Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)     

Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5

Glycoprotein hormones play important roles in thyroid and gonadal function in vertebrates. The glycoprotein hormone alpha-subunit forms heterodimers with different beta-subunits to activate TSH or gonadotropin (LH and FSH) receptors. Recent genomic analyses allowed the identification of another alpha-subunit, GPA2, and another beta-subunit, GPB5, in human, capable of forming heterodimers to activate TSH receptors. Based on comparative genomic searches, we isolated the fly orthologs for human GPA2 and GPB5, each consisting of 10 cysteine residues likely involved in cystine-knot formation. RT-PCR analyses in Drosophila melanogaster demonstrated the expression of GPA2 and GPB5 at different developmental stages. Immunoblot analyses further showed that fly GPA2 and GPB5 subunit proteins are of approximately 16 kDa, and coexpression of these subunits yielded heterodimers. Purified recombinant fly GPA2/GPB5 heterodimers were found to be glycoproteins with N-linked glycosylated alpha-subunits and nonglycosylated beta-subunits, capable of stimulating cAMP production mediated by fly orphan receptor DLGR1 but not DLGR2. Although the fly GPA2/GPB5 heterodimers did not activate human TSH or gonadotropin receptors, chimeric fly GPA2/human GPB5 heterodimers stimulated human TSH receptors. These findings indicated that fly GPA2/GPB5 is a ligand for DLGR1, thus showing the ancient origin of this glycoprotein hormone-seven transmembrane receptor-G protein signaling system. The fly GPA2 also could form heterodimers with human GPB5 to activate human TSH receptors, indicating the evolutionary conservation of these genes and suggesting that the GPA2 subunit may serve as a scaffold for the beta-subunit to activate downstream G protein-mediated signaling.     

Peritoneal pregnancy with massive hemoperitoneum in early gestation: two case reports

Peritoneal pregnancy may cause severe abdominal bleeding without genital bleeding as early as the fifth week of gestation. Awareness that pregnancy can exist in unusual locations is imperative.     

Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development

It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis--but not aging--in this model.     

Moderate-to-vigorous physical activity and the risk of stroke recurrence in patients with a history of minor ischemic stroke in Japan: a retrospective analysis

Background: Physical activity (PA) is beneficial for stroke prevention; in particular, moderate-to-vigorous physical activity (MVPA). However, few studies have investigated its relationship with recurrent ischemic stroke (RIS).

Objectives: To clarify the relationship between MVPA and RIS and the burden of risk factors after a first-ever ischemic stroke.

Methods: A total of 45 outpatients (mean age 67.1 ± 10.2 years) who had previously experienced a transient ischemic attack or a minor non-cardioembolic ischemic stroke at a single hospital in Japan (mean 6.4 ± 4.2 years previously), were enrolled between March and June 2016. All patients wore an accelerometer around their hips for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL) were measured by bioelectrical impedance. Retrospective information about the history of RIS and risk factors (blood pressure, lipoprotein cholesterol and estimated glomerular filtration rate) were extracted from the clinical records. Binary logistic regression models were used to estimate the relevance of the RIS history to MVPA and potential risk factors such as sociodemographic and clinical variables (obesity, smoking and hypertension).

Results: RIS occurred in 9 patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007) values and lower MVPA (p = 0.011) values than patients without recurrence. A multivariate analysis of these factors indicated that age, VFL and MVPA were signi?cant independent predictors of RIS.

Conclusions: Patients with a history of mild ischemic stroke had low MVPA and high VFL values, which together may be a risk factor for RIS.     

Improved Orange and Red Ca2+ Indicators and Photophysical Considerations for Optogenetic Applications

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Intrahepatic biliary ablation with pure ethanol: an experimental model of biliary atresia

Purpose

We describe a new rat model of biliary atresia, induced by biliary ablation with pure ethanol.

Methods

A catheter was inserted and fixed in the common bile duct of male rats. Saline or pure ethanol was injected through the catheter and the animals were monitored for 8 weeks thereafter. We measured total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid (HA) and examined liver biopsy specimens immunohistochemically for α-smooth muscle actin staining (α-SMA) and transforming growth factor-β1 (TGF-β1).

Results

The ethanol injection group animals were further divided into a temporary and a persistent liver dysfunction group. In the persistent group, T-Bil, AST, ALT and HA levels were significantly higher after 8 weeks in the persistent group than in the control group and the temporary group. In the ethanol injection group, α-SMA expression was prominent in the surrounding proliferative bile ducts and portal areas. The distribution of TGF-β1 was found prominently in hepatocytes in the center of nodules and in ductular epithelial cells.

Conclusions

This study characterizes the effects of ethanol-induced bile duct injury in rats, resulting in sclerosing cholangitis and its secondary effects. We believe that this experimental model will prove useful in the study of biliary atresia.     

Discrimination between schizophrenia and major depressive disorder by magnetic resonance imaging of the female brain

Background

Although schizophrenia and major depressive disorder (MDD) differ on a variety of neuroanatomical measures, a diagnostic tool to discriminate these disorders has not yet been established. We tried to identify structural changes of the brain that best discriminate between schizophrenia and MDD on the basis of gray matter volume, ventricle volume, and diffusion tensor imaging (DTI).

Method

The first exploration sample consisted of 25 female patients with schizophrenia and 25 females with MDD. Regional brain volumes and fractional anisotropy (FA) values were entered into a discriminant analysis. The second validation sample consisted of 18 female schizophrenia and 16 female MDD patients.

Results

The stepwise discriminant analysis resulted in correct classification rates of 0.80 in the schizophrenic group and 0.76 in MDD. In the second validation sample, the obtained model yielded correct classification rates of 0.72 in the schizophrenia group and 0.88 in the MDD group.

Conclusion

Our results suggest that schizophrenia and MDD have differential structural changes in the examined brain regions and that the obtained discriminant score may be useful to discriminate the two disorders.