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1.  Extracellular Vesicles Derived from Gut Microbiota, Especially Akkermansia muciniphila, Protect the Progression of Dextran Sulfate Sodium-Induced Colitis 
PLoS ONE  2013;8(10):e76520.
Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
PMCID: PMC3811976  PMID: 24204633
2.  Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in Human Gastric Carcinogenesis 
Helicobacter pylori (H pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-hydroxyprostaglandin dehydrogenase (15–PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H pylori. 15-PGDH expression in gastric biopsies from H pylori-infected (n=25) and non-infected (n=15) subjects was analyzed by quantitative real-time PCR, western blot analysis, and immunohistochemisty. 15-PGDH DNA methylation was evaluated by methylation specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, ERK1/2, TLR4 and MyD88 in response to H pylori infection was assessed by immunoblot analysis. Compared to negative specimens, H pylori positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H pylori infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of epidermal growth factor receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression and small interfering Myd88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. Heliocobacter pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR - Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H pylori-induced gastric carcinogenesis.
PMCID: PMC3796116  PMID: 23430757
Gastric cancer; Helicobacter pylori; 15-prostaglandin dehydrogenase
3.  Electrical Stimulation Therapy in Chronic Functional Constipation: Five Years' Experience in Patients Refractory to Biofeedback Therapy and With Rectal Hyposensitivity 
Biofeedback therapy (BFT) can be unsuccessful in constipated patients, even those with pelvic floor dysfunction. Electrical stimulation therapy (EST) has been introduced as a novel therapeutic modality in patients with chronic constipation, especially those who have rectal hyposensitivity. We evaluated the efficacy of EST based on five years' clinical experience.
From January 2002 to February 2007, 159 patients underwent EST. After exclusion of 12 drop-outs, 147 (M:F = 61:86, 49 ± 17 years) finished all treatment sessions. Among them, 88 (M:F = 29:59, 49 ± 17 years) were refractory to BFT without rectal hyposensitivity (RH), and 59 (M:F = 32:27, 54 ± 17 years) were those with RH.
The overall response to EST was 59.2% (87/147) by per-protocol analysis. In the EST-responsive group, overall satisfaction improved significantly (from 7.3 ± 3.0 to 4.3 ± 2.5, P < 0.05). Subgroup analysis showed that the response rate was 64.8% (57/88) in patients refractory to BFT without RH, and 50.8% (30/59) in those with RH.
EST may have additional therapeutic efficacy in patients who are refractory to BFT. EST may also be effective in patients with RH, including restoration of rectal sensation. Therefore, EST could be considered as an alternative choice in patients refractory to BFT and with or without RH.
PMCID: PMC3714415  PMID: 23875104
Biofeedback; Constipation; Electric stimulation therapy
4.  Toxoplasma Encephalitis in an Allogeneic Hematopoietic Stem Cell Transplant Recipient in Korea 
PMCID: PMC3372812  PMID: 22707900
Toxoplasmosis; Cerebrum; Hematopoietic stem cell transplantation
5.  Regression of Advanced Gastric MALT Lymphoma after the Eradication of Helicobacter pylori 
Gut and Liver  2012;6(2):270-274.
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
PMCID: PMC3343168  PMID: 22570759
Marginal zone B-cell lymphoma; Stomach
6.  The effect of tracheal tube size on air leak around the cuffs 
This randomized single-blinded, cross-over study was done to evaluate the influence of the size of tracheal tubes on air leaks around the cuffs.
In a benchtop model, the number of longitudinal folds on the cuffs was evaluated for different sizes of tracheal tubes. In an anesthetized patient study, thirty patients scheduled for elective surgery under general anesthesia were included. After induction of anesthesia, the trachea was intubated with two sizes of tracheal tubes in a random sequence: in men, internal diameter of 7.5 mm and 8.0 mm; in women, internal diameter of 7.0 mm and 7.5 mm. After tracheal intubation with each tube, air leak pressures were evaluated at intracuff pressures of 20, 25 and 30 cmH2O by auscultation. To calculate the tracheal tube resistance (R), an inspiratory pause of 20% was applied and the resulting peak airway pressure (Ppeak), plateau pressure (Ppl) and mean expiratory tidal volume (Flow) were inserted in the formula R = (Ppeak - Ppl)/Flow.
More longitudinal folds of the tracheal tube cuffs occurred in larger sized tubes compared to the smaller ones in a benchtop model. Air leakage was significantly less for the smaller tracheal tubes than for the larger ones for each gender at intracuff pressures of 20, 25 and 30 cmH2O. Tracheal tube resistances were not significantly altered by the size of tracheal tube.
The use of a smaller tracheal tube within an acceptable size can reduce air leakage around the cuff without significantly changing the tracheal tube resistance.
PMCID: PMC3155132  PMID: 21860747
Anesthesia; Intratracheal; Intubation
7.  Genetic polymorphism at codon 10 of the transforming growth factor-β1 gene in patients with alcoholic liver cirrhosis 
Transforming growth factor beta1 (TGF-β1) is a key cytokine in the production of extracellular matrix. A genetic polymorphism at codon 10 of the TGF-β1 gene is associated with liver fibrosis. We investigated the effect of genetic polymorphisms at codon 10 on the development of alcoholic liver cirrhosis (ALC).
In total, 119 controls and 182 patients with ALC, were enrolled in the study. Clinical and laboratory data including total lifetime alcohol intake were collected at enrollment. The genotype at codon 10 was determined for each patient by single-strand conformation polymorphism.
There were three types of genetic polymorphism at codon 10: homozygous proline (P/P), heterozygous proline/leucine (P/L), and homozygous leucine (L/L). Among the controls, the proportions of P/P, P/L, and L/L were 26.1%, 44.5%, and 29.4%, respectively in the ALC group, these proportions were 23.1%, 43.4%, and 33.5%, respectively. The genotype distribution did not differ between the controls and the ALC group. In the ALC group, age, total lifetime alcohol intake, and distribution of Child-Pugh class did not differ with the genotype. Of the male patients with ALC (n=164), the proportions of P/P, P/L, and L/L were 20.1%, 44.5%, and 35.4%, respectively the genotype distribution did not differ between the male controls and the male ALC patients.
The genotype at codon 10 in TGF-β1 does not appear to influence the development of ALC. Further study is needed to investigate other genetic factors that influence the development of ALC in patients with chronic alcohol intake.
PMCID: PMC3304620  PMID: 21494076
Transforming growth factor beta1; Alcoholic liver cirrhosis; Genetic polymorphism
8.  Additional Evidence for the Affective Dimension of Dyspnea in Patients with COPD 
Research in nursing & health  2010;33(1):4-19.
The primary purpose of this secondary analysis was to determine whether 103 participants with chronic obstructive pulmonary disease rated the affective dimension of dyspnea (dyspnea-related anxiety and dyspnea-related distress) separately from the sensory dimension (intensity) during baseline exercise testing conducted as part of a randomized clinical trial. A secondary purpose was to determine if dyspnea-related anxiety and distress were rated distinctly different from other measurements of anxiety. At the end of a 6-minute walk and an incremental treadmill test, participant ratings of the magnitude of dyspnea-related anxiety and distress on the Modified Borg Scale were significantly different from their ratings of the intensity of dyspnea. Dyspnea-related anxiety and distress also appeared to be concepts independent from measures of state anxiety, negative affect, and anxiety before a treadmill test.
PMCID: PMC3000805  PMID: 19937752
COPD; dyspnea; anxiety; affective dimension

Results 1-8 (8)