Predictive DNA damage signaling for low­dose ionizing radiation.

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low­dose radiation­sensitive markers. The HuT 78 and IM­9 cell lines were irradiated in a concentration­dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration­dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub­lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub­lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML­277, pifithrin­α, and nutlin­3a were evaluated for their ability to modulate radiation­induced cell death. The use of BML­277 led to a decrease in radiation­induced p­CHK2 and γH2AX levels and mitigated radiation­induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation­sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.

Radiation-induced IL-1ß expression and secretion promote cancer cell migration/invasion via activation of the NF-κB-RIP1 pathway.

Here, we demonstrate that interleukin-1ß (IL-1ß) contributes to the γ-ionizing radiation (IR)-induced increase of migration/invasion in A549 lung cancer cells, and that this occurs via RIP1 upregulation. We initially observed that the protein expression and secreted concentration of IL-1ß were increased upon exposure of A549 cells to IR. We then demonstrated that IR-induced IL-1ß is located downstream of the NF-κB-RIP1 signaling pathway. Treatments with siRNA and specific pharmaceutical inhibitors of RIP1 and NF-κB suppressed the IR-induced increases in the protein expression and secreted concentration of IL-1ß. IL-1Ra, an antagonist of IL-1ß, treatment suppressed the IR-induced epithelial-mesenchymal transition (EMT) and IR-induced invasion/migration in vitro. These results suggest that IL-1ß could regulate IR-induced EMT. We also found that IR could induce the expression of IL-1ß expression in vivo and that of IL-1 receptor (R) I/II in vitro and in vivo. The IR-induced increases in the protein levels of IL-1 RI/II and IL-1ß suggest that an autocrine loop between IL-1ß and IL-1 RI/II might play important roles in IR-induced EMT and migration/invasion. Based on these collective results, we propose that IR concomitantly activates NF-κB and RIP1 to trigger the NF-κB-RIP1-IL-1ß-IL-1RI/II-EMT pathway, ultimately promoting metastasis.

Pressure control of a proton beam-irradiated water target through an internal flow channel-induced thermosyphon.

A water target was designed to enhance cooling efficiency using a thermosyphon, which is a system that uses natural convection to induce heat exchange. Two water targets were fabricated: a square target without any flow channel and a target with a flow channel design to induce a thermosyphon mechanism. These two targets had the same internal volume of 8 ml. First, visualization experiments were performed to observe the internal flow by natural convection. Subsequently, an experiment was conducted to compare the cooling performance of both water targets by measuring the temperature and pressure. A 30-MeV proton beam with a beam current of 20 µA was used to irradiate both targets. Consequently, the target with an internal flow channel had a lower mean temperature and a 50% pressure drop compared to the target without a flow channel during proton beam irradiation.

Endoscopic evaluation of gastric emptying and effect of mosapride citrate on gastric emptying.

PURPOSE: Gastric emptying has been evaluated by scintigraphy in spite of its limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a simple technique, however, its validation for gastric emptying and quantification of food has not yet been investigated. The aim of our study was to assess endoscopic gastric emptying compared with scintigraphy and radiopaque markers (ROMs) studies. We also investigated the effect of a single dose of mosapride on gastric emptying. MATERIALS AND METHODS: Fifteen healthy volunteers underwent scintigraphy. Next day, subjects received a standard solid meal with ROMs and underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the same procedure was repeated after ingestion of mosapride (5 mg for group 1, n = 8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric residue by endoscopy was scored from 0 to 3, and the scores were added up. RESULTS: All subjects completed the study without any complication. The gastric emptying rate [T(1/2) (min)] was in normal range (65.6 +/- 12.6 min). Endoscopic gastric emptying was correlated significantly with gastric clearance of ROMs (r = 0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs after administration of mosapride showed significant differences in the 10 mg group (p < 0.05). CONCLUSION: Endoscopy can evaluate gastric emptying safely and simply on an outpatient basis. A 10 mg dose of mosapride enhanced gastric emptying, assessed by both endoscopy and ROMs.

The clinical course of postinfectious irritable bowel syndrome: a five-year follow-up study.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common disorder seen in general practice. Bacterial gastroenteritis has been known to be a risk factor for IBS. We investigated the clinical course, risk factors, and prognosis of postinfectious IBS (PI-IBS) 5 years after Shigella infection. METHODS: We recruited 153 individuals and used a questionnaire to investigate their current bowel habits. We also looked for the presence of other functional bowel disorders (FBDs). The Shigella-exposed group consisted of hospital employees and medical students who experienced abdominal pain, diarrhea, or fever during the shigellosis outbreak and whose stool culture revealed Shigella sonnei. The control group consisted of age-matched and sex-matched subjects who corresponded fairly well with patients, considering that they were enrolled from the same hospital and were not infected. RESULTS: Complete data were obtained from 119 individuals who were divided into the Shigella-exposed group (59) and the control group (60). In the Shigella-exposed group, 3 patients had IBS before infection (previous IBS) and 6 out of 13 cases of PI-IBS after 3 years showed persistent IBS after 5 years. Five out of 11 PI-IBS patients (45.5%, 2 excluded), 3 out of 6 previous IBS patients (50%) in the Shigella-exposed group, and 7 out of 11 previous IBS patients (63.6%) in the control group recovered after 5 years (P>0.05). Five cases in the Shigella-exposed group and 3 in the control group developed new cases of IBS after 5 years. The prevalence of PI-IBS after 5 years in the previous FBD groups was 63.6%, whereas the prevalence of PI-IBS without a history of FBDs was 36.4% (P<0.05). There were no significant differences among the other risk factors in each group. CONCLUSIONS: About half of PI-IBS and previous IBS patients with or without infection recover over 5 years. Previous IBS and FBDs are risk factors of PI-IBS after 5 years. We suggest that our results support the understanding of the clinical course and prognosis of PI-IBS.

[Correlation between clinical symptoms and radiologic findings before and after pneumatic balloon dilatation for achalasia].

BACKGROUND/AIMS: We investigated the risk factors for short-term recurrence and analyzed the correlation between subjective clinical symtoms and objective radiological findings in patients with achalasia undergoing pneumatic balloon dilatation. METHODS: Twenty patients who were treated by pneumatic balloon dilatation were enrolled. We compared prospectively various indices before and after the treatment as follows: 1) Eckardt symptom score and dysphagia grade, 2) The ratio of the maximal width in mid-esophageal lumen to the minimal width in distal esophagus around lower esophageal sphincter, and 3) the percentage of maximum activity retained in the esophagus at 30 seconds and T in esophageal scan two days after the treatment. RESULTS: 1) Clinical indices and radiologic indices significantly improved after pneumatic dilatation. 2) There was no significant correlation between the clinical indices and the radiologic indices before and after the treatment. 3) The difference percentage of clinical indices did not show significant correlation with the difference percentage of the radiologic indices. 4) Compared to the group above 20% in the difference percentage of 30 second residual fraction, the one below 20% had a four-fold risk in short-term recurrence. CONCLUSIONS: Clinical symptoms and radiologic indices significantly improve after pneumatic dilatation but have no significant correlation to each other. The group below 20% in the difference percentage of 30 second residual fraction has a high risk of recurrence and may need careful examination and early repeated pneumatic dilation.

[A case of colonic cryptococcosis].

We experienced a rare case of colonic cryptococcosis in an apparently immunocompetent individual. A 27-year- old woman admitted our hospital for intermittent melena. Initial abdominal CT scan revealed a mass lesion obstructing most of the lumen in ascending colon. Colonoscopy showed huge ulcerofungating mass in proximal ascending colon. Colonoscopic biopsy was performed and pathologic diagnosis was made as colonic cryptococcosis with positive PAS stain. Laboratory test evaluating immune status and bone marrow examination was normal. The patient was treated with intravenous amphotericin B for four weeks and six months of oral fluconazole afterwards. Follow-up abdominal CT scan and colonoscopy were taken at four weeks and seven months after the beginning of treatment. On completion of intravenous amphotericin B treatment, the mass lesion was decreased in abdominal CT and colonoscopy. After seven months, abdominal CT and colonoscopy showed near-complete resolution of the colonic lesion so the treatment ended. Cryptococcosis in a healthy individual is a rare disease and there have been only several sporadic case reports on pulmonary or central nervous system involvement. Hence, we report a case of colonic cryptococcosis in an apparently immunocompetent individual.

A systematic approach for yielding a potential pool of enzymes: practical case for chiral resolution of (R,S)-ketoprofen ethyl ester.

A systematic approach for the selection of potential biocatalysts from a natural source was developed and then a practical application was addressed. The approach that involves systematically combined conventional screening methods and current tools comprises the following consecutive steps: strain enrichment for activity screening, identification of positive strains, choosing whole genome-sequenced strains as candidates, gathering information about responsible enzymes, bioinformatic analyses and gene mining, probing genetic molecules and then functional expression. The target compound (R,S)-ketoprofen ethyl ester was to be resolved into an enantiomer, and a potential esterase from Pseudomonas fluorescens KCTC 1767 was prepared by the proposed procedure. The enzyme had a high activity and also strict selectivity for the enantiomer (S)-ketoprofen and was suitable therefore as a biocatalyst for practical use. The result achieved by the combined approach could not easily be obtained using other approaches with typical procedures. Hence the approach proposed here should be of considerable use for the screening of potential enzymes, particularly for enzymes with desired activity to unnatural substrates, from conditionally expressed and/or repressed proteins that are distributed widely in natural pools under normal conditions.