Rebamipide abolishes Helicobacter pylori CagA-induced phospholipase D1 expression via inhibition of NFκB and suppresses invasion of gastric cancer cells.

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway.

Molecular dynamics study of the effect of surfactants on droplet deformation in shear flows.

We use molecular dynamics simulations to study the effect of surfactants on the mechanism of drop deformation in shear flows. Our results show deviations from fluid mechanics predictions, in both the high and the low surfactant concentration limits. We find that these deviations are a result of the local conformation of the surfactant layer which mediates the stress transfer across the interface. We show that the ability of the surfactant to affect the stress transfer across the interface is a result of the interplay between the architecture of the surfactant and the surface coverage.

Performance of WSSV-infected and WSSV-negative Penaeus monodon postlarvae in culture ponds.

In a survey of 27 Penaeus monodon culture ponds stocked with postlarvae (approximately PL10) at medium density (approximately 40 shrimp m(-2)), single-step nested white spot syndrome virus (WSSV) PCR was used to measure the WSSV infection rates in the shrimp populations within 1 mo after stocking. Seven ponds were initially WSSV-free, and the shrimp in 5 of these were harvested successfully. In the ponds (n = 6) where detection rates were higher than 50%, mass mortality occurred during the growth period, and none of these ponds was harvested successfully. In a subsequent study, P. monodon brooders were classified into 3 groups according to their WSSV infection status before and after spawning: brooders that were WSSV-positive before spawning were assigned to group A; spawners that became WSSV-positive only after spawning were assigned to group B; and group C consisted of brooders that were still WSSV-negative after spawning. WSSV screening showed that 75, 44 and 14%, respectively, of group A, B and C brooders produced nauplii that were WSSV-positive. Most (57%; 16/28) of the brooders in group A produced nauplii in which the WSSV prevalence was high (>50%). When a pond was stocked with high-prevalence nauplii from 1 of these group A brooders, an outbreak of white spot syndrome occurred within 3 wk and only approximately 20% of the initial population survived through to harvest (after 174 d). By contrast, 2 other ponds stocked with low-prevalence and WSSV-negative nauplii (derived respectively from 2 brooders in group B), both had much higher survival rates (70 to 80%) and yielded much larger (approximately 3x by weight) total harvests. We conclude that testing the nauplii is an effective and practical screening strategy for commercially cultured P. monodon.

Invasiveness of Helicobacter pylori into human gastric mucosa.

BACKGROUND: Helicobacter pylori has generally been observed only in the gastric mucous layer or in the spaces between gastric mucus-secreting cells and not in the gastric epithelial cells or in the lamina propria. The purpose of this study is to determine whether H. pylori invades the gastric mucosa, using an immunoelectron microscopical examination of human gastric mucosa infected with H. pylori. MATERIALS AND METHODS: Five hundred gastric antral biopsy specimens were fixed in a periodate-lysin-paraformaldehyde solution, embedded in Lowicryl, sectioned, and examined with a light microscope. One hundred specimens moderately or severely infected with H. pylori were selected and were incubated with polyclonal rabbit anti-H. pylori antibody. The specimens were washed, incubated with 20 nm of colloidal gold-conjugated goat anti-rabbit IgG, stained with uranyl acetate and lead citrate, and observed with a transmission electron microscope. RESULTS: In one case, a bacterium was observed within the cytoplasm of a gastric mucus-secreting cell; in another case, a few bacteria were observed within the cytoplasm of a stromal cell in the lamina propria. The bacteria could be differentiated from degenerated intracellular organelles by gold particles attached to the bacteria. CONCLUSION: H. pylori rarely invade the lamina propria and gastric cells.

Papillary adenocarcinoma of the stomach with psammoma bodies: report of two cases.

Calcification of gastric carcinoma is unusual and most of the reported cases were of the mucinous type. This report describes two cases of papillo-tubular adenocarcinoma of the stomach with psammomatous calcification confined only to the papillary portion. Calcification was so heavy that specimen X-ray was able to clearly delineate its distribution. Microscopically, the calcification was confined to the papillary carcinoma area and was not found in the area of the tubular adenocarcinoma. Polymorphic calcific bodies were found in the supportive stroma of papillae and extrapapillary spaces as concentrically laminated psammoma bodies. They were also found in tumor cells as minute corpuscles. The mechanism of neoplastic mineralization in these cases seemed different from ontogenic calcification of mucinous gastric carcinoma and we postulated the mechanism of psammomatous calcification which is referred as intracellular calcification.

Comparison of Helicobacter pylori infection between Fukuoka, Japan and Chinju, Korea.

BACKGROUND: Helicobacter pylori is the causative agent of type B chronic gastritis, and plays a major role in the pathogenesis of gastroduodenal ulcer and gastric cancer. Because gastric cancer has been the leading cause of cancer mortality in Japan and Korea, we conducted a seroepidemiological study to estimate the prevalence of H. pylori infection in Japan and Korea in order to explain the current change in the gastric cancer incidences between two countries. MATERIALS AND METHODS: Samples used for this study included 1204 sera from Chinju, Korea and 580 sera from Fukuoka, Japan. Immunoblotting, using a sonicated crude H. pylori antigen and 1:5 dilution of serum, was performed, considering the immunoblot shows reactivity to the 120 Kd antigen of H. pylori as a specific marker of H. pylori infection. RESULTS: Seroepidemiology data from Fukuoka, Japan showed a prevalence of H. pylori infection of 20% before school age, 40% by teenage years, and over 80% beyond 20 years of age. Seroepidemiology data from Chinju, Korea, showed a 50% infection rate in preschool ages, and over 80% prevalence rate after 7 years of age. CONCLUSIONS: Lower rates of childhood H. pylori infection in Fukuoka may explain the recent decline and shift in the incidence of stomach cancer in Japan, supporting the hypothesis that H. pylori is a major determinant in the pathogenesis of stomach cancer.

Monoclonal antibodies against Helicobacter pylori cross-react with human tissue.

BACKGROUND: H. pylori is a causative agent of chronic gastritis. However, the pathogenic mechanism by which H. pylori induces chronic inflammation and epithelial injuries in the gastric and duodenal mucosa is not well known. Investigators have recently reported that some monoclonal antibodies against H. pylori cross-react with the gastric epithelial cells. So, there exists the possibility that the autoimmune mechanism may be involved in the pathogenesis of chronic gastritis caused by H. pylori. The purpose of his study is to investigate whether the antibodies against H. pylori react with human tissues or not, using a large panel of monoclonal antibodies. MATERIALS AND METHODS: Two hundred and fourteen monoclonal antibodies against H. pylori were produced. An immunohistochemical staining of human tissues, including H. pylori-infected gastric mucosa, was performed using the antibodies. RESULTS: Of 214 monoclonal antibodies, 71 antibodies reacted with H. pylori in the gastric mucosa. Of 71 antibodies, 25 antibodies also reacted with gastric epithelial cells, 11 antibodies reacted with ductal cells of the salivary gland, 11 antibodies reacted with renal tubular cells, and 8 antibodies reacted with duodenal epithelial cells. The antibodies which showed cross-reactivity with gastric epithelial cells included those against urease, flagella, lipopolysaccharide, and heat shock protein of H. pylori. CONCLUSIONS: It is believed that the autoimmune reaction might be involved in the pathogenesis of chronic gastritis due to H. pylori infection, and that the autoimmune reaction induced by H. pylori infection might also be involved in the pathogenesis of various diseases in other organs.

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.

A case of bleomycin-induced scleroderma.

The association of exposure to bleomycin with the development of scleroderma-like cutaneous abnormalities has been reported. We experienced a case of scleroderma involving the hands, feet, and forearms after bleomycin chemotherapy. The present report supports the possible causal relation of bleomycin with scleroderma. Regarding the widespread use of bleomycin, this complication is thought to be under appreciated.

Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.

Helicobacter pylori causes type B gastritis. It shows strong association with the development of gastric carcinoma. A plausible hypothesis for the missing link between H. pylori infection and gastric carcinogenesis involves oxygen free radical-induced DNA damage. To test this hypothesis, we compared the amount of 9-hydroxydeoxyguanosine, a marker for oxygen free radical-induced DNA damage, in the DNA of human gastric mucosa with and without H. pylori infection. Gastric antral biopsies were taken from pediatric patients and volunteers to select H. pylori-positive and H. pylori-negative specimens. The 8-hydroxydeoxyguanosine content of the gastric mucosal DNA was measured after H. pylori-positive and H. pylori-negative volunteers were identified. The increased level of oxidative DNA damage suggests the mechanistic link between H. pylori infection and gastric carcinoma.

Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression.

We performed a randomised trial on 37 hips (33 patients) with early-stage osteonecrosis (ON). After the initial clinical evaluation, including plain radiography and MRI, 18 hips were randomly assigned to a core-decompression group and 19 to a conservatively-treated group. All the patients were regularly followed up by clinical evaluation, plain radiography and MRI at intervals of three months. Hip pain was relieved in nine out of ten initially symptomatic hips in the core-decompression group but persisted in three out of four initially painful hips in the conservatively-treated group at the second assessment (p < 0.05). At a minimum follow-up of 24 months, 14 of the 18 core-decompressed hips (78%) and 15 of the 19 non-operated hips (79%) developed collapse of the femoral head. By survival analysis, there was no significant difference in the time to collapse between the two groups (log-rank test p = 0.79). Core decompression may be effective tin symptomatic relief, but is of no greater value than conservative management in preventing collapse in early osteonecrosis of the femoral head.

Angiography, scintigraphy, intraosseous pressure, and histologic findings in high-risk osteonecrotic femoral heads with negative magnetic resonance images.

One hundred twenty-six hips of 68 patients who were suspected of having osteonecrosis or being at risk for osteonecrosis were studied with magnetic resonance (MR) imaging. Abnormal patterns on MR imaging characteristic of osteonecrosis were observed in 98 hips. The remaining 28 hips (22 patients) with negative MR images underwent superselective angiography of the medial femoral circumflex artery. Angiography showed interruption of the superior retinacular arteries in 13 hips (12 patients), including 6 of 7 symptomatic hips. Bone scans were performed on 8 of 13 hips angiographically positive for osteonecrosis. Decrease of radionuclide uptake (cold lesions) was observed in all 8 of these femoral heads. Thirteen femoral heads with interruption of superior retinacular arteries underwent intraosseous pressure measurement and core biopsy. Intraosseous pressure was elevated in 11 hips. The results of histologic study showed evidence of early necrosis in 10 femoral heads. This study indicates that there are a considerable number of femoral heads at high risk, even when they have negative MR images. They do, however, show positive findings on angiography, scintigraphy (cold lesions), intraosseous pressure measurement, and histologic study.