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Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18-C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18-C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys.

An arsenite biosensor plasmid was constructed in Escherichia coli by inserting the operator/promoter region of the ars operon and the arsR gene from E. coli and the crtA gene, which is responsible for carotenoid synthesis in the photosynthetic bacterium, Rhodovulum sulfidophilum, into the broad-host-range plasmid vector, pRK415. The biosensor plasmid, pSENSE-As, was introduced into a crtA-deleted mutant strain of R. sulfidophilum (CDM2), which is yellow in culture due to its content of spheroiden (SE) and demethylspheroidene (DMSE). CDM2 containing pSENSE-As changed from yellow to red by the addition of arsenite, which caused enzymatic transformation of SE and DMSE to spheroidenone (SO) and demethylspheroidenone (DMSO). Reverse transcriptase PCR analysis showed that the color change depended on transcription of the crtA gene in pSENSE-As. The color change could be clearly recognized with the naked eye at 5 μg/l arsenite. The biosensor strain did not respond to other metals except for bismuth and antimony, which caused significant accumulation of SO and DMSO in the cells at 60 and 600 μg/l, respectively. This biosensor indicates the presence of arsenite with a bacterial color change without the need to add a special reagent or substrate for color development, enabling this pollutant to be monitored in samples by the naked eye in sunlight, even where electricity is not available.

To examine fatty acid accumulation and its toxic effects in cells, we analyzed skin fibroblasts from six patients with mitochondrial trifunctional protein deficiency, who had abnormalities in the second through fourth reactions in fatty acid β-oxidation system. We found free fatty acid accumulation, enhanced three acyl-CoA dehydrogenases, catalyzing the first reaction in the β-oxidation system and being assumed to have normal activities in these patients, and PPARα activation that was confirmed in the experiments using MK886, a PPARα specific antagonist and fenofibrate, a PPARα specific agonist. These novel findings suggest that the fatty acid accumulation and the resulting PPARα activation are major causes of the increase in the β-oxidation ability as probable compensation for fatty acid metabolism in the patients’ fibroblasts, and that enhanced cell proliferation and increased oxidative stress due to the PPARα activation relate to the development of specific clinical features such as hypertrophic cardiomyopathy, slight hepatomegaly, and skeletal myopathy. Additionally, significant suppression of the PPARα activation by means of MK886 treatment is assumed to provide a new method of treating this deficiency.

Papillary serous carcinoma of the peritoneum (PSCP) is a primary neoplasm of peritoneal origin, and is histologically difficult to differentiate from papillary serous carcinoma of the ovary (PSCO). PSCP is frequently accompanied by many peritoneal tumors, and has been managed as a disseminated disease. In previous reports, however, the clonality of the tumors has not been fully discussed. Recently, the significant roles of the p53 and BRCA1 genes in PSCP have been reported. In this study, we investigated immunohistochemical staining for p53 proteins, and investigated p53 gene mutations, using DNA sequencing analysis, to clarify the clonality of PSCP tumors. Immunohistochemically, all the tumor samples demonstrated nuclear overexpression of p53 proteins, and the DNA sequencing analysis of the p53 gene showed diverse point mutations at codons 167 and 192 in two of four anatomically different tumors. In conclusion, the possibility of polyclonality of PSCP tumors is suggested.

To examine fatty acid accumulation and its toxic effects in cells, we analyzed skin fibroblasts from six patients with mitochondrial trifunctional protein deficiency, who had abnormalities in the second through fourth reactions in fatty acid β-oxidation system. We found free fatty acid accumulation, enhanced three acyl-CoA dehydrogenases, catalyzing the first reaction in the β-oxidation system and being assumed to have normal activities in these patients, and PPARα activation that was confirmed in the experiments using MK886, a PPARα specific antagonist and fenofibrate, a PPARα specific agonist. These novel findings suggest that the fatty acid accumulation and the resulting PPARα activation are major causes of the increase in the β-oxidation ability as probable compensation for fatty acid metabolism in the patients' fibroblasts, and that enhanced cell proliferation and increased oxidative stress due to the PPARα activation relate to the development of specific clinical features such as hypertrophic cardiomyopathy, slight hepatomegaly, and skeletal myopathy. Additionally, significant suppression of the PPARα activation by means of MK886 treatment is assumed to provide a new method of treating this deficiency.

In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings. First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined. In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors. Among subjects who underwent successful HP eradication therapy, advanced atrophy and aging were observed to be crucial risk factors. In the univariate analysis, there were 12,941 subjects. Gastric cancer occurred more frequently in the more severe atrophy group (P < 0.001). The annual rate of cancer occurrence in the most severe atrophy group was 0.31%, which was approximately thrice as that in the less atrophy group. Risk stratification was possible based on endoscopic examination alone. The interval should be set depending on each case.

Successful adaptation to wearing dentures with palatal coverage may be associated with cortical activity changes related to tongue motor control. The purpose was to investigate the brain activity changes during tongue movement in response to a new oral environment. Twenty-eight fully dentate subjects (mean age: 28.6-years-old) who had no experience with removable dentures wore experimental palatal plates for 7 days. We measured tongue motor dexterity, difficulty with tongue movement, and brain activity using functional magnetic resonance imaging during tongue movement at pre-insertion (Day 0), as well as immediately (Day 1), 3 days (Day 3), and 7 days (Day 7) post-insertion. Difficulty with tongue movement was significantly higher on Day 1 than on Days 0, 3, and 7. In the subtraction analysis of brain activity across each day, activations in the angular gyrus and right precuneus on Day 1 were significantly higher than on Day 7. Tongue motor impairment induced activation of the angular gyrus, which was associated with monitoring of the tongue’s spatial information, as well as the activation of the precuneus, which was associated with constructing the tongue motor imagery. As the tongue regained the smoothness in its motor functions, the activation of the angular gyrus and precuneus decreased.