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Matsushita Y Ishikawa M Abe K Utsunomiya I Chikuma T Hojo H Hoshi K Quock RM Taguchi K 《Neuroscience》2007,148(2):541-547
Prolonged exposure to nitrous oxide (N2O) results in development of acute tolerance to its antinociceptive effect. Cross-tolerance to N2O-induced antinociception is also observed in morphine-tolerant animals. Despite increasing evidence of tolerance development to N2O-induced antinociception, the details of the mechanisms that underlie this tolerance remain unknown. The present study was conducted to investigate the involvement of brain protein kinase C (PKC) isoform in these two types of tolerance to N2O-induced antinociception in mice. Prolonged exposure (41 min in total, including 30 min pre-exposure and 11 min of antinociceptive testing) to 70% N2O produced a reduction in N2O-induced antinociception, indicating development of acute tolerance. The prolonged exposure to 70% N2O caused an activation of PKCgamma isoform in the brain, but not the PKCepsilon isoform. Pretreatment with a PKCgamma-antisense oligonucleotide but not the corresponding mismatch oligonucleotide (i.c.v.) prevented the development of acute tolerance to N2O-induced antinociception. Chronic morphine treatment (10 mg/kg, s.c., b.i.d. for 5 days) resulted in development of tolerance to morphine-induced antinociception and cross-tolerance to N2O-induced antinociception. The development of tolerance to morphine and cross-tolerance to N2O were both inhibited by pretreatment with PKC inhibitor, chelerythrine (1 nmol, i.c.v.). Morphine-tolerant mice showed an activation of PKC within the brain, which was suppressed by pretreatment with chelerythrine (1 nmol, i.c.v.). Thus, activation of brain PKC, in particular, the PKCgamma isoform, appears to play an important role in the development of both acute tolerance and cross-tolerance to N2O-induced antinociception in mice. 相似文献
86.
Gastric mucin is expressed in a subset of endocervical tunnel clusters: type A tunnel clusters of gastric phenotype 总被引:1,自引:0,他引:1
Kondo T Hashi A Murata SI Fischer SE Nara M Nakazawa T Yuminamochi T Hoshi K Katoh R 《Histopathology》2007,50(7):843-850
AIMS: Gastric mucin expression has been demonstrated in a group of endocervical glandular lesions. The aim of this study was to gain further insight into endocervical lesions with a gastric phenotype. METHODS AND RESULTS: Various types of tunnel clusters (TC) were examined for gastric mucin by alcian blue/periodic acid-Schiff staining and immunohistochemistry for HIK1083. Five of 34 cases of TC expressed gastric mucin defined by PAS dominant neutral mucin and immunopositivity for pyloric gland mucin. Histologically, TC expressing gastric mucin showed lobular arrangements of small to medium-sized glands composed of mucin-rich columnar cells and were classified as Flumann's type A TC. Neither type B TC nor normal endocervical glands expressed PAS dominant neutral mucin and none of them was immunopositive for pyloric gland mucin. Five patients with type A TC of gastric phenotype ranged in age from 33 to 79 years (mean 58 years) and were multiparous. Type A TC of gastric phenotype, ranging from 2 to 4 mm in maximum diameter, were incidental findings in hysterectomy specimens. CONCLUSION: Type A TC of gastric phenotype could be related to lobular endocervical glandular hyperplasia of gastric phenotype. The pathogenesis of gastric metaplasia in TC remains unclear. 相似文献
87.
Shingo Hatakeyama Shintaro Narita Masahiro Takahashi Toshihiko Sakurai Sadafumi Kawamura Senji Hoshi Masanori Ishida Toshiaki Kawaguchi Shigeto Ishidoya Jiro Shimoda Hiromi Sato Itsuto Hamano Teppei Okamoto Koji Mitsuzuka Akihiro Ito Norihiko Tsuchiya Yoichi Arai Tomonori Habuchi Chikara Ohyama 《International journal of urology》2020,27(7):610-617
88.
Naoyuki Maeda Kanako Okumura Emi Tanaka Tomokazu Suzuki Taku Miyasho Satoko Haeno Hiromi Ueda Nobuhiko Hoshi Hiroshi Yokota 《Environmental toxicology》2014,29(12):1452-1459
Reproductive toxicities and endocrine disruptions caused by chemicals in adult males are still poorly understood. It is our objectives to understand further details of the initial adverse effects leading severe testicular toxicities of a pharmaceutical endocrine disruptor, diethylstilbestrol (DES). Downregulations of both testicular regulatory proteins, such as the steroidogenic acute regulatory protein (StAR) and the peripheral benzodiazepine receptor (PBR), which play important roles in the transport of cholesterol into the mitochondria, and cytochrome P450 mediating the cholesterol side chain cleavage reaction (P450scc), were observed in the rat orally administered DES (340 μg/kg/2 days) for 2 weeks. We found that after only 1 week treatment with DES, the blood and testicular testosterone (TS) levels were drastically decreased without abnormalities of the StAR and PBR; however, the protein and mRNA levels of P450scc were diminished. Decrease in the conversion rate of cholesterol to pregnenolone was delayed in the in vitro assay using the testicular mitochondrial fraction from the rat treated with DES for 1 week. When the precursors in TS biosynthesis containing the testis were identified and determined by liquid chromatography‐mass spectrometry analysis, decreased levels of all precursors except cholesterol were observed. In conclusion, suppressed cytochrome P450scc expression in adult male rat was identified as an initial target of DES in testicular steroidogenesis disorder leading reproductive toxicities. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1452–1459, 2014. 相似文献
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Yuichi Saito Nobumasa Takahashi Atsuka Matsui Satoru Michiyuki Yoshikane Yamauchi Yoshihiko Shimizu Eishin Hoshi Yukinori Sakao Masafumi Kawamura 《Journal of thoracic disease》2021,13(2):743
BackgroundEpidermal growth factor receptor (EGFR) mutations are important biomarkers in the treatment of patients with advanced or metastatic diseases. The therascreen EGFR Rotor-Gene Q (RGQ) PCR Kit® (Qiagen, Inc.) is an approved diagnostic test for EGFR mutations in non-small cell lung cancer (NSCLC). This study aims to investigate the diagnostic capability of a loop-mediated isothermal amplification (LAMP) assay as an accurate, efficient, and cost-effective alternative to the therascreen assay.MethodsEGFR mutations were investigated by LAMP and therascreen assays using tissue samples that were surgically resected or biopsied from 117 consecutive patients with NSCLC tumors. The EGFR status from the LAMP assay was compared with that of the therascreen assay. Next-generation sequencing (NGS) was performed to confirm EGFR status of tumors that did not match in both assays. To establish an optimal LAMP AUC value, receiver operating characteristics (ROC) curve analysis was performed within tumors with exon 19 deletion or L858R point mutation.ResultsOf the 117 tumors assayed, 45 tumors with EGFR mutations and 68 tumors with EGFR wild type were matched in both assays, four tumors having mismatched EGFR statuses. NGS further confirmed that two of the four discordant tumors had the same EGFR status that was determined by the LAMP assay. The AUC values were 0.973 (95% CI: 0.929–1.00) in exon 19 deletion, and 0.952 (95% CI: 0.885–1.00) in L858R point mutation. In exon 19 deletion, sensitivity, specificity, and accuracy were 89.3%, 98.9%, and 96.6%, respectively, and 94.7%, 95.9%, and 95.7%, respectively, in L858R using AUC value of 0.222.ConclusionsThe LAMP assay compared favorably with the therascreen assay and has potential as an effective, simple, rapid, and low-cost diagnostic alternative. Based on these results, a liquid biopsy LAMP system should be developed for point-of-care testing of oncogenes in the near future. 相似文献
90.
Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG in a patient with long QT syndrome 总被引:5,自引:0,他引:5
Hayashi K Shimizu M Ino H Yamaguchi M Mabuchi H Hoshi N Higashida H 《Cardiovascular research》2002,54(1):67-76
OBJECTIVE: In a 32-year-old woman with marked QT prolongation (QTc=0.61 s) and repeated episodes of syncope, we identified a single pertinent base substitution (G to A at 1909) in HERG by genetic analysis. This novel missense mutation is predicted to cause an amino acid substitution of lysine for glutamic acid at position 637 (E637K) in the pore-S6 loop. Therefore, we investigated the role of a glutamic acid at the vicinity of the pore in HERG channels by mutating it to a lysine. METHODS: We characterized the electrophysiological properties of the E637K mutation using a Xenopus oocyte heterologous expression system. RESULTS: Injection of the E637K mutant cRNA alone into Xenopus oocytes did not result in any expression of detectable currents. Coexpression of wild-type (WT) and E637K (E637K/WT) elicited only about 30% of the control peak tail current that was expected from expression of WT alone. Kinetic analyses revealed that E637K/WT decelerated the rate of channel activation and enhanced steady-state inactivation. Furthermore, the reversal potentials at low concentrations of K+ showed a positive shift in oocytes injected with E637K/WT compared with WT alone. CONCLUSIONS: These results indicated that the E637K mutation causes apparent dominant negative suppression of WT HERG channel function and suggest that E637 at the Pore-S6 is a crucial component of the activation and inactivation gate of HERG channels. 相似文献