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Biomedical subjects

Atsushi Maeda

Publications and source records attributed to Atsushi Maeda.

14 recordsLinked to original sources

Simple colorimetric inhibition assay of heme crystallization for high-throughput screening of antimalarial compounds.

Current assays for screening new antimalarials need initiators of beta-hematin formation that require laborious preparation, special devices, and substrates. In this study, based on reduction of heme absorption in beta-hematin formation, we developed a simple colorimetric assay using Tween 20 as an initiator and a microplate reader for high-throughput screening of inhibitors of beta-hematin formation.

Animals↗

Incorporation into a biodegradable hyaluronic acid matrix enhances in vivo efficacy of recombinant human interleukin 11 (rhIL11).

In order to improve the therapeutic efficacy of recombinant human interleukin 11 (rhIL11) and to reduce its frequency of administration, the feasibility of a sustained release formulation consisting of hyaluronic acid (HyA) was investigated. rhIL11 was mixed together with an aqueous solution of HyA or HyA and protamine, and the mixture was lyophilized. The resulting powder was compressed into pellet and was subcutaneously administered in the rats. The plasma profile of rhIL11 was determined by ELISA. The mean residence time and t(max) of rhIL11 were much prolonged by administration in an HyA pellet. The additional incorporation of protamine into the formulation further enhanced the plasma duration of the protein. Separately, peripheral platelet counts were measured for several rhIL11-containing solution and pellets. Platelet counts much increased after administration of rhIL11-containing pellets, whereas the effect of bolus subcutaneous administration of rhIL11 solution was limited. The degree of platelet increase in rats treated with the pellets was comparable to that for rats treated with 1- or 2-day continuous infusion from an osmotic mini-pump; these data reflect the importance of increased plasma duration of rhIL11. These data indicate that use of hyaluronic acid as a polymer matrix might enhance the therapeutic efficacy of rhIL11.

Animals↗

Potential roles of large mafs in cell lineages and developing pancreas.

OBJECTIVES: Maf is a family of transcription factor proteins characterized by a typical bZip structure, and mafA, a member of the large-maf family, is a strong transactivator of insulin in cell lines. The present study investigated the expression profiles of the large-maf family proteins in porcine pancreatic tissue and in primary culture cells. METHODS: Immunohistochemical staining was performed to localize each maf protein. Messenger RNA expression was quantitated by real-time polymerase chain reaction, and protein expression was assessed by Western blotting. RESULTS: Islet formation was not as clear in newborn pancreatic tissue as in adult pancreatic tissue. MafA- and c-maf-positive cells were more diffusely localized in pancreatic tissue with fewer mafB-positive cell clusters scattered throughout. By contrast, islet formation was clearer, and positive staining for mafA and c-maf tended to be more prominent in the islets of adult pancreatic tissue. Messenger RNA and protein expressions were consistent with the immunohistochemical findings. MafA, mafB, and c-maf coexpressed with insulin-positive cells, and c-maf coexpressed with glucagon-positive cells in adult porcine pancreas based on the results of a double-staining study. CONCLUSIONS: Large mafs were identified in normal porcine and human pancreas, and the expression levels and localizations of the large mafs in newborn and adult pancreatic tissues differed. Mafs may play important roles in establishing endocrine function during pancreatic cell differentiation.

Animals↗

Effects of antisecretory agents on angiogenesis during healing of gastric ulcers.

BACKGROUND: We studied the effects of a proton pump inhibitor (PPI) and an H2-receptor antagonist (H2-blocker) on angiogenesis during gastric ulcer healing, by examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4 (CXCR4) expression in the gastric mucosa. METHODS: Patients with gastric ulcers were allocated to an untreated control group, consisting of patients with active ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given rabeprazole at 20 mg/day), or an H2-blocker group (H; given nizatidine at 800 mg/day). Frozen sections of biopsy specimens were examined by reverse transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA. RESULTS: CXCR4 mRNA levels were elevated in the control (GH and GS patients) group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA subgroup of the PPI group (P<0.01), but its level decreased with time. CONCLUSIONS: In the PPI group, CXCR4 levels were increased in the early phase of ulcer healing and returned to a level similar to that in the control group during the scar phase. These results suggest that PPIs increase the expression of CXCR4 mRNA and thus promote vessel regeneration and maturation, facilitating ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Relation of hypoxia-inducible factor-1alpha to vascular endothelial growth factor and vasoactive factors during healing of gastric ulcers.

We studied the relation of hypoxia-inducible factor-1alpha (HIF-1alpha) to vascular endothelial growth factor and vasoactive factors during the healing of gastric ulcers. The gastric ulcers were divided into three stages (active stage, healing stage and scar stage). The expression of HIF-1alpha, endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor mRNA was highest during the active stage of ulcer healing, and endothelin-1, vascular endothelial growth factor protein levels and nitric oxide were higher during the healing stage. Thus, levels of HIF-1alpha mRNA tend to increase during the active stage of gastric ulcer healing, suggesting that this factor participates in the induction of endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor. Also, the HIF-1alpha mRNA level did not differ significantly among the various stages of ulcer healing, and detectable levels of HIF-1alpha protein were not found during any stage. This suggests that these angiogenic factors and vasoactive substances may be induced by HIF-1alpha. During the active stage on endoscopic examination, considered the initial phase of ulcer healing, the process of ulcer healing has begun, and the tissue at the ulcer margin has already been reoxygenated.

Case-Control Studies↗

Transformation of cellobiose to 3-ketocellobiose by the EDTA-treated Agrobacterium tumefaciens cells.

Agrobacterium tumefaciens cells treated with EDTA were used as a biocatalyst for the transformation of cellobiose to 3-ketocellobiose. The effects of pH of the reaction medium and temperature on the reaction rate and the selectivity during the transformation by the cells were examined, and it was found that the optimum reaction conditions were pH 6 and 15 degrees C. The selectivity was about 0.8 under these conditions. The substrate concentration had no significant effect on the selectivity up to 300 mmol/I.

Journal Article↗

Roles of angiogenic factors and endothelin-1 in gastric ulcer healing.

Endothelins (ETs) participate directly and indirectly in angiogenesis via ET receptors. During early fetal angiogenesis, vascular endothelial growth factor (VEGF) and its receptors kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 (Flt-1) are required for the development of the systemic vasculature. In late angiogenesis, stromal-cell-derived factor (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) act in an organ-specific manner to promote the formation and development of large blood vessels supplying the gastrointestinal tract. We studied the roles of these ligand receptors in angiogenesis during healing of gastric ulcers. We studied the following five groups, each consisting of ten cases of endoscopically confirmed gastric ulcer: active stage (GA), healing stage (GH) and scar stage (GS) of gastric ulcers located in the angulus; Helicobacter pylori (Hp)-positive gastritis (gast+); and Hp-negative gastritis (gast-). All cases in the ulcer groups were Hp-positive. The study materials consisted of frozen biopsy specimens of lesions arising in the angulus. ET-1 was measured by enzyme immunoassay. The other factors were assayed by reverse-transcription-PCR. The distributions of ET-1, ETA receptor (ETAR), SDF-1 and CXCR4 in the gastric mucosa were evaluated by enzyme immunoassay. ET-1 and ETAR reached peak levels during the GH (ET: P<0.05, ETAR: P<0.01). VEGF mRNA increased slightly during the GA, but did not differ significantly among the groups. KDR and Flt-1 levels were high during the GA, the level being significantly higher than those during the GH and GS (P<0.05). SDF-1 levels significantly decreased during the GH and GS compared with levels during the GA, and CXCR4 significantly increased during the GH and GS (P<0.01). On immunostaining, ET-1-positive cells and ETAR-positive cells were found in the endothelium, vascular smooth muscle and gastric epithelium, and CXCR4-positive cells were found in the endothelium and gastric epithelium during the GH and GS. Our results suggest that VEGF receptors are mainly expressed early in ulcer development and participate in the initial stage of angiogenesis. SDF-1 receptors and ETAR are primarily expressed during the GH and GS and are involved in vascular maturation and gastric mucosal regeneration during late angiogenesis.

Chemokine CXCL12↗

Condensation reaction between angiotensin II and dicarboxylic acid in water at high temperature without any catalytic agent additive.

The condensation reaction of angiotensin II and tartaric acid in water at 100-140 degrees C proceeded without any added catalytic agent. One of the products, N-CO-tartarylangiotensin II, was confirmed by LC-MS, positive-ion MALDI-MS, and the fluorescamine method as a condensation product. The initial concentration of the substrates, temperatures, and initial pH affected the yield of the product. The higher concentrations and temperatures increased the concentration of the condensation product. The optimal pH for the condensation reaction was 3.0. The other C4 saturated dicarboxylic acids, malic and succinic acids, were also condensed by angiotensin II.

Angiotensin II↗