Summary Factors impacting the developing neonatal gut microbiome and immune networks may increase risk for developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence are lacking. We therefore examined the temporal impact of the commonly used antibiotic, cefoperazone, on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10 deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact in genetically susceptible offspring to increase IBD risk.

Background and aim: This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutinbased triple therapy as a third-or fourth-line rescue therapy. Methods: Patients who failed first-and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. Results: Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n ¼ 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. Conclusion: Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy.

There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin-containing rescue therapies.

Murine models are widely used to explore host-microbe interactions because of the challenges and limitations inherent to human studies. However, microbiome studies in murine models are not without their nuances. Inter-individual variations in gut microbiota are frequent even in animals housed within the same room. We therefore sought to find an efficient and effective standard operating procedure (SOP) to minimize these effects to improve consistency and reproducibility in murine microbiota studies. Mice were housed in a single room under specific-pathogen free conditions. Soiled cage bedding was routinely mixed weekly and distributed among all cages from weaning (three weeks old) until the onset of the study. Females and males were separated by sex and group-housed (up to five mice/cage) at weaning. 16S rRNA gene analyses of fecal samples showed that this protocol significantly reduced pre-study variability of gut microbiota amongst animals compared to other conventional measures used to normalize microbiota when large experimental cohorts have been required. A significant and consistent effect size was observed in gut microbiota when mice were switched from regular chow to purified diet in both sexes. However, sex and aging appeared to be independent drivers of gut microbial assemblage and should be taken into account in studies of this nature. In summary, we report a practical and effective pre-study SOP for normalizing the gut microbiome of murine cohorts that minimizes inter-individual variability and resolves co-housing problems inherent to male mice. This SOP may increase quality, rigor, and reproducibility of data acquisition and analysis.

Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.Gastric cancer is the fifth leading cancer and the third most common cause of cancer-related deaths worldwide (1-3). Helicobacter pylori infection causes atrophic gastritis leading to gastric cancer. H. pylori is classified as a class I carcinogen and is estimated to account for about 89% of gastric cancer cases (4). H. pylori produces CagA protein, which is an effector protein of the type IV secretion system and the bacterial oncoprotein implicated in gastric carcinogenesis (5). However, translocated CagA is usually degraded by autophagy in host epithelial cells. In contrast, CagA specifically accumulates within CD44 variant 9 (CD44v9)-expressing cancer stem cells (CSCs) by escaping autophagic degradation (6). Additionally, we recently reported that CAPZA1 functions as a negative regulator of autophagy, and thereby, translocated CagA accumulates in CAPZA1-overexpressing cells. These findings suggest that the presence of CAPZA1-overexpressing cells remaining in the gastric mucosa even after eradication therapy, increases the risk of metachronous gastric cancer (7).Chemotherapy is one of the main therapeutic options for advanced gastric cancers. Recent studies have demonstrated that CSCs strongly contribute to chemotherapeutic resistance and tumor recurrence in several types of cancers (8-11). CD44, a major adhesion molecule of the extracellular matrix, is one of the cell surface markers of CSCs in many types of solid tumors (12)(13)(14)(15)(16). Especially CD44v9 interacts with xCT, a subunit of the glutamate-cystine transporter, and stabilizes xCT leading to increased intracellular levels of reduced glutathione (GSH). This mechanism enables CD44v9expressing CSCs to survive under various conditions of stress by suppressing intracellular reactive oxygen species (ROS). GSH induction and ROS suppression via CD44v9-xCT interaction leads to drug resistance against cisplatin (CDDP), which is one of the most widely used platinum drugs (17). Administration of sulfasalazine (SASP)...

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Background and Aim: Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptideexpressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection. Methods: Male H2R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H

Summary Three familial cases of juvenile type of paralysis agitans have been reported with the following results H A parkinsonian syndrom not due to a latcrit encephalitis can develop before 20 years of age. 2) Its clinical and anatomical findings are very similar to that of classical paralysis agitans. 3) By a detailed genetic study it is demonstrated that the disease is inherited in a recessive mode. The author's heartfelt thanks are due to Prof. Mitsuda, Prof. Yoshida, and Dr. Kawai for their kind advice in genetics and pathological anatomy in completing this report.