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Articles by K Mori
Total Records ( 7 ) for K Mori
  K Mori , S Jono , M Emoto , T Kawagishi , H Yasumoto , T Konishi , Y Furumitsu , A Shioi , T Shoji , M Inaba and Y. Nishizawa
 

Osteoprotegerin is a secretory glycoprotein. Recent experimental findings have suggested that osteoprotegerin may protect against vascular calcification and/or atherosclerosis. In humans, osteoprotegerin levels are positively correlated with the presence and severity of coronary artery disease and the progression of atherosclerosis. However, it is unclear how osteoprotegerin levels are regulated. Statins are known to have beneficial pleiotropic effects against atherosclerosis beyond their lipid-lowering effects. In this study, we examined whether treatment with pravastatin can alter osteoprotegerin levels in patients with hypercholesterolemia and type 2 diabetes. Osteoprotegerin levels were significantly increased from 6.64 ± 2.18 pmol/L at baseline to 7.08 ± 2.29 pmol/L (P = .024) after 3-month treatment with pravastatin. These increases in osteoprotegerin levels remained after 6 months of treatment (7.05 ± 2.22 pmol/L, P = .026). These findings suggest that pravastatin may exert its pleiotropic effects in part through alteration of osteoprotegerin levels.

  T Tashiro , E Sekine Kondo , T Shigeura , R Nakagawa , S Inoue , M Omori Miyake , T Chiba , N Hongo , S. i Fujii , K Shimizu , Y Yoshiga , T Sumida , K Mori , H Watarai and M. Taniguchi
 

NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with -galactosylceramide (-GalCer), which is composed of -galactopyranose linked to ceramide (itself composed of sphingosine and fatty-acyl chains); the chain length of the ceramide varies and this affects the ability of -GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized -carba-GalCer, which has an -linked carba-galactosyl moiety; here, the 5a'-oxygen atom of the D-galactopyranose ring of -GalCer is replaced by a methylene group. The -carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN- compared with -GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The -carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was -GalCer, which has an acetal bond. Modulation of the sugar moiety in glycolipids might therefore provide optimal therapeutic reagents for protective immune responses against tumor or pathogens.

  T Fujii , H Kunikane , H Okamoto , K Watanabe , H Kunitoh , K Mori , A Yokoyama , H Fukuda , T Tamura and N. Saijo
  Objective

It is important to find optimal regimens of cisplatin (CDDP)-based third-generation chemotherapy and radiotherapy for patients with unresectable Stage III non-small cell lung cancer (NSCLC).

Methods

This Phase II study was designed to determine the toxicity and efficacy of two courses of chemotherapy (CDDP 80 mg/m2 on day 1 and irinotecan 60 mg/m2 on days 1 and 8) followed by accelerated hyperfractionated thoracic radiotherapy (60 Gy/40 fractions in 4 weeks) combined with daily carboplatin (CBDCA) administration. CBDCA was administered at a target area under the plasma level–time curve of 0.4 x (24 h creatinine clearance + 25), according to Calvert's formula.

Results

Twenty-six patients were enrolled in the study. The patients' median age was 63 years (range 40–74 years) and included 22 males and 4 females. Seven patients were Stage IIIA and 19 were Stage IIIB. Twenty had a performance status (PS) of 1 versus six with a PS of 0. There was one treatment-related death due to sepsis and pneumonia associated with Grade 4 neutropenia and diarrhea during chemotherapy. Grade 3 or 4 neutropenia and diarrhea were observed in 14 and 5 patients, respectively. Toxicity of the radiotherapy was mild. There were 0 complete response and 13 partial responses, giving a response rate of 50.0%. Median survival time and 2-year survival were 16.4 months and 21.5%, respectively. This study was designed with Simon's two-stage design, and the response rate did not meet the criteria to proceed to the second stage and the study was terminated early.

Conclusions

This regimen might be inactive for patients with unresectable Stage III NSCLC.

  K Yamasaki , K Omori , E. I Takaoka , N Sekido , M Shigai , K Mori , M Minami , Y Watanabe , T Shimazui and H. Akaza
 

We present the clinical course of a ureteroiliac arterial fistula in a patient who had been managed by ureteral stenting for 8 years for severe ureteral stricture after abdominoperineal resection with pelvic irradiation for advanced rectal cancer. A multidisciplinary team approach including provocative angiography and an endovascular stent saved the life of the patient. Ureteroarterial fistula is a rare complication of a long-term indwelling ureteral stent that is potentially fatal unless a prompt diagnosis and adequate therapy are provided. Heightened awareness and a high index of suspicion for this condition are required to make an early diagnosis.

  I Kobayashi , E Ishimura , K Hirowatari , T Tsuchida , A Nishihira , H Shima , K Shidara , K Mori , M Inaba , K. i Wakasa and Y. Nishizawa
 

A renal biopsy was performed in a 47-year-old man with haemophilia A. Thirty minutes after administration of an intravenous bolus of 4000 units of recombinant factor VIII, which increased the activity to 74–91%, a needle renal biopsy was successfully performed, followed by administration of 3000 units of factor VIII in the evening, and then the subsequent morning and evening. The patient was diagnosed with hepatitis C virus-associated membranoproliferative glomerulonephritis. Treatment with interferon, ribavirin, prednisolone and cyclosporine A improved the nephrotic syndrome. This is the first report of a successful renal biopsy in a patient with haemophilia A after factor VIII injection.

  F Ishikawa , T Akimoto , H Yamamoto , Y Araki , T Yoshie , K Mori , H Hayashi , K Nose and M. Shibanuma
 

Mitochondrial dysfunction, in particular, interference in the respiratory chain, is often responsible for the toxicogenic effects of xenobiotics. In this study, changes in gene expression resulting from pharmacological inhibition of the respiratory chain were studied by DNA microarray analysis using cells treated with rotenone or antimycin A, which inhibit complexes I and III of the electron transport system, respectively. Forty-eight genes were either up- or down-regulated more than 3-fold. These included stress- and/or metabolic-related effector genes and several transcriptional regulators represented by CHOP-10. Further study using siRNA showed that among the four genes studied, up-regulation of three was dependent on CHOP-10. C/EBPβ, a dimerizing partner of CHOP-10, was also involved in two of the three genes including Trib3, implying that CHOP-10, heterodimerizing with C/EBPβ or another partner played a key role in the expression of a set of genes under stress. Although CHOP-10 and Trib3 were both ER-stress response genes, signal inducing Trib3 during mitochondrial stress was distinct from that during ER stress. Cytotoxicity caused by inhibition of the respiratory chain was attenuated by treatment with siRNA for CHOP-10. This study demonstrated the importance of CHOP-10 in coordinating individual gene expression in response to the mitochondrial stress.

  K Akita , N Hieda , N Baba , S Kawaguchi , H Sakamoto , Y Nakanishi , M Yamanishi , K Mori and T. Toraya
 

The methods of homologous high-level expression and simple large-scale purification for coenzyme B12-dependent ethanolamine ammonia-lyase of Escherichia coli were developed. The eutB and eutC genes in the eut operon encoded the large and small subunits of the enzyme, respectively. The enzyme existed as the heterododecamer 6β6. Upon active-site titration with adeninylpentylcobalamin, a strong competitive inhibitor for coenzyme B12, the binding of 1 mol of the inhibitor per mol of the β unit caused complete inhibition of enzyme, in consistent with its subunit structure. EPR spectra indicated the formation of substrate-derived radicals during catalysis and the binding of cobalamin in the base-on mode, i.e. with 5,6-dimethylbenzimidazole coordinating to the cobalt atom. The purified wild-type enzyme underwent aggregation and inactivation at high concentrations. Limited proteolysis with trypsin indicated that the N-terminal region is not essential for catalysis. His-tagged truncated enzymes were similar to the wild-type enzyme in catalytic properties, but more resistant to p-chloromercuribenzoate than the wild-type enzyme. A truncated enzyme was highly soluble even in the absence of detergent and resistant to aggregation and oxidative inactivation at high concentrations, indicating that a short N-terminal sequence is sufficient to change the solubility and stability of the enzyme.

 
 
 
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