As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedancepH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

We studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 micron in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Background: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. Aims: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. Subjects: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. Methods: We identified the IL-8 2251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. Results: IL-8 2251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 2251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in 2251A carriers than in T/T carriers. In the in vitro assay, IL-8 2251A showed enhanced promoter activity in response to IL-1b or tumour necrosis factor a. Conclusions: The IL-8 2251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

EGE is more prevalent than EoE in Japan. Patients with EGE have abdominal pain and diarrhea, high peripheral eosinophil counts, and gastrointestinal wall thickening identifiable by CT findings, while EoE is characterized by dysphagia and characteristic endoscopic features.

In recent years Helicobacter pylori infection has been implicated in the etiology of a variety of upper gastrointestinal diseases. The aim of this multi-center trial was to search for the cut-off value of the simple 13C-urea breath test (13C-UBT) for diagnosis of H. pylori infection, and to examine the sensitivity and specificity of 13C-UBT for culture, the rapid urease test (CLO test), histology, and serological tests. Two hundred and forty-eight patients participated in this study after giving their informed consent. Endoscopic biopsy specimens were taken from gastric antrum and corpus for culture (190 patients), CLO test (222 patients), and histology (98 patients). A serological test was carried out for all patients. H. pylori infection was established when culture was positive or more than two of the tests, histology, CLO test, and serological test, were positive, and non-infection status was established when the all tests more than two tests were negative. After baseline breath samples were taken, the patients (who had fasted) were given 100mg of 13C-urea in 100ml water while sitting; they washed out the mouth with water. They were then placed in the left lateral decubitus position for 5 min, and additional breath samples were taken 10, 20, 30, 45, and 60 min after urea administration, with patients in the sitting position. One hundred and sixty-five of the 248 patients were infected, 48 were not infected, and H. pylori infection status was not evaluated in 35 by endoscopic and serological tests. Breath samples at 20 min were employed to determine the cut-off value. Using the receiver operating characteristic (ROC) curve, we determined the cut-off value for a positive UBT at 2.5 delta per thousand. The sensitivities of UBT for culture, CLO test, histology, and serological test were 98.4%, 98.6%, 100.0%, and 92.5%, and the specificities were 78.8%, 82.5%, 83.3%, and 87.3%, respectively. The cut-off value of 13C-UBT for the diagnosis of H. pylori infection was 2.5 delta per thousand; this test is a simple and noninvasive method for the diagnosis of this infection and has high sensitivity and specificity.

The infrared reflectivities of crystalline forsterite (Mg2SiO4) were measured for the temperature range 295–50 K for each crystal axis, between wavenumber 5000 and 100 cm−1. The reflection spectra show clear dependence of temperature; most of the bands become more intense, sharper and their peak positions shift to higher wavenumber with decreasing temperature. Reflection spectra were fitted with dispersion formula of damped oscillator model of the dielectric constants and the oscillator parameters in the model were derived. The absorption spectra of forsterite particle are calculated with the derived dielectric constants to show that the forsterite features are good thermal indicator for cold temperature range below 295 K.

We investigated movement-related change in the cortical EEG signal by simultaneous recording from the primary sensorimotor area (S1-M1) and the supplementary motor area proper (SMA proper) in four patients with intractable partial epilepsy. By the use of temporal spectral evolution (TSE) analysis, the change in background cortical activity in relation to self-paced finger/wrist extension was compared among the SMA proper, S1 and M1. All three areas showed a decrease in the amount of activity for the frequency range between 10 and 40 Hz before the onset of movement [event-related desynchronization (ERD)]. The SMA proper showed earlier onset of ERD for 18-22 Hz activity (-3.4 +/- 0.5 s, mean +/- standard deviation) than M1 (-1.7 +/- 0.7 s) and S1 (-1.4 +/- 0.5 s). The degree of ERD in S1 was greatest for 10-14 Hz and that in M1 for 18-22 Hz, whereas in the SMA proper ERD was observed throughout the frequency bands from 10 to 40 Hz. Neither the degree nor the onset time of ERD in the SMA proper was lateralized to either the ipsilateral or the contralateral side with respect to the movement. A transient increase in activity after movement [event-related synchronization (ERS)] was observed in all three areas. In the SMA proper, two out of four subjects showed ERS for frequency bands below 40 Hz with both ipsilateral and contralateral movements. By contrast, in S1 and M1, ERS was recorded for frequency bands between 20 and 90 Hz, and was predominantly associated with the contralateral movement. The present study suggests that the background cortical activity in the SMA proper has a specific temporal pattern with respect to self-paced movement, and that the SMA proper is involved in motor preparation earlier than S1-M1 in a bilaterally organized manner.

Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long‐term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC‐specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC‐1) is a candidate gene for cancer‐specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme‐linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean ± SE, 36.3 ± 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 ± 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19‐9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC. © 2009 UICC