Kazuo Matsubara

Publications (31)49.63 Total impact

• Article: Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells.

  Tomohiro Omura, Masaru Asari, Joe Yamamoto, Kumiko Oka, Chisato Hoshina, Chikatoshi Maseda, Toshio Awaya, Yoshikazu Tasaki, Hiroshi Shiono, Atsushi Yonezawa, Satohiro Masuda, Kazuo Matsubara, Keiko Shimizu
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  ABSTRACT: Paraquat is a commonly used herbicide; however, it is highly toxic to humans and animals. Exposure to paraquat causes severe lung damage, leading to pulmonary fibrosis. However, it has not been well clarified as how paraquat causes cellular damage, and there is no established standard therapy for paraquat poisoning. Meanwhile, endoplasmic reticulum stress (ERS) is reported to be one of the causative factors in many diseases, although mammalian cells have a defense mechanism against ERS-induced apoptosis (unfolded protein response). Here, we demonstrated that paraquat changed the expression levels of unfolded protein response-related molecules, resulting in ERS-related cell death in human lung epithelial A549 cells. Moreover, treatment with sodium tauroursodeoxycholate (TUDCA), a chemical chaperone, crucially rescued cells from death caused by exposure to paraquat. These results indicate that paraquat toxicity may be associated with ERS-related molecules/events. Through chemical chaperone activity, treatment with TUDCA reduced paraquat-induced ERS and mildly suppressed cell death. Our findings also suggest that TUDCA treatment represses the onset of pulmonary fibrosis caused by paraquat, and therefore chemical chaperones may have novel therapeutic potential for the treatment of paraquat poisoning.
  Biochemical and Biophysical Research Communications 02/2013; · 2.48 Impact Factor
• Article: Universal fluorescent labeling of amplification products using locked nucleic acids.

  Masaru Asari, Kumiko Oka, Tomohiro Omura, Chikatoshi Maseda, Yoshikazu Tasaki, Hiroshi Shiono, Kazuo Matsubara, Mitsuyoshi Matsuda, Keiko Shimizu
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  ABSTRACT: Amplification/hybridization-based genetic analyses using primers containing locked nucleic acids (LNAs) present many benefits. Here, we developed a novel design for universal fluorescent PCR using LNAs. Universal fluorescent PCR generates intermediate non-labeled fragments and final fluorescent fragments in a two-step amplification process that uses locus-specific primers with universal tails and universal fluorescent primers. In this study, a few standard nucleotides were replaced with LNAs only in the fluorescent universal primers. The sequence of the fluorescent universal primer significantly affected the amplification efficiency. For primers with three LNAs, the fluorescent primers with stable M13(-47) sequences provided the most efficient signal (approximately 10-fold higher than the primers with M13(-21) sequences at lower Tm values). Moreover, AT-rich LNA substitutions in the fluorescent primers produced much lower amplification efficiencies than GC-rich substitutions. GC-rich LNAs produced greater differences in Tm values among primers, and resulted in the preferential production of fluorescently labeled amplicons. The specificity and sensitivity of LNA-containing fluorescent primers were assessed by genotyping eight short tandem repeats (STRs) in Japanese individuals, and full STR profiles could be generated using as little as 0.25 ng of genomic DNA. The method permitted clear discrimination of alleles and represents sensitive STR genotyping at a reduced cost.
  Electrophoresis 11/2012; · 3.30 Impact Factor
• Article: Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model.

  Yoshikazu Tasaki, Joe Yamamoto, Tomohiro Omura, Tomoki Sakaguchi, Norihisa Kimura, Ko-Ichi Ohtaki, Takashi Ono, Manabu Suno, Masaru Asari, Tomoko Ohkubo, Toshihiro Noda, Toshio Awaya, Keiko Shimizu, Kazuo Matsubara
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  ABSTRACT: A series of oxicam non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be neuroprotective against 1-methyl-4-phenyl pyridinium in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway independent of cyclooxygenase (COX) inhibition. The present study endeavored to establish this novel effect of meloxicam (MLX), an oxicam NSAID, in a mouse Parkinson's disease (PD) model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice, which received MPTP (30 mg/kg/day; s.c.) for 5 consecutive days (chronic model) with 10-day follow-up saline administrations, showed significant motor dysfunction in the pole test due to reduced tyrosine hydroxylase (TH) protein levels in the brain on day 16 after MPTP/saline treatment. Daily coadministrations of MLX (10mg/kg/day; i.p.) and MPTP for the first 5 days and follow-up 10 days with MLX administrations alone (MPTP/MLX treatment) significantly ameliorated MPTP-induced behavioral abnormalities in mice. Concomitant decreases of TH protein levels in the striatum and midbrain of MPTP/MLX-treated mice were not only significantly (p<0.01 and p<0.05, respectively) ameliorated but phosphorylated Akt (pAkt473) expression in the midbrain was also significantly (p<0.01) increased in the midbrain when compared with MPTP/saline-treated mice. These results suggest that MLX, an oxicam NSAID, attenuated dopaminergic neuronal death in the experimental MPTP-PD model by maintenance of the Akt-signaling. Oxicam NSAIDs may serve as potential drugs for PD treatment via a novel mechanism of action.
  Neuroscience Letters 05/2012; 521(1):15-9. · 2.11 Impact Factor
• Article: Estimation of the duration after methamphetamine injection using a pharmacokinetic model in suspects who caused fatal traffic accidents.

  Kazuo Matsubara, Masaru Asari, Manabu Suno, Toshio Awaya, Mitsuru Sugawara, Tomohiro Omura, Joe Yamamoto, Chikatoshi Maseda, Yoshikazu Tasaki, Hiroshi Shiono, Keiko Shimizu
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  ABSTRACT: When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention. In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures. If the injected amount can be determined to a certain extent, it is easy to calculate the average time-elapse after injection by referring to reference values. However, there is considerable individual variability in the elimination rate based on genetic polymorphism and a considerably large error range in the estimated time-elapse results. To minimize estimation errors in such cases, we also analyzed genotype of CYP2D6, which influenced methamphetamine metabolism. Estimation based on two time-point blood samples would usefully benefit legal authorities in passing ruling sentences in cases involving similar personalities and circumstances as those involved in the present study.
  Legal Medicine 04/2012; 14(4):191-6.
• Article: Multiplex PCR-based Alu insertion polymorphisms genotyping for identifying individuals of Japanese ethnicity.

  Masaru Asari, Tomohiro Omura, Kumiko Oka, Chikatoshi Maseda, Yoshikazu Tasaki, Hiroshi Shiono, Kazuo Matsubara, Mitsuyoshi Matsuda, Keiko Shimizu
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  ABSTRACT: Discrimination of Alu insertions is a useful tool for geographic ancestry analysis, and is usually performed by Alu element amplification and agarose gel electrophoresis. Here, we have developed a new fluorescence-based method for multiple Alu genotyping in forensic identification. Allele frequencies were determined in 70 Japanese individuals, and we selected 30 polymorphic Alu insertions. Three primers were designed for each Alu locus to discriminate alleles using the 3-6 bp differences in amplicon sizes. Furthermore, we classified the amplification primers for the 30 loci into three different sets, and PCR using each set of primers provided 10 loci fragments ranging from 50 to 137 bp. Based on population data, the probability of incorrectly assigning a match was 3.7×10(-13). Three independent amplifications and subsequent capillary electrophoresis enabled the sensitive genotyping of small amounts of DNA, indicating that this method is suitable for identifying individuals of Japanese ethnicity.
  Genomics 01/2012; 99(4):227-32. · 3.02 Impact Factor
• Source

  Available from: PubMed Central

  Article: Oxaliplatin-induced neurotoxicity involves TRPM8 in the mechanism of acute hypersensitivity to cold sensation.

  Toru Kono, Machiko Satomi, Manabu Suno, Norihisa Kimura, Hirotaka Yamazaki, Hiroyuki Furukawa, Kazuo Matsubara
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  ABSTRACT: Oxaliplatin-induced peripheral neurotoxicity (OPN) is commonly associated with peripheral hypersensitivity to cold sensations (CS) but the mechanism is unknown. We hypothesized that the transient receptor potential melastatin 8 (TRPM8), a putative cold and menthol receptor, contributes to oxaliplatin cold hypersensitivity. To determine whether the TRPM8 is involved in acute OPN, varying concentrations of menthol were topically applied to the tongues of healthy subjects (n = 40) and colorectal cancer patients (n = 36) before and after oxaliplatin administration. The minimum concentration of menthol to evoke CS at the menthol application site was determined as the CS detection threshold (CDT). In healthy subjects, the mean CDT was 0.068. Sex and age differences were not found in the CDT. In advanced colorectal cancer patients, the mean CDT significantly decreased from 0.067% to 0.028% (P = 0.0039) after the first course of oxaliplatin infusions, and this marked CS occurred in patients who had grade 1 or less neurotoxicity, and grade 2 neurotoxicity, but not in those with grade 3 neurotoxicity. Further, the mean baseline CDT in oxaliplatin-treated patients was significantly higher than that of chemotherapy-naïve patients and healthy subjects (0.151% vs. 0.066%, P = 0.0225), suggesting that acute sensory changes may be concealed by progressive abnormalities in sensory axons in severe neurotoxicity, and that TRPM8 is subject to desensitization on repeat stimulation. Our study demonstrates the feasibility of undertaking CDT test in a clinical setting to facilitate the identification of early neurotoxicity. Moreover, our results indicate potential TRPM8 involvement in acute OPN.
  Brain and behavior. 01/2012; 2(1):68-73.
• Article: Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.

  Yoshikazu Tasaki, Joe Yamamoto, Tomohiro Omura, Toshihiro Noda, Naoya Kamiyama, Koichi Yoshida, Machiko Satomi, Tomoki Sakaguchi, Masaru Asari, Tomoko Ohkubo, Keiko Shimizu, Kazuo Matsubara
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  ABSTRACT: In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism.
  European journal of pharmacology 12/2011; 676(1-3):57-63. · 2.59 Impact Factor
• Article: HRD1 levels increased by zonisamide prevented cell death and caspase-3 activation caused by endoplasmic reticulum stress in SH-SY5Y cells.

  Tomohiro Omura, Masaru Asari, Joe Yamamoto, Naoya Kamiyama, Kumiko Oka, Chisato Hoshina, Chikatoshi Maseda, Toshio Awaya, Yoshikazu Tasaki, Hiroshi Shiono, Keiko Shimizu, Kazuo Matsubara
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  ABSTRACT: Zonisamide, which is commonly prescribed at high doses (200-400 mg/day) for the treatment of partial seizures, has recently been used at a low dose (25 mg/day) for improving parkinsonian syndrome. However, the molecular mechanisms that underlie the antiparkinsonian effects of zonisamide have not been clarified. Here we show that low micromolar concentrations of zonisamide prevented cleavage of caspase-3 and cell death in human dopaminergic SH-SY5Y neuroblastoma cells that were subjected to endoplasmic reticulum stress induced by tunicamycin or 6-hydroxydopamine. Hypodense zonisamide increased the expression levels of SEL1L, which is known to stabilize the ubiquitin ligase HRD1. Indeed, upregulation of HRD1 protein was observed. Thus, the results of this study strongly suggest that low concentrations of zonisamide inhibit neuronal cell death by increasing HRD1 protein levels in patients with Parkinson's disease. Consequently, in addition to the treatment of Parkinson's disease, the therapeutic potential of zonisamide should be considered for the treatment of several neurodegenerative disorders with pathophysiological mechanisms involving endoplasmic reticulum stress.
  Journal of Molecular Neuroscience 09/2011; 46(3):527-35. · 2.50 Impact Factor
• Article: [Longer working hours of pharmacists in the ward resulted in lower medication-related errors--survey of national university hospitals in Japan].

  Kazuo Matsubara, Akira Toyama, Hiroshi Satoh, Hiroshi Suzuki, Toshio Awaya, Yoshikazu Tasaki, Toshiaki Yasuoka, Ryuya Horiuchi
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  ABSTRACT: It is obvious that pharmacists play a critical role as risk managers in the healthcare system, especially in medication treatment. Hitherto, there is not a single multicenter-survey report describing the effectiveness of clinical pharmacists in preventing medical errors from occurring in the wards in Japan. Thus, we conducted a 1-month survey to elucidate the relationship between the number of errors and working hours of pharmacists in the ward, and verified whether the assignment of clinical pharmacists to the ward would prevent medical errors between October 1-31, 2009. Questionnaire items for the pharmacists at 42 national university hospitals and a medical institute included the total and the respective numbers of medication-related errors, beds and working hours of pharmacist in 2 internal medicine and 2 surgical departments in each hospital. Regardless of severity, errors were consecutively reported to the Medical Security and Safety Management Section in each hospital. The analysis of errors revealed that longer working hours of pharmacists in the ward resulted in less medication-related errors; this was especially significant in the internal medicine ward (where a variety of drugs were used) compared with the surgical ward. However, the nurse assignment mode (nurse/inpatients ratio: 1 : 7-10) did not influence the error frequency. The results of this survey strongly indicate that assignment of clinical pharmacists to the ward is critically essential in promoting medication safety and efficacy.
  YAKUGAKU ZASSHI 04/2011; 131(4):635-41. · 0.37 Impact Factor
• Article: [Dissolution behaviors of tablet and capsule covered with oblate or agar jelly for taking medicine easily].

  Nobumasa Hayase, Kuninori Iwayama, Ko-Ichi Ohtaki, Yasunori Yamashita, Toshio Awaya, Kazuo Matsubara
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  ABSTRACT: Drugs are sometimes covered with oblate or agar jelly. It is said that the medicinal effect of drugs covered with oblate is slow, but no studies have reported results confirming this. Therefore, we examined the dissolution behavior when the drug was covered with oblate or agar jelly. Three types of commercially available formulations of benzodiazepine were used: medazepam sugarcoated tablets, prazepam uncoated tablets, and clorazepate dipotassium capsules. Dissolution tests were performed using solutions of pH 1.2 and 5.6 to simulate normal gastric juice and gastric anacidity, respectively. Drugs covered with oblate were tested by the paddle method, and those covered with agar jelly were tested using the rotating basket method. Dissolution of clorazepate capsules not covered with oblate increased by approximately 10% when the pH was adjusted from 1.2 to 5.6, while those of medazepam and prazepam tablets decreased by approximately 40-60%. In contrast, the dissolution decreased significantly at both pH values for each drug covered with oblate. Dissolution further decreased when the amount of oblate was doubled. No detectable dissolution of medazepam tablets or of clorazepate capsules occurred when the drug was covered with agar jelly. Dissolution of prazepam tablets covered with agar jelly was only about 10% at the end of the test. These results indicate that dissolution is slowed and prolonged when a drug is covered with oblate or agar jelly, permitting sustained release of the drug. But, it is necessary to improve a suitable method for the dissolution.
  Yakugaku zasshi journal of the Pharmaceutical Society of Japan 01/2011; 131(1):161-8. · 0.39 Impact Factor
• Article: Enhanced discrimination of single nucleotide polymorphisms using 3' nucleotide differences in ligase detection reaction probes.

  Masaru Asari, Tomohiro Omura, Chikatoshi Maseda, Hiroshi Shiono, Yoshikazu Tasaki, Kazuo Matsubara, Keiko Shimizu
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  ABSTRACT: The ligase detection reaction (LDR) is a highly specific genotyping method for single nucleotide variations. Although LDR typically discriminates single nucleotide polymorphism (SNP) alleles at the 3' end of so-called LDR discriminating probes, we designed probes in which the position of nucleotide differences for discrimination was shifted to the second and third nucleotides from the 3' end. Using the 3'-modified probes, we targeted SNPs of the human ABO group and investigated the specificity and efficiency of ligation by a universal LDR assay. We demonstrated that one or two nucleotide shifts of differences in discriminating probes improve the allele balance in detecting both base substitutions and short deletions. In regard to short deletions, moreover, the shifts of nucleotide differences in discriminating probes form the perfect-machted or multiple-mismatched structures (the bulge structures) in the discriminating probe-target DNA duplex and may contribute to enhance ligation efficiency.
  Molecular and Cellular Probes 12/2010; 24(6):381-6. · 2.08 Impact Factor
• Article: Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin.

  Toru Kono, Machiko Satomi, Toshiyuki Asama, Yoshiaki Ebisawa, Naoyuki Chisato, Manabu Suno, Hidenori Karasaki, Hiroyuki Furukawa, Kazuo Matsubara
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  ABSTRACT: Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity.
  Journal of gastrointestinal oncology 12/2010; 1(2):97-101.
• Article: A new method for human ABO genotyping using a universal reporter primer system.

  Masaru Asari, Tomohiro Omura, Chikatoshi Maseda, Kazuo Matsubara, Hiroshi Shiono, Keiko Shimizu
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  ABSTRACT: We developed a new method for forensic ABO genotyping based on a universal reporter primer (URP) system. This allows for the simultaneous detection of six single nucleotide polymorphism (SNP) sites in the ABO gene (nucleotide positions 261, 297, 526, 703, 796, and 803). This URP system provides obvious peaks, ranging from 82 to 151 bp in length. ABO genotypes were classified and successfully genotyped by our method, including minor alleles that may cause a discrepancy between the genetic data and serological phenotypes. Full profiles were identified using as little as 0.1 ng (0.05 ng ⁄ reaction) of standard K562 and 9947A DNA. Moreover, the success rate of genotyping from a URP system was much higher than that from a conventional primer extension method in degraded DNA. This method enables simple and rapid detection of multiple SNP sites on human ABO genes and is highly specific and sensitive when using limited and degraded DNA.
  Journal of Forensic Sciences 11/2010; 55(6):1576-81. · 1.23 Impact Factor
• Article: Meloxicam protects cell damage from 1-methyl-4-phenyl pyridinium toxicity via the phosphatidylinositol 3-kinase/Akt pathway in human dopaminergic neuroblastoma SH-SY5Y cells.

  Yoshikazu Tasaki, Tomohiro Omura, Takehiro Yamada, Tomoko Ohkubo, Manabu Suno, Shinya Iida, Tomoki Sakaguchi, Masaru Asari, Keiko Shimizu, Kazuo Matsubara
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  ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal death in the substantia nigra pars compacta. There is growing interest in the effects of nonsteroidal antiinflammatory drugs (NSAIDs) against PD progression. In this study, we investigated the neuroprotective effect of NSAIDs on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP(+)) in human dopaminergic SH-SY5Y neuroblastoma cells. Of the NSAIDs tested, only meloxicam indicated protective effect on MPP(+)-induced neurotoxicity in SH-SY5Y cells, although such an effect was not established with indomethacin, ibuprofen and cyclooxygenase (COX)-2 selective inhibitors (NS-398 and CAY-10404). The neuroprotective effect of meloxicam against MPP(+) toxicity was specific, as toxicities induced by other cytotoxic agents (such as rotenone, MG-132, tunicamycin and ethacrynic acid) were not attenuated by meloxicam. The neuroprotective effect of meloxicam on MPP(+)-induced apoptosis was abolished by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, but not by a MEK inhibitor, PD98059. The Akt phosphorylation levels were predominantly suppressed 4h after MPP(+) incubation (i.e. when the cell toxicity was not apparently observed yet). Meloxicam completely prevented the Akt phosphorylation suppression caused by MPP(+) exposure, while meloxicam per se did not promote the Akt phosphorylation. These results strongly suggest that the neuroprotective effect of meloxicam is mediated by the maintenance of cell survival signaling in the PI3K/Akt pathway, but not by COX-2 inhibition. Therefore, meloxicam may have therapeutic potential in preventing development or delaying progress of PD.
  Brain research 05/2010; 1344:25-33. · 2.46 Impact Factor
• Article: [Survey of oxaliplatin-associated peripheral sensory neuropathy using an interview-based questionnaire in patients with advanced colorectal cancer].

  Machiko Satomi, Toru Kono, Noriaki Mamiya, Naoyuki Chisato, Yoshiaki Ebisawa, Mutsubu Sugawara, Takashige Saito, Kazuo Matsubara, Shinichi Kasai
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  ABSTRACT: In performing FOLFOX chemotherapy (infusional 5-FU/LV with oxaliplatin) for advanced colorectal cancer, the neurotoxicity of oxaliplatin (L-OHP) is the dose-limiting factor. A retrospective study of 25 consecutive patients, receiving modified FOLFOX6 (mFOLFOX6) for advanced colorectal cancer, was conducted. From March 2006 to February 2008, we investigated the process of development of sensory neuropathy by adverse effect grading and our original interview-based intake about the afflicted regions. Neurotoxicity developed in 21 cases (84%) after 6 courses and the cumulative L-OHP dose was 410 mg/m(2) in median. In 11 cases (52%), it developed from the fingers, while in 8 cases (38%), it occurred from the fingers and toes simultaneously. It developed from the toes or tongue only in one case each. In 6 cases (55%), in which it occurred from the fingers, the symptom aggravated to grade 2 (G2) according to the Neurotoxicity Criteria of DEBIOPHARM (DEBNTC). On the other hand, in cases of coexpression of the fingers and toes, 7 cases (88%) developed G2 neuropathy, among one of whom suffered from grade 3 (G3). The coexistence of diabetes mellitus without neuropathy had no influence on the development of the neurotoxicity in the grading of DEB-NTC. One month after the last mFOLFOX6 therapy, neurotoxicity newly developed in one case, and was aggravated in two cases two months after cessation of the chemotherapy. Therefore, careful observation of the course should be continued even after the end of mFOLFOX6 therapy. Our results suggest that L-OHP neurotoxicity develops on fingers or fingers and toes simultaneously in most cases. And when it occurred on fingers and toes simultaneously, it would aggravate to G2 or G3 during the chemotherapy. The interviewed-based intake about the afflicted region, such as ours, can be used to predict the deterioration of the neurotoxicity.
  Gan to kagaku ryoho. Cancer & chemotherapy 09/2009; 36(8):1321-5.
• Article: Detection of landiolol using high-performance liquid chromatography/fluorescence: a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.

  Manabu Suno, Takayuki Kunisawa, Akio Yamagishi, Takashi Ono, Joe Yamamoto, Takehiro Yamada, Yoshikazu Tasaki, Keiko Shimizu, Hiroshi Iwasaki, Kazuo Matsubara
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  ABSTRACT: Landiolol hydrochloride, a new adrenergic beta(1)-selective antagonist having an ultra-short half-life, is used to prevent tachyarrhythmia during surgery. Since landiolol is thought to be rapidly hydrolyzed to an inactivate metabolite by esterases, quantification of the drug concentration in the blood is impractical. The landiolol concentration in blood was halved within 5 min after blood sampling. This degradation was effectively prevented by pre-treatment with neostigmine (100 microg) in the sampling tube, but not by EDTA pre-treatment, indicating that landiolol could be metabolized by pseudocholinesterase in plasma. After the one-step solid-phase extraction, fluorescence detection of landiolol reduced chromatographic background signals and then improved assay sensitivity to the lower limit of 10 ng/ml in blood; this reproducible approach yielded coefficient variation of less than 6%. The blood concentration-time profile of landiolol hydrochloride in patients of the present investigation afforded more practical assessment than previously reported studies, thus improving accuracy and facilitating detailed pharmacokinetic study in relation to the pharmacological action of drug.
  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2009; 877(16-17):1705-8. · 2.78 Impact Factor
• Article: Single nucleotide polymorphism genotyping by mini-primer allele-specific amplification with universal reporter primers for identification of degraded DNA.

  Masaru Asari, Satoshi Watanabe, Kazuo Matsubara, Hiroshi Shiono, Keiko Shimizu
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  ABSTRACT: Single nucleotide polymorphism (SNP) is informative for human identification, and much shorter regions are targeted in analysis of biallelic SNP compared with highly polymorphic short tandem repeat (STR). Therefore, SNP genotyping is expected to be more sensitive than STR genotyping of degraded human DNA. To achieve simple, economical, and sensitive SNP genotyping for identification of degraded human DNA, we developed 18 loci for a SNP genotyping technique based on the mini-primer allele-specific amplification (ASA) combined with universal reporter primers (URP). The URP/ASA-based genotyping consisted of two amplifications followed by detection using capillary electrophoresis. The sizes of the target genome fragments ranged from 40 to 67bp in length. In the Japanese population, the frequencies of minor alleles of 18 SNPs ranged from 0.36 to 0.50, and these SNPs are informative for identification. The success rate of SNP genotyping was much higher than that of STR genotyping of artificially degraded DNA. Moreover, we applied this genotyping method to case samples and showed successful SNP genotyping of severely degraded DNA from a 4-year buffered formalin-fixed tissue sample for human identification.
  Analytical Biochemistry 12/2008; 386(1):85-90. · 3.00 Impact Factor
• Article: An autopsy case of sudden death due to acute gastric dilatation without rupture.

  Satoshi Watanabe, Koichi Terazawa, Masaru Asari, Kazuo Matsubara, Hiroshi Shiono, Keiko Shimizu
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  ABSTRACT: We report the first autopsy case of fatal gastric dilatation without rupture. A 31-year-old woman who lived alone was found dead in her living room. Despite being very thin, she showed marked abdominal distention. Autopsy and histological findings revealed that a severely distended stomach, of which walls notably thin and displayed transmural necrosis, occupied the entire abdominal cavity. Severe congestion was observed in the intestine and cecum. Theses findings suggest that bulimia nervosa together with anorexia nervosa resulted in rapid dilation of the stomach. We conclude that the cause of death was acute circulatory failure from hypovolemic shock that occurred following compression of the inferior vena cava and superior mesenteric vein, and by loss of circulatory volume to the third space.
  Forensic science international 09/2008; 180(2-3):e6-e10. · 2.10 Impact Factor
• Article: Improved high-performance liquid chromatographic detection of paclitaxel in patient's plasma using solid-phase extraction, and semi-micro-bore C18 separation and UV detection.

  Manabu Suno, Takashi Ono, Shinya Iida, Noriko Umetsu, Ko-ichi Ohtaki, Takehiro Yamada, Toshio Awaya, Machiko Satomi, Yoshikazu Tasaki, Keiko Shimizu, Kazuo Matsubara
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  ABSTRACT: Although a number of analytical methods for taxanes have been published, none of them are sufficiently suitable for use in a medical setting. In this study, we established an improved analytical HPLC/UV detection method using a Sep-Pak C18 cartridge for extraction and a semi-micro-borecolumn for separation. This method employed here reduced chromatographic background signals, and allowed a more sensitive analysis of taxanes in human blood sample. The recovery of taxanes after the solid-phase extraction procedure was over 90%. Chromatographic separation of paclitaxel and docetaxel was achieved within 30 min with no interference peak by a semi-micro-bore column, packed either with C18 (Wakosil 5C18 RS) or pentafluorophenyl (Curosil/Taxol) materials. The method was reproducible with coefficients of variation less than 6%. This analytical procedure was simple and sensitive with lower quantification limit of 3 ng/ml. The improved sensitivity achieved by the popular HPLC/UV apparatus, which is available in hospitals, would vouch safer and more efficient therapy with taxane.
  Journal of Chromatography B 01/2008; 860(1):141-4. · 2.89 Impact Factor
• Source

  Available from: Yoshikazu Tasaki

  Article: Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.

  Kazuo Matsubara, Keiko Shimizu, Manabu Suno, Kento Ogawa, Toshio Awaya, Takehiro Yamada, Toshihiro Noda, Machiko Satomi, Ko-ichi Ohtaki, Kaoru Chiba, Yoshikazu Tasaki, Hiroshi Shiono
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  ABSTRACT: Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their highest concentrations in the frontal cortex, subthalamic nucleus and entopeduncular nucleus as well as the dorsal and median raphe nucleus. There is growing evidence that 5-HT1A receptor agonists have an antidepressant effect in individuals with major depressive disorders. Recent clinical studies suggest that tandospirone, a highly potent and selective 5-HT1A receptor agonist used clinically as an antidepressant in Japan and China, may act as an antiparkinsonian drug. In the present study, we investigated the effect of tandospirone on contralateral rotational behavior in a unilateral hemiparkinsonian rat model produced with 6-hydroxydopamine (6-OHDA). Tandospirone, as well as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), significantly increased contralateral turnings in a dose-dependent manner (0.5-10 mg/kg). Tandospirone also remarkably potentiated the contralateral turning induced by 0.025 mg/kg of apomorphine. Pretreatment with WAY-100635, a 5-HT1A receptor antagonist, almost completely blocked the contralateral turning behavior evoked by tandospirone and 8-OHDPAT, but not that by apomorphine. SCH-23390, a selective dopamine D1 receptor antagonist, did not affect on the tandospirone-induced rotational behavior. These results suggested that tandospirone could act on postsynaptic 5-HT1A receptors and modulate excitatory amino acid pathways in the basal ganglia. Thus, tandospirone could have therapeutic potential for the treatment of Parkinson's disease by modulating neuronal activities of non-dopaminergic pathways.
  Brain Research 10/2006; 1112(1):126-33. · 2.73 Impact Factor