Shokei College

Reactive oxygen species (ROS) are accidentally generated in the human body due to radiation, harmful chemicals, and imbalance in electron transport in mitochondria and so on, thus involved in aging, carcinogenesis and onset of various lifestyle-related diseases. In contrast, several organs and cells in the body possess systems for producing ROS themselves [NADPH oxidases (Noxs)], which is known to play important roles in the human body, such as bacteria-killing ability by phagocytes. Colon cells mainly possess a ROS production system called Nox1, which has been shown to be involved in cell proliferation and response to oxidative stress. Because ROS are highly toxic, the amount, timing and location of their generation are crucial. Interestingly, the colon is an organ constantly exposed to food components and their derivatives that may affect Nox1 activity. Therefore, understanding the modifications of Nox1 activity by these substances is crucial for prevention of colorectal cancer, but unfortunately, knowledge about them remains still poor. In this study, as a first step in investigating the effects of various substances on Nox1 activity in human colon, we used a human colon carcinoma cell line LS513, which constitutively expresses Nox1 and stably produces superoxide anion (O2-) without stimulation, and demonstrated the possibility that 1α, 25-dihydroxyvitamin D3 up-regulates Nox1 activity by up-regulating transcription of Nox1 and NoxA1 genes in LS513 cells. LS513 cell line is expected to be a useful tool for analyzing and evaluating the effects of various substances on the O2--generating activity of colon cells.

A perception experiment and analyses were conducted to clarify the acoustic features of pop-out voice. Speech items pronounced by 779 native Japanese speakers were prepared for stimuli by mixing them with a babble noise that consisted of overlapping short sentences spoken by 10 Japanese speakers. Using a 5-point scale, 12 Japanese participants rated the pop-out score of the speech items listened using headphones. The scores and acoustic features of the speech items were investigated using correlation analysis and principal coordinate analysis. It was revealed that the pop-out score relates to the acoustic features such as overall intensity, relative intensity in the high-frequency range, fundamental frequency, dynamic feature of the spectrum, and a spectrum shape in high frequency. The results suggest that these are crucial acoustic features for the pop-out voice.

Cases of infection by microalgae of Prototheca species are increasing. However, effective treatment has not been established yet. In this study, gene and structure of Prototheca's CYP51/ERG11, an enzyme which might serve as a target for therapeutic drugs, were characterized for the first time.

Serum specimens obtained from 680 individuals were examined to measure the amounts of pepsinogens 1 and 2, anti-CagA antibodies, and anti-Helicobacter pylori antibodies. We examined sera obtained from 610 Mongolian individuals living in the capital city, Ulaanbaatar. Seventy serum specimens were collected from Japanese people who were health-screened: These were stored at the gastroenterology laboratory of Jichi Medical University. The sera of the Japanese people were used as a control specimen. Two enzyme-linked immunosorbent assay (ELISA) kits, an E-plate ELISA kit from Eiken Chemical Co., Ltd. (Tokyo, Japan), and a Biohit ELISA kit from Biohit Oyj (Helsinki, Finland), were used for the detection of anti-H. pylori IgG antibodies in the sera of the 610 Mongolian people. An ELISA kit EIA-4138 from DRG Instruments GmbH (Germany) was used for the detection of anti-CagA IgG antibodies in the serum specimens. Serum pepsinogens were detected by an ELISA kit from Biohit Oyj. Of the 610 serum specimens, 385 specimens tested positive for the detection of anti-H. pylori antibodies using the two ELISA kits, and 47 tested negative. For the detection of anti-H. pylori antibodies by the Biohit ELISA kit, 560 and 50 specimens were positive and negative, respectively. The ratio of serum pepsinogen 1/2 was statistically lower (p < 0.0001) in the H. pylori-positive (560 specimens) than in the H. pylori-negative (50 specimens) specimens. However, the levels of serum pepsinogen 1 had no statistical significance (p = 0.465) between the specimens of the H. pylori-positive and -negative specimens. The ratio of serum pepsinogen 1/2 was 6.74 ± 0.12 in the H. pylori-positive specimens, whereas the ratio of serum pepsinogen 1/2 was 12.69 ± 1.02 in the H. pylori-negative specimens. This study demonstrated the high prevalence of H. pylori infection in Mongolian people, including young generations, and the people infected with H. pylori possessed low pepsinogen 1/2 ratios, indicating atrophic gastritis. The serological examinations by the two ELISA kits did not consistently reflect the prevalence of H. pylori infection in Mongolian people.

Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia.

Lithium (Li) has been widely used to treat bipolar disorder, and industrial use of Li has been increasing; thus, environmental pollution and ecological impacts of Li have become a concern. This study was conducted to clarify the potential biological effects of LiCl and Li(2)CO(3) on a nematode, Caenorhabditis elegans as a model system for evaluating soil contaminated with Li. Exposure of C. elegans to LiCl and Li(2)CO(3) decreased growth/maturation and reproduction. The lowest observed effect concentrations for growth, maturation and reproduction were 1250, 313 and 10 000 µm, respectively, for LiCl and 750, 750 and 3000 µm, respectively, for Li(2)CO(3). We also investigated the physiological function of LiCl and LiCO(3) in C. elegans using DNA microarray analysis as an eco-toxicogenomic approach. Among approximately 300 unique genes, including metabolic genes, the exposure to 78 µm LiCl downregulated the expression of 36 cytochrome P450, 16 ABC transporter, 10 glutathione S-transferase, 16 lipid metabolism and two vitellogenin genes. On the other hand, exposure to 375 µm Li(2)CO(3) downregulated the expression of 11 cytochrome P450, 13 ABC transporter, 13 lipid metabolism and one vitellogenin genes. No gene was upregulated by LiCl or Li(2)CO(3). These results suggest that LiCl and Li(2)CO(3) potentially affect the biological and physiological function in C. elegans associated with alteration of the gene expression such as metabolic genes. Our data also provide experimental support for the utility of toxicogenomics by integrating gene expression profiling into a toxicological study of an environmentally important organism such as C. elegans.