Effect of chlorpyrifos-exposure on the expression levels of CYP genes in Daphnia magna and examination of a possibility that an up-regulated clan 3 CYP, CYP360A8, reacts with pesticides.

Daphnia magna is a test organism used for ecological risk assessments of pesticides, but little is known about the expression levels of cytochrome P450s (CYP)s and their changes after pesticide exposure in the less than 24-h-olds used for ecotoxicity tests. In this study, D. magna juveniles were exposed to 0.2 µg/L of chlorpyrifos under the conditions for acute immobilization test as specified by the OECD test guideline for 24 h, and then the gene expression was compared between the control and chlorpyrifos-exposure groups by RNA-sequencing analysis, with a focus on CYP genes. Among 38 CYP genes expressed in the control group, seven were significantly up-regulated while two were significantly down-regulated in the chlorpyrifos-exposure group. Although the sublethal concentration of chlorpyrifos did not change their expression levels so drastically (0.8 < fold change < 2.6), CY360A8 of D. magna (DmCYP360A8), which had been proposed to be responsible for metabolism of xenobiotics, was abundantly expressed in controls yet up-regulated by chlorpyrifos. Therefore, homology modeling of DmCYP360A8 was performed based on the amino acid sequence, and then molecular docking simulations with the insecticides that were indicated to be metabolized by CYPs in D. magna were conducted. The results indicated that DmCYP360A8 could contribute to the metabolism of diazinon and chlorfenapyr but not chlorpyrifos. These findings suggest that chlorpyrifos is probably detoxified by other CYP(s) including up-regulated and/or constitutively expressed one(s).

Host-specific activation of a pathogen effector Aave_4606 from Acidovorax citrulli, the causal agent for bacterial fruit blotch.

RipAY, an effector protein from the plant bacterial pathogen Ralstonia solanacearum, exhibits γ-glutamyl cyclotransferase (GGCT) activity to degrade the host cellular glutathione (GSH) when stimulated by host eukaryotic-type thioredoxins (Trxs). Aave_4606 from Acidovorax citrulli, the causal agent of bacterial fruit blotch of cucurbit plants, shows significant homology to RipAY. Based on its homology, it was predicted that the GGCT activity of Aave_4606 is also stimulated by host Trxs. The GGCT activity of a recombinant Aave_4606 protein was investigated in the presence of various Trxs, such as yeast (ScTrx1), Arabidopsis thaliana (AtTrx-h1, AtTrx-h2, AtTrx-h3, and AtTrx-h5), or watermelon (Cla022460/ClTrx). Unlike RipAY, the GGCT activity of Aave_4606 is stimulated only by AtTrx-h1, AtTrx-h3, AtTrx-h5 and ClTrx from a watermelon, the primary host of A. citrulli, but not by ScTrx1, AtTrx-h2. Interestingly, GGCT activity of Aave_4606 is more efficiently stimulated by AtTrx-h1 and ClTrx than AtTrx-h5. These results suggested that Aave_4606 recognizes host-specific Trxs, which specifically activates the GGCT activity of Aave_4606 to decrease the host cellular GSH. These findings provide new insights into that effector is one of the host-range determinants for pathogenic bacteria via its host-dependent activation.

Carbonic anhydrase inhibitor induces otic hair cell apoptosis via an intrinsic pathway and ER stress in zebrafish larvae.

Carbonic anhydrase (CA) catalyzes reversible hydration of CO2 to HCO3 - to mediate pH and ion homeostasis. Some chemical pollutants have been reported to have inhibitory effects on fish CA. In this study, we investigated effects of a CA inhibitor ethoxyzolamide (EZA) on neuromasts development during zebrafish embryogenesis, since embryogenesis in aquatic organisms can be particularly sensitive to water pollution. EZA caused alteration of pH and calcium concentration and production of reactive oxygen species (ROS) in larvae, and induced apoptosis in hair cells especially in the otic neuromast, in which CA2 was distributed on the body surface. mRNA levels of apoptotic genes and caspase activities were increased by EZA, whereas anti-oxidants and apoptotic inhibitors, Bax, NF-κB, and p53 inhibitors significantly relieved the induction of hair cell death. Also, mRNA levels of Bip and CHOP, which are induced in response to ER stress, were upregulated by EZA, suggesting that EZA induces otic hair cell apoptosis via the intrinsic mitochondrial pathway and ER stress. Our results demonstrated an essential role of CA in neuromast development via maintenance of ion transport and pH, and that the CA, which is directly exposed to the ambient water, shows marked sensitivity to EZA.

Requirement of the exopolyphosphatase gene for cellular acclimation to phosphorus starvation in a cyanobacterium, Synechocystis sp. PCC 6803.

Polyphosphate, which is ubiquitous in cells in nature, is involved in a myriad of cellular functions, and has been recently focused on its metabolism related with microbial acclimation to phosphorus-source fluctuation. In view of the ecological importance of cyanobacteria as the primary producers, this study investigated the responsibility of polyphosphate metabolism for cellular acclimation to phosphorus starvation in a cyanobacterium, Synechocystis sp. PCC 6803, with the use of a disruptant (Δppx) as to the gene of exopolyphosphatase that is responsible for polyphosphate degradation. Δppx was similar to the wild type in the cellular content of polyphosphate to show no defect in cell growth under phosphorus-replete conditions. However, under phosphorus-starved conditions, Δppx cells were defective in a phosphorus-starvation dependent decrease of polyphosphate to show deleterious phenotypes as to their survival and the stabilization of the photosystem complexes. These results demonstrated some crucial role of exopolyphosphatase to degrade polyP in the acclimation of cyanobacterial cells to phosphorus-starved conditions. Besides, it was found that ppx expression is induced in Synechocystis cells in response to phosphorus starvation through the action of the two-component system, SphS and SphR, in the phosphate regulon. The information will be a foundation for a fuller understanding of the process of cyanobacterial acclimation to phosphorus fluctuation.

Characterization of the mechanism of thioredoxin-dependent activation of γ-glutamylcyclotransferase, RipAY, from Ralstonia solanacearum.

A class II ChaC protein, RipAY, from phytopathogenic bacterium, Ralstonia solanacearum exhibits γ-glutamylcyclotransferase (GGCT) activity to degrade intracellular glutathione in host cells upon its interaction with host thioredoxins (Trxs). To understand the Trx-dependent activation of RipAY, we constructed various deletion mutants of RipAY and found the determinant region for GGCT activation in the N- and C-terminal sequences of RipAY by analyzing their yeast growth inhibition activity and the interaction with Trxs. Mutational analysis of the active site cysteine residues of Arabidopsis thaliana Trx-h5 (AtTrx-h5), one of the most efficiently stimulating Trxs, revealed that each active site cysteine residue of AtTrx-h5 contributes to efficient RipAY-binding and -activation activity. We also estimated that RipAY and AtTrx-h5 form a complex at a 1:2 M ratio. Furthermore, we found that the constitutive GGCT activity of Gcg1, a yeast class I ChaC protein, is also stimulated by yeast Trx1. These results indicate that class I ChaC proteins can sense the intracellular redox state and interact with Trxs to promote more efficient degradation of glutathione and regulate intracellular redox homeostasis. We hypothesize that RipAY acquired a more efficient and specific Trx-dependent activation mechanism to activate its GGCT activity only in the host eukaryotic cells during the evolution.

Factors Associated with Neck and Shoulder Pain in Volunteers.

INTRODUCTION: The aims of the present study were 1) to examine the association between neck and shoulder pain (NSP) and lifestyle in the general population and 2) to examine if sagittal spino-pelvic malalignment is more prevalent in NSP. METHODS: A total of 107 volunteers (mean age, 64.5 years) were recruited in this study from listings of resident registrations in Kihoku region, Wakayama, Japan. Feeling pain or stiffness in the neck or shoulders was defined as an NSP. The items studied were: 1) the existence or lack of NSP and their severity (using VAS scale), 2) Short Form-36 (SF-36), 3) Self-Rating Questionnaire for Depression (SRQ-D), 4) Pain Catastrophizing Scale (PCS), 5) a detailed history consisting of 5 domains as being relevant to the psychosocial situation of patients with chronic pain, 6) A VAS of pain and numbness to the arm, and from thoracic region to legs. The radiographic parameters evaluated were also measured. Participants with a VAS score of 40 mm or higher and less were divided into 2 groups. Association of SF-36, SRQ-D, and PCS with NSP were assessed using multiple regression analysis. RESULTS: In terms of QoL, psychological assessment and a detailed history, bodily pain in SF-36, SRQ-D, and family stress were significantly associated with NSP. A VAS of pain and numbness to the arm, and from thoracic region to legs, was significantly associated with NSP. There were no statistical correlations between the VAS and radiographic parameters of the cervical spine. Among the whole spine sagittal measurements, multiple logistic regression analysis showed that sacral slope (SS) and sagittal vertical axis (SVA) were significantly associated with NSP. CONCLUSION: In this study, we showed the factors associated with NSP. Large SS and reduced SVA were significantly associated with NSP, while cervical spine measurements were not.

Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker.

Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % - 50.0 %) and 100.0 % (95 %CI 85.0 % - 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % - 65.9 %) and 93.8 % (95 %CI 76.7 % - 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % - 90.9 %) and 93.8 % (95 %CI 77.9 % - 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.

RipAY, a Plant Pathogen Effector Protein, Exhibits Robust γ-Glutamyl Cyclotransferase Activity When Stimulated by Eukaryotic Thioredoxins.

The plant pathogenic bacterium Ralstonia solanacearum injects more than 70 effector proteins (virulence factors) into the host plant cells via the needle-like structure of a type III secretion system. The type III secretion system effector proteins manipulate host regulatory networks to suppress defense responses with diverse molecular activities. Uncovering the molecular function of these effectors is essential for a mechanistic understanding of R. solanacearum pathogenicity. However, few of the effectors from R. solanacearum have been functionally characterized, and their plant targets remain largely unknown. Here, we show that the ChaC domain-containing effector RipAY/RSp1022 from R. solanacearum exhibits γ-glutamyl cyclotransferase (GGCT) activity to degrade the major intracellular redox buffer, glutathione. Heterologous expression of RipAY, but not other ChaC family proteins conserved in various organisms, caused growth inhibition of yeast Saccharomyces cerevisiae, and the intracellular glutathione level was decreased to ∼30% of the normal level following expression of RipAY in yeast. Although active site mutants of GGCT activity were non-toxic, the addition of glutathione did not reverse the toxicity, suggesting that the toxicity might be a consequence of activity against other γ-glutamyl compounds. Intriguingly, RipAY protein purified from a bacterial expression system did not exhibit any GGCT activity, whereas it exhibited robust GGCT activity upon its interaction with eukaryotic thioredoxins, which are important for intracellular redox homeostasis during bacterial infection in plants. Our results suggest that RipAY has evolved to sense the host intracellular redox environment, which triggers its enzymatic activity to create a favorable environment for R. solanacearum infection.

Lipid is absorbed in the stomach by epithelial neoplasms (adenomas and early cancers): a novel functional endoscopy technique.

BACKGROUND AND STUDY AIMS: The authors have successfully demonstrated that the white opaque substance (WOS) identified in gastric epithelial neoplasms is an accumulation of minute lipid droplets on the epithelial neoplasm. It is not known whether the lipid droplets originate from externally ingested lipids (typically foods). The purpose of this study was to investigate whether the oral ingestion of foods containing emulsified fats increases the density of the WOS in epithelial neoplasms. PATIENTS AND METHODS: We examined 92 gastric epithelial neoplastic lesions in 89 patients. The patients were given emulsified fatty foods before the procedure, and magnifying endoscopy with narrow-band imaging (M-NBI) was used to image the lesions. An increase in WOS density after the ingestion of emulsified fatty foods was defined as a positive fat-loading test result. The patients were divided into the following groups: control group, no emulsified fat administered; group 1, fatty food administered 16 hours prior; group 3, fatty food administered both 16 and 4 hours prior. The proportion of positive fat-loading test results was determined in all groups. RESULTS: The rates of positive fat-loading test results were as follows: control group, 9 %; group 1, 26 %; group 2, 52 %; group 3, 78 %. The increase in the rates of positive fat-loading test results in groups 2 and 3 relative to the rate in the control group was statistically significant (chi-squared test). CONCLUSIONS: This study demonstrated for the first time that the ingestion of external lipids causes lipid droplets to aggregate in situ on the gastric epithelial neoplasm. These results can be used to develop a novel functional endoscopy technique that harnesses the lipid absorption capacity of neoplasms.

Can we accurately diagnose minute gastric cancers (≤5 mm)? Chromoendoscopy (CE) vs magnifying endoscopy with narrow band imaging (M-NBI).

BACKGROUND: Chromoendoscopy (CE) is relatively ineffective at identifying the cancer-specific morphological characteristics of minute gastric cancers less than or equal to 5 mm in diameter, and on its own is insufficient to make an accurate diagnosis. The aim of this study is to assess the diagnostic performance of magnifying endoscopy with narrow band imaging (M-NBI) for minute gastric cancers. METHODS: The minute cancer group comprised consecutive endoscopic submucosal dissection-resected minute gastric cancers histologically measured as no larger than 5 mm in diameter. The non-cancer group comprised consecutive non-cancer lesions no larger than 5 mm in diameter. The two groups were subject to retrospective analysis to evaluate the diagnostic ability (sensitivity, specificity, and diagnostic accuracy) and reproducibility of CE and M-NBI. RESULTS: The results for CE versus M-NBI were as follows: sensitivity 43.7 % (95 % CI, 26.5-61.0 %) versus 78.0 % (95 % CI, 64.0-92.0 %); specificity 81.6 % (95 % CI, 72.6-90.6 %) versus 92.9 % (95 % CI, 87.0-98.9 %); and diagnostic accuracy 69.9 % (95 % CI, 61.0-78.6 %) versus 88.3 % (95 % CI, 82.0-94.5 %). The sensitivity and diagnostic accuracy were, therefore, significantly higher for M-NBI than for CE. The inter-observer variability was κ = 0.08 for CE and κ = 0.56 for M-NBI, while the intra-observer variability was κ = 0.38 and κ = 0.65, respectively. CONCLUSIONS: M-NBI has greater sensitivity and reproducibility than CE for the diagnosis of minute gastric cancers.

The vessels within epithelial circle (VEC) pattern as visualized by magnifying endoscopy with narrow-band imaging (ME-NBI) is a useful marker for the diagnosis of papillary adenocarcinoma: a case-controlled study.

BACKGROUND AND AIMS: Pathological studies indicate papillary adenocarcinomas are more aggressive than tubular adenocarcinomas, but a definitive diagnosis is difficult using conventional endoscopy alone. The vessels within an epithelial circle (VEC) pattern, visualized using magnifying endoscopy with narrow-band imaging (ME-NBI), may be a feature of papillary adenocarcinoma. The aims of our study were to investigate whether the VEC pattern is useful in the preoperative diagnosis of papillary adenocarcinoma and to determine whether VEC-positive adenocarcinomas are more malignant than VEC-negative lesions. PATIENTS AND MATERIALS: From 395 consecutive early gastric cancers resected using the endoscopic submucosal dissection method, we analyzed 35 VEC-positive lesions and 70 VEC-negative control lesions matched for size and macroscopic type. We evaluated (1) the correlation between the incidence of VEC-positive cancers and the histological papillary structure and (2) differences in the incidence of coexisting undifferentiated carcinoma in VEC-positive and VEC-negative cancers and the incidence of submucosal and vascular invasion. RESULTS: Histological papillary structure was seen in 94 % (33/35) of VEC-positive and 9 % (6/70) of VEC-negative cancers, a significant difference (P < 0.001). The incidence of coexisting undifferentiated carcinoma was 23 % (8/35) in VEC-positive and 3 % (2/70) in VEC-negative cancers (P = 0.002). The incidence of submucosal invasion by the carcinoma was 26 % (9/35) in VEC-positive cancers and 10 % (7/70) in VEC-negative cancers (P = 0.045). CONCLUSIONS: The VEC pattern as visualized using ME-NBI is a promising preoperative diagnostic marker of papillary adenocarcinoma. Coexisting undifferentiated carcinoma and submucosal invasion were each seen in approximately one fourth of VEC-positive cancers.

Incidence, clinical characteristics, long-term course, and comparison of progressive and nonprogressive cases of aphthous-type Crohn's disease: a single-center cohort study.

BACKGROUND/AIMS: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. METHODS: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. RESULTS: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). CONCLUSION: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan.

Clinicopathological characteristics of abnormal micro-lesions at the oro-hypopharynx detected by a magnifying narrow band imaging system.

BACKGROUND: Narrow band imaging (NBI) with magnifying endoscopy (NBI-ME) allows the detection of abnormal micro-lesions smaller than 5 mm in diameter in the oro-hypopharynx that could not be visualized previously. The purpose of the present study was to clarify the clinicopathological characteristics of abnormal micro-lesions of the oro-hypopharynx detected by NBI-ME. METHODS: Of the 62 lesions detected by NBI-ME, 40 abnormal micro-lesions in 37 patients were removed by endoscopic treatment and were pathologically evaluated. We reviewed the medical records of patients with these lesions and investigated the relationship between NBI-ME findings and pathological findings. RESULTS: Pathological examination revealed the following: high-grade intraepithelial neoplasia (HGIN) in nine (23%) lesions, low-grade intraepithelial neoplasia (LGIN) in 22 (55%), pharyngitis in seven (18%) and papilloma in two (5%). Two NBI-ME findings, high microvascular density (MVD) and a brownish area (BA), were recognized more frequently as the grade of malignancy advanced. The likelihood ratio (confidential interval) for having HGIN in the patients with both MVD and BA was 13 (3.62-127). CONCLUSIONS: The pathological diagnosis of abnormal micro-lesions ranged from pharyngitis to HGIN. High MVD and BA may be important findings for grading the malignancy of abnormal micro-lesions.

Conflicting clinical environment about the management of antithrombotic agents during the periendoscopic period in Japan.

BACKGROUND AND AIMS: Although there are guidelines for the management of antithrombotic agents during the periendoscopic period, gaps between various guidelines create a confusing situation in daily clinical practice. The purpose of this study was to examine the current management of antithrombotic agents during the periendoscopic period in Japan. METHODS: This is a prospective cohort study in 12 high-volume endoscopy centers in Japan. A total of 970 outpatients receiving antithrombotic agents underwent endoscopies (705 esophagogastroduodenoscopies and 265 colonoscopies) with or without invasive procedures. Main outcome measures are adverse events in these patients. RESULTS: Need for cessation of antithrombotics before endoscopy was mostly determined by non-gastroenterologists (51%) who are unfamiliar with the Japan Gastroenterological Endoscopy Society (JGES) guideline, although cessation periods after endoscopy for most patients were determined by endoscopists (78%). Consequently, most patients underwent endoscopy without cessation (25%) or after a cessation period of 6-7 days (33%), indicating low permeation of the JGES guideline in Japan. Among 970 patients, two patients experienced major complications that may be related to thromboembolic events or gastrointestinal bleeding (95% confidence interval [CI]: 0-0.7%). One of these patients died due to sudden onset ventricular tachycardia. Invasive procedures, including 40 biopsies and two mucosal resections, were performed in 42 patients without cessation of antithrombotics, and no patients experienced major complications (95% CI: 0-8.4%). CONCLUSIONS: This study revealed a conflicting clinical environment due to absence of a unified guideline in Japan. Further accumulation of data is mandatory to establish a unified guideline based upon solid evidence.

A case of small early gastric cancer that was successfully detected by narrow band imaging magnifying endoscopy.

Endoscopic diagnosis of gastric cancer is very often made by conventional white light endoscopy and/or by indigo carmine chromoendoscopy. However, with this method it is difficult to detect and demarcate a small lesion affected by inflammation or a biopsy procedure. We considered it is useful for diagnosis of such small cancers to observe a lesion with a magnifying endoscope combined with a narrow band imaging system.

da Vinci robotic single-incision cholecystectomy and hepatectomy using single-channel GelPort access.

BACKGROUND/PURPOSE: Minimally invasive surgery including laparoscopic and robotic surgery was recently approved for clinical use in hepatobiliary surgery. The purpose of this article is to evaluate the feasibility and technical aspects of robotic single incision for hepatobiliary surgery using the GelPort laparoscopic system in a preliminary animal study. METHODS: We performed eight robotic single-incision laparoscopic surgery (SILS) procedures, including four cholecystectomies and four lateral segmentectomy of the liver, in a porcine study using the da Vinci S-HD Surgical System. A single-channel GelPort access was placed through a 2.5-cm single incision for robotic access. A 12-mm camera port, two 8-mm ports for the robotic arms and one 5-mm port for the patient-side assistant were inserted. A Mini Loop Retractor was applied to retract the fundus of the gallbladder. The EndoWrist dissector and grasping forceps was introduced to fine-dissect Calot's triangle. The instruments were crossed to avoid "sword fighting" and clashing of instruments in the abdomen. The cystic duct was divided after double ligation and the gallbladder was removed. Hepatic transection was performed with bipolar Harmonic shears and LigaSure for vascular pedicles. RESULTS: All robotic SILS procedures were completed (8/8, 100%). The cholecystectomies and hepatectomies were safely performed in average operating times of 70 min (±15) and 60 min (±20), respectively, with minimal blood loss. There were no conversions, re-interventions or extension of the skin incision. CONCLUSIONS: Robotic hepatobiliary SILS is technically feasible and safe using GelPort as a single-incision access platform. Robotic SILS is becoming established and is enormously advantageous to the patient.

A randomized controlled trial of rebamipide plus rabeprazole for the healing of artificial ulcers after endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an increasingly common technique for the resection of early gastric cancers. Although 8 weeks of treatment with a proton pump inhibitor (PPI) reportedly heals most patients with ESD-derived artificial ulcers, it does not heal those with severe atrophic gastritis, for whom there is little data. This study examined whether healing rates of the latter especially were improved by the addition of the non-PPI mucosal healing agent rebamipide after ESD. METHODS: Patients were randomly assigned to two treatment groups for 8 weeks following ESD: patients in the PPI group received daily rabeprazole alone (20 mg), whereas those in the combination group received daily rabeprazole (20 mg) and rebamipide (300 mg). At the primary endpoint (56 days after ESD) we determined the proportion of patients in whom ulcers had healed to scar-stage (S-stage, complete healing). A pre-specified subgroup analysis examined ulcer healing in patients with severe atrophic gastritis. RESULTS: Overall, progression to S-stage occurred in 54.8% in the PPI group, and 86.7% in the combination group (odds ratio 5.3, 95% confidence interval 1.50-19.02, p = 0.006). Among those patients with severe atrophic gastritis, healing to S-stage occurred in 30.0% in the PPI group, and in 92.9% in the combination group (odds ratio 30.3, 95% confidence interval 2.63-348.91, p = 0.0023). CONCLUSION: Treatment with a PPI plus rebamipide improved healing rates at 8 weeks for patients with ESD-derived artificial ulcer, and appeared to be particularly effective for patients with severe atrophic gastritis.

Rosaceiform dermatitis associated with topical tacrolimus treatment.

We describe herein 3 patients who developed rosacea-like dermatitis eruptions while using 0.03% or 0.1% tacrolimus ointment for facial dermatitis. Skin biopsy specimens showed telangiectasia and noncaseating epithelioid granulomatous tissue formation in the papillary to mid dermis. Continuous topical use of immunomodulators such as tacrolimus or pimecrolimus should be regarded as a potential cause of rosaceiform dermatitis, although many cases have not been reported.

Carbohydrate metabolism in mutants of the cyanobacterium Synechococcus elongatus PCC 7942 defective in glycogen synthesis.

ADP-glucose pyrophosphorylase (AGPase) and glycogen synthase (GS) catalyze the first two reactions of glycogen synthesis in cyanobacteria. Mutants defective in each of these enzymes in Synechococcus elongatus PCC 7942 were constructed and characterized. Activities of the corresponding enzymes in the selected mutants were virtually undetectable, and their ability to synthesize glycogen was entirely abolished. The maximal activities of photosynthetic O(2) evolution and the rates of respiration in the dark were significantly decreased in the mutants compared to those in wild-type cells. Addition of 0.2 M NaCl or 3 mM H(2)O(2) to liquid cultures markedly inhibited the growth of the AGPase and GS mutants, while the same treatment had only marginal effects on the wild type. These results suggest a significant role for storage polysaccharides in tolerance to salt or oxidative stress.

Endoluminal MR imaging of porcine gastric structure in vivo.

BACKGROUND AND AIMS: Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy. METHODS: Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer. RESULTS: Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA. CONCLUSION: Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.