Takeshi Fujisaki

Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44

For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers, including breast cancer, do not express integrins. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using breast carcinoma cell lines. Our results showed the following features of breast cancer cells: (1) HGF stimulated breast cancer cells by up-regulating CD44 expression in a concentration-dependent manner. (2) the maximum level of HGF-induced CD44 up-regulation on breast cancer cell lines occurred within 3 h. (3) HGF-induced up-regulation of CD44 was mediated by the tyrosine kinase signaling pathway. (4) HGF induced CD44-mediated adhesion of tumor cell lines to bone marrow-derived endothelial cells. (5) HGF did not change rolling of breast cancer cell lines on bone marrow-derived endothelial cells, but enhanced firm adhesion of cancer cells on endothelial cells under shear stress conditions. (6) HGF increased transendothelial migration of cancer cells. Our results indicate that HGF stimulates CD44-mediated adhesion of breast cancer cells to bone marrow-derived endothelial cells, which subsequently results in transendothelial migration of tumor cells. These results suggest that CD44 may confer the metastatic properties of breast cancer cells and, therefore, could be used as a target in future molecular cancer therapy.

Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and transendothelial migration of monocytes via the protein kinase C pathway

Inflammatory and immune responses are highly relevant processes in the pathogenesis of atherosclerosis, as illustrated by the central event of monocyte accumulation in atherosclerotic plaques. Integrin LFA-1-mediated adhesion of circulating monocytes to the endothelium is a prerequisite for recruitment of monocytes to these areas. Integrin-mediated adhesion is tightly regulated and integrins are only functional in response to particular monocyte activation stimuli. We investigated the role of oxidized low-density lipoprotein (LDL) in adhesion of resting monocytes prepared by elutriation from endothelium. Our results showed that: (1) oxidized LDL (and MCP-1) induced both LFA-1-mediated adhesion of monocytes to endothelial cells and transendothelial migration of monocytes; (2) oxidized LDL functionally transformed monocyte LFA-1 to an activated form; (3) oxidized LDL induced F-actin polymerization and cytoskeletal rearrangement within seconds; and (4) the LDL-associated antioxidant, alpha-tocopherol, but not beta-tocopherol, inhibited both F-actin polymerization and LFA-1-mediated adhesion of monocytes, which paralleled the effect of protein kinase C (PKC) inhibitors. Our results indicate that oxidized LDL plays a pivotal role in triggering LFA-1 activation and LFA-1-mediated adhesion and transmigration of monocytes to sites of atherosclerotic plaques, via the PKC pathway.

Hepatic sarcoidosis associated with chronic hepatitis C.

A 57-year-old woman with sarcoidosis was referred because of the appearance of multiple small low-attenuation areas in the liver on computed tomography (CT). A liver biopsy specimen showed chronic active hepatitis accompanied by sarcoid granulomas. The patient received prednisolone and, later, interferon-alpha. CT at 5 months of prednisolone treatment showed disappearance of the hepatic low-attenuation nodules. During long-term follow-up, however, these nodules reappeared on CT and liver cirrhosis finally developed. We present this case for two reasons: (1) hepatic sarcoidosis was associated with chronic active hepatitis C; (2) hepatic nodular lesions were evaluated by CT throughout the entire course, with CT scans having been taken from 2 years prior to their appearance.

Occupational safety and health aspects of corporate social responsibility (CSR) in Japanese companies listed on the Tokyo Stock Exchange (TSE) first section.

Occupational Safety and Health Aspects of Corporate Social Responsibility (CSR) in Japanese Companies listed on the Tokyo Stock Exchange (TSE) First Section: Futoshi Kawashita, et al. Occupational Health Training Center, University of Occupational and Environmental Health—Recently, corporate social responsibility (CSR) is becoming widely recognized as an issue for Japanese companies. Corporate responsibility for employees is considered important by various stakeholders, and occupational safety and health is regarded as one of these responsibilities. The present authors examined this issue from the viewpoint of corporate management by analysis of statements found in CSR‐related reports. For companies listed on the First Section of the Tokyo Stock Exchange (TSE), we searched for CSR‐related reports, and titles and contents, based on two established guidelines: the GRI Sustainability Reporting Guidelines 2002 as the international reference and the Environmental Reporting Guidelines of the Ministry of the Environment, Government of Japan, as the domestic reference. Corporations that published CSR reports were 26.3% (416/1,581) of the total, and large differences were recognized by type of industry. Comparing the numbers of pages for various contents, more concern was shown about the environment than about social activity, indicating the environment to be the main issue of CSR in Japan. In the items included in the guidelines, many matters about occupational accidents were mentioned, but it was found that statements regarding HIV/AIDS, which is not of such strong social concern in Japan, and statements regarding the costs of safety that are difficult to calculate were few. However, statements regarding mental health, which is of high interest socially, were many, even though this issue is not included in the two guidelines used. In revising the guidelines, these matters should be reviewed. In the future, continuance of analysis of CSR‐related reports with regard to changes and comparisons with overseas reports will help improve occupational safety and health.

Ultrasonographic evaluation of lansoprazole-induced improvement of submucosal injury in patients with gastroesophageal reflux.

OBJECTIVE:Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD.METHODS:Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment.RESULTS:Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p < 0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall.CONCLUSIONS:EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.

Fatigue evaluation for work load of Visual Display Terminals (VDT) operation

A method for the analysis of fatigue parameters has been rarely researched in VDT operation. Up to now, fatigue was evaluated by changing of biological information. If signals regarding fatigue are detected, fatigue can be measured. This study proposes an experiment and analysis method to extract parameters related to fatigue from the biological information during VDT operation using the independent component analysis (ICA). An experiment had 11 subjects. As for the experiment were light loaded VDT operation and heavy loaded VDT operation. A measurement item were amount of work, a mistake number, subjective symptom, surface skin temperature (forehead and apex nasi), heart rate, skin blood flow of forearm and respiratory rate. In the heavy loaded operation group, mistake number and subjective symptom score were increased to compare with the other. And Two-factor ANOVA was used for analysis. The result of mistake number was confirmed that heavy loaded. After the moving averages of waveshapes were calculated, it was made to extract independent components by using the ICA. The results of the ICA suggest that the independent components increase according to accumulation of fatigue. Thus, the independent components would be a possible parameter of fatigue.