions were repeated until 36 months of follow-up using the Korean version of the Mini-Mental State Examination (K-MMSE) and the modified Mini-Mental State (3MS) test. We calculated the rate of cognitive decline (K-MMSE and 3MS score changes/month) and compared it between the two groups. The decreased BMI group showed lower level of cognitive function than that of stable BMI group, especially at the 36th month of follow-up (p<0.05). In addition, the rate of cognitive decline was also significantly faster in the decreased BMI group, particularly at the 36th month of follow-up (p<0.05). This study suggests that decreased BMI during initial 6 months of follow-up in PD might be a useful indicator for future risk of dementia and let clinicians predict faster rate of cognitive decline in patients with PD.
Archives of gerontology and geriatrics 07/2011; 55(1):70-2. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor (EGFR) gene mutation status is critical to predicting responsiveness to EGFR tyrosine kinase inhibitor (TKI) therapies in non-small cell lung cancer (NSCLC) patients. However, a vast majority of the patients experience recurrence of the cancers by a secondary mutation of EGFR (T790M). Earlier studies suggested evidence that subclones bearing EGFR T790M mutation pre-exist in NSCLCs even prior to the therapies. However, to date, the status of T790M mutation in primary NSCLC is largely known. In this study, we developed an assay using peptide nucleic acid (PNA)-clamping PCR for detection of low-level EGFR T790M mutation. We found that the assay showed the highest sensitivity (0.01% mutation detection) in the clamping condition. We analyzed 147 NSCLC tissues [70 adenocarcinomas (AD), 62 squamous cell carcinomas (SQ), 12 large cell carcinomas (LC), and three adenosquamous carcinomas] that had not been exposed to the TKI therapies, and found 12 (8.2%; 12/147) EGFR T790M mutation in eight AD (11.4%), three SQ (4.8%), and one LC (8.3%) by the PNA-clamping PCR. However, this mutation was not detected by conventional DNA sequencing. Our data indicate that EGFR T790M exists in pretreatment NSCLC at low levels irrespective of histologic types. This study provides a basis for developing an applicable protocol for detecting low-level EGFR T790M mutation in primary NSCLC, which might contribute to predicting recurrence of the tumor in response to the TKI therapies.
[Show abstract][Hide abstract] ABSTRACT: Eccrine porocarcinoma (EP) is a rare malignant tumor arising from the intraepidermal eccrine duct. The tumor cells frequently contain glycogen, but prominent clear cell changes in EP are rarely reported. A 78-year-old woman presented with a slightly pruritic, erythematous, verrucous plaque on her left thigh. Histopathological examination revealed intraepidermal tumor cell nests composed of small basaloid cells and duct-like structures lined by periodic acid-Schiff (PAS)-positive cuticles. Besides the typical findings of EP, clear cell changes were predominantly observed in the tumor cell aggregations. Herein we report a case of the clear cell variant of EP rarely reported in previous literature.
Annals of Dermatology 08/2010; 22(3):330-2. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detection of somatic mutations in clinical cancer specimens is often hampered by excess wild-type DNA. The aim of this study was to develop a simple and economical protocol without using fluorescent probes to detect low-level mutations. In this study, we combined peptide nucleic acid (PNA)-clamping PCR with asymmetric primers and a melting curve analysis using an unlabeled detection probe. PNA-clamping PCR, which suppressed amplification of the wild-type allele, was more sensitive for KRAS codon 12 mutation detection than nonclamping PCR in 5 different mutant cell lines. Three detection probes were tested (a perfectly matched antisense, a mismatched antisense, and a mismatched sense), and the mismatched sense detection probe showed the highest sensitivity (0.1% mutant detection) under clamping conditions. With this probe, we were able to detect not only the perfectly matched KRAS mutation, but also 4 other mismatched mutations of KRAS. We then applied this protocol to 10 human colon cancer tissues with KRAS codon 12 mutations, successfully detecting the mutations in all of them. Our data indicate that the combination of perfectly matched antisense PNA and a mismatched sense detection probe can detect KRAS mutations with a high sensitivity in both cell lines and human tissues. Moreover, this study might prove an easily applicable protocol for the detection of low-level mutations in other cancer genes.
The Journal of molecular diagnostics: JMD 04/2010; 12(4):418-24. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing.
Journal of Korean medical science 03/2010; 25(3):425-8. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evasion of apoptosis is a feature of cancer cells. As a mechanism of apoptosis inactivation in cancer cells, somatic mutations of pro-apoptotic genes have been reported in many cancers. Caspase-10 is an initiation-phase caspase, and somatic mutation of CASP10 that encodes caspase-10 has been found in non-Hodgkin's lymphoma and gastric carcinoma.
The aim of this study was to explore whether CASP10 gene is somatically mutated in colon, breast, lung, and hepatocellular carcinomas. We analysed the entire coding region and all splice sites of CASP10 in 47 colon, 47 breast, 47 lung, and 47 hepatocellular carcinomas by a single-strand conformation polymorphism (SSCP) assay.
We found two CASP10 mutations in the colon cancers (2/47; 4.3%), but none in breast, lung or hepatocellular carcinomas. One mutation [c.41A > C (p.Lys14Thr)] was a missense mutation, while the other was a substitution mutation in a splice site (c.684 + 4G > A). The colon cancer with the CASP10 missense mutation harboured additional CASP gene mutations (CASP3, 7 and 8).
Our data indicate that somatic mutation of CASP10 is rare in colon, breast, lung, and hepatocellular carcinomas. However, the data also suggest that CASP10 mutation might contribute to the pathogenesis of some colon carcinomas together with other CASP gene mutations.
[Show abstract][Hide abstract] ABSTRACT: Colonoscopy is the principal method for diagnosis, treatment, and follow up of colorectal disease. The study aimed to assess the incidence, clinical features, and management of colonoscopic perforations at a local general hospital.
A retrospective review of patient record was performed for all patients with iatrogenic colonic perforation after sigmoidoscopy and colonoscopy between 1997 and 2007.
In the 10-year period, 16,388 colonoscopic and sigmoidscopic procedure were performed. All 10 cases of procedure related colonic perforation were developed. Perforation occurred in 9 cases during therapeutic procedure; 5 cases due to polypectomy and 4 cases due to endoscopic submucosal dissection. Perforation occurred in one case during diagnostic procedure.
Therapeutic procedure is a clear risk factor of colonic perforation. When colonic perforation occurs, we should be able to make early diagnosis. Early diagnosis can lead to a good treatment and can produce good prognosis with short hospital days.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 12/2009; 54(6):371-6.
[Show abstract][Hide abstract] ABSTRACT: Nuclear factor erythroid-related factor 2 (NRF2) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic NRF2 mutations have been found in lung and head/neck cancers that inactivate KEAP1-mediated degradation of NRF2. The aim of this study was to catalogue NRF2 mutations in other human cancers. For this, we analysed 1145 cancer tissues from carcinomas from oesophagus, skin, uterine cervix, lung, larynx, breast, colon, stomach, liver, prostate, urinary bladder, ovary, uterine cervix, and kidney, and meningiomas, multiple myelomas, and acute leukaemias by single-strand conformation polymorphism (SSCP) assay. We detected NRF2 mutations in oesophagus (8/70; 11.4%), skin (1/17; 6.3%), lung (10/125; 8.0%), and larynx (3/23; 13.0%) cancers. Of note, all of the 22 mutations except one were found in squamous cell carcinomas (SCCs) (95.5%). The mutations were observed within or near DLG and ETGE motifs that are important in NRF2 and KEAP1 interaction. All of the oesophageal SCCs and skin SCCs with the NRF2 mutations showed increased NRF2 expression in the nuclei. However, none of the SCCs from oesophagus and skin harboured KEAP1 mutation. Our study demonstrated here that NRF2 mutation occurs not only in lung and head/neck cancers, but also in oesophageal and skin cancers. Our data suggest that the NRF2 mutation plays a role in the development of SCC and is a feature of SCC.
The Journal of Pathology 10/2009; 220(4):446-51. · 7.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activation of nuclear factor-kappa B (NF-kappaB) signaling is considered an important mechanism in the development of prostate cancers. A recent study revealed that IkappaB kinase epsilon (IKKepsilon), an activator of NF-kappaB, was overexpressed in breast cancers and acted as an oncogene. Expression of NF-kappaB members has been reported in prostate cancer tissues, but expression of IKKepsilon has not yet been studied in prostate cancers. In this study, we attempted to explore as to whether expressions of IKKepsilon and NF-kappaB members p50/105, p52/p100 and RelA are altered in prostate cancers. We analyzed the expression of IKKepsilon, p50/105, p52/p100 and RelA in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray (TMA) method. In the TMA, IKKepsilon is expressed in basal cells, but not in alveolar cells in normal prostate glands. IKKepsilon is expressed in 60.0% of prostate intraepithelial neoplasm (PIN) and 70.1% of the prostate cancers in the cytoplasm. Nuclear immunostainings of NF-kappaB members p50/105, p52/p100 and RelA, which are considered activation of NF-kappaB signaling, were observed respectively in 28.0%, 18.7% and 37.4% of the cancers. Nuclear staining was detected neither in normal alveolar cells nor in PIN. However, none of the expression of p50/105 nor p52/p100 nor RelA nor IKKepsilon was associated with pathologic characteristics, including size of the cancers, age, Gleason score and stage. The increased cytoplasmic expression of IKKepsilon as well as the increased nuclear expressions of p50/105, p52/p100 and RelA in the prostate cancers compared to normal alveolar cells suggested that overexpression of these proteins may be related to activation of the NF-kappaB pathway and might play a role in tumorigenesis of prostate cancers.