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Naoki Tanaka

Publications and source records attributed to Naoki Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effect of the polypeptide binding on the thermodynamic stability of the substrate binding domain of the DnaK chaperone.

The effect of polypeptide binding on the stability of the substrate binding domain of the molecular chaperone DnaK has been studied by thermodynamic analysis. The calorimetric scan of the fragment of the substrate binding domain DnaK384-638, consisting of a beta-domain and an alpha-helical lid, showed two transitions centered at 56.2 and 76.0 degrees C. On the other hand, the thermal unfolding of the shorter fragment DnaK386-561, which lacks half of the alpha-helical lid, exhibited a single transition at 57.0 degrees C. Therefore, the transition of DnaK384-638 at 56.2 degrees C is mainly attributed to the unfolding of the beta-domain. The calorimetric scan of DnaK384-638D526N showed that the unfolding of the beta-domain was composed of two transitions. The polypeptide bound DnaK384-638 exhibited a symmetrical DSC peak at 58.6 degrees C, indicating that the substrate binding shifts the beta-domain toward a single cooperative unit. A low concentration of GdnHCl (<1.0 M) induced a conformational change in the beta-domain of DnaK384-638 without changes in the secondary structure. While the thermal unfolding of the beta-domain of DnaK384-638 was composed of two transitions in the presence of GdnHCl, the beta-domain of the substrate bound DnaK384-638 exhibited a single symmetrical DSC peak in the same condition. All together, our results indicate that complex between DnaK384-638 and substrate forms a rigid conformation in the beta-domain.

Escherichia coli Proteins↗
PubMed2005

Rice proteome analysis: a step toward functional analysis of the rice genome.

The technique of proteome analysis using 2-DE has the power to monitor global changes that occur in the protein complement of tissues and subcellular compartments. In this review, we describe construction of the rice proteome database, the cataloging of rice proteins, and the functional characterization of some of the proteins identified. Initially, proteins extracted from various tissues and organelles were separated by 2-DE and an image analyzer was used to construct a display or reference map of the proteins. The rice proteome database currently contains 23 reference maps based on 2-DE of proteins from different rice tissues and subcellular compartments. These reference maps comprise 13 129 rice proteins, and the amino acid sequences of 5092 of these proteins are entered in the database. Major proteins involved in growth or stress responses have been identified by using a proteomics approach and some of these proteins have unique functions. Furthermore, initial work has also begun on analyzing the phosphoproteome and protein-protein interactions in rice. The information obtained from the rice proteome database will aid in the molecular cloning of rice genes and in predicting the function of unknown proteins.

Calreticulin↗
PubMed2005

Acute colorectal obstruction treated by means of transanal drainage tube: effectiveness before surgery and stenting.

OBJECTIVES: The aim of this study was to clarify the usefulness of the management of acute colorectal obstruction using a transanal drainage tube before surgery or stenting. METHODS: Fifty-four patients (34 males and 20 females, aged 46-94 yr, mean = 69.7) treated between May 1998 and March 2004 for acute colorectal obstruction were identified in a colorectal obstruction database, and their clinical and radiological features were reviewed. Based on abdominal computed tomography findings, urgent colonoscopy was performed. Subsequently, endoscopic decompression using a Dennis Colorectal Tube (DCT) was attempted. RESULTS: Endoscopic decompression using the DCT was technically successful in 52 of 54 patients (96.3%). The site of obstruction was the cecum in 4, the ascending colon in 2, the transverse colon in 7, the descending colon in 11, the sigmoid colon in 18, and the rectum in 12. The etiology of obstruction was primary colorectal carcinoma in 45, non-colonic metastatic carcinoma in 4, postoperative obstruction in 4, and retrograde intussusception in 1. Following adequate cleansing of the colon, 44 patients underwent a one-stage surgery after 7+/- 3 days (SD; range, 4-10 days). Stenting was successfully used as the final palliative treatment in 4. The use of the DCT alone relieved postoperative stenosis (3 patients) and retrograde intussusception (Prognosis in patients with obstructing colorectal carcinoma. Am J Surg 1982;143:742-7). During these treatments, perforation occurred in one patient with postoperative stenosis of the cecum. CONCLUSIONS: Management of acute colorectal obstruction using the DCT was found to be effective and safe, irrespective of the site or etiology of the obstruction. Therefore, this procedure should be considered as a primary method for decompression of the obstructed colon before considering surgery or stenting.

Acute Disease↗
PubMed2005

A two-generation reproductive toxicity study of 2,4-dichlorophenol in rats.

A two-generation reproductive toxicity study was conducted with 2,4-dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting effects. Wistar-Hannover rats, 24/sex/group, were given diet containing 2,4-DCP at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of the test substance on parental animals and their offspring over 2 successive generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and food consumption of females were lowered significantly during the treatment period. Effects on body weights and food consumption were more serious in the 8000 ppm group, both males and females being significantly affected. Reproductive effects of the test substance were also observed in the 2000 and 8000 ppm groups dose-dependently. Observations included significantly increased uterine weights of F1 and/or F2 female weanlings and reduced numbers of implantation sites and live births of F1 parental females. These results suggest that 2,4-DCP has weak reproductive toxicity, possibly based on endocrine activity. However, the basic mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.

Administration, Oral↗
PubMed2004

Interaction of the N-terminal domain of Escherichia coli heat-shock protein ClpB and protein aggregates during chaperone activity.

The Escherichia coli heat-shock protein ClpB reactivates protein aggregates in cooperation with the DnaK chaperone system. The ClpB N-terminal domain plays an important role in the chaperone activity, but its mechanism remains unknown. In this study, we investigated the effect of the ClpB N-terminal domain on malate dehydrogenase (MDH) refolding. ClpB reduced the yield of MDH refolding by a strong interaction with the intermediate. However, the refolding kinetics was not affected by deletion of the ClpB N-terminal domain (ClpBDeltaN), indicating that MDH refolding was affected by interaction with the N-terminal domain. In addition, the MDH refolding yield increased 50% in the presence of the ClpB N-terminal fragment (ClpBN). Fluorescence polarization analysis showed that this chaperone-like activity is explained best by a weak interaction between ClpBN and the reversible aggregate of MDH. The dissociation constant of ClpBN and the reversible aggregate was estimated as 45 muM from the calculation of the refolding kinetics. Amino acid substitutions at Leu 97 and Leu 110 on the ClpBN surface reduced the chaperone-like activity and the affinity to the substrate. In addition, these residues are involved in stimulation of ATPase activity in ClpB. Thus, Leu 97 and Leu 110 are responsible for the substrate recognition and the regulation of ATP-induced ClpB conformational change.

Animals↗
PubMed2004

Methylmalonate-semialdehyde dehydrogenase is induced in auxin-stimulated and zinc-stimulated root formation in rice.

Proteins induced in rice by auxin and zinc were determined by proteome analysis. Cultured suspension cells of rice were treated with 2,4-dichlorophenoxyacetic acid and ZnSO4 and then proteins were separated by two-dimensional polyacrylamide gel electrophoresis; seven proteins were found to be induced by auxin and zinc. Of these seven, methylmalonate-semialdehyde dehydrogenase (MMSDH) was elevated by treatment with auxin alone. MMSDH was detected in cultured suspension cells, root and leaf sheath, but not in leaf blades. MMSDH responded to auxin and gibberellin, but did not respond to brassinolide and cytokinin. Furthermore, the amount of MMSDH in slr1, a constitutive gibberellin response mutant, was 2-fold that of wild type. MMSDH mRNA and protein were stimulated in root formation induced by auxin and/or zinc over a 4-week period. These results suggest that MMSDH may be necessary for root formation in rice induced by auxin and/or zinc.

Aldehyde Oxidoreductases↗
PubMed2004

Peroxisome proliferator-activated receptor alpha protects against alcohol-induced liver damage.

The mechanisms underlying alcoholic liver disease are not completely understood, but lipid accumulation seems to be central to the cause of this disease. The peroxisome proliferator-activated receptor alpha (PPARalpha) plays an important role in the control of lipid homeostasis, metabolism of bioactive molecules, and modulation of inflammatory responses. To investigate the roles of PPARalpha in alcoholic liver injury, wild-type and PPARalpha-null mice were continuously fed a diet containing 4% ethanol, and liver injury was analyzed. PPARalpha-null mice fed ethanol exhibited marked hepatomegaly, hepatic inflammation, cell toxicity, fibrosis, apoptosis, and mitochondrial swelling. Some of these hepatic abnormalities were consistent with those of patients with alcoholic liver injury and were not found in wild-type mice. Next, the molecular mechanisms of ethanol-induced liver injury in PPARalpha-null mice were investigated, and changes related to ethanol and acetaldehyde metabolism, oxidative stress, inflammation, hepatocyte proliferation, fibrosis, and mitochondrial permeability transition activation occurred specifically in PPARalpha-null mice as compared with wild-type mice. In conclusion, these studies suggest a protective role for PPARalpha in alcoholic liver disease. Humans may be more susceptible to liver toxicity induced by ethanol as PPARalpha expression in human liver is considerably lower compared to that of rodents.

Acetaldehyde↗
PubMed2004

Effects of R-102444, an orally active 5-HT2A receptor antagonist, in rat models of peripheral vascular disease.

R-102444 is a prodrug that is metabolized into R-96544, a potent and selective 5-hydroxytryptamine2A (5-HT2A) receptor antagonist. The effects of R-102444 on peripheral vascular disease were examined using two different rat models: one induced by lauric acid and the other by ergotamine plus epinephrine. R-96544 (0.3-30 nM) relaxed the 5-HT (3 microM)-precontracted rat caudal artery in a concentration-dependent manner. The intravenous administration of R-96544 (0.3-3 microg/kg) to anesthetized rats inhibited the pressor response to 5-HT (50 microg/kg i.v.) dose dependently. The oral administration of R-102444 (1 mg/kg) to rats resulted in a marked inhibition of platelet aggregation induced by 5-HT plus ADP, and statistically significant inhibition was still evident 8 h after the dosing. In contrast, sarpogrelate, at a dose of 100 mg/kg p.o., produced only a moderate antiplatelet effect. Oral administration of R-102444 (1 mg/kg/day, o.d.) significantly prevented the progression of peripheral vascular lesion induced by the injection of lauric acid into a rat femoral artery, whereas sarpogrelate (100 mg/kg/day) showed only a minimal effect. Both 5-day treatments with R-102444 (1-30 mg/kg/day p.o., o.d.), one commenced 1 h before the injection of epinephrine plus ergotamine and one just after injection, resulted in the prevention of rat tail gangrene in a dose-dependent manner, whereas sarpogrelate (100 mg/kg) produced a minimal protection in this model. Based on these results, we conclude that 5-HT2A receptor activation is involved in peripheral vascular disease in the rat and that R-102444 is a useful oral agent for the investigation of diseases involving 5-HT2A receptor activation.

Administration, Oral↗
PubMed2004

Characterization of NADPH-dependent oxidoreductase induced by auxin in rice.

An NADPH-dependent oxidoreductase (NADPH-DO) with an isoelectric point of 5.2 and a molecular mass of 35 kDa was isolated from suspension-cultured rice cells. NADPH-DO was inducible by auxin and gibberellin. NADPH-DO mRNA was expressed in roots and leaf sheaths of rice seedlings, but not in leaf blades. The levels of NADPH-DO mRNA and protein in suspension-cultured cells were increased by auxin; they were further raised by the application of zinc. In contrast, NADPH-DO mRNA and protein accumulation in intact roots was stimulated by auxin, but in this case the stimulation was inhibited by zinc. Auxin-induced callus growth and root formation in intact rice plants were further enhanced by zinc. These results indicate that high levels of NADPH-DO are necessary for auxin- and zinc-induced callus formation, and imply that zinc plays a role in the regulation of NADPH-DO induction by auxin.

Journal Article↗
PubMed2004

The structure of starch can be manipulated by changing the expression levels of starch branching enzyme IIb in rice endosperm.

When the starch branching enzyme IIb (BEIIb) gene was introduced into a BEIIb-defective mutant, the resulting transgenic rice plants showed a wide range of BEIIb activity and the fine structure of their amylopectins showed considerable variation despite having the two other BE isoforms, BEI and BEIIa, in their endosperm at the same levels as in the wild-type. The properties of the starch granules, such as their gelatinization behaviour, morphology and X-ray diffraction pattern, also changed dramatically depending on the level of BEIIb activity, even when this was either slightly lower or higher than that of the wild-type. The over-expression of BEIIb resulted in the accumulation of excessive branched, water-soluble polysaccharides instead of amylopectin. These results imply that the manipulation of BEIIb activity is an effective strategy for the generation of novel starches for use in foodstuffs and industrial applications.

Journal Article↗
PubMed2004

Usefulness of a small-caliber, variable-stiffness colonoscope as a backup in patients with difficult or incomplete colonoscopy.

OBJECTIVES: Although variable-stiffness colonoscopes have been developed, difficult or incomplete colonoscopies occasionally occur. The aim of this study was to evaluate the usefulness of a small-caliber, variable-stiffness colonoscope (scVSC) as a backup in patients with difficult or incomplete colonoscopies. METHODS: First, we retrospectively reviewed the cecal intubation rate of colonoscopies in which an adult standard colonoscope (AC) was immediately switched to an scVSC in all patients in whom a colonoscopy with an AC was incomplete. Second, 374 consecutive patients were randomized to undergo colonoscopy with a pediatric variable-stiffness colonoscope (PVSC, n = 123), AC (n = 125), or scVSC (n = 126). The scVSC was used by the same endoscopist to reattempt colonoscopy immediately after colonoscopy with a PVSC or an AC had been assessed as difficult or incomplete. The cecal intubation rate and time and the ancillary maneuvers used were evaluated. RESULTS: Fifty-two (2.5%) of the 2,056 attempted colonoscopies with an AC did not reach the cecum. Fifty-one of the 52 patients (98.1%) had complete colonoscopies after the switch from the AC to the scVSC. The initial intubation rate and time were not statistically different among the groups: PVSC, 95% and 6.8 min; AC, 91% and 7.5 min; and scVSC, 98% and 8.2 min. Cecal intubation was achieved in all five patients (100%) and in 10 out of 11 (91%) patients, respectively, after the PVSC or AC was switched to the scVSC. CONCLUSIONS: The completion rate markedly improved after switching from an AC or PVSC to an scVSC in difficult or incomplete colonoscopies, although the scVSC does not appear to offer any distinct advantage over the AC or PVSC for routine colonoscopies.

Colonoscopes↗
PubMed2004

[Possible mechanisms of hepatitis C virus-related hepatocarcinogenesis].

Persistent infection of hepatitis C virus (HCV) can lead to a high risk for hepatocellular carcinoma(HCC). HCV core protein plays important roles in HCV-induced hepatocarcinogenesis, because its expression in mice causes hepatic steatosis and HCC without accompanying hepatitis. However, its precise mechanisms remain unclear. We investigated whether the HCV core protein alters the expression of the factors associated with hepatic steatosis and HCC in vivo. By Western immunoblot and Northern blot analyses, expression of the proteins including fatty acid-metabolizing enzymes and cell cycle regulators, which are induced by the activation of peroxisome proliferator-activated receptor alpha (PPARalpha), significantly increased in HCV core protein transgenic mice. This result suggests the possibility that PPARalpha activation might contribute to HCV core protein-mediated hepatocarcinogenesis.

Animals↗
PubMed2003

A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesion with long clinical course and diffuse brain involvement.

Lymphomatoid granulomatosis (LYG)/angiocentric immunoproliferative lesions (AIL) consist of angiocentric and angiodestructive lymphoreticular proliferation predominantly involving the lungs and other extranodal sites, such as the central nervous system (CNS). This clinical entity is considered as a B cell process related to Epstein-Barr virus (EBV) infection and EBV positive diffuse large B-cell lymphoma. The CNS is involved in 20% of cases of LYG, but initial involvement is rare. In cases without pulmonary symptoms, diagnosis may be difficult. We report a rare case involving initial progression of CNS symptoms followed by a pulmonary abnormality.A 14-year-old girl suffered from high fever, ataxic gait and paraparesis. MRI revealed diffuse T2 high signals with multiple gadolinium enhancements in the cerebellum, brain stem and cerebral white matter. Her symptoms briefly improved after steroid therapy, but ataxia gradually progressed. Dyspnea due to pulmonary interstitial involvement appeared when she was 18 years old. Steroid therapy proved effective for respiratory symptoms. At 20 years old she suffered from disseminated intravascular coagulopathy (DIC) and hemophagocytic syndrome (HPS) with respiratory symptoms and repeated seizures. Her symptoms improved after the administration of cyclophosphamide. Mild hemiparesis and gait disturbance appeared when she was 22 years old. MRI revealed new lesions at the basal ganglia and subcortical white matter, brain atrophy and diffuse T2 high intensity of cerebral white matter. Cyclophosphamide was effective and there has been no recurrence of symptoms in the last 5 years. We reviewed the non-tumorous LYG/AIL involving the CNS, and discussed the clinical features, MRI imaging and diagnosis of the LYG/AIL.

Adolescent↗
PubMed2003

In vivo stabilization of nuclear retinoid X receptor alpha in the presence of peroxisome proliferator-activated receptor alpha.

Retinoid X receptor alpha (RXRalpha) can reveal diverse functions through forming a heterodimer with peroxisome proliferator-activated receptor alpha (PPARalpha). However, the mechanism of regulation of the cellular RXRalpha level is unclear. Thus, quantitative change of RXRalpha was investigated in mouse liver. Nuclear RXRalpha level was constitutively lower in PPARalpha-null mice than in wild-type mice. The level was also increased by clofibrate treatment in wild-type mice without a concomitant increase of RXRalpha mRNA, but not in PPARalpha-null mice. Pulse chase experiments demonstrated that the presence of PPARalpha and its activation by ligands significantly affected the stability of nuclear RXRalpha. These findings suggest a novel regulatory mechanism of nuclear RXRalpha in vivo.

Animals↗
PubMed2002

Pharmacological profiles of R-96544, the active form of a novel 5-HT2A receptor antagonist R-102444.

We examined the pharmacology of (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine hydrochloride (R-96544), the active form of a novel 5-HT(2A) receptor antagonist, (2R,4R)-4-lauroyloxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine hydrochloride (R-102444). R-96544 produced a concentration-dependent inhibition of platelet aggregation induced by serotonin (5-hydroxytryptamine, 5-HT) alone or in combination with ADP in platelets from humans, monkeys, cats, rabbits, rats and mice. An intravenous administration of R-96544 to rabbits significantly inhibited ex vivo platelet aggregation induced by 5-hydroxytryptamine (5-HT) combined with epinephrine. An oral administration of R-102444 to rats also resulted in significant inhibition of ex vivo platelet aggregation, whereas R-102444 was ineffective in an in vitro platelet aggregation assay. These antiplatelet effects of R-96544 and R-102444 were more potent than those of two other 5-HT(2A) receptor antagonists, sarpogrelate and its active metabolite (+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propanol hydrochloride (M-1). A binding study using cat platelet membranes showed that R-96544 has high affinity for 5-HT(2A) receptors but no effect on non-serotonergic [3H]ketanserin-binding sites. R-96544 caused a parallel shift to the right of concentration-response curves for 5-HT in rat caudal artery contraction mediated by 5-HT(2A) receptors. Schild plot analysis gave a pA(2) value of 10.4 with a slope near unity (1.04). R-96544 also inhibited 5-HT(2A) receptor-mediated contraction of guinea pig trachea but not 5-HT(3) receptor-mediated contraction of guinea pig ileum and 5-HT(2B) receptor-mediated contraction of rat fundus preparation. R-96544 (i.v.) attenuated the pressor responses evoked by 5-HT (15 microg/kg, i.v.) but not by phenylephrine (5 microg/kg, i.v.) and angiotensin II (0.1 microg/kg, i.v.), after ganglionic blockade in anesthetized spontaneously hypertensive rats. These results show that R-96544, the active form of R-102444, is a novel 5-HT receptor antagonist with potent, competitive, and 5-HT(2A)-selective activity.

Adult↗