Sunhye Shin

Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.

BACKGROUND AND STUDY AIMS Controversy persists around the treatment of gastric low-grade dysplasia (LGD). The aim of this study was to investigate possible indications for the endoscopic resection of gastric LGD through analysis of the histologic discrepancies between specimens of gastric LGD obtained by forceps biopsy and by endoscopic mucosal resection (EMR), and of their clinicopathologic characteristics. PATIENTS AND METHODS The study involved 293 gastric LGD that were histologically proven on the basis of forceps biopsy in Severance Hospital between January 2004 and December 2007. Twenty cases were regularly followed up, and the remaining 273 were resected by EMR. We performed univariate and multivariate analyses of clinical and endoscopic characteristics including lesion size, number of biopsy fragments, and endoscopic appearance, in order to analyze the factors affecting histologic discrepancies. RESULTS Of the 273 lesions resected by EMR, 207 (75.8 %) showed concordant histology, whereas for 51 (18.7 %) the histology was upgraded after endoscopic resection. Lesion size, absence of whitish discoloration, and the presence of spontaneous bleeding were found by univariate analysis to be statistically significant factors predicting an upgraded histology after EMR ( P = 0.026, P < 0.001, and P = 0.025, respectively). Multivariate analysis also showed absence of whitish discoloration to be a statistically significant factor influencing histologic discrepancies ( P = 0.001, odds ratio 5.29, 95 % confidence interval 1.95 - 14.37). Perforation and bleeding rates associated with EMR for LGD were 0.7 % and 6.2 %, respectively. Twenty patients who did not undergo EMR were followed up for a mean of 22 months, and 3 were revealed to have adenocarcinoma and 1 high-grade dysplasia on the latest histologic exam. CONCLUSIONS We should consider endoscopic resection for gastric LGD that are 2 cm or more in size and do not have whitish discoloration.

The effects of statins on the clinical outcomes of Clostridium difficile infection in hospitalised patients

An association between exposure to statin drugs and favourable treatment outcomes for various types of infections has been established.

Glyceollins, a novel class of soybean phytoalexins, inhibit SCF-induced melanogenesis through attenuation of SCF/c-kit downstream signaling pathways

The anti-melanogenesis effect of glyceollins was examined by melanin synthesis, tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When developing zebrafish embryos were treated with glyceollins, pigmentation of the embryos, melanin synthesis and tyrosinase activity were all decreased compared with control zebrafish embryos. In situ expression of a pigment cell-specific gene, Sox10, was dramatically decreased by glyceollin treatment in the neural tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling pathways as well as expression of microphthalmia-associated transcription factor (MITF) were determined by western blot analysis. Glyceollins inhibited melanin synthesis, as well as the expression and activity of tyrosinase induced by SCF, in a dose-dependent manner in B16F10 melanoma cells. Pretreatment of B16F10 cells with glyceollins dose-dependently inhibited SCF-induced c-kit and Akt phosphorylation. Glyceollins significantly impaired the expression and activity of MITF. An additional inhibitory function of glyceollins was to effectively downregulate intracellular cyclic AMP levels stimulated by SCF in B16F10 cells. Glyceollins have a depigmentation/whitening activity in vitro and in vivo, and that this effect may be due to the inhibition of SCF-induced c-kit and tyrosinase activity through the blockade of downstream signaling pathway.

Heterogeneity of mucosal mast cell infiltration in subgroups of patients with esophageal chest pain

Although there is growing evidence that an increase in mucosal mast cells (MMCs) in the small and large intestine is associated with visceral hypersensitivity, few studies have evaluated MMCs in humans with esophageal symptoms. The aim of this study was to investigate esophageal MMC distribution in patients with non‐cardiac chest pain (NCCP) and to examine the association between the number of gut MMCs and other functional gastrointestinal disorders.

Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation

Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs) mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.

Rapid Induction of Osteogenic Markers in Mesenchymal Stem Cells by Adipose-Derived Stromal Vascular Fraction Cells

Background/Aims: Stromal vascular fraction (SVF) cells are a mixed cell population, and their regenerative capacity has been validated in various therapeutic models. The purpose of this study was to investigate the regenerative mechanisms utilized by implanted SVF cells. Using an in vitro co-culture system, we sought to determine whether SVF implantation into impaired tissue affects endogenous mesenchymal stem cell (MSC) differentiation; MSCs can differentiate into a variety of cell types, and they have a strong regenerative capacity despite their low numbers in impaired tissue. Methods: Adipose-derived SVF cells obtained from four donors were co-cultured with bone marrow-derived MSCs, and the differential expression of osteogenic markers and osteogenic differentiation inducers over time was analyzed in mono-cultured MSCs and MSCs co-cultured with SVF cells. Results: The co-cultivation of MSCs with SVF cells significantly and mutually induced the expression of osteogenic-specific markers via paracrine and/or autocrine regulation but did not induce adipocyte, chondrocyte or myoblast marker expression. More surprisingly, subsequent osteogenesis and/or comparable effects were rapidly induced within 48 h. Conclusion: To the best of our knowledge, this is the first study in which osteogenesis and/or comparable effects were rapidly induced in bone marrow-derived MSCs and adipose-derived SVF cells through co-cultivation. Our findings suggest that the positive effects of SVF implantation into impaired bone may be attributed to the rapid induction of MSC osteogenesis, and the transplantation of co-cultured and preconditioned SVF cells and/or MSCs may be more effective than the transplantation of untreated cells for the treatment of bone defects.

Interaction of small G protein signaling modulator 3 with connexin 43 contributes to myocardial infarction in rat hearts

Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection. MALDI-TOF mass spectrometry analysis of Cx43 co-immunoprecipitated proteins showed that Cx43 interacts with several proteins related to metabolism. In GeneMANIA network analysis, SGSM3, which has not been previously associated with Cx43, was highly correlated with Cx43 in heart functions, and high levels of SGSM3 appeared to induce the turnover of Cx43 through lysosomal degradation in myocardial infarcted rat hearts. Moreover, we confirmed that lysosomal degradation of Cx43 is dependent upon the interaction between SGSM3 and Cx43 in H9c2 cardiomyocytes. The functional importance of the interaction between SGSM3 and Cx43 was confirmed by results showing that Cx43 expression was enhanced by SGSM3 siRNA knockdown in H9c2 cells. In summary, the results of this study elucidate the molecular mechanisms in which Cx43 with SGSM3 is degraded in myocardial infarcted rat hearts, which may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions.

Self‐expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.

Esophageal mucosal mast cell infiltration and changes in segmental smooth muscle contraction in noncardiac chest pain

Mast cells release potent mediators that alter enteric nerve and smooth muscle functions and may contribute to the pathogenesis of functional gastrointestinal disorders. The goal of this study was to determine if mucosal mast cell infiltration was associated with smooth muscle segmental changes in esophageal contraction. All patients with noncardiac chest pain (NCCP) were divided into two groups consisting of patients with non-erosive reflux disease or functional chest pain (FCP) according to the results of ambulatory 24 hours esophageal pH monitoring and high-resolution manometry. Pressure-volume (PV) was calculated by multiplying the length of the esophageal segment, duration of the contraction, and mean pressure over the entire space-time box (P mean). Quantification of mast cells was performed in five consecutive nonoverlapping immunostained sections. Spearman correlation analysis showed that the distal segment PV correlated with the mast cell count in all of the patients combined and in patients with FCP with correlation coefficients of 0.509 and 0.436, respectively (P = 0.004 and P = 0.042). Similar findings were observed for the segmental ratio of distal to proximal smooth muscle PV in all patients and in patients with FCP (correlation coefficients 0.566; P = 0.001 and correlation coefficients 0.525; P = 0.012, respectively). Mucosal mast cell infiltration was associated with distal esophageal contraction as a key pathophysiologic factor of NCCP.

Heart rate variability dynamics during controlled hypotension with nicardipine, remifentanil and dexmedetomidine

This study was done to investigate how nicardipine, remifentanil and dexmedetomidine affect the balance of the autonomic nervous system in patients receiving controlled hypotension under general anaesthesia by evaluating heart rate variability indices.