Kiyoshi Mori

Interleukin-8 Production in Primary Cultures of Human Gastric Epithelial Cells Induced by Helicobacter pylori

Interleukin-8 (IL-8) production by the gastricmucosa is increased in Helicobacter pylori infection.Previous studies indicated that H. pylori induces IL-8synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production issupposed to be associated with cag A and other cagpathogenicity island genes, including pic B gene. In thepresent study, we investigated the induction of IL-8 in primary cultures of normal human gastricepithelial cells to elucidate the IL-8 induction by wildtype strains and by the pic B knockout strain. Humangastric epithelial cells were obtained from surgically resected specimens from four patients. Three H.pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1;isogenic pic B mutant of TN2F4, Tx30a; type 2 strain)were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels inculture medium were determined by enzyme immunoassay.Human gastric epithelial cells produced IL-8 at a 10 -50times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 atsignificantly lower levels than the parent strain. Cellsfrom four patients behaved similarly on IL-8 production.The results of the present study demonstrated the induction of IL-8 in normal gastricepithelial cells, suggesting that pic B gene product mayplay an essential role in vivo.

Effect of Age on the Relationship between Gastric Cancer and Helicobacter pylori

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10‐year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20–29, 14.5 for those aged 30–39, 9.1 for those aged 40–49, 3.5 for those aged 50–59, and 1.5 for those aged 60–69 (trend in odds ratios: P < 0.01). However, there was no such age‐dependent trend for early diffuse‐type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P=0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age‐class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age‐dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age‐independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and/or irreversible damage to gastric mucosa in childhood or the teenage years.

U-shaped effect of drinking and linear effect of smoking on risk for stomach cancer in Japan.

A case‐control study was conducted to evaluate the relationship between smoking or drinking doses and risk for stomach cancer, and to clarify whether the relationship is dose‐dependent or U‐shaped. Smoking dose was categorized as 0,1–399, 400–799, or 800+ cigarette‐years, and drinking dose as 0, occasional/0.1–134.9, 135–1349.9, or 1350+ alcohol‐years (ml of pure alcohol intake per day multiplied by years of drinking). Helicobacter pylori status was determined by serology for adjustment. Using logistic regression, the adjusted effects of smoking and drinking doses on risk for stomach cancer were calculated for both genders. Among male subjects, the odds ratios (95% confidence intervals (CIs)) were 1.29 (0.76, 2.18) for 1–399, 1.71 (1.05, 2.80) for 400–799 and 2.46 (1.49, 4.07) for 800+ cigarette‐years compared with never‐smokers, and 1.89 (0.97, 3.69) for never‐drinkers, 2.82 (1.63, 4.86) for 135–1349.9 and 2.84 (1.97, 4.83) for 1350.0+, compared with occasional/0.1–134.9 alcohol‐years. Among female subjects, they were 0.44 (0.20, 1.00) for 1–399 and 2.471 (0.91, 6.68) for 400+ cigarette‐years compared with never‐smokers, and 1.54 (0.90, 2.63) for never‐drinkers and 1.39 (0.66, 2.93) for 135.0+ alcohol‐years. Smoking seems to exert a linear effect and drinking, a J‐ or U‐shaped effect on risk for stomach cancer, although there might be a dip of risk in light smokers among female subjects.

Promoters of epithelialization induce expression of vascular endothelial growth factor in human gastric epithelial cells in primary culture

Both epithelialization and angiogenesis are indispensable processes in gastric ulcer healing. Coordination between these processes has not been well studied. In the present study, we have established a new primary culture system of human gastric epithelial cells and investigated the effect of epithelialization stimulants on a specific angiogenic factor, vascular endothelial growth characterized as epithelial cells. Both epithelialization stimulants, hepatocyte growth factor (HGF) and epidermal growth factor (EGF), significantly stimulated vascular EGF expression in gastric epithelial cells. HGF and EGF receptors were expressed by the cells, suggesting that regulation may be mediated through specific receptors.

Development of a real-time data processing system for a prototype of the Tomo-e Gozen wide field CMOS camera

The Tomo-e Gozen camera is a next-generation, extremely wide field optical camera, equipped with 84 CMOS sensors. The camera records about a 20 square degree area at 2 Hz, providing “astronomical movie data”. We have developed a prototype of the Tomo-e Gozen camera (hereafter, Tomo-e PM), to evaluate the basic design of the Tomo-e Gozen camera. Tomo-e PM, equipped with 8 CMOS sensors, can capture a 2 square degree area at up to 2 Hz. Each CMOS sensor has about 2.6 M pixels. The data rate of Tomo-e PM is about 80 MB/s, corresponding to about 280 GB/hour. We have developed an operating system and reduction softwares to handle such a large amount of data. Tomo-e PM was mounted on 1.0-m Schmidt Telescope in Kiso Observatory at the University of Tokyo. Experimental observations were carried out in the winter of 2015 and the spring of 2016. The observations and software implementation were successfully completed. The data reduction is now in execution.

Development of a prototype of the Tomo-e Gozen wide-field CMOS camera

The Tomo-e Gozen is an extremely wide-field optical camera for the Kiso 1.0-m Schmidt telescope. It is capable of taking consecutive frames with a field-of-view of 20 deg2 and a sub-second time-resolution, which are achieved by 84 chips of 2k×1k CMOS sensor. This camera adopts unconventional designs including a lightweight structure, a nonvacuumed and naturally-air cooled system, front-side-illuminated CMOS sensors with microlens arrays, a sensor alignment along a spherical focal plane of the telescope, and massive readout electronics. To develop technical components necessary for the Tomo-e Gozen and confirm a feasibility of its basic design, we have developed a prototype-model (PM) of the Tomo-e Gozen prior to the final-model (FM). The Tomo-e PM is equipped with eight chips of the CMOS sensor arranged in a line along the RA direction, covering a sky area of 2.0 deg2. The maximum frame rate is 2 fps. The total data production rate is 80 MByte sec-1 at 2 fps, corresponding to approximately 3 TByte night-1. After laboratory testing, we have successfully obtained consecutive movie data at 2 fps with the Tomo-e PM in the first commissioning run conducted in the end of 2015.

Gastroesophageal Reflux After Gastric Surgery

Esophageal and gastric pH monitoring and endoscopic examination of the esophagus were performed in patients after gastric surgery. The duration time and frequency of gastroesophageal reflux were studied using an ambulatory 24-h pH monitoring system. The subjects consisted of 43 patients with distal gastrectomy, 3 patients with proximal gastrectomy, 19 patients with total gastrectomy, 9 patients with reflux esophagitis without previous gastric surgery, and 53 preoperative patients. Esophageal and gastric pH were measured 5 cm above and 5 cm or 10 cm below the esophagogastric junction (EGJ). The duration, ratio and frequency of acid (pH 7.4) reflux, acid and alkaline clearance time, and mean and median pH were measured. From the pattern of the esophageal pH curve, patients were divided into four groups: normal, acid reflux, alkaline reflux, and mixed type. In patients who received distal gastrectomy, acid reflux time (pH 7.4) and alkaline clearance time were longer than in preoperative patients. There were a few patients who showed small changes in esophageal pH in spite of esophagitis; the esophagitis in these patients was considered to be due to pancreatic enzymes.

Leucovorin, Cisplatin, and 5-Fluorouracil for Advanced Esophageal Cancer

Biochemical modulation involves the use of one drug (modulating agent; modulator) to change the pharmacokinetics and/or pharmacodynamics of a cytotoxic agent (effector), in a way that the therapeutic index of the effector is enhanced [1]. The modulator is often also a cytotoxic agent, but a non-cytotoxic agent like leucovorin is sometimes used as well. The modulating agent improves selectivity or sensitivity of an effector and decreases its toxicity to normal cells via a biochemical or metabolical mechanism. Currently, several biochemical modulations such as the sequential methotrexate (MTX)/5-fluorouracil (5-FU), leucovorin (LV)/5-FU, and cisplatin (CDDP)/5-FU have been evaluated clinically in terms of their efficacy for alimentary tract malignancies.

NIR camera and spectrograph SWIMS for TAO 6.5m telescope: overview and development status

Simultaneous-color Wide-field Infrared Multi-object Spectrograph, SWIMS, is one of the first generation instruments for University of Tokyo Atacama Observatory 6.5m Telescope where almost continuous atmospheric window from 0.9 to 2.5μm appears, thanks to the high altitude and dry climate of the site. To utilize this excellent condition, SWIMS is capable of simultaneous two-color imaging with a field of view of 9’. in diameter and λ/Δλ ~1000 multi-object spectroscopy at 0.9–2.5μm in a single exposure, utilizing a dichroic mirror inserted in the collimated beam. Here, we overview the instrument, report results of its full-assembly tests in the laboratory and present the future plan.

Development status of the mid-infrared two-field camera and spectrograph MIMIZUKU for the TAO 6.5-m Telescope

MIMIZUKU is the first-generation mid-infrared instrument for the university of Tokyo Atacama Observatory (TAO) 6.5-m telescope. MIMIZUKU provides imaging and spectroscopic monitoring capabilities in a wide wavelength range from 2 to 38 μm, including unique bands like 2.7-μm and 30-μm band. Recently, we decided to add spectroscopic functions, KL-band mode (λ= 2.1-4.0 μm; R =λ/Δλ ~ 210) and 2.7-μm band mode ( λ= 2.4-2.95 μm; R ~ 620), and continuous spectroscopic coverage from 2.1 to 26 μm is realized by this update. Their optical designing is completed, and fabrications of optical elements are ongoing. As recent progress, we also report the completion of the cryogenic system and optics. The cryogenic system has been updated by changing materials and structures of thermal links, and the temperatures of the optical bench and detector mounting stages finally achieved required temperatures. Their stability against instrument attitude is also confirmed through an inclination test. As for the optics, its gold-plated mirrors have been recovered from galvanic corrosion by refabrication and reconstruction. Enough image quality and stability are confirmed by room-temperature tests. MIMIZUKU is intended to be completed in this autumn, and commissioning at the Subaru telescope and scientific operations on the TAO telescope are planned in 2017 and around 2019, respectively. In this paper, these development activities and future prospects of MIMIZUKU are reported.