Author Report for: Tanaka MNo contact information in database for Tanaka M
Selvaraj P, Tanaka M, Wen J, Zhang Y Ref: Cells, 10:, 2021 : PubMed ESTHER: Selvaraj_2021_Cells_10_3454 PubMedSearch: Selvaraj 2021 Cells 10 3454 PubMedID: 34943962 Inhibitor(s) related to this paper: MJN110 Abstract Modulation of the endocannabinoid system has emerged as an effective approach for the treatment of many neurodegenerative and neuropsychological diseases. However, the underlying mechanisms are still uncertain. Using a repetitive mild traumatic brain injury (mTBI) mouse model, we found that there was an impairment in locomotor function and working memory within two weeks post-injury, and that treatment with MJN110, a novel inhibitor of the principal 2-arachidononyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase dose-dependently ameliorated those behavioral changes. Spatial learning and memory deficits examined by Morris water maze between three and four weeks post-TBI were also reversed in the drug treated animals. Administration of MJN110 selectively elevated the levels of 2-AG and reduced the production of arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) in the TBI mouse brain. The increased production of proinflammatory cytokines, accumulation of astrocytes and microglia in the TBI mouse ipsilateral cerebral cortex and hippocampus were significantly reduced by MJN110 treatment. Neuronal cell death was also attenuated in the drug treated animals. MJN110 treatment normalized the expression of the NMDA receptor subunits NR2A and NR2B, the AMPA receptor subunits GluR1 and GluR2, and the GABA(A) receptor subunits alpha1, beta2,3 and gamma2, which were all reduced at 1, 2 and 4 weeks post-injury. The reduced inflammatory response and restored glutamate and GABA receptor expression likely contribute to the improved motor function, learning and memory in the MJN110 treated animals. The therapeutic effects of MJN110 were partially mediated by activation of CB1 and CB2 cannabinoid receptors and were eliminated when it was co-administered with DO34, a novel inhibitor of the 2-AG biosynthetic enzymes. Our results suggest that augmentation of the endogenous levels of 2-AG can be therapeutically useful in the treatment of TBI by suppressing neuroinflammation and maintaining the balance between excitatory and inhibitory neurotransmission. Title: Prepregnancy Assessment of Liver Function to Predict Perinatal and Postpregnancy Outcomes in Biliary Atresia Patients with Native Liver Takahashi N, Ochiai D, Yamada Y, Tamagawa M, Kanamori H, Kato M, Ikenoue S, Kasuga Y, Kuroda T, Tanaka M Ref: J Clin Med, 10:, 2021 : PubMed ESTHER: Takahashi_2021_J.Clin.Med_10_ PubMedSearch: Takahashi 2021 J.Clin.Med 10 PubMedID: 34501403 Abstract Considering that some biliary atresia (BA) survivors with native liver have reached reproductive age and face long-lasting complications, specific attention needs to be paid to pregnant cases. This study aimed to investigate the relationship between liver function, perinatal outcomes, and prognosis. A database review was conducted to identify pregnant BA cases with native liver and perinatal data, and clinical information on BA-related complications was analyzed. Perinatal serum cholinesterase (ChE) levels, model for end-stage liver-disease (MELD) score, and platelet trends were analyzed, and the association between these indicators and perinatal outcomes was investigated. Patients were categorized into three groups according to the perinatal clinical outcomes: favorable (term babies with or without several episodes of cholangitis; n = 3), borderline (term baby and following liver dysfunction; n = 1), and unfavorable (premature delivery with subsequent liver failure; n = 1). Lower serum ChE levels, lower platelet counts, and higher MELD scores were observed in the unfavorable category. Borderline and unfavorable patients displayed a continuous increase in MELD score, with one eventually needing a liver transplantation. Pregnancy in patients with BA requires special attention. Serum ChE levels, platelet counts, and MELD scores are all important markers for predicting perinatal prognosis. Title: Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat Kitadokoro K, Tanaka M, Hikima T, Okuno Y, Yamamoto M, Kamitani S Ref: Sci Rep, 10:5469, 2020 : PubMed ESTHER: Kitadokoro_2020_Sci.Rep_10_5469 PubMedSearch: Kitadokoro 2020 Sci.Rep 10 5469 PubMedID: 32214208 Gene_locus related to this paper: staau-lipas Inhibitor(s) related to this paper: Orlistat Abstract Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical alpha/beta hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat-lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases. Title: Identification and Characterization of a New Carboxylesterase 2 Isozyme, mfCES2C, in the Small Intestine of Cynomolgus Monkeys Ohura K, Igawa Y, Tanaka M, Matsumoto K, Kasahara A, Wada N, Kubota K, Uno Y, Imai T Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 48:146, 2020 : PubMed ESTHER: Ohura_2020_Drug.Metab.Dispos_48_146 PubMedSearch: Ohura 2020 Drug.Metab.Dispos 48 146 PubMedID: 31836607 Gene_locus related to this paper: macfa-a0a2k5uar1 Abstract In contrast to a single human carboxylesterase 2 (CES2) isozyme (hCE2), three CES2 genes have been identified in cynomolgus monkeys: mfCES2A, mfCES2B, and mfCES2C . Although mfCES2A protein is expressed in several organs, mfCES2B is a pseudogene and the phenotype of the mfCES2C gene has not yet been clarified in tissues. In previous studies, we detected an unidentified esterase in the region of CES2 mobility upon nondenaturing PAGE analysis of monkey intestinal microsomes, which showed immunoreactivity for anti-mfCES2A antibody. The aim of the present study was to identify this unidentified esterase from monkey small intestine. The esterase was separated on nondenaturing PAGE gel and digested in-gel with trypsin. The amino acid sequences of fragmented peptides were analyzed by tandem mass spectrometry. The unidentified esterase was shown to be identical to mfCES2C (XP_015298642.1, predicted from the genome sequence data). mfCES2C consists of 559 amino acid residues and shows approximately 90% homology with mfCES2A (561 amino acid residues). In contrast to the ubiquitous expression of mfCES2A, mfCES2C is only expressed in the small intestine, kidney, and skin. The hydrolytic properties of recombinant mfCES2C, expressed in HEK293 cells, with respect to p-nitrophenyl derivatives, 4-methylumbelliferyl acetate, and irinotecan were similar to those of recombinant mfCES2A. However, mfCES2C showed a hydrolase activity for O-n-valeryl propranolol higher than mfCES2A. It is concluded that the previously unidentified monkey intestinal CES2 is mfCES2C, which shows different hydrolytic properties to mfCES2A, depending on the substrate. SIGNIFICANCE STATEMENT: In the present research, we determined that mfCES2C, a novel monkey CES2 isozyme, is expressed in the small intestine and kidney of the cynomolgus monkey. Interestingly, mfCES2C showed a relatively wide substrate specificity for ester-containing compounds. These findings may, in early stages of drug development, support the use of in vitro-to-in vivo extrapolation for the intestinal hydrolysis of ester drugs in the cynomolgus monkey. Title: TAK-071, a novel M1 positive allosteric modulator with low cooperativity, improves cognitive function in rodents with few cholinergic side effects Sako Y, Kurimoto E, Mandai T, Suzuki A, Tanaka M, Suzuki M, Shimizu Y, Yamada M, Kimura H Ref: Neuropsychopharmacology, 44:950, 2019 : PubMed ESTHER: Sako_2019_Neuropsychopharmacology_44_950 PubMedSearch: Sako 2019 Neuropsychopharmacology 44 950 PubMedID: 30089885 Abstract The muscarinic M1 receptor (M1R) is a promising target for treating cognitive impairment associated with cholinergic deficits in disorders such as Alzheimer's disease and schizophrenia. We previously reported that cooperativity (alpha-value) was key to lowering the risk of diarrhea by M1R positive allosteric modulators (M1 PAMs). Based on this, we discovered a low alpha-value M1 PAM, TAK-071 (alpha-value: 199), and characterized TAK-071 using T-662 as a reference M1 PAM with high alpha-value of 1786. Both TAK-071 and T-662 were potent and highly selective M1 PAMs, with inflection points of 2.7 and 0.62 nM, respectively. However, T-662 but not TAK-071 augmented isolated ileum motility. TAK-071 and T-662 increased hippocampal inositol monophosphate production through M1R activation and improved scopolamine-induced cognitive deficits in rats at 0.3 and 0.1 mg/kg, respectively. TAK-071 and T-662 also induced diarrhea at 10 and 0.1 mg/kg, respectively, in rats. Thus, taking into consideration the fourfold lower brain penetration ratio of T-662, TAK-071 had a wider margin between cognitive improvement and diarrhea induction than T-662. Activation of M1R increases neural excitability via membrane depolarization, reduced afterhyperpolarization, and generation of afterdepolarization in prefrontal cortical pyramidal neurons. T-662 induced all three processes, whereas TAK-071 selectively induced afterdepolarization. Combining sub-effective doses of TAK-071, but not T-662, with an acetylcholinesterase inhibitor, significantly ameliorated scopolamine-induced cognitive deficits in rats. TAK-071 may therefore provide therapeutic opportunities for cognitive dysfunction related to cholinergic deficits or reduced M1R expression, while minimizing peripheral cholinergic side effects. Title: Staphylococcus aureus lipase: purification, kinetic characterization, crystallization and crystallographic study Tanaka M, Kamitani S, Kitadokoro K Ref: Acta Crystallographica F Struct Biol Commun, 74:567, 2018 : PubMed ESTHER: Tanaka_2018_Acta.Crystallogr.F.Struct.Biol.Commun_74_567 PubMedSearch: Tanaka 2018 Acta.Crystallogr.F.Struct.Biol.Commun 74 567 PubMedID: 30198889 Gene_locus related to this paper: staau-lipas Abstract Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor in S. aureus and may be a therapeutic target for infectious diseases caused by S. aureus. For the purposes of anti-SAL drug development using structure-based drug design, X-ray crystallographic analysis of SAL overexpressed in Escherichia coli was performed. The recombinant protein was purified using a three-step protocol involving immobilized metal-affinity chromatography, cation-exchange chromatography and anion-exchange chromatography flowthrough methods, yielding 40 mg of protein per litre of bacterial culture. Crystals were obtained using the sitting-drop vapor-diffusion technique. Diffraction data to 3.0 A resolution were collected on the BL44XU beamline at SPring-8 at the zinc peak of 1.2842 A for SAD phasing. The crystals belonged to space group P4122 or P4322, with unit-cell parameters a = 131.0, b = 131.0, c = 250.6 A, and are likely to contain four SAL molecules (408 residues) per asymmetric unit. Title: Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver Uno Y, Igawa Y, Tanaka M, Kayoko O, Hosokawa M, Imai T Ref: Xenobiotica, :1, 2018 : PubMed ESTHER: Uno_2018_Xenobiotica__1 PubMedSearch: Uno 2018 Xenobiotica 1 PubMedID: 29384423 Abstract 1. Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. 2. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1), and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. 3. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. 4. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. 5. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1. Title: WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms Wen J, Jones M, Tanaka M, Selvaraj P, Symes AJ, Cox B, Zhang Y Ref: J Neuroinflammation, 15:9, 2018 : PubMed ESTHER: Wen_2018_J.Neuroinflammation_15_9 PubMedSearch: Wen 2018 J.Neuroinflammation 15 9 PubMedID: 29310667 Inhibitor(s) related to this paper: WWL70 Abstract BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects. We have shown that inhibition of ABHD6 significantly reduces neuroinflammation and exerts neuroprotection in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 inhibition on neuropathic pain has not been explored. METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the mouse sciatic nerve and examined by Hargreaves and Von Frey tests. Activation of inflammatory cells and the production of cytokines and chemokines in the spinal cord dorsal horn, dorsal root ganglion (DRG), and sciatic nerve were assessed by qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The levels of 2-AG and arachidonic acid (AA) in sciatic nerve were quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: Treatment with the selective ABHD6 inhibitor WWL70 significantly alleviated CCI-induced thermal hyperalgesia and mechanical allodynia. Microglia activation, macrophage infiltration, and the production of nociceptive mediators were reduced in the ipsilateral lumbar spinal cord dorsal horn, DRG, and sciatic nerve of WWL70-treated animals. The diminished cytokine and chemokine production is likely due to the inhibitory effect of WWL70 on NF-kappaB phosphorylation. Surprisingly, the anti-nociceptive and anti-inflammatory effects of WWL70 were not reversed by addition of the cannabinoid receptor antagonists. Treatment with WWL70 did not alter the levels of 2-AG, AA, and the phosphorylation of cytosolic phospholipase A2 (cPLA2), but significantly reduced the production of prostaglandin E2 (PGE2) and the expression of cyclooxygenase-2 (COX-2) and prostaglandin E synthase-2 (PGES2) in the injured sciatic nerve. CONCLUSIONS: This study reveals a novel mechanism for the antinociceptive effect of the 2-AG catabolic enzyme ABHD6 inhibitor WWL70. Understanding the interaction between endocannabinoid and eicosanoid pathways might provide a new avenue for the treatment of inflammatory and neuropathic pain. Title: The karrikin receptor KAI2 promotes drought resistance in Arabidopsis thaliana Li W, Nguyen KH, Chu HD, Ha CV, Watanabe Y, Osakabe Y, Leyva-Gonzalez MA, Sato M, Toyooka K and Tran LP <9 more author(s)> Li W, Nguyen KH, Chu HD, Ha CV, Watanabe Y, Osakabe Y, Leyva-Gonzalez MA, Sato M, Toyooka K, Voges L, Tanaka M, Mostofa MG, Seki M, Seo M, Yamaguchi S, Nelson DC, Tian C, Herrera-Estrella L, Tran LP (- 9) Ref: PLoS Genet, 13:e1007076, 2017 : PubMed ESTHER: Li_2017_PLoS.Genet_13_e1007076 PubMedSearch: Li 2017 PLoS.Genet 13 e1007076 PubMedID: 29131815 Gene_locus related to this paper: arath-KAI2.D14L Abstract Drought causes substantial reductions in crop yields worldwide. Therefore, we set out to identify new chemical and genetic factors that regulate drought resistance in Arabidopsis thaliana. Karrikins (KARs) are a class of butenolide compounds found in smoke that promote seed germination, and have been reported to improve seedling vigor under stressful growth conditions. Here, we discovered that mutations in KARRIKIN INSENSITIVE2 (KAI2), encoding the proposed karrikin receptor, result in hypersensitivity to water deprivation. We performed transcriptomic, physiological and biochemical analyses of kai2 plants to understand the basis for KAI2-regulated drought resistance. We found that kai2 mutants have increased rates of water loss and drought-induced cell membrane damage, enlarged stomatal apertures, and higher cuticular permeability. In addition, kai2 plants have reduced anthocyanin biosynthesis during drought, and are hyposensitive to abscisic acid (ABA) in stomatal closure and cotyledon opening assays. We identified genes that are likely associated with the observed physiological and biochemical changes through a genome-wide transcriptome analysis of kai2 under both well-watered and dehydration conditions. These data provide evidence for crosstalk between ABA- and KAI2-dependent signaling pathways in regulating plant responses to drought. A comparison of the strigolactone receptor mutant d14 (DWARF14) to kai2 indicated that strigolactones also contributes to plant drought adaptation, although not by affecting cuticle development. Our findings suggest that chemical or genetic manipulation of KAI2 and D14 signaling may provide novel ways to improve drought resistance. Title: WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism Tanaka M, Moran S, Wen J, Affram K, Chen T, Symes AJ, Zhang Y Ref: J Neuroinflammation, 14:7, 2017 : PubMed ESTHER: Tanaka_2017_J.Neuroinflammation_14_7 PubMedSearch: Tanaka 2017 J.Neuroinflammation 14 7 PubMedID: 28086912 Inhibitor(s) related to this paper: KT182, WWL70 Abstract BACKGROUND: alpha/beta-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia. Title: Single administration of soluble epoxide hydrolase inhibitor suppresses neuroinflammation and improves neuronal damage after cardiac arrest in mice Taguchi N, Nakayama S, Tanaka M Ref: Neurosci Res, 111:56, 2016 : PubMed ESTHER: Taguchi_2016_Neurosci.Res_111_56 PubMedSearch: Taguchi 2016 Neurosci.Res 111 56 PubMedID: 27184295 Inhibitor(s) related to this paper: AS2586144 Abstract Cardiac arrest (CA) causes ischemia-reperfusion injury in the whole body among victims. Especially in the brain, inflammation and neuronal cell death can lead to irreversible dysfunction. Our goal was to determine whether a single administration of soluble epoxide hydrolase inhibitor (AS2586144-CL) has a neuroprotective effect and decreases the inflammatory response after CA and cardiopulmonary resuscitation (CPR). Global cerebral ischemia was induced in male C57BL/6 mice with 8min of CA. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned to three groups and administered AS2586144-CL: 1mg/kg (n=25), 10mg/kg (n=25), or 0mg/kg (vehicle, n=25). At 6 and 7 days after CA/CPR, behavioral tests were conducted and brains were removed for histological evaluation. Analysis of histological damage 7 days after CA/CPR revealed that 10mg/kg of AS2586144-CL protected neurons, and suppressed cytokine production and microglial migration into the hippocampus. Two hours after CA/CPR, 10mg/kg of AS2586144-CL suppressed serum tumor necrosis factor-alpha and hippocampal nuclear factor kappaB expression. Our data show that 10mg/kg of AS2586144-CL administered following CA/CPR suppresses inflammation and decreases neuronal damage. Title: Oil accumulation by the oleaginous diatom Fistulifera solaris as revealed by the genome and transcriptome Tanaka T, Maeda Y, Veluchamy A, Tanaka M, Abida H, Marechal E, Bowler C, Muto M, Sunaga Y and Fujibuchi W <7 more author(s)> Tanaka T, Maeda Y, Veluchamy A, Tanaka M, Abida H, Marechal E, Bowler C, Muto M, Sunaga Y, Yoshino T, Taniguchi T, Fukuda Y, Nemoto M, Matsumoto M, Wong PS, Aburatani S, Fujibuchi W (- 7) Ref: Plant Cell, 27:162, 2015 : PubMed ESTHER: Tanaka_2015_Plant.Cell_27_162 PubMedSearch: Tanaka 2015 Plant.Cell 27 162 PubMedID: 25634988 Abstract Oleaginous photosynthetic organisms such as microalgae are promising sources for biofuel production through the generation of carbon-neutral sustainable energy. However, the metabolic mechanisms driving high-rate lipid production in these oleaginous organisms remain unclear, thus impeding efforts to improve productivity through genetic modifications. We analyzed the genome and transcriptome of the oleaginous diatom Fistulifera solaris JPCC DA0580. Next-generation sequencing technology provided evidence of an allodiploid genome structure, suggesting unorthodox molecular evolutionary and genetic regulatory systems for reinforcing metabolic efficiencies. Although major metabolic pathways were shared with nonoleaginous diatoms, transcriptome analysis revealed unique expression patterns, such as concomitant upregulation of fatty acid/triacylglycerol biosynthesis and fatty acid degradation (beta-oxidation) in concert with ATP production. This peculiar pattern of gene expression may account for the simultaneous growth and oil accumulation phenotype and may inspire novel biofuel production technology based on this oleaginous microalga. Title: Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis Wen J, Ribeiro R, Tanaka M, Zhang Y Ref: Neuropharmacology, 99:196, 2015 : PubMed ESTHER: Wen_2015_Neuropharmacol_99_196 PubMedSearch: Wen 2015 Neuropharmacol 99 196 PubMedID: 26189763 Inhibitor(s) related to this paper: WWL70 Abstract Alpha/beta-hydrolase domain 6 (ABHD6) is a novel 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, that can fine-tune the endocannabinoid signaling in the central nervous system. Recently we and others have demonstrated the protective effect of ABHD6 inhibition in the animal models of traumatic brain injury and epileptic seizures. In this study, we investigated the role of targeting ABHD6 in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Post-symptom treatment with an ABHD6 inhibitor WWL70 increased the brain levels of 2-AG and ameliorated the clinical signs of EAE, T cells infiltration, microglia activation and the expression of activated leukocyte cell adhesion molecules. The production of iNOS, COX-2, TNF-alpha and IL-1beta and the phosphorylation of NF-kappaB were also significantly reduced by WWL70 treatment. The neuroprotective effect of WWL70 was demonstrated by increased survival of mature oligodendrocytes, reduced demyelination and axonal loss in WWL70 treated EAE mouse spinal cord. The therapeutic effect of WWL70 on EAE was absent by co-administration of CB2 receptor antagonist, but not CB1 receptor antagonist. Consistently, WWL70 did not afford any protection in CB2 receptor knockout mice after EAE induction. Given the increased expression of ABHD6 in microglia/macrophages, but not in T cells, we speculated that inhibition of ABHD6 might enhance 2-AG signaling particularly in microglia/macrophages to exert anti-inflammatory effects via activation of CB2 receptors. These results suggest that inhibition of ABHD6 might be used as an ideal strategy for the treatment of MS and other neurodegenerative diseases. Title: Pepsinogen I/II ratio is related to glucose, triacylglycerol, and uric acid levels Tanaka M, Fukui M, Kuroda M, Yamazaki M, Hasegawa G, Oda Y, Naito Y, Toda H, Yoshikawa T, Nakamura N Ref: Nutrition, 28:418, 2012 : PubMed ESTHER: Tanaka_2012_Nutrition_28_418 PubMedSearch: Tanaka 2012 Nutrition 28 418 PubMedID: 22304859 Abstract OBJECTIVE: Under- and overnutrition are associated with a worse prognosis and constitute independent risk factors for morbidity and mortality. It is increasingly important to understand the factors that affect nutritional and metabolic statuses. The purpose of this study was to assess the relation between the pepsinogen I/II ratio and several biochemical markers. METHODS: A cross-sectional study was performed in 1985 subjects who underwent a health screening test. Subjects had no medications for hyperuricemia, dyslipidemia, diabetes mellitus, or hypertension. All subjects were classified into two groups. Subjects with a pepsinogen I/II ratio below 3 were defined as having atrophic gastritis. The relations between the pepsinogen I/II ratio and several biochemical markers, including total cholesterol, triacylglycerol, uric acid, cholinesterase, and glucose levels, were evaluated. RESULTS: The presence of atrophic gastritis was significantly associated with age, smoking status, alcohol consumption, body mass index, and triacylglycerol, uric acid, cholinesterase, and hemoglobin levels. Multiple linear regression analysis demonstrated that the pepsinogen I/II ratio was an independent determinant of glucose level (beta = 0.104, P < 0.0001), triacylglycerol level (beta = 0.072, P = 0.0014), uric acid level (beta = 0.048, P = 0.0138), and hemoglobin (beta = 0.037, P = 0.0429) after adjustments for age, sex, smoking status, alcohol consumption, and body mass index. CONCLUSION: The pepsinogen I/II ratio was related to glucose, triacylglycerol, and uric acid levels. Such an association fosters the idea that a decreased pepsinogen I/II ratio seems favorable for the prevention of overnutrition. Title: Polyphenols extracted from black tea (Camellia sinensis) residue by hot-compressed water and their inhibitory effect on pancreatic lipase in vitro Yuda N, Tanaka M, Suzuki M, Asano Y, Ochi H, Iwatsuki K Ref: J Food Sci, 77:H254, 2012 : PubMed ESTHER: Yuda_2012_J.Food.Sci_77_H254 PubMedSearch: Yuda 2012 J.Food.Sci 77 H254 PubMedID: 23106349 Abstract Polyphenols, retained in black tea wastes following the commercial production of tea beverages, represent an underutilized resource. The purpose of this study was to investigate the potential use of hot-compressed water (HCW) for the extraction of pancreatic lipase-inhibiting polyphenols from black tea residues. Black tea residues were treated with HCW at 10 degreesC intervals, from 100 to 200 degreesC. The resulting extracts were analyzed using high-performance liquid chromatography-mass spectrometry and assayed to determine their inhibitory effect on pancreatic lipase activity in vitro. Four theaflavins (TF), 5 catechins, 2 quercetin glycosides, quinic acid, gallic acid, and caffeine were identified. The total polyphenol content of extracts increased with increasing temperature but lipase inhibitors (TF, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3,3'-O-gallate, epigallocatechin gallate, and epicatechin gallate) decreased over 150 degreesC. All extracts inhibited pancreatic lipase but extracts obtained at 100 to 140 degreesC showed the greatest lipase inhibition (IC(50) s of 0.9 to 1.3 microg/mL), consistent with the optimal extraction of TFs and catechins except catechin by HCW between 130 and 150 degreesC. HCW can be used to extract pancreatic lipase-inhibiting polyphenols from black tea waste. These extracts have potential uses, as dietary supplements and medications, for the prevention and treatment of obesity. Title: Molecular cloning and expression of a novel cholinephosphotransferase involved in glycoglycerophospholipid biosynthesis of Mycoplasma fermentans Ishida N, Irikura D, Matsuda K, Sato S, Sone T, Tanaka M, Asano K Ref: Curr Microbiol, 58:535, 2009 : PubMed ESTHER: Ishida_2009_Curr.Microbiol_58_535 PubMedSearch: Ishida 2009 Curr.Microbiol 58 535 PubMedID: 19219498 Gene_locus related to this paper: mycfe-c4xfi7, mycfe-c4xfu4, mycfp-c4xfg3 Abstract A gene, mf1, encoding a novel cholinephosphotransferase in glycoglycerophospholipid (GGPL) biosynthesis of Mycoplasma fermentans PG18 was identified by genomic analysis, cloned, and expressed in Escherichia coli. The mf1 gene comprises an open reading frame of 777 bp encoding 258 amino acids. The mf1 gene product, Mf1, has 23% amino acid homology with LicD of Haemophilus influenzae but no homology with genes of other Mycoplasma species in the GenBank database. The reaction product of Mf1 using alpha-glucopyranosyl-1,2-dipalmitoilglycerol and cytidine 5'-diphosphocholine (CDP-choline) as substrates showed the specific protonated molecule at m/z 896, which corresponded to GGPL-I as determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, the product ions of choline, phosphocholine, and hexose-bound phosphocholine were detected by tandem mass spectrometry (MS) analysis of protonated molecules at m/z 896. These results identified mf1 as a novel cholinephosphotransferase and showed that the phosphocholine transfer step is involved in the GGPL biosynthesis pathway of M. fermentans. This is the first report of a GGPL biosynthesis enzyme. Title: Evaluation of the biodegradability of polyurethane and its derivatives by using lipase-displaying arming yeast Shibasaki S, Kawabata A, Tanino T, Kondo A, Ueda M, Tanaka M Ref: Biocontrol Sci, 14:171, 2009 : PubMed ESTHER: Shibasaki_2009_Biocontrol.Sci_14_171 PubMedSearch: Shibasaki 2009 Biocontrol.Sci 14 171 PubMedID: 20055222 Abstract Candida antarctica lipase B (CALB) has been used to polymerize and degrade polyesters. We developed a convenient method for investigating the biodegradability of plastics that involves the use of CALB-displaying "arming yeast." Polyurethane containing dulcitol units was prepared and used as the model material. Additionally, standard polyurethane with no dulcitol units was prepared by reacting 2,4-toluene diisocyanate with ethylene glycol. These polymers were incubated with CALB-displaying yeast cells. The polyurethane containing dulcitol was degraded, while the standard polyurethane was relatively unaffected. Arming yeast displaying appropriate enzymes can be used to investigate the biodegradability of synthetic plastics. It was also revealed that arming yeasts were applicable to evaluate the degradation of the film state of polyurethane. Title: Putative role of endothelial lipase in dialysis patients with hypoalbuminemia and inflammation Fujii H, Fukuda A, Tanaka M, Kojima Y, Ishida T, Hirata K, Fukagawa M Ref: Am J Nephrol, 28:974, 2008 : PubMed ESTHER: Fujii_2008_Am.J.Nephrol_28_974 PubMedSearch: Fujii 2008 Am.J.Nephrol 28 974 PubMedID: 18612200 Abstract BACKGROUND/AIMS: A recent study suggests that inflammation and malnutrition are strongly associated with cardiovascular disease in dialysis patients. Endothelial lipase (EL) is a newly cloned physiological regulator of high-density lipoprotein cholesterol (HDL), which is associated with the progression of atherosclerosis. To clarify the role of EL in dialysis patients, we evaluated serum markers on the basis of the presence of hypoalbuminemia and inflammation. Title: Donepezil in the treatment of musical hallucinations Ukai S, Yamamoto M, Tanaka M, Shinosaki K, Takeda M Ref: Psychiatry Clin Neurosci, 61:190, 2007 : PubMed ESTHER: Ukai_2007_Psychiatry.Clin.Neurosci_61_190 PubMedSearch: Ukai 2007 Psychiatry.Clin.Neurosci 61 190 PubMedID: 17362438 Abstract Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH. Title: Pancreatic pseudocyst after acute organophosphate poisoning Kawabe K, Ito T, Arita Y, Sadamoto Y, Harada N, Yamaguchi K, Tanaka M, Nakano I, Nawata H, Takayanagi R Ref: Fukuoka Igaku Zasshi, 97:123, 2006 : PubMed ESTHER: Kawabe_2006_Fukuoka.Igaku.Zasshi_97_123 PubMedSearch: Kawabe 2006 Fukuoka.Igaku.Zasshi 97 123 PubMedID: 16850858 Abstract Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP. Title: Autophagic vacuoles with sarcolemmal features delineate Danon disease and related myopathies Sugie K, Noguchi S, Kozuka Y, Arikawa-Hirasawa E, Tanaka M, Yan C, Saftig P, von Figura K, Hirano M and Nishino I <2 more author(s)> Sugie K, Noguchi S, Kozuka Y, Arikawa-Hirasawa E, Tanaka M, Yan C, Saftig P, von Figura K, Hirano M, Ueno S, Nonaka I, Nishino I (- 2) Ref: J Neuropathol Experimental Neurology, 64:513, 2005 : PubMed ESTHER: Sugie_2005_J.Neuropathol.Exp.Neurol_64_513 PubMedSearch: Sugie 2005 J.Neuropathol.Exp.Neurol 64 513 PubMedID: 15977643 Abstract Among the autophagic vacuolar myopathies (AVMs), a subgroup is characterized pathologically by unusual autophagic vacuoles with sarcolemmal features (AVSF) and includes Danon disease and X-linked myopathy with excessive autophagy. The diagnostic importance and detailed morphologic features of AVSF in different AVMs have not been well established, and the mechanism of AVSF formation is not known. To address these issues, we have performed detailed histologic studies of myopathies with AVSF and other AVMs. In Danon disease and related AVMs, at the light microscopic level, autophagic vacuoles appeared to be accumulations of lysosomes, which, by electron microscopy consisted of clusters of autophagic vacuoles, indicative of autolysosomes. Some autolysosomes were surrounded by membranes with sarcolemmal proteins, acetylcholinesterase activity, and basal lamina. In Danon disease, the number of fibers with AVSF increased linearly with age while the number with autolysosomal accumulations decreased slightly, suggesting that AVSF are produced secondarily in response to autolysosomes. Most of the AVSF form enclosed spaces, indicating that the vacuolar membranes may be formed in situ rather than through sarcolemmal indentation. This unique intracytoplasmic membrane structure was not found in other AVMs. In conclusion, AVSF with acetylcholinesterase activity are autolysosomes surrounded by secondarily generated intracytoplasmic sarcolemma-like structure and delineates a subgroup of AVMs. Title: Role of leukotrienes on hepatic ischemia/reperfusion injury in rats Takamatsu Y, Shimada K, Chijiiwa K, Kuroki S, Yamaguchi K, Tanaka M Ref: J Surg Res, 119:14, 2004 : PubMed ESTHER: Takamatsu_2004_J.Surg.Res_119_14 PubMedSearch: Takamatsu 2004 J.Surg.Res 119 14 PubMedID: 15126076 Abstract BACKGROUND: Leukotrienes (LT), composed of cysteinyl LT (cLT; LTC(4), LTD(4), and LTE(4)) and LTB(4), are potent lipid mediators enhancing the vascular permeability and recruitment of neutrophils, which are common features of hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to investigate whether LT can mediate the liver and lung injuries following hepatic I/R. MATERIALS AND Title: Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease Tanaka M, Namiki C, Thuy DH, Yoshida H, Kawasaki K, Hashikawa K, Fukuyama H, Kita T Ref: Journal of Neurology Sci, 225:135, 2004 : PubMed ESTHER: Tanaka_2004_J.Neurol.Sci_225_135 PubMedSearch: Tanaka 2004 J.Neurol.Sci 225 135 PubMedID: 15465097 Abstract Donepezil is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Since behavioral symptoms severely affect quality of life for AD patients and their caregivers, predicting behavioral responses to donepezil will be useful in managing patients with AD. In this study, we analyzed 70 consecutive cases with mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric Inventory for behavioral assessment and 4-point improvement at week 12 was accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened. Dysphoria, anxiety and apathy significantly improved after treatment among the responder group. The baseline profile including age, sex, Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Geriatric Depression Scale did not differ significantly among the three groups. Statistical Parametric Mapping analysis of single photon emission computed tomography (SPECT) images at baseline showed that cerebral blood flow in the premotor and parietotemporal cortices was significantly higher in the responder group than in the worse group. The present study suggested usefulness of SPECT imaging in the prediction of behavioral response to donepezil among AD patients even with similar psychiatric symptoms and cognitive functions. Title: Treatment of typical Charles Bonnet syndrome with donepezil Ukai S, Yamamoto M, Tanaka M, Takeda M Ref: Int Clin Psychopharmacol, 19:355, 2004 : PubMed ESTHER: Ukai_2004_Int.Clin.Psychopharmacol_19_355 PubMedSearch: Ukai 2004 Int.Clin.Psychopharmacol 19 355 PubMedID: 15486523 Abstract Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. Although visual hallucinations in the elderly are often associated with dementia with Lewy body (DLB), Alzheimer's disease and delirium, they are excluded from the diagnosis of typical CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal neurological lesions. Here, we describe a patient with typical CBS, who responded to donepezil, a cholinesterase inhibitor, and has not shown any symptoms suggestive of Alzheimer's disease or DLB for approximately the past 40 months. However, follow-up examination of her clinical symptoms is necessary for a definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil indicates that the patient's visual hallucinations might be related to dysfunction of cholinergic neurones, although she did not exhibit any cognitive decline, or morphological and physiological brain pathology. Because donepezil has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a safer option for the treatment of CBS in the elderly. Title: Nefiracetam and physostigmine: separate and combined effects on learning in older rabbits Woodruff-Pak DS, Ewers M, Shiotani T, Watabe S, Tanaka M, Wenk GL Ref: Neurobiology of Aging, 25:807, 2004 : PubMed ESTHER: Woodruff-Pak_2004_Neurobiol.Aging_25_807 PubMedSearch: Woodruff-Pak 2004 Neurobiol.Aging 25 807 PubMedID: 15165705 Abstract Physostigmine and nefiracetam were tested alone and in combination in 104 rabbits with a mean age of 28 months conditioned in the 750 ms delay eyeblink classical conditioning procedure. In Experiment 1, five doses of physostigmine (0.0005-0.2 mg/kg) enhanced conditioning. In Experiment 2, combinations of 10 mg/kg nefiracetam and 0.01, 0.1 and 0.2 mg/kg physostigmine improved the rate and magnitude of learning over rabbits treated with vehicle or 10 mg/kg nefiracetam alone. Brain AChE levels were significantly lower than vehicle for all doses of physostigmine and physostigmine plus nefiracetam. Control rabbits tested in the explicitly unpaired condition demonstrated that physostigmine alone and nefiracetam plus physostigmine had no non-associative effects. Physostigmine had a dramatic cognition-enhancing effect in older rabbits, and when nefiracetam was combined with physostigmine at a low dose, the ameliorating effect of physostigmine on learning was improved indicating that drug combinations for cognition enhancement may have therapeutic efficacy. Title: Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida Anzai Y, Saito N, Tanaka M, Kinoshita K, Koyama Y, Kato F Ref: FEMS Microbiology Letters, 218:135, 2003 : PubMed ESTHER: Anzai_2003_FEMS.Microbiol.Lett_218_135 PubMedSearch: Anzai 2003 FEMS.Microbiol.Lett 218 135 PubMedID: 12583909 Gene_locus related to this paper: micgr-MYCAV Abstract Mycinamicin, composed of a branched lactone and two sugars, desosamine and mycinose, at the C-5 and C-21 positions, is a 16-membered macrolide antibiotic produced by Micromonospora griseorubida A11725, which shows strong antimicrobial activity against Gram-positive bacteria. The nucleotide sequence (62 kb) of the mycinamicin biosynthetic gene cluster, in which there were 22 open reading frames (ORFs), was completely determined. All of the products from the 22 ORFs are responsible for the biosynthesis of mycinamicin II and self-protection against the compounds synthesized. Central to the cluster is a polyketide synthase locus (mycA), which encodes a seven-module system comprised of five multifunctional proteins. Immediately downstream of mycA, there is a set of genes for desosamine biosynthesis (mydA-G and mycB). Moreover, mydH, whose product is responsible for the biosynthesis of mycinose, lies between mydA and B. On the other hand, eight ORFs were detected upstream of the mycinamicin PKS gene. The myrB, mycG, and mycF genes had already been characterized by Inouye et al. The other five ORFs (mycCI, mycCII, mydI, mycE, and mycD) lie between mycA1 and mycF, and these five genes and mycF are responsible for the biosynthesis of mycinose. In the PKS gene, four regions of KS and AT domains in modules 1, 4, 5, and 6 indicated that it does not show the high GC content typical for Streptomyces genes, nor the unusual frame plot patterns for Streptomyces genes. Methylmalonyl-CoA was used as substrate in the functional units of those four modules. The relationship between the substrate and the unusual frame plot pattern of the KS and AT domains was observed in the other PKS genes, and it is suggested that the KS-AT original region was horizontally transferred into the PKS genes on the chromosomal DNA of several actinomycetes strains. Title: Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders Tanaka M, Naruo T, Nagai N, Kuroki N, Shiiya T, Nakazato M, Matsukura S, Nozoe S Ref: J Psychiatr Res, 37:17, 2003 : PubMed ESTHER: Tanaka_2003_J.Psychiatr.Res_37_17 PubMedSearch: Tanaka 2003 J.Psychiatr.Res 37 17 PubMedID: 12482466 Abstract Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 non-purging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders. Title: Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12 Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K and Shinagawa H <12 more author(s)> Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K, Murata T, Tanaka M, Tobe T, Iida T, Takami H, Honda T, Sasakawa C, Ogasawara N, Yasunaga T, Kuhara S, Shiba T, Hattori M, Shinagawa H (- 12) Ref: DNA Research, 8:11, 2001 : PubMed ESTHER: Hayashi_2001_DNA.Res_8_11 PubMedSearch: Hayashi 2001 DNA.Res 8 11 PubMedID: 11258796 Gene_locus related to this paper: ecoli-rutD, ecoli-bioh, ecoli-C0410, ecoli-entf, ecoli-fes, ecoli-MCMK, ecoli-mhpc, ecoli-pldb, ecoli-ptrb, ecoli-yafa, ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-ycjy, ecoli-YFBB, ecoli-yghX, ecoli-yhet, ecoli-yjfp, ecoli-YNBC, ecoli-ypfh, ecoli-yqia, ecoli-Z0347, ecoli-Z1341, ecoli-Z1930, ecoli-Z2445, ecoli-YfhR Abstract Escherichia coli O157:H7 is a major food-borne infectious pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Here we report the complete chromosome sequence of an O157:H7 strain isolated from the Sakai outbreak, and the results of genomic comparison with a benign laboratory strain, K-12 MG1655. The chromosome is 5.5 Mb in size, 859 Kb larger than that of K-12. We identified a 4.1-Mb sequence highly conserved between the two strains, which may represent the fundamental backbone of the E. coli chromosome. The remaining 1.4-Mb sequence comprises of O157:H7-specific sequences, most of which are horizontally transferred foreign DNAs. The predominant roles of bacteriophages in the emergence of O157:H7 is evident by the presence of 24 prophages and prophage-like elements that occupy more than half of the O157:H7-specific sequences. The O157:H7 chromosome encodes 1632 proteins and 20 tRNAs that are not present in K-12. Among these, at least 131 proteins are assumed to have virulence-related functions. Genome-wide codon usage analysis suggested that the O157:H7-specific tRNAs are involved in the efficient expression of the strain-specific genes. A complete set of the genes specific to O157:H7 presented here sheds new insight into the pathogenicity and the physiology of O157:H7, and will open a way to fully understand the molecular mechanisms underlying the O157:H7 infection. Title: Biliary indocyanine green excretion as a predictor of hepatic adenosine triphosphate levels in patients with obstructive jaundice Chijiiwa K, Watanabe M, Nakano K, Noshiro H, Tanaka M Ref: American Journal of Surgery, 179:161, 2000 : PubMed ESTHER: Chijiiwa_2000_Am.J.Surg_179_161 PubMedSearch: Chijiiwa 2000 Am.J.Surg 179 161 PubMedID: 10773154 Abstract BACKGROUND: Correlation of the hepatic adenosine triphosphate (ATP) level with indocyanine green (ICG) excretion into bile was examined in patients with obstructive jaundice after the relief of hyperbilirubinemia by preoperative percutaneous transhepatic biliary drainage (PTBD). Title: Effects of oral clonidine on heart rate changes after neostigmine- atropine administration Kimura T, Tanaka M, Nishikawa T Ref: Anesthesiology, 88:1507, 1998 : PubMed ESTHER: Kimura_1998_Anesthesiology_88_1507 PubMedSearch: Kimura 1998 Anesthesiology 88 1507 PubMedID: 9637644 Inhibitor(s) related to this paper: Neostigmine~Prostigmine Abstract BACKGROUND Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration. METHODS: Fifty adult patients without cardiovascular disorders who were scheduled for elective surgeries were randomly assigned to receive approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine (control group, n=25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/-5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min. RESULTS: Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine--atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min; means+/-SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group. Title: Genetic polymorphisms and mutations of the lipoprotein lipase gene in Japanese schoolchildren with hypoalphalipoproteinemia Yamana K, Yanagi H, Hirano C, Kobayashi K, Tanaka M, Tomura S, Tsuchiya S, Hamaguchi H Ref: J Atheroscler Thromb, 4:97, 1998 : PubMed ESTHER: Yamana_1998_J.Atheroscler.Thromb_4_97 PubMedSearch: Yamana 1998 J.Atheroscler.Thromb 4 97 PubMedID: 9730139 Abstract Lipoprotein lipase (LPL) is an important enzyme for the hydrolysis of TG on lipoproteins, and its activity is positively correlated with the plasma levels of high density lipoprotein cholesterol (HDL-C). To investigate the association between the LPL gene and low HDL-C levels, we studied two polymorphisms (Hind III and Pvu II) and three mutations (Asn291Ser, Gly188Glu and LPL(Arita)) of the LPL gene in 114 children with low HDL-C levels (<40 mg/dl) and 194 control children using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques (PCR-RFLP). The frequency of the Pvu II +/+ genotype was significantly higher in the children with low-HDL/high-TG (TG>100 mg/dl, 90th percentile level among Japanese schoolchildren) than in the other children (vs the low-HDL/normal-TG children, chi2 = 7.49, p < 0.01; vs control children, chi2 = 7.23, p < 0.01). Pvu II+ allele of the LPL gene was associated with elevated TG levels in low HDL-C groups. In addition, we found one heterozygote of LPL(Arita) (deletion of G at base 916 in exon 5, the most common mutation of LPL deficiency in Japanese), among the low-HDL/high-TG subjects. The other two variants were not detected in either the low-HDL children or control children. LPL Asn291Ser and Gly188Glu have been presumed to be rare in the Japanese population. In conclusion, our results suggest that hypoalphalipoproteinemia with elevated TG level may be associated with genetic variations of the LPL gene. Title: Carbachol depolarizes and evokes an inward current in heart muscle: a novel action of muscarinic agonist Pappano AJ, Matsumoto K, Meszaros J, Tanaka M Ref: Prog Clin Biol Res, 334:313, 1990 : PubMed ESTHER: Pappano_1990_Prog.Clin.Biol.Res_334_313 PubMedSearch: Pappano 1990 Prog.Clin.Biol.Res 334 313 PubMedID: 2309008 Title: Nucleotide sequence of an Rts1 fragment causing temperature-dependent instability Tanaka M, Okawa N, Mori K, Suyama Y, Kaji A Ref: Journal of Bacteriology, 170:1175, 1988 : PubMed ESTHER: Tanaka_1988_J.Bacteriol_170_1175 PubMedSearch: Tanaka 1988 J.Bacteriol 170 1175 PubMedID: 3277947 Gene_locus related to this paper: provu-ORF12 Abstract Rts1 is a multiphenotypic drug resistance plasmid which is eliminated from host bacteria at 42 degrees C but not at 32 degrees C. This phenotype has been called temperature-dependent instability (Tdi). We determined the nucleotide sequence of the Rts1 DNA b' segment which causes this phenotype. Within this 786-base-pair segment, several open reading frames (ORFs) were found, including one which encodes a protein with a molecular weight of 16,000. A protein approximately corresponding to this protein is expressed in Escherichia coli minicells harboring plasmids containing the b' segment. In addition, we found the chi sequence at 112 bases proximal to this ORF. Temperature-dependent elimination due to this segment was not observed in the RecA strain of E. coli, but the RecB protein was not required for expression of this phenotype. We constructed various deletion derivatives and found that three portions, the region containing the chi (nucleotides 1 to 24), ORF (nucleotides 25 to 546), and tail (nucleotides 631 to 786) sequences are necessary for Tdi activity. Site-directed mutagenesis studies indicated that ORF I is required for Tdi expression. | |||||||
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