Incidence and risk factors of delayed postpolypectomy bleeding in patients with chronic liver disease

Objective Hepatologists and colonoscopists often hesitate to perform a colonoscopic polypectomy in patients with chronic liver disease (CLD), especially those with cirrhosis, because of the risk of postpolypectomy bleeding (PPB). We aimed to investigate the incidence and risk factors of delayed PPB after a colonoscopic polypectomy in patients with CLD. Materials and methods In total, 152 patients with CLD who underwent colonoscopic polypectomy from December 2005 to December 2012 were retrospectively reviewed. Results Cirrhosis was identified in 80 (52.6%) patients. During the study period, 442 polyps were removed and delayed PPB developed in 14 (9.2%) patients. The incidence of delayed PPB was significantly higher in patients with cirrhosis than in those without the disease (13.8% [n?=?11] vs. 4.2% [n?=?3], p?=?0.041). The polyp size (odds ratio, 1.087; 95% confidence interval, 1.009–1.172) and cirrhosis (odds ratio, 8.535; 95% confidence interval, 2.417–30.140) were independent risk factors for delayed PPB. In patients with cirrhosis, the optimal cut-off size to identify high-risk polyps for delayed PPB was 10 mm (area under the receiver operating characteristics curve, 0.737; sensitivity, 52%; specificity, 88%). Conclusion Caution is needed when colonoscopic polypectomy is planned in patients with CLD who have larger polyps and cirrhosis.     

A computational model of cytosolic and mitochondrial [ca] in paced rat ventricular myocytes

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca(2+) transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [Ca(2+)] bigger in mitochondria as well as in cytosol. As L-type Ca(2+) channel has key influence on the amplitude of Ca(2+)-induced Ca(2+) release, the relation between stimulus frequency and the amplitude of Ca(2+) transients was examined under the low density (1/10 of control) of L-type Ca(2+) channel in model simulation, where the relation was reversed. In experiment, block of Ca(2+) uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca(2+) transients, while it failed to affect the cytosolic Ca(2+) transients. In computer simulation, the amplitude of cytosolic Ca(2+) transients was not affected by removal of Ca(2+) uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca(2+)] in cytosol and eventually abolished the Ca(2+) transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca(2+) channel to total transsarcolemmal Ca(2+) flux could determine whether the cytosolic Ca(2+) transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca(2+) affects mitochondrial Ca(2+) in a beat-to-beat manner, however, removal of Ca(2+) influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca(2+) transients.     

Erratum to: Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity

Our analyses of three human induced pluripotent stem cell (hiPSC) and six human embryonic stem cell (hESC) lines showed marked variability in differentiation potential into specific lineages, which often hampers their differentiation into specific cell types or cell lineages of interest. Simultaneous inhibition of both Activin/Nodal and BMP pathways with small molecules, SB431542 and dorsomorphin (DM), respectively, promoted significant neural differentiation from all human pluripotent stem cell (hPSC) lines tested, regardless of their differentiation propensity. On the contrary, differentiation into other cell lineages and the number of undifferentiated cells were significantly reduced after differentiation by the dual inhibition. These results demonstrate that innate differentiation propensity of hPSCs could be overcome, at least in part, by modulation of intracellular signaling pathways, resulting in efficient generation of desirable cell types, such as neural cells.     

Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit cancer growth by inhibiting the activity of cyclooxygenase (COX). However, there is increasing evidence that the COX-independent pathway may be also involved in the inhibitory effect of NSAIDs against tumor progression. Tolfenamic acid is a NSAID that exhibits anticancer activity in pancreatic and colorectal cancer models. In the present study, the anti-tumor effect of tolfenamic acid in KB human oral cancer cells is investigated. The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G₁ population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase. In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells. These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway. These results suggest that tolfenamic acid-induced apoptotic cell death inhibits cancer growth by activating the p38 MAPK pathway for cancer prevention.     

The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions

In this work, the full-length hTERT gene was isolated and the sequence of the previously unknown region in intron 6 as well as that of upstream and downstream hTERT regions was determined. We have shown that intron 6 includes a variable number of tandem repeats (VNTR) of a 38 bp sequence, (hTERT-VNTR 6-1). Eight alleles of hTERT-VNTR 6-1 were identified among 103 unrelated individuals, ranging from 27 to 47 repeats. hTERT-VNTR 2-2 is another new 61 bp minisatellite repeat found in intron 2 of hTERT. At least four alleles of hTERT-VNTR 2-2 can be distinguished. Previous studies have described polymorphisms for minisatellites hTERT-VNTR 2-1, a 42 bp repeat in intron 2, and hTERT-VNTR 6-2, a 36 bp repeat in intron 6. These, together with another minisatellite found in intron 12, add up to five such structures within the hTERT gene. The segregation of hTERT minisatellites was analysed in families, revealing that the VNTRs are transmitted through meiosis following a Mendelian inheritance. Minisatellites in hTERT were also analysed in matching normal and cancer tissues from patients with tumors; in one patient with a kidney tumor, the two VNTRs in intron 6 had undergone concomitant rearrangements. This observation suggests that chromosomal rearrangements implicating these VNTRs may be associated with the activation of telomerase expression in cancer cells.