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631.
Shota Tokai Tomohiro Bito Katsuhiko Shimizu 《Bioscience, biotechnology, and biochemistry》2018,82(7):1107-1115
Family S9 prolyl oligopeptidases (POPs) are of interest as pharmacological targets. We recently found that an S9 POP from Pleurotus eryngii showed altered substrate specificity following H2O2 treatment. Oxidation of Met203 on the non-catalytic β-propeller domain resulted in decreased activity toward non-aromatic aminoacyl-para-nitroanilides (pNAs) while maintaining its activity toward aromatic aminoacyl-pNAs. Given that the other Met residues should also be oxidized by H2O2 treatment, we constructed mutants in which all the Met residues were substituted with other amino acids. Analysis of the mutants showed that Met570 in the catalytic domain is another potent residue for the altered substrate specificity following oxidation. Met203 and Met570 lie on the surfaces of two different domains and form part of a funnel from the surface to the active center. Our findings indicate that the funnel forms the substrate pathway and plays a role in substrate recognition. 相似文献
632.
Ryoji Joko Daisuke Yamada Masahiro Nakamura Aki Yoshida Shota Takihira Tomoka Takao Ming Lu Kohei Sato Tatsuo Ito Toshiyuki Kunisada Eiji Nakata Toshifumi Ozaki Takeshi Takarada 《Translational oncology》2021,14(1)
Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma. 相似文献
633.
We synthesized two oligodeoxyribonucleotides bearing an isopropyl phosphotriester at defined positions using new phosphorobisamidite chemistry. Diastereomers were separated with HPLC and their template properties were analyzed. Priming oligodeoxyribonucleotides labeled with 32P at the 5'-end were annealed to the modified oligodeoxyribonucleotides and elongated with DNA polymerase I large fragment from Escherichia coli. Results show that the phosphotriester inhibits the DNA chain elongation partially and the extents of the inhibition are remarkably different between the two diastereomers. 相似文献
634.
Tongues of mice were fixed in 10% Baker's Ca-formalin and sectioned at 50 μ with a freezing microtome. The thiolacetic acid method (Wachstein et al., J. Histochem. Cytochem., 9: 325-39) was used for motor endplates and after this cholinesterase staining, the Bielschowsky method was applied for nerve fibers. Thus, both motor endplates and nerve fibers were fully demonstrated. 相似文献
635.
Y Oka M Ogawa Y Matsuda A Murata J Nishijima K Miyauchi K Uda T Yasuda T Mori 《Enzyme》1990,43(2):80-88
The high incidence (40.6%) of elevated serum pancreatic phospholipase A2 (PLA2) was demonstrated in patients with various malignancies. Serum PLA2 was significantly increased in cancer patients compared with healthy sex- and age-matched blood donors (358.4 +/- 168.0 vs. 241.7 +/- 69.0 ng/dl; p less than 0.01). No correlation was observed between serum PLA2 and carcinoembryonic antigen (CEA) in these patients. Although patients with advanced and distantly metastatic cancer of the liver, gallbladder and pancreas showed higher PLA2 levels in serum than those with early cancer, patients with other cancers showed no correlation between serum PLA2 and clinical stage. A combined assay of PLA2 and CEA increased the sensitivity of detection of cancers to 60.8%. 相似文献
636.
Akiko Hida Shota Oku Manami Miura Hiroki Matsuda Takahisa Tajima 《Bioscience, biotechnology, and biochemistry》2020,84(9):1948-1957
ABSTRACT
Pseudomonas protegens CHA0, known as plant-growth-promoting rhizobacterium, showed positive chemotactic responses toward proteinaceous L-amino acids. Genomic analysis revealed that P. protegens CHA0 possesses four putative chemoreceptors for amino acids (designated CtaA, CtaB, CtaC, and CtaD, respectively). Pseudomonas aeruginosa PCT2, a mutant defective in chemotaxis to amino acids, harboring a plasmid containing each of ctaA, ctaB, ctaC, and ctaD showed chemotactic responses to 20, 4, 4, and 11 types of amino acids, respectively. To enhance chemotaxis toward amino acids, we introduced the plasmids containing ctaA, ctaB, ctaC, or ctaD into P. protegens CHA0. By overexpression of the genes, we succeeded in enhancing chemotaxis toward more than half of the tested ligands. However, unexpectedly, the P. protegens CHA0 transformants showed unchanged or decreased responses to some amino acids when compared to wild-type CHA0. We speculate that alternation of expression of a chemoreceptor may affect the abundance of other chemoreceptors. 相似文献
637.
Hiroki Ishii Kazuaki Chikamatsu Satoshi Igarashi Hideyuki Takahashi Kaname Sakamoto Hiroji Higuchi Shota Tanaka Tomokazu Matsuoka Keisuke Masuyama 《Translational oncology》2018,11(1):132-139
The lack of available tumor antigens with strong immunogenicity, human leukocyte antigen restriction, and immunosuppression via regulatory T-cells (Tregs) and myeloid-derived suppressor cells are limitations for dendritic cell (DC)–based immunotherapy in patients with advanced head and neck cancer (HNC). We sought to overcome these limitations and induce effective antitumor immunity in the host. The effect of low-dose docetaxel (DTX) treatment on DC maturation was examined in an ex vivo study, and a phase I clinical trial of combination therapy with direct peritumoral immature DC (iDC) injection with OK-432 and low-dose cyclophosphamide (CTX) plus DTX was designed. Low-dose DTX did not negatively affect iDC viability and instead promoted maturation and IL-12 production. Five patients with metastatic or recurrent HNC were enrolled for the trial. All patients experienced grade 1 to 3 fevers. Intriguingly, elevated CD8+ effector T-cells and reduced Tregs were observed in four patients who completed two treatment cycles. All patients were judged to have progressive disease, but tumor regressions were observed in a subset of targeted metastatic lesions in two of five patients. Our results show that the combination of direct peritumoral iDC injection with OK-432 and low-dose CTX plus DTX is well tolerated and should give rise to changing the immune profile of T-cell subsets and improvement of immunosuppression in advanced HNC patients. Additionally, our ex vivo data on the effect of low-dose DTX treatment on DC maturation may contribute to developing new combination therapies with low-dose chemotherapy and immunotherapy. 相似文献
638.
Shota Miyaguchi Nobutomo Matsunaga Shigeyasu Kawaji 《Biomedical signal processing and control》2009,4(4):294-301
Continuous passive motion (CPM) is an orthopedic treatment or a physiotherapy and has been applied after surgery. After surgery for the injured ulna collateral ligament (UCL) which is a major clinical case in the elbow joint, the reaction force at the hand of the patient increases and may be excessively large due to an increase of the joint stiffness. For this, it will be effective to reduce the excessive reaction force by controlling pro-/supination of forearm. The UCL in the elbow joint is extended due to pro-/supination of forearm, but the excessive extension may aggravate the injury of the UCL. Thus, it is required to suppress both the excessive extension of the UCL and the reaction force. In this paper, a control scheme of CPM device that can suppress both the excessive extension of the UCL and the reaction force is proposed, and its effectiveness is confirmed from the experimental results. 相似文献
639.
Abstract: Using a brain microdialysis technique, we have shown in the rat that local infusion of a selective and competitive N -methyl- d -aspartate (NMDA) receptor antagonist, cis -4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755), into the medial frontal cortex via dialysis tubing caused a concentration-related increase in the extracellular release of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the cortical region. Coinfusion of a sodium channel blocker, tetrodotoxin, completely inhibited the ability of the NMDA antagonist to augment frontal dopamine metabolism. These findings suggest that dopamine neurons projecting to the frontal cortex might be under a tonic transsynaptic inhibition exerted by excitatory amino acid neurotransmission via the NMDA receptor at the level of dopamine terminal fields. 相似文献
640.
Ichthyological Research - Larvae and juveniles of three species in the family Gobiidae were described based on reared material; Priolepis borea survived to post-settlement, and Priolepis cincta and... 相似文献