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This case involved a 69-year-old female patient with peritoneal dissemination of an advanced gastric cancer. She underwent chemotherapy comprisingintravenous and intraperitoneal paclitaxel combined with S-1. After 20 courses, a staging laparoscopy was performed, and pathological analysis of the peritoneal dissemination and cytologic analysis of ascites fluid yielded negative results. A radical robot-assisted total gastrectomy was successfully performed. The pathological stage was determined to be ypT4aN2M0, ypStage ⅢB. We continued to administer the same chemotherapy regimen for 15 courses (total: 35 courses)after surgery. No recurrence has been detected during the 1-year period after surgery.

A 60-year-old male was admitted to our hospital on account of a duodenal submucosal tumor on the opposite side of Vater's papilla identified on a screening gastroduodenoscopy. The tumor was diagnosed as a duodenal gastrointestinal stromal tumor(GIST)due to positive c-kit and DOG1tests. Gastroduodenography and enhanced computed tomography showed a 50mm tumor widely invadingthe descendingportion of the duodenum close to the papilla of Vater and indicated the need for extended resection includingpancreaticoduodenectomy to achieve curation. Preoperative chemotherapy was initiated with imatinib mesylate(imatinib)to preserve the pancreas. A 16 month course of imatinib shrunk the tumor up to 21mm and laparoscopic partial duodenectomy was performed as a curative resection. So far, no local tumor recurrence has been seen for 26 months after the surgery. Herein, we report this case with a review of the literature.

Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kitgene (exons 8, 9, 11, 13, and 17) but also in thePDGFRAgene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor.

Inhibitors of angiotensin I-converting enzyme (ACE) are useful in treating hypertension, and many have been derived from food products, including soybeans. Using the industrial protease PROTIN SD-NY10, we developed a processed soya milk (PSM) with enhanced ACE inhibitory activity. The ACE inhibitory activity of PSM (IC 50 = 0.26 μg/ml) was greater than that of regular soya milk (IC 50 = 8.75 μg/ml). Eight novel ACE inhibitory peptides were purified from PSM by reversed-phase chromatography: FFYY (IC 50 ,1.9 μM), WHP (4.8 μM), FVP (10.1 μM), LHPGDAQR (10.3 μM), IAV (27.0 μM), VNP (32.5 μM), LEPP (100.1 μM), and WNPR (880.0 μM). The IC 50 values of these peptides are comparable to those reported for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc. Due to the relatively low IC 50 values of several peptides identified in this study, they may serve as ideal base components of food supplements for patients with hypertension.

本研究は活断層による都市直下地震を対象に、36パターンの断層パラメータを設定して実施された複数の被害評価結果に基づき、自治体が最優先すべき想定地震を決定するための手法を提案するものである。防災対策項目を構造化し、防災対策を実施する自治体関係部局に対して、階層分析法（AHP：Analytic Hierarchy Process）を応用し防災対策項目の重要度評価を行う。さらにこの重要度と複数の被害評価結果を用いて、複数の想定地震の優先度を求め、優先地震を決定する。

The first specifications for fire zones in Asahikawa City, Hokkaido, were laid down fifty years ago; since then, the city has undergone considerable expansion. Because of changes in the requirements related to urban structures and buildings, the fire zone specifications have changed considerably in comparison with the initial specifications. Consequently, it has become very difficult to assign accurate fire hazard ratings for fire zones and semi-fire zones in urban areas. To overcome this problem, it is necessary to adopt an objectively specified standard. In this study, we evaluated the fire prevention performance of Asahikawa City by using CVF, aiming at a specified review in fire prevention and a semi-fire zone and settled on a specified standard of a fire zone and a semi-fire zone based on the evaluation result.

Textures of cooked rice prepared from aged rice and improvements in cooked rice through removal of its external layer were investigated. Cooked rice prepared from aged rice became hard and stickiness/hardness (S/H) ratios were significantly lowered in comparison to that of new rice. The cooked rice prepared from aged rice with 7% of the external layer removed became soft and no significant differences existed between the S/H ratios of new rice and aged rice. The soaking solution of rice became starchy solution at the time of heating. The amount of the solid of starchy solution was significantly decreased in aged rice compared with new rice, and that of further polished and aged rice was increased. Therefore, we presumed that the starchy solution became a gelatinous paste layer of starch on the rice grain surface after cooking, and that the amount of the solid of starchy solution was related to the textural deterioration of aged rice and the textural improvement by partial removal of the external layer in aged rice. The RVA pasting properties of the flour in aged rice were also different from those of new rice. However, their changes were different from those for cooked rice texture.

To search for a novel angiotensin I-converting enzyme (ACE) inhibitory peptide, porcine skeletal troponin was hydrolyzed with pepsin. This hydrolysate showed ACE inhibitory activity, and was applied to various kinds of chromatography to separate an active peptide. Analysis using a protein sequencer identified this peptide as RMLGQTPTK (9mer). This sequence was estimated to occur at the 44–52 position of troponin C, and its 50% inhibitory protein concentration (IC50) was 34 µM. RMLGQTP (7mer), a partial peptide of 9mer, showed activity with an IC50 of 503 µM. RP-HPLC analysis of a reaction mixture of 9mer and ACE showed that 9mer was slowly hydrolyzed by ACE. On the other hand, 7mer was rapidly hydrolyzed by ACE. Activity of 9mer was reduced as its hydrolysis by ACE proceeded. To estimate the resistance of 9mer to digestive proteases after oral administration, it was reacted with pepsin, α-chymotrypsin, or trypsin. In each of these reaction mixtures, a significant amount of 9mer remained as a substrate after digestion. Remaining ACE inhibitory activity was close to that of 9mer. These results suggest that 9mer might not be digested after oral administration, because of its relatively high resistance to digestive proteases. Therefore, 9mer might be expected to work well in vivo as an ACE inhibitor.

The inhibitory effect of beer on aldose reductase was investigated. Components present in beer strongly inhibited aldose reductase. Inhibition activity was observed primarily in the methanol-soluble fraction of the beer and active components were identified to be of hop origin. Further, a component was identified as iso-α-acids, which are well known as main bitter components of beer. The inhibition rate of iso-α-acids was similar to quercetin, which is known to be a strong inhibitor of aldose reductase activity.

Aralin from Aralia elata is a newly identified type II ribosome- inactivating protein, which preferentially induces apoptosis in cancer cells. In this study, we identified that the aralin receptor is a 110-kDa high-density lipoprotein-binding protein (HDLBP), which functions as a HDL receptor. The sensitivities of tumor cell lines to aralin were dependent on the expression levels of the 110-kDa HDLBP and its forced expression in aralin-resistant Huh7 cells conferred aralin sensitivity. HDLBP-knockdown HeLa cells showed a significant aralin resistance in vitro and in vivo. Conversely, ectopic expression of the 150-kDa HDLBP resulted in increased aralin sensitivity in vivo, accompanying enhanced expression of the 110-kDa HDLBP. Thus, these results showed that the 110-kDa HDLBP in lipid rafts acted as an aralin receptor and that its expression levels determined aralin sensitivity, suggesting that aralin could be a promising anticancer drug for HDLBP-overexpressing tumors.

The textures of cooked rice prepared from aged rice grains and their improvement by reducing agents were investigated. For aged rice that was stored for 5 months without air by the operation of a vacuum packing machine, the stickiness/hardness ratio of cooked rice was as low as that of aged rice stored in air. The results of electrophoresis showed that oxidation of proteins in the former was advanced to the same degree as in the latter. The stickiness/hardness ratios of the aged rice were increased by the addition of sodium sulfite, cysteine, and dithiothreitol to the cooking water. Sodium sulfite, cysteine, and dithiothreitol cleave disulfide bonds to sulfhydryl groups. Therefore, cleaving disulfide bonds to sulfhydryl groups improved the texture. The addition of them to the cooking water also increased the extractable solids at the time of heating. Hence cleaving disulfide bonds to sulfhydryl groups must increase extractable solids. Consequently, the gelatinized paste layer thickened and the thick paste layer softened the cooked rice.

Recently we found that aralin, a novel lectin, from Aralia elata selectively induces apoptosis in human virus-transformed and cancer cells compared with normal cells. To overcome the reduction of aralin biosynthesis according to the development of leaves, we established callus tissues from the young shoots. The N-terminal amino acid sequence and immunochemical analyses revealed that ca-aralin, an aralin synthesized in the callus, was structurally identical with aralin except for the glycosylation of the B chain. The selective cytotoxic index (ratio of IC 50 value against human lung normal cells versus virus-transformed cells) of ca-aralin was 2-fold higher than that of aralin. Thus, these results suggest that ca-aralin is more useful than aralin as an anticancer agent.

A novel angiotensin I-converting enzyme (ACE) inhibitory peptide (RMLGQTPTK; 9mer) from porcine skeletal troponin C was investigated for its inhibitory profile. This peptide was noncompetitive and as hydrophobic as the known ACE inhibitory peptides. Aminopeptidase M quickly hydrolyzed 9mer, resulting in production of MLGQTPTK and LGQTPTK with inhibitory activities similar to those of 9mer. The main hydrolysis product of 9mer with carboxypeptidase A and B was RMLGQTPT showing very weak activity. Most products derived from 9mer hydrolysis by ACE, aminopeptidase, or carboxypeptidase showed weak but definite ACE inhibitory activities. Thus, 9mer was estimated to be a wholly efficient inhibitor with these fragment peptides.

We recently found that aralin, a novel cytotoxic protein consisting of two subunits, from Aralia elata selectively induces apoptosis in transformed cells as compared to normal cells. Here we report that aralin is a lectin specific for galactose (Gal) and its derivatives, and possesses RNA N-glycosidase activity as a new type II ribosome-inactivating protein (RIP). The RNA N-glycosidase activity of aralin was detected in cell-free and whole cell systems by the generation of an R-fragment from 28S rRNA. Coinciding with appearance of the R-fragment in aralin-treated cells, significant inhibition of protein synthesis was observed prior to the onset of apoptosis. Aralin-evoked cell death was efficiently repressed by the addition of Gal and its derivatives. Interestingly, melibiose preferentially protected normal cells from apoptosis as compared with transformed cells. Using rhodamine-coupled aralin, the aralin receptor could be clearly detected around the cell surface of transformed cells, but to a lesser extent on normal cells. Receptor binding was suppressed by Gal. These results indicate that aralin is incorporated into cells via its Gal-containing cell surface receptor and induces apoptosis through its RIP activity. Moreover, the expression level and/or structural changes of the aralin receptor may affect the sensitivity toward aralin.

In this study, we purified a novel cytotoxic protein, aralin, from the shoots of Aralia elata. Aralin is composed of two subunits, A and B chains whose molecular weights are 29,100 and 32,200, respectively. In the assay using a normal human lung fibroblast cells (WI-38) and its SV40-transformed cells (VA-13), aralin demonstrated selective cytotoxicity against the virus-transformed cell line; the IC50 values of WI-38 and VA-13 were 10 and 0.8 ng/ml, respectively. Aralin showed positive response to DNA fragmentation in human lymphocyte HL-60 cells, and caspase specific inhibitors suppressed aralin-induced DNA fragmentation. These results indicate that the cytotoxicity of aralin is brought about primarily through the induction of apoptosis. Aralin also exhibited potent cytotoxic activity against various types of human cancer cell lines; cervical carcinoma cells (HeLa) proved the most sensitive, with an IC50 value of 0.08 ng/ml.

Renin-binding protein (RnBP) is an endogenous renin inhibitor originally isolated from porcine kidney as a complex of renin, so-called high molecular weight (HMW) renin. Our recent studies demonstrated that human RnBP is the enzyme N-acetyl-D-glucosamine (GlcNAc) 2-epimerase [Takahashi, S. et al. (1999) J. Biochem. 125, 348-353]. We have purified recombinant human, rat, and porcine RnBPs expressed in Escherichia coli JM 109 cells. The purified recombinant RnBPs existed as dimers and inhibited porcine renin activity strongly. On the other hand, porcine renin inhibited recombinant GlcNAc 2-epimerase activities. The human GlcNAc 2-epimerase activity could not be detected in the absence of a nucleotide, whereas ATP, dATP, ddATP, ADP, and GTP enhanced the human GlcNAc 2-epimerase activity. Other nucleotides had no effect on human GlcNAc 2-epimerase activity. Rat and porcine GlcNAc 2-epimerases were activated by several nucleotides. Nucleotides that enhance the activity of GlcNAc 2-epimerases protect these enzymes against degradation by thermolysin. These results indicate that mammalian RnBPs have GlcNAc 2-epimerase activity and that nucleotides are essential for formation of the catalytic domain of the enzyme.