Publications by authors named "Shimotsuma M"

Imidazole dipeptides (IDPs) are found in the skeletal muscles and brains of various animals, and they exhibit unique functions like antioxidant and antiaging properties. Despite their importance, the metabolic mechanisms and physiological roles of IDPs remain unclear. Herein, we propose a method for the simultaneous analysis of IDPs, their constituent amino acids, and taurine, which are difficult to separate using conventional labeling reagents or columns, using liquid chromatography-single quadrupole mass spectrometry with PBr column and our highly sensitive labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-l-valine-,-dimethylethylenediamineamide (l-FDVDA).

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Amino acids with various functions are abundant in living organisms and foods. Recent advances in analytical technology show that trace amounts of D-amino acids exist in living organisms and foods. In addition, studies show that these amino acids are involved in various physiological functions that differ from those of L-amino acids.

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Nucleic acids, which have been employed in medicines for various diseases, are attracting attention as a new pharmaceutical model. Depending on the target substances, nucleic acid medicines with various nucleic acid chain lengths (several tens of nucleotides [nt] to several thousands of nt) exist. The purification of synthesized nucleic acids is crucial as various impurities remain in the crude product after synthesis.

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Aminobutyric acid has structural isomers (α-, β-, and γ-aminobutyric acids) and enantiomers (D/L-forms) with various unique functions. Therefore, a quantitative method for determining the content of each aminobutyric acid must be developed. In general, quantitative simultaneous analysis of multiple compounds is conducted high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS).

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D-Amino acids, which are present in small amounts in living organisms, are responsible for a variety of physiological functions. Some bioactive/biomolecular peptides also contain D-amino acids in their sequences; such peptides express different functions than peptides composed only of L-form amino acids. Among the 20 amino acids that make up proteins, threonine (Thr) and isoleucine (Ile) have two chiral carbons and thus have two enantiomers and diastereomers.

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Highly hydrophilic compounds such as nicotinamide metabolites are very difficult to separate via high-performance liquid chromatography (HPLC) using octadecyl (C) columns. In general, for the separation of hydrophilic compounds, hydrophilic interaction liquid chromatography (HILIC) columns are used instead of reversed phase chromatography using C columns. However, HILIC columns generally obey complex separation mechanisms because ionic interactions are involved in the retention process, which hinders the optimization of the separation conditions.

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We developed a system to separate and identify racemised and isomerised aspartic acid (Asp) residues in amyloid β (Aβ) by labeling with an original chiral resolution labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-D-leucine-,-dimethylethylenediamine-amide (D-FDLDA). The racemised and isomerised Asp residues labeled with D-FDLDA in Aβ fragments generated by digesting with trypsin and endoproteinase Glu-C were separated and identified by liquid chromatography-mass spectrometry (LC-MS) under simple gradient conditions. Furthermore, the labeled Aβ fragments did not aggregate and remained stable at least for 1 week at 4 °C.

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Messenger ribonucleic acids (mRNAs) have been used in vaccines for various diseases and are attracting attention as a new pharmaceutical paradigm. The purification of mRNAs is necessary because various impurities, such as template DNAs and transcription enzymes, remain in the crude product after mRNA synthesis. Among the various purification methods, reversed-phase high-performance liquid chromatography (RP-HPLC) is currently attracting attention.

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Nicotinamide adenine dinucleotide, a coenzyme involved in the activation of sirtuins, contributes to various regulations in vivo. However, highly hydrophilic nicotinamide metabolites are difficult to separate by high-performance liquid chromatography (HPLC) using octadecyl (C) columns, which operate via hydrophobic interaction. PBr columns packed with silica gel modified with the pentabromobenzyl group having strong dispersion forces show good retention ability for various highly hydrophilic compounds.

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Background: Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost.

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There are several reports of D-amino acids being the causative molecules of serious diseases, resulting in the formation of, for example, prion protein and amyloid β. D-Amino acids in peptides and proteins are typically identified by sequencing each residue by Edman degradation or by hydrolysis with hydrochloric acid for amino acid analysis. However, these approaches can result in racemization of the L-form to the D-form by hydrolysis and long pre-treatment for hydrolysis.

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A 30s male was diagnosed as having the left testicular tumor in 2010. He received the anti-neoplastic chemotherapy, and could achieve the complete remission. But, he relapsed with solitary retroperitoneal lymph node swelling in 2012, and he was referred to our hospital.

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Background: A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer.

Methods: Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2) on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.

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Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments.

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The imprinted expression of the mouse Igf2/H19 locus is governed by the differential methylation of the imprinting control region (ICR), which is established initially in germ cells and subsequently maintained in somatic cells, depending on its parental origin. By grafting a 2.9-kbp H19 ICR fragment into a human beta-globin yeast artificial chromosome in transgenic mice, we previously showed that the ICR could recapitulate imprinted methylation and expression at a heterologous locus, suggesting that the H19 ICR in the beta-globin locus contained sufficient information to maintain the methylation mark (K.

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Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, including the proximal embryonic epsilon- and the distal adult beta-globin genes. To test for possible distance sensitivity of the genes to the LCR, we extended the distance between the LCR and genes by 2.

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For postoperative adjuvant chemotherapy, UFT was administered to 69 cases of stage II and III colonic cancer following surgery with a radical curability of A. Among these patients, 8 developed hyperbilirubinemia. UFT administration was discontinued for those who developed overt jaundice or dermatological symptoms, experienced a relapse of an earlier asthmatic respiratory difficulty, or for those who were found with multiple hepatic metastases.

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Objective: A phase I study of weekly intravenous paclitaxel combined with a fixed dose of S-1, a dihydropyrimidine-dehydrogenase-inhibitory oral fluoropyrimidine, was conducted for patients with advanced or recurrent gastric cancer (ARGC). Endpoints of this study were to examine the toxicity profile OF this regimen and to determine the recommended dose (rd) of paclitaxel.

Methods: S-1 was fixed at a dose of 80 mg/m(2) per day and was administered for 2 weeks (days 1--14) followed by a 2-week rest.

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A subset of genes in mammals are subject to genomic imprinting. The mouse H19 gene, for example, is active only when maternally inherited and the neighboring Igf2 gene is paternally expressed. This imprinted expression pattern is regulated by the imprinting control region (ICR) upstream of the H19 gene.

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Peritoneal metastasis is the most frequent form of recurrence for advanced gastric cancer. We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal metastasis with cDNA microarray. One of the up-regulated genes is L-3 phosphoserine phosphatase (L3-PP).

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Surgical practice for gastric cancer in Japan is based on the Gastric Cancer Treatment Guidelines issued in 2001 by the Japanese Gastric Cancer Association. These recommendations list options for treatment of each stage of cancer, with clear distinctions between interventions recommended for routine use and those that should be confined to trial settings until further evidence for their curative potential becomes available. In this review, we discuss standard surgery, local resection, segmental resection, and pylorus-preserving gastrectomy (PPG) as examples of limited resection and describe in detail the indications for limited lymph-node dissection in cases of early-stage gastric cancer.

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We reported a clinical case of intra-right atrial giant thrombus adhering to an intravenous hyperalimentation(IVH) catheter. The patient was a 63 years-aged male, and was indwelled the IVH catheter for one month from right subclavian vein to right atrium to improve a malnutrition due to his advanced gastric cancer. Intra-cardiac mass was found in the right atrium by routine transthoracic echocardiography for the preoperative inspection; the giant mass(22 x 20 mm) had a low-echo density with a portion of high-echo density.

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In order to rationalize lymph node dissection for breast cancer, we reviewed regional lymphatic flow from the mesial and outer half of the breast using intra-tumoral injection of activated carbon particles (CH40). Seventy patients with breast cancer were included in this study. Cancers were located in the mesial half of the breast in 25 cases and in its outer half in 41 cases.

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We investigated the significance of milky spots for malignant cells in peritoneal dissemination using three mouse carcinomatous peritonitis models. P388 leukemia and Colon 26 cancer cells were labeled with bromodeoxyuridine (BrdU) and mice were inoculated intraperitoneally. After 24 h the greater omentum and the mesenterium were removed and stained immunohistochemically with anti-BrdU antibody.

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