YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
Volume 122, Issue 7
Displaying 1-9 of 9 articles from this issue
Reviews
  • Mitsuo WATANABE
    Article type: Review
    2002 Volume 122 Issue 7 Pages 429-434
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    We developed methods for the fluorometric assay of 3-hydroxykynurenine and 3-hydroxy-anthranilic acid, which are suspected as carcinogens in bladder cancer. It was shown that the urinary excretion of 3-hydroxyanthranilic acid increased in patients with bladder cancer. We also developed methods for the fluorometric assay of glucuronide and sulfate of 3-hydroxyanthranilic acid and showed that the excretion of these conjugated forms was minor in humans. The distribution of 3-hydroxykynurenine was studied and data obtained suggested that it has an affinity for the pancreas. We then developed methods for determination of the related compounds of tryptophan. Fluorescence reaction with UV radiation was applied to the determinations of kynurenic acid, kynurenine, quinolinic acid, nicotinic acid, nicotinamide, N1-methyl-nicotinamide, isatin, xanthrenic acid, and melatonin in the serum or urine. Furthermore, the fluorescence reaction with UV radiation was applied to some drugs, e.g., indomethacin, isoniazid, naldixic acid, nicorandil, and disodium cromoglycate. The relationship was investigated between the tumor promoter, 12-tetradecanoyl-phobol-13-acetate (TPA), and delayed hypersensitivity in mice. The foot pad reaction (FPR) in mice was suppressed by the application of TPA following the application of 7,12-dimethylbenz[α]-anthracene (DMBA), a tumor initiator, in BALB/c mice, while the FPR was suppressed by the application of TPA alone in C3H/He mice. CD8+ and CD4+ T cells, which suppress the FPR, were induced in BALB/c and C3H/He mice, respectively. These T cells produced soluble factors that inhibited the FPR in mice.
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  • Hiroshi KITAGAWA
    Article type: Review
    2002 Volume 122 Issue 7 Pages 435-450
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    Sulfated glycosaminoglycans including heparin/heparan sulfate and chondroitin/dermatan sulfate have been implicated in numerous pathophysiological phenomena in vertebrates and invertebrates. The critical roles of glycosaminoglycans, especially heparan sulfate, in developmental processes involving the signaling of morphogens such as Wingless and Hedgehog proteins, as well as of fibroblast growth factor, in Drosophila have recently become evident. In biosynthesis, the tetrasaccharide sequence (GlcA-Gal-Gal-Xyl-), designated the protein linkage region, is first built on a specific Ser residue at the glycosaminoglycan attachment site of a core protein. A heparin/heparan sulfate chain is then polymerized on this fragment by alternate additions of N-acetylglucosamine and glucuronic acid (GlcA) through the actions of glycosyltransferases with overlapping specificity encoded by the tumor suppressor EXT family genes. In contrast, a chondroitin/dermatan sulfate chain is synthesized on the linkage region by alternate additions of N-acetylgalactosamine and GlcA through the actions of glycosyltransferases, designated chondroitin synthases. Recent studies have achieved purification of a few and molecular cloning of all of the glycosyltransferases responsible for these reactions and have revealed the bifunctional nature of a few of these enzymes. The availability of the cDNA probes has provided several important clues to help solve the molecular mechanisms of the biosynthetic sorting of heparin/heparan sulfate and chondroitin/dermatan sulfate chains, as well as of the chain elongation and polymerization of these glycosaminoglycans.
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  • Masahiro HIRATSUKA
    Article type: Review
    2002 Volume 122 Issue 7 Pages 451-463
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    Clinically important genetic polymorphisms influencing drug metabolism and drug response have typically been discovered on the basis of phenotypic differences among individuals from different populations. Routine genotyping before drug therapy may enable the identification of responders, nonresponders, or patients at increased risk of toxicity. Automated, high-throughput detecting methods for single-nucleotide polymorphisms (SNPs) are highly desirable in many clinical laboratories. The aim of this study is to develop a high-throughput genotyping method for detecting SNPs influencing drug response in the Japanese population. We have developed three real-time PCR assays for detecting SNPs in the human drug-metabolizing enzymes and drug targets. The assay for simultaneously detecting CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A5, NAT2, TPMT, DPYD, UGT1A1, ALDH2, ADH2, MDR1, CETP, DCP-1, ADRB2, HTR2A, INPP1, SDF1, and mitochondrial DNA polymorphisms takes less than 1.5h. With the clinical application of NAT2 genotyping, we found statistically significant difference between the incidence of adverse drug reactions (ADRs) and the NAT2 genotype. The incidence of the ADRs was significantly higher in the slow type than the in other two types, as 5 of the 6 patients were of the slowtype, and the other was the intermediatetype, while no patients of the rapidtype has developed any ADRs.
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  • Naozumi NISHIZONO
    Article type: Review
    2002 Volume 122 Issue 7 Pages 465-469
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    Neomycin B has been found to block the binding of HIV-1 Rev protein to its viral RNA recognition site, thereby inhibiting the production of the virus. This paper describes the synthesis of analogues of neomycin B, which are potential anti-HIV compounds designed as inhibitors of Rev/RRE binding.
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  • Kazuya OOI
    Article type: Review
    2002 Volume 122 Issue 7 Pages 471-480
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    The sequence dependency of the antitumor effect of etoposide and cytarabine (ara-C) was investigated against the L1210 ascites tumor in BDF1 mice. Etoposide (7.5mg/kg or 15mg/kg) and ara-C (25mg/kg or 500mg/kg) were administered intraperitoneally on days 1,4, and 7 after inoculation of L1210 cells with or without a time interval of 3 or 6h. Simultaneous administration of etoposide and ara-C produced a 70% cure rate. At every dosage examined, pretreatment with etoposide given 6h before ara-C was the most effective antitumor schedule in L1210 leukemia. At 1h after injection of ara-C, 3h and 6h pretreatment with etoposide 15mg/kg increased ara-C incorporation to more than 200% as compared with that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. Deoxycytidine kinase (dCK) is a rate-limiting enzyme for the activation of ara-C. We demonstrated that dCK activity was increased within 1h after exposure to etoposide. Much more attention must be paid to the timing of the administration of etoposide in combination chemotherapy with etoposide and ara-C.
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Notes
  • Keiko KANAYA, Hironori NAGAHIRA, Hiroyuki HURUKAWA, Ryo MATSUSHITA, Hi ...
    Article type: Note
    2002 Volume 122 Issue 7 Pages 481-485
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    This paper analyzes the effects of the revision of medical repayment standards in April 2000 on pharmaceutical care and economics. The total number of sessions of counseling that can be claimed in 1 month has apparently improved at the Pediatrics Department of Kanazawa University Hospital. On the other hand, actual repayment for said services has not necessarily risen accordingly. This was shown by adopting new calculation modalities for actual claims before revision. We believe that this discrepancy occurs because the charge for each service has decreased from 480 points to 350 points, while maximum number of effective claims per month has risen from twice to four times.
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  • Chikaku DOGASAKI, Tetsuya SHINDO, Katsunori FURUHATA, Masafumi FUKUYAM ...
    Article type: Note
    2002 Volume 122 Issue 7 Pages 487-494
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    We previously reported that certain constituents in brewed coffee exhibited antibacterial activities against a strain of Legionella pneumophila. The constituents showing antibacterial activities were included only in extracts cold with water or hot water. To determine the antibacterial substances in coffee extract, the extract was fractionated by HPLC using a UV/photodiode array detector. The optimum HPLC conditions for analysis were UV wavelength of 250nm and eluents of methanol/acetic acid (10/90), pH3.0. When several fractions separated by HPLC were investigated for antibacterial activities against L. pneumophila, it was found that three peak fractions exhibited strong antibacterial activities. Each product from these fractions was analyzed by NMR and LC-mass spectrometry, and the chemical structure of each was determined. It was shown that the antibacterial substances was were protocatechuic acid (3,4-dihydroxy benzoic acid), chlorogenic acid, and caffeic acid.
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  • Yukihiro YAMAGUCHI, Sachiko NIMBARI, Hiroko OBATA, Tomomi OOKAWARA, Hi ...
    Article type: Note
    2002 Volume 122 Issue 7 Pages 495-498
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    The direct sequencing of PCR products, a bacterial colony (plasmid DNA), or a phage plaque (λDNA) is a very powerful technique in several molecular biological applications. Recently, we reported the successful application of this direct sequencing methodology, called recyclesequencing. Occasionally, however, our sequencing efforts failed due to the presence of agarose gel containing Luria-Bertani (LB) medium. Consequently, we pursued a semiquantitative investigation of the inhibitory effects of agarose and LB medium on the direct sequencing reaction. We found that LB medium concentrations greater than 26.7% inhibited the sequencing reaction. Furthermore, agarose concentrations greater than 0.20% in a reaction mixture also inhibited the sequencing reaction.
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Articles
  • Kazuko UJITA, Keiko OHNO, Masayuki HASHIGUCHI, Hirotoshi ECHIZEN, Tada ...
    Article type: Article
    2002 Volume 122 Issue 7 Pages 499-506
    Published: July 01, 2002
    Released on J-STAGE: February 18, 2003
    JOURNAL FREE ACCESS
    Objectives: In recent years, the therapeutic implications of dyslipidemias have been clarified in large-scale epidemiologic surveys, and the validity of pharmacotherapy has been established. We investigated the practical realities of pharmacotherapy for dyslipidemias at a community hospital in Japan.
    Methods: Medical chart surveys were performed retrospectively on 451 dyslipidemic outpatients who visited a community hospital in Japan in July 1997. We collected clinical data from medical charts regarding selected drugs for dyslipidemias, serum lipid levels before drug treatment and after one year of treatment, and risk factors for coronary heart disease (CHD).
    Results: Regardless of dyslipidemia phenotype, approximately 80% of patients were administered statins. The possibility was raised that physicians recorded risk factors in medical charts incompletely, particularly with regard to family CHD history, smoking, and obesity. Based on Japanese and us guidelines for dyslipidemias, low-density lipoprotein (LDL) cholesterol levels fully satisfied the requirements for initiating pharmacotherapy in the present study. However, the higher the risk of CHD, the lower the percentage of subjects who met the treatment goals defined by both guidelines. Only 23% of patients at high risk for CHD controlled LDLcholesterol sufficiently based on Japanese guidelines.
    Conclusion: To optimize pharmacotherapy for dyslipidemias, medical staff should assess risk factors for CHD more completely and attempt to achieve full control of serum lipids, particularly in patients at high risk for CHD.
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