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Biomedical subjects

T Maruyama

Publications and source records attributed to T Maruyama.

At least 55 records · Page 3Linked to original sources

Detection of cardiovascular risk factors by indices of obesity obtained from anthropometry and dual-energy X-ray absorptiometry in Japanese individuals.

OBJECTIVE: To determine the cut-off points of indices of obesity for detecting hypertension, dyslipidemia and diabetes mellitus in Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: A total of 2728 Japanese individuals (768 males and 1960 females, aged 20-79 y) who attended the Fukuoka Health Promotion Center, Japan for health check-up. MEASUREMENTS: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) were measured. Percentage fat mass (%FM), trunk fat mass (FM(trunk)) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry (DXA). Cardiovascular risk factors were determined by blood pressure, serum lipids, fasting blood glucose and hemoglobin A(1C). RESULTS: The cut-off points of BMI, WC and WHR were around 23.5 kg/m(2), 84 cm and 0.9 for males, and 22.5 kg/m(2), 72 cm and 0.8 for females. The cut-off points of %FM, FM(trunk) and FM(trunk)/FM(legs) were around 24%, 8 kg and 1.6 for males, and 35%, 9 kg and 1.4 for females. WHR and FM(trunk)/FM(legs) most accurately detected the risk factors. CONCLUSIONS: For Japanese individuals, the cut-off points for detecting cardiovascular risk factors are lower than the criteria by the World Health Organization. Indices of fat distribution detected the cardiovascular risk factors more accurately than those of overall adiposity. The accuracy of detecting the risk factors was comparable between the anthropometric indices and indices obtained by DXA.

Absorptiometry, Photon↗

Novel LPL mutation (L303F) found in a patient associated with coronary artery disease and severe systemic atherosclerosis.

BACKGROUND: Patients with lipoprotein lipase (LPL) deficiency had been generally thought to be spared accelerated atherosclerosis in spite of a marked elevation of plasma triglyceride levels. However, it has been recently reported that some heterozygous and homozygous LPL-deficient patients are associated with premature atherosclerosis. In this paper, we report a 55-year-old type I hyperlipidaemic patient with a novel missense mutation in the LPL gene. PATIENT AND RESULTS: The patient had suffered from coronary artery disease, abdominal aortic aneurysm, and stenoses of the bilateral renal arteries and superficial femoral arteries. Sequencing of the genomic DNA revealed that the patient was a homozygote for the mutation, a G to C transition at nucleotide position 1069 in the exon 6, resulting in an amino acid substitution of Phe for Leu303 (L303F). Approximately 6% and approximately 40% of normal LPL activity and LPL mass, respectively, were detected in the patient's postheparin plasma. An in vitro expression study demonstrated that COS7 cells transfected with L303F mutant cDNA produced a 40% amount of LPL protein in cell lysates compared with normal cDNA, but no protein was detected in the media. Lipoprotein lipase activity was completely absent in both lysates and media of the cells transfected with the mutant cDNA, suggesting that this mutation in the LPL gene results in the production of a functionally inactive protein. CONCLUSION: This case suggests that the LPL missense mutation (L303F), which impairs lipolysis but preserves the LPL mass, is proatherogenic.

Arteriosclerosis↗

Mechanisms of cytosolic Ca2+ suppression by prostaglandin E2 receptors in rat melanotrophs.

We have previously reported that voltage-dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR), Ca2+-imaging and whole-cell, patch-clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1-4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT-PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO-AE-248, whereas three other EP agonists, ONO-DI-004 (EP1), ONO-AE1-259 (EP2) and ONO-AE1-329 (EP4), had little or no effect on [Ca2+]i. All four G-protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT-PCR. Dopamine concentration-dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.

Animals↗

Event based and time based prospective memory in Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease have been reported to have retrospective memory impairment, while prospective memory, which is memory for actions to be performed in the future, has not yet been investigated. OBJECTIVE: To investigate the prospective memory of patients with Parkinson's disease. METHODS: Twenty Parkinson's disease patients and 20 age matched normal controls were given event based and time based prospective memory tasks. In the event based prospective memory task, the subject was asked to perform an action whenever particular words were presented. In the time based prospective memory task, the subject was asked to perform an action at certain times. RESULTS: The Parkinson's disease patients were impaired on the event based prospective memory task but not on the time based prospective memory task. The impairment of the Parkinson's disease patients on the event based prospective memory task was not the result of their forgetting the content of the prospective memory instructions, but the result of their failure to retrieve it spontaneously when the target words appeared. CONCLUSIONS: These results suggest that event based prospective memory is impaired in patients with Parkinson's disease, presumably relating to frontal lobe dysfunction.

Female↗

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Journal Article↗

Involvement of postsynaptic EP4 and presynaptic EP3 receptors in actions of prostaglandin E2 in rat supraoptic neurones.

We have reported that supraoptic nucleus (SON) neurones are excited by prostaglandin E2 (PGE2) presumably via dual postsynaptic PG receptors, FP receptors and unidentified EP receptors, and that presynaptic EP receptors may also be involved in the excitation. In the present study, to clarify the receptor mechanism of the PGE2-mediated actions on SON neurones, we studied the pre- and postsynaptic effects of four newly developed EP agonists that are selective for each of the four EP receptors, EP1-4, on rat SON neurones using extracellular recording and whole-cell patch-clamp techniques. The EP4 agonist ONO-AE1-329 mimicked the excitatory effects of PGE2, whereas the EP1 agonist ONO-DI-004, the EP2 agonist ONO-AE1-257 and the EP3 agonist ONO-AE-248 had little or no effect. The effects of ONO-AE1-329 were unaffected by the EP1/FP/TP antagonist, ONO-NT-012, which potently suppressed the excitation caused by the FP agonist fluprostenol and PGE2. ONO-AE1-329 caused marked excitation when responses to fluprostenol were desensitized by repeated applications of fluprostenol. Patch-clamp analysis in SON neurones showed that ONO-AE1-329 induced inward currents at a holding potential of -70 mV and the reversal potential of the currents was -35.1 +/- 2.3 mV. On the other hand, the frequency of spontaneous inhibitory postsynaptic currents recorded from SON slice preparations was suppressed by ONO-AE-248, but unaffected by the other three EP agonists. These results suggest that SON neurones possess postsynaptic EP4 receptors and that gamma-aminobutyric acid neurones innervating SON neurones possess presynaptic EP3 receptors in their terminals. Activation of the two EP receptors may be involved in the excitatory regulation of SON neurones by PGE2.

Animals↗

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody.

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.

Adult↗

Removal of suspended substances by coagulation and foam separation from municipal wastewater.

A new method for solid-liquid separation for wastewater incorporating simple operation and shortened treatment time is necessary for improvement of sewage systems. In this study, removal of suspended solids from municipal wastewater by coagulation and foam separation using coagulant and milk casein was examined. By adding casein before the foam separation process, the removal of suspended substances was dramatically improved. The optimum condition for treating sewage was 20 mg-Fe/L of FeCl3, 3 mg/L of casein, and pH 5.5, which resulted in a removal rates of over 98% for turbidity and SS. A removal of 96-98% was also possible for phosphate and anionic surfactant. When PAC was used, the floc was also efficiently recovered in foam by the addition of casein. It became clear that coagulation and foam separation using casein as the collector is an effective method for removing suspended solids in municipal wastewater in a short time (within 10 min).

Caseins↗

Glycine at the 65th position plays an essential role in ATP-dependent protein folding by Archael group II chaperonin.

In the previous study, we have found that G65C and I125T double mutant of alpha chaperonin homo-oligomer from a hyperthermophilic archaeum, Thermococcus sp. strain KS-1, lacks ATP-dependent protein refolding activity despite showing ATPase activity and the ability to bind the denatured proteins. In this study, we have characterized several mutant Thermococcus chaperonin homo-oligomers with the amino acid substitutions of Gly-65 or Ile-125. The results showed that amino acid residue at 65th position should be a small amino acid such as glycine or alanine for the ATP-dependent refolding activity. The alpha chaperonin homo-oligomers with amino acid substitution of Gly-65 by amino acids whose side chains are larger than the methyl group did not have ATP-dependent protein refolding activity, but exhibited an increase of the binding affinity for unfolded proteins in the presence of ATP or AMP-PNP. (c)2001 Elsevier Science.

Adenosine Triphosphatases↗

Up-regulation by clarithromycin of alpha(1)-acid glycoprotein expression in liver and primary cultured hepatocytes.

alpha(1)-Acid glycoprotein (AGP) is the major transport protein for cationic drugs, endogenous ligands, and some anionic drugs in plasma. Hepatic synthesis and secretion of AGP are altered during acute inflammation as well as by a number of drugs. This alteration could influence the binding of drugs and its biological function. Macrolide antibiotics are widely used in the treatment of a variety of infectious diseases. The effects of macrolide antibiotics have been studied with respect to rat AGP expression in vivo. After the individual administration of six macrolides to rats, with the exception of oleandomycin, five increased AGP levels in serum. Of these five, clarithromycin (CAM) was the most potent inducer of AGP, which reached a maximum level between 3 to 7 days after administration. CAM increased the steady-state level of AGP mRNA in liver as well as protein level in serum in a dose-dependent manner. In addition, CAM increased AGP mRNA levels in primary cultured hepatocytes. In the luciferase promoter assay, CAM potentiated dexamethasone-increased promoter activity of the AGP gene, which contained the glucocorticoid response element, in cultured rat hepatocytes, although CAM itself had no effect on its activity. The effect of CAM and dexamethasone was diminished by glucocorticoid response element deletion or mutation or by adding the antiglucocorticoid, RU486. Further, in the mouse mammary tumor virus (MMTV) promoter containing functional glucocorticoid response element, CAM potentiated dexamethasone-increased promoter activity. In the adrenalectomized rats, CAM did not increase AGP levels in serum. These findings suggest that CAM may cause transcriptional induction of AGP, at least in part, via a glucocorticoid-mediated mechanism.

5' Untranslated Regions↗

Synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside.

A synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (1, FddA) via a 6-chloro-9-(3-deoxy-beta-D-erythro-pentofuranosyl)-9H-purine (9), which was readily obtained from inosine (5), is described. Fluorination at the C2'-beta position of the purine 3'-deoxynucleoside with diethylaminosulfur trifluoride was improved by the introduction of a 6-chloro group and proceeded in moderate yield. Purine 3'-deoxynucleoside derivatives were also subjected to nucleophilic reactions with triethylamine trihydrofluoride and gave the desired fluorinated nucleoside in good yield. The safety and yield of the fluorination process were greatly improved by the use of triethylamine trihydrofluoride. The influence of the sugar ring conformation and 6-chloro group on the rate of the nucleophilic reaction against elimination are also discussed.

Anti-HIV Agents↗

Mechanism of bovine serum albumin aggregation during ultrafiltration.

Protein fouling is a critical problem for ultrafiltration. In this study, we adopted bovine serum albumin (BSA) as a model protein and polysulfone membrane as a typical ultrafiltration membrane. We then investigated the factors of the protein denaturation and aggregation, such as stirring shear stress and intermolecular exchange of disulfide during ultrafiltration, and discussed the BSA fouling mechanism. Fourier transform-infrared analysis revealed that magnetic stirring did not cause any difference in the secondary structural change of BSA gel-like deposits on the ultrafiltration membrane. BSA aggregates were collected from BSA gel-like deposits on the ultrafiltration membrane by centrifugation. Polyacrylamide gel electrophoresis in SDS analysis of BSA aggregates proved that the major binding of the BSA aggregates involved intermolecular disulfhydryl binding and that capping the free thiol group in BSA molecules with cysteine induced a remarkable decrease in the amount of the BSA aggregates during ultrafiltration. We concluded that one of the main factors in the BSA aggregation during ultrafiltration is the intermolecular exchange of disulfide through cysteinyl residue. We also found that the BSA aggregation caused a decrease in alpha-helix from 66% to 50% and an increase in beta-sheet from 20% to 36%, which was presumably because the cysteine residues associated with the intermolecular disulfide bonds had been located in alpha-helices.

Animals↗

Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins.

We have recently identified the TSLC1 gene as a novel tumor suppressor in human non-small cell lung cancers. TSLC1 encodes a membrane glycoprotein with an extracellular domain homologous to those of immunoglobulin superfamily proteins. Truncation of TSLC1 in the cytoplasmic domain in a primary human tumor suggests that this domain is important for tumor suppressor activity. Here, we report the isolation of two TSLC1-like genes, TSLL1 and TSLL2, based on their structural homology with the sequences corresponding to the cytoplasmic domain of TSLC1. Significant similarity was also observed in the extracellular domain as well as in the overall gene structure, indicating that these three genes form a unique subfamily (the TSLC1-gene family) in the immunoglobulin superfamily genes. In contrast to the ubiquitous expression of TSLC1, TSLL1 is expressed exclusively in adult and fetal human brain, while TSLL2 is expressed in several specific tissues including prostate, brain, kidney and some other organs. Expression of TSLL1 and TSLL2 was lost or markedly reduced in many human glioma cell lines or some prostate cancer cell lines, suggesting that loss of expression of these genes might be involved in some human cancers.

Adult↗

Identification of tumor suppressor candidate genes by physical and sequence mapping of the TSLC1 region of human chromosome 11q23.

Loss of heterozygosity for a locus on human chromosome 11q22-23 is observed at high frequency in non-small cell lung carcinoma (NSCLC). Introduction of a 1.1 Mb fragmented yeast artificial chromosome (YAC) mapping to this region completely suppresses the tumorigenic properties of a human NSCLC cell line, A549. Smaller fragmented YACs give partial but not complete suppression. To further localize the gene(s) responsible for this partial suppression, a bacterial artificial chromosome (BAC) and P1-based artificial chromosome (PAC) contig was constructed, completely spanning the candidate region. End sequence generated in the construction of the BAC/PAC contig identified a previously unmapped EST and served to order genomic sequence contigs from the publicly available Celera Genomics (CG) and Human Genome Project (HGP) efforts. Comparison showed that CG provided larger contigs, while HGP provided more coverage. Neither CG nor HGP provided complete sequence coverage, alone or in combination. The sequence was used to map 110 ESTs and to predict new genes, including two GenScan gene predictions that overlapped ESTs and were shown to be differentially expressed in tumorigenic and suppressed A549 cell lines.

Cell Adhesion Molecule-1↗

Design and synthesis of a highly selective EP2-receptor agonist.

EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.

Alprostadil↗