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T Omura

Publications and source records attributed to T Omura.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of the amino acid sequences of RNA-dependent RNA polymerases of cypoviruses in the family Reoviridae.

The nucleotide sequences of the genome segment S2 of Bombyx mori cypovirus 1, S2 of Lymantria dispar cypovirus 1, S1 of Lymantria dispar cypovirus 14 and S1 of a proposed new electropherotype of Trichoplusia ni cypovirus 15 were determined. These segments encoded putative RNA-dependent RNA polymerases (RDRPs). The deduced amino acid sequences of RDRPs within the genus Cypovirus showed 32% to 94% identities, while extent of homology between RDRPs in the genera Cypovirus and Oryzavirus, a genus most closely related, was approximately 26% identity. Both the genera Cypovirus and Oryzavirus might have originated from a common insect virus ancestor.

Amino Acid Sequence↗
PubMed2002

A single amino acid substitution in 126-kDa protein of Pepper mild mottle virus associates with symptom attenuation in pepper; the complete nucleotide sequence of an attenuated strain, C-1421.

The complete nucleotide sequence of an attenuated Pepper mild mottle virus (PMMoV C-1421) RNA genome has been determined. There were two differences from the type isolate in Japan (PMMoV-J). The mutations were located in the middle of the 126-kDa protein (126 K) gene; one mutation influenced amino acid substitution at 649th Val to Ala (V649A), and the other was silent. The analyses using the reverse genetic system of PMMoV-J revealed that symptom attenuation on pepper related to V649A. Accumulations of 126 K and coat protein (CP) in V649A mutant-infected pepper were lower than those of PMMoV-J in immunoblotting. These results suggest that V649A substitution in 126 K affects the accumulation of 126 K leading to a limitation of CP accumulation.

Amino Acid Substitution↗
PubMed2002

Changes in the concentration of plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) after total joint replacement in patients with arthritis.

Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) have been reported to be associated with arthritis. Total joint replacement results in total resection of cartilage and synovium at the joint. We investigated longitudinal changes in plasma MMP and TIMP after total joint replacement. Eight patients with osteoarthritis (OA) and 15 patients with rheumatoid arthritis (RA) had total knee or total hip replacements. Plasma was collected from all patients before surgery and at 1 week and 6 weeks after surgery. In RA patients the plasma MMP-3 and the MMP-3/TIMP-1 ratio decreased after total joint replacement, whereas CRP and ESR did not change. Therefore, CRP and ESR reflect systemic inflammation; however, plasma MMP-3 and the MMP-3/TIMP-1 ratio may reflect inflammation and/or degeneration of the affected joint.

Aged↗
PubMed2002

Risk evaluation for pathogenic bacteria and viruses in sewage sludge compost.

Composting can be regarded as the most available option for recycling of sewage sludge. However, the existence of pathogenic bacteria and viruses in the compost has been scarcely investigated until now. So there is little information on the infectious risk through agricultural activities or gardening in using the compost. In this study, several kinds of composts were investigated for detection of pathogenic bacteria (Salmonella spp. and Escherichia coli O157) and enteric viruses. It was concluded from the result that these bacteria and viruses could not be detected in 1.0 g-wet of any kinds of composts. Infectious risks through agricultural activities or gardening were evaluated by Monte Carlo simulation in the case that the compost was polluted by Salmonella spp., E. coli O157:117 and Poliovirus 1. Criteria satisfying the acceptable risk (less than 10(-4) per year) for these pathogenic bacteria and virus in the compost were determined from the result of simulations. 1.0 [CFU or PFU/g-wet] was available as the criteria for E. coli O157 and Poliovirus 1 in the compost. On the other hand, the criterion for Salmonella spp. in the compost should be established on a lower concentration than 0.001 CFU/g-wet.

Agriculture↗
PubMed2001

Neuropharmacological profiles of a novel atypical antipsychotic, NRA0562, in rats.

Neuropharmacological profiles of 5-(2-[4-(6-fluoro-1H-indole-3-yl) piperidine-1-yl] ethyl)-4-(4-fluorophenyl) thiazole-2-carboxylic acid amide (NRA0562) in rats were examined using electrophysiological and immunohistochemical methods. The firing rates of the substantia nigra pars compacta (A9) and the ventral tegmental area (A10) dopamine neurons were inhibited by methamphetamine (1 mg/kg, i.v.). NRA0562 dose-dependently reversed the inhibitory effects of methamphetamine on A9 and on A10 dopamine neurons. NRA0562 was more potent to reverse the inhibitory effects of methamphetamine on A10 (ED(50)=0.3 mg/kg) than on A9 (ED(50)=0.9 mg/kg) dopamine neurons. NRA0562 produced significant increases in Fos-like immunoreactivity in both the nucleus accumbens and the dorsolateral striatum. The difference between the number of Fos-like immunoreactivity produced by NRA0562 in the nucleus accumbens vs. dorsolateral striatum, referred to as the atypical index, was positive. Similar results could be observed with risperidone, an atypical antipsychotic. These results suggest that NRA0562 may have the atypical antipsychotic activities seen with risperidone, but without the liability of motor side effects typical of classical antipsychotics.

Action Potentials↗
PubMed2001

Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl(-) current in acutely dissociated rat hippocampal CA1 neurons.

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl(-) current (I(GABA)) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced I(GABA) and the muscimol (Mus)-induced current (I(Mus)) in a concentration-dependent manner. The IC(50) values for VA against I(GABA) and I(Mus) were 9.6x10(-7) and 9.8x10(-7) M, respectively. VA shifted the EC(50) value of I(GABA) from 6.5x10(-6) to 2.1x10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I(GABA) in a competitive manner. VA had no apparent effect on current-voltage relationships for I(GABA), thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce the I(GABA) suppressed by >10(-5) M picrotoxin. VA but not bicuculline accelerated the decay phase of I(GABA), as was seen with picrotoxin. Moreover, pre-application of 10(-5) M VA reduced I(GABA). VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I(GABA) by acting both on the GABA agonist site and on the Cl(-) channel of the GABA(A) receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABA(A) receptor-Cl(-) channel complexes in mammalian central nervous system neurons.

Animals↗
PubMed2001

Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction.

Recent studies have shown that oxidative stress plays an important role in cardiovascular diseases. NADPH oxidase is one of the major sources of superoxide anions and a candidate for the initiation and development of atherosclerosis, which involves the remodeling of vasculature. However, the relevance of NADPH oxidase in ventricular remodeling has not been well-characterized. This is the first report showing that the expression of p22-phox and gp91-phox, essential components of NADPH oxidase, are increased in the infarcted sites after myocardial infarction. The levels of thiobarbituric acid reactive substance, which indicates the lipid peroxidation level, and nuclear factor-kappaB (NF-kappaB) DNA binding activity are also increased in infarcted sites. Our results suggest that the increased expression of NADPH oxidase may have an effect on left ventricular remodeling by increasing the redox-sensitive NF-kappaB DNA binding activity as well as the lipid peroxidation level.

Animals↗
PubMed2001

Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats.

There have been many studies concerning the hemodynamics and physiological mechanisms in ischemic heart disease, little is known about molecular mechanisms during myocardial ischemia in in vivo study. As the signal transduction pathway responsible for myocardial hypertrophy and apoptosis, janus kinase (JAK) and signal transducers and activators of transcription (STAT) are suggested to play an important role. However, whether in vivo activation of JAK-STAT pathway occurs during myocardial ischemia is still unknown. The purpose of this study was to determine whether myocardial JAK or STAT is activated in ischemic heart, and to evaluate the angiotensin blockade on the pathway. Myocardial infarction was produced by ligation of the coronary artery in Wistar rats. After myocardial ischemia, we analysed both activated levels and total amounts of JAK1, JAK2, STAT1 and STAT3 by Western blot analyses at 0, 5, 15, 30, 60, 120 and 240 min. Compared with JAK activities at 0 min, JAK1 activities were significantly increased at 60 and 120 min (3.0- and 3.7-fold, respectively, P<0.01). JAK2 and STAT1 activities of ischemic myocardium were unchanged through the time course. STAT3 activities were increased at 5 min (3.3-fold, P<0.01) and markedly enhanced at 30, 60 and 120 min (4.6-, 7.7- and 8.7-fold, respectively, P<0.01). Pretreatment with imidapril (ACE inhibitor) and candesartan cilexitil (AT1 receptor antagonist) significantly prevented the increase in the phosphorylation of JAK1 at 120 min and STAT3 at 30 and 120 min. Sis-inducing factor (SIF) DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in ischemic myocardium. Imidapril and candesartan cilexitil inhibited the activation of SIF DNA binding at 1 day after coronary ligation. In conclusion, we showed that JAK1 and STAT3 were activated by ischemia from the basal activities in in vivo rat myocardial ischemia model. Imidapril and candesartan cilexitil prevented the increase in phosphorylated JAK1 and STAT3, thereby suggesting that angiotensin II, especially angiotensin II type I receptor, partially mediates activation of myocardial JAK-STAT pathway in acute myocardial ischemia.

Angiotensin II↗
PubMed2001

Angiotensin blockade inhibits increased JNKs, AP-1 and NF- kappa B DNA-binding activities in myocardial infarcted rats.

Inhibition of the renin-angiotensin system has been shown to prevent left ventricular remodeling after myocardial infarction. However, the effect of angiotensin on the signal transduction pathway of left ventricular remodeling after myocardial infarction is as yet unknown. The purpose of this study was to measure myocardial MAPKs and AP-1, NF- kappa B, and Sp-1 DNA-binding activities after myocardial infarction. Moreover, we evaluated the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on signal transduction pathway. Myocardial infarction was produced by ligation of the coronary artery in Wistar rats. Temocapril (ACE inhibitor) (3 and 30 mg/kg/day) and candesartan cilexitil (ARB) (1 and 10 mg/kg/day) were orally administered once a day. After ligation of the left descending coronary artery, JNKs (p46JNK and p55JNK) increased to 2.0- (P<0.01) and 2.8-fold (P<0.01) at 7 days, respectively. ERKs (p44ERK and p42ERK) and p38 activities did not increase significantly. AP-1 and NF- kappa B binding activities increased at 5 days, reached their peak 2.2- and 2.0-fold at 7 days. Sp-1 did not change. ACE inhibitor and ARB inhibited JNKs, NF- kappa B and AP-1 activities. Increased JNKs, AP-1, NF- kappa B, and Sp-1 DNA-binding activities were suppressed by both drugs in the infarcted region. Doppler-echocardiography showed that ACE inhibitor and ARB prevented the dilatation of left ventricular cavity at 14 days and improved diastolic filling pattern. JNKs, AP-1 and NF- kappa B activation in myocardial infarcted rats could be responsible for left ventricular remodeling after myocardial infarction and angiotensin may be related to the activation of these signals.

Angiotensin Receptor Antagonists↗
PubMed2001

Effect of diltiazem on cardiac function assessed by echocardiography and neurohumoral factors after reperfused myocardial infarction without congestive heart failure.

The purpose of this study was to examine the effect of diltiazem on cardiac function and neurohumoral factors (BNP, epinephrine, norepinephrine) after reperfused myocardial infarction without congestive heart failure (Killip class I). On the first day after myocardial infarction following reperfusion therapy patients were randomly assigned to diltiazem treatment (group 1, n=33) or no treatment (group 2, n=39). We then performed echocardiographic examinations on the patients and measured heart rate, mean blood pressure and neurohormones (BNP, epinephrine and norepinephrine). Follow-up evaluations of echocardiography were performed at 4 and 12 weeks and of neurohormones at 1 and 4 weeks after acute myocardial infarction. The highest peaks of plasma BNP, epinephrine, and norepinephrine levels were observed before treatment and decreased with time in both groups. After 4 weeks the level of plasma BNP in the diltiazem treatment group was lower than in the no treatment group [55+/-3 pg/mL vs 85+/-5 pg/mL (P < 0.05)]. Other neurohormones did not differ between groups. Fractional shortening (FS) and ejection fraction (EF)improved after myocardial infarction in both groups, but significantly more in the diltiazem group (P < 0.05) after 12 weeks of treatment. Changes in BNP correlated significantly with changes in left ventricular end systolic volumes, FS and EF. In this study, diltiazem significantly improved systolic function and reduced the level of plasma BNP after myocardial infarction, which suggest that diltiazem may have a beneficial effect on myocardial infarction without congestive heart failure.

Aged↗
PubMed2001

Two possible mechanisms underlying nitrate tolerance in monkey coronary arteries.

1. Previous studies using isolated arteries have demonstrated cross-tolerance between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect of atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase, is affected by treatment with NO donors. To investigate the cross-tolerance and interactions between NTG and ANP in coronary vasorelaxant responses, we used two models of monkey coronary arterial strips (Macaca fuscata). 2. In one model, which was induced by a 1 h treatment with 4.4 x 10(-4) mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of subsequent NTG were markedly attenuated, whereas those of ANP and NO were not affected. These findings suggest that the development of NTG tolerance is associated with a biotransformation process from NTG to NO. In the other model, which did not include washout after exposure to 3 x 10(-6) mol/L NTG, the vasorelaxant responses to 10(-8) mol/L ANP (31.1+/-5.4 vs 5.1+/-2.1%, respectively; P < 0.001), 10(-6) mol/L NO (61.5+/-2.4 vs 29.5+/-8.5%, respectively; P < 0.001) and 10(-8) mol/L SNP (49.4+/-6.4 vs 8.0+/-2.0%, respectively; P < 0.001) were significantly attenuated. The concentration- response curve for 8-bromo-cGMP (8-Br-cGMP) was shifted to the right, whereas responses to papaverine and forskolin were unchanged. These findings suggest that an intracellular process that occurs after the synthesis of cGMP is responsible for this interaction. 3. As a mechanism of NTG tolerance, two possible processes may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular process that occurs after the synthesis of cGMP.

Animals↗
PubMed2001

Simultaneous anterior and posterior interosseous nerve paralysis with several hourglass-like fascicular constrictions in both nerves.

A patient with simultaneous anterior and posterior interosseous nerve paralysis was treated surgically with interfascicular neurolysis and found to have several hourglass-like fascicular constrictions in both nerves. Anterior and posterior interosseous nerve paralyses with hourglass-like fascicular constrictions have been described previously, but not the combination of the two.

Adult↗
PubMed2001

Microsomal p450s use specific proline-rich sequences for efficient folding, but not for maintenance of the folded structure.

The amino-terminal region of microsomal P450s contains three distinct sequence motifs, the signal-anchor sequence (SA), the basic sequence (BS), and the proline-rich sequence (PR). Studies with two P450s of the CYP2C subfamily, P4502C11 (CYP2C11) and P4502C2 (CYP2C2), have indicated that upon expression in eukaryotic cells (yeast, COS cells, and insect cells), specific proline residues in PR are important for proper folding. In the present study, we have established that the PR region in a very different CYP gene family, P450c17 (CYP17), is also important for efficient folding. These studies have been carried out using expression in Escherichia coli. Using P4502C11, we have established that the folding requirements for P450s in bacteria are very similar to those in eukaryotic cells. Interestingly, when the PR from P450c17 is swapped for that of P4502C11 and visa versa, complete misfolding is observed. However, both the BS and SA can be swapped between these P450s without affecting folding. After proper folding of P450c17, removal of the PR by factor Xa protease has no effect on the maintenance of the P450 structure. Inspection of the sequences of many different CYP gene families indicates that the PR sequence is conserved within a gene family but varies considerably between families. We conclude that PR is important for directing the folding pathway leading to the functional P450, but not for maintaining the functional form.

Cytochrome P-450 Enzyme System↗
PubMed2001

Importance of a proline-rich sequence in the amino-terminal region for correct folding of mitochondrial and soluble microbial p450s.

All microsomal P450s have a proline-rich sequence (PR) in the amino-terminal region that is needed for proper folding [Kusano, K., Sakaguchi, M., Kagawa, N., Waterman, M.R. and Omura, T. (2001) J. Biochem., 129, 259-269]. There are also multiple proline residues near the amino-termini of the mature forms of all mitochondrial P450s and the amino-termini of soluble microbial P450s. To examine the functional significance of the PR in mitochondrial P450s, we expressed human P450c27 (CYP27) and bovine P450scc (CYP11A1) in an Escherichia coli heterologous expression system, and found that in each one specific proline residue is important for correct folding. Deletions from the amino-terminus further indicated the importance of the PR for the expression of a spectrally normal P450c27. Essentially the same results were obtained with two soluble microbial P450s, P450cam (CYP101) and P450nor, in each of which a PR is important for proper folding. We conclude that in all P450s (mitochondrial, microbial and microsomal P450s), a proline-rich sequence located in the amino-terminal region is important for proper folding. Furthermore, we predict that the importance of the PR in P450 folding is to reduce the tendency of the polypeptide to misfold prior to heme binding.

Amino Acid Sequence↗
PubMed2001

Evaluation of ppk-specified polyphosphate as a mercury remedial tool.

To evaluate the utility of polyphosphate kinase gene (ppk)-specified polyphosphate in mercury remediation, a fusion plasmid, pMK27, with ppk from Klebsiella aerogenes and mercury transport genes, merT and merP, from Pseudomonas K-62, was constructed. The transcription and translation of ppk, merT and merP were found to be mercury-inducible. The ppk-specified polyphosphate was identified in cells preinduced by Hg2+, but not in cells without mercury induction, suggesting that the synthesis of polyphosphate is regulated by merR. The hypersensitive phenotype to Hg2+, shown by bacteria with pMRD141, which contains merT and merP, was almost completely restored to its original levels when the ppk was introduced into the plasmid, suggesting that the Hg2+-toxicity was reduced by the polyphosphate, probably via chelation formation. Bacteria with pMK27 accumulated approximately 6-fold more mercury than the bacteria with cloning vector, pUC119. These results clearly demonstrate that the polyphosphate is capable of retaining mercury in the cells without taxing the cells. Based on the results obtained in the present study, the fusion plasmid pMK27 may serve as a strategy for mercury remediation.

Bacterial Proteins↗
PubMed2001

Activation of mitogen-activated protein kinases in the non-ischemic myocardium of an acute myocardial infarction in rats.

As one of the signal transduction pathways related to myocardial remodeling, mitogen-activated protein kinases (MAPKs) possibly play an important role in ischemic heart disease, but it is still unknown whether myocardial MAPKs are activated in the non-ischemic region of an acute myocardial infarction (AMI). Therefore, the present study investigated the myocardial activity of extracellular signal-regulated kinases (ERKs), c-Jun NH2 terminal kinases (JNKs) and p38MAPK during the acute phase of an infarction of the rat heart, and measured the geometrical ventricular changes by echocardiography. All MAPKs were significantly activated in the ischemic myocardium (IM), non-ischemic septal wall (SW), and right ventricular wall (RV). Furthermore, the activation patterns of MAPKs differed in each region. The activation of p44ERK, JNKs and p38MAPK in the IM occurred rapidly after myocardial ischemia, followed by those in the SW and RV. The activator protein-1 DNA binding activities of the IM, SW and RV increased significantly at I day after coronary ligation. Echocardiography showed increased SW motion and RV dilatation. In conclusion, this is the first in vivo evidence that myocardial MAPKs are activated in the non-ischemic region of an AMI. Echocardiographic results suggest that acceleration of workload and/or stretch may partially induce the activation of MAPKs.

Animals↗
PubMed2001

Ecological co-inhabitance index (ECI) as a management tool for ecosystem preservation in rivers.

The number of novel man-made hazardous substances produced by industries is increasing year after year, resulting in conventional discharge standards ineffective to preserve the natural ecological environment. A novel index, ecological co-inhabitance index (ECI), was proposed in order to evaluate the river ecosystem sensitively. The river benthic community with a high value of ECI is formed in the healthy ecosystem where benthic animals can share resources in the river environment efficiently, keep the ecosystem functioning, and give the least adverse effect to lower reaches of the river. In order to clarify the characteristic of ECI, the relationship between ECI and water quality in the river was investigated using the data on benthic animals obtained from 17 various rivers. Results of this investigation indicated that ECI could synthetically evaluate the river environment without a bias toward a specific water quality. Moreover, ECI had the significant correlation coefficients with diversity index, biotic index and pollution index at significance level 0.05, respectively. Therefore, ECI is a promising index for managing the river ecosystem.

Animals↗