Biomedical subjects

Naoki Tanaka

Publications and source records attributed to Naoki Tanaka.

At least 19 recordsLinked to original sources

PubMed2006

Haploinsufficiency in the PPARalpha and LDL receptor genes leads to gender- and age-specific obesity and hyperinsulinemia.

When preparing peroxisome proliferator-activated receptor (PPAR)alpha:low-density lipoprotein receptor (LDLR) (-/-) double knockout mice, we unexpectedly found a unique gender- and age-specific obesity in the F1 generation, PPARalpha (+/-):LDLR (+/-), even in mice fed standard chow. Body weights of the male heterozygous mice increased up to about 60 g at 75 weeks of age, then decreased by about 30 g at 100 weeks of age. More than 95% of the heterozygous mice between 35- and 75-week-olds were overweight. Of interest, the obese heterozygous mice also exhibited hyperinsulinemia correlating with moderate insulin resistance. Hepatic gene expression of LDLR was lower than expected in the heterozygous mice, particularly at 50 and 75 weeks of age. In contrast, the hepatic expression of PPARalpha was higher than expected in obese heterozygous mice, but decreased in non-obese older heterozygous mice. Modulated expression of these genes may be partially associated with the onset of the hyperinsulinemia.

Age Factors↗

PubMed2006

Wavelet analysis for detecting body-movement artifacts in optical topography signals.

We have developed a wavelet-based method of detecting body-movement artifacts in optical topography (OT) signals. Although OT, which is a noninvasive imaging technique for measuring hemodynamic response related to brain activation, is particularly useful for studying infants, the signals occasionally contain undesirable artifacts caused by body movements, so data corrupted by body-movement artifacts must be eliminated to obtain reliable results. For this purpose, we applied a wavelet transform to automatically detect body-movement artifacts in OT signals. We measured OT signals from nine healthy infants in response to speech stimuli. After the continuous signals had been divided into blocks (a block is a time series of OT signal in a 30-s period including a 10-s stimulation period), they were classified into two groups (movement blocks and non-movement blocks) according to whether the participants moved or not by video judgment. Using those data, we developed a wavelet-based algorithm for detecting body-movement artifacts at a high discrimination rate being consistent with the actual body-movement state. The wavelet method has two parameters (scale and threshold), and a Monte Carlo analysis gave the mean optimal parameters as 9+/-1.9 (mean+/-standard deviation) for the scale and as 42.7+/-1.9 for the threshold. Our wavelet method with the mean optimal parameters (scale=9, threshold=43) achieved a higher discrimination rate (mean+/-standard deviation: 86.3+/-8.8%) for actual body movement than a previous method (mean+/-standard deviation: 80.6+/-8.7%) among different participants (paired t test: t(8)=2.92, p<0.05). These results demonstrate that our wavelet method is useful in practice for eliminating blocks containing body-movement artifacts in OT signals. It will contribute to obtaining reliable results from OT studies of infants.

Artifacts↗

PubMed2006

A lean man with nonalcoholic fatty liver disease.

Explore the source record for details and available documents.

Adult↗

PubMed2006

The roles of conserved amino acids on substrate binding and conformational integrity of ClpB N-terminal domain.

Escherichia coli heat shock protein ClpB disaggregates denatured protein in cooperation with the DnaK chaperone system. Several studies showed that the N-terminal domain is essential for the chaperone activity, but its role is still largely unknown. The N-terminal domain contains two structurally similar subdomains, and conserved amino acids Thr7 and Ser84 share the same position in two apparent sequence repeats. T7A and S84A substitutions affected chaperone activity of ClpB without significantly changing the native conformation [Liu, Z. et al. (2002) J. Mol. Biol. 321, 111-120]. In this study, we aimed to better understand the roles of several conserved amino acid residues, including Thr7 and Ser84, in the N-terminal domain. We investigated the effects of mutagenesis on substrate binding and conformational states of ClpB N-terminal domain fragment (ClpBN). Fluorescence polarization analysis showed that the T7A and S84A substitutions enhanced the interaction between ClpBN and protein aggregates. Interestingly, further analyses suggested that the mechanisms by which they do so are quite different. For T7A substitution, the increased substrate affinity could be due to a conformational change in the hydrophobic core as revealed by NMR spectroscopy. In contrast, for S84A, increased substrate binding would be explained by a unique conformational state of this mutant as revealed by pressure perturbation analysis. The thermal transition temperature of the S84A mutant, monitored by DSC, was 6.1 degrees C lower than that of wild-type. Our results revealed that conserved amino acids Thr7 and Ser84 both participated in maintaining the conformational integrity of the ClpB N-terminal domain.

Amino Acid Sequence↗

PubMed2006

Peroxisome proliferator-activated receptor alpha-independent peroxisome proliferation.

Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor alpha (PPARalpha) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPARalpha-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPARalpha dependence in the assay system. Surprisingly, a novel type of PPARalpha-independent peroxisome proliferation and enlargement was uncovered in PPARalpha-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11alpha, might be associated with the PPARalpha-independent peroxisome proliferation at least in part.

Acyl-CoA Oxidase↗

PubMed2006

Chiral silanes via asymmetric hydrosilylation with catalytic CuH.

[reaction: see text] CuH-catalyzed asymmetric conjugate reduction of beta-silyl-alpha,beta-unsaturated esters has been developed. Using PMHS as a stoichiometric source of hydride and in situ generated CuH ligated by Solvias' JOSIPHOS analogue PPF-P(t-Bu)(2) leads to highly enantioselective 1,4-reductions.

Journal Article↗

PubMed2006

Quantitative evaluation of interrelations between spontaneous low-frequency oscillations in cerebral hemodynamics and systemic cardiovascular dynamics.

A common issue in blood-related brain-function measurements, such as optical topography, is that the observed signals are usually corrupted with strong noise that is primarily spontaneous low-frequency oscillations (LFOs) in cerebral hemodynamics, which are difficult to separate from the signals due to functional brain activity because of their common spectral range. We discuss the analysis of information transfer between LFOs around 0.1 Hz in the hemoglobin concentration change (HbCC) in the cerebral cortex, the heart rate (HR), and the mean arterial blood pressure (ABP) to understand the origin of spontaneous LFOs in cerebral hemodynamics. As measures of information transfer, we used transfer entropy (TE) for two-variable system analysis and introduced intrinsic transfer entropy for further analysis of three-variable systems by extending the original TE. Data for analysis were obtained from simultaneous measurements with optical topography and infrared finger plethysmography under rest conditions. The analysis revealed that the LFOs in oxy HbCC, a parameter of cerebral hemodynamics, mainly stem from HR, but its contribution is only about 20%. In addition, the intrinsic contribution of ABP is about 5% and the common contribution of HR and ABP is about 10%. From these, HR and ABP cannot account for more than the half the information carried with variable oxy HbCC, which suggests the origin of LFOs in cerebral hemodynamics may lie in the regulation of regional cerebral blood flow change and energetic metabolism rather than due to the systemic regulation of the cardiovascular system.

Aged↗

PubMed2006

Comparison of two proteomics techniques used to identify proteins regulated by gibberellin in rice.

Proteomics has become an essential methodology for large-scale analysis of proteins in various fields of plant biology. We compared two proteomics techniques, two-dimensional liquid chromatography (2D-LC) and fluorescence two-dimensional difference gel electrophoresis (2D-DIGE), for their ability to identify proteins regulated by gibberellin (GA) in rice. Two-week-old rice seedlings were treated with or without 5 microM GA3 for 48 h and proteins extracted from the basal region of the leaf sheath. After separation of the proteins by the two techniques, the amino acid sequences of GA3-responsive proteins were analyzed using a protein sequencer and mass spectrometry. 2D-LC and 2D-DIGE were able to resolve 1248 protein fractions and 1500 proteins, respectively. Out of these, 2D-LC identified 9 proteins that were up-regulated and 9 that were down-regulated by GA treatment; 2D-DIGE identified 4 up-regulated and 4 down-regulated proteins. The two techniques detected overlapping sets of proteins. For example, cytosolic glyceraldehyde-3-phosphate dehydrogenase and photosystem II oxygen-evolving complex protein were identified as GA3-regulated proteins by both methods. In addition, these two methods uncovered GA3-regulated unknown proteins which had not been reported previously, and novel proteins which are not detected in 2D-PAGE followed by Coomassie brilliant blue staining. These results suggest that these two methods are among some of the very useful tools for detecting proteins that may function in various physiological and developmental processes in plants.

Chromatography, Liquid↗

PubMed2006

gid1, a gibberellin-insensitive dwarf mutant, shows altered regulation of probenazole-inducible protein (PBZ1) in response to cold stress and pathogen attack.

A recessive gibberellin (GA)-insensitive dwarf mutant of rice, gibberellin-insensitive dwarf1 (gid1), has been identified, which shows a severe dwarf phenotype and contains high concentrations of endogenous GA. To elucidate the function of gid1, proteins regulated downstream of gid1 were analysed using a proteomic approach. Proteins extracted from suspension-cultured cells of gid1 and its wild type were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Of a total of 962 proteins identified from the suspension-cultured cells, 16 were increased and 14 were decreased in gid1 compared with its wild type. Among the proteins hyper-accumulated in gid1 were osmotin, triosephosphate isomerase, probenazole inducible protein (PBZ1) and pathogenesis-related protein 10. Of these four genes, only the expression of PBZ1 was increased by exogenous GA3 application. Expression of this gene was also enhanced in shoots of the wild type by cold stress or by rice blast fungus infection. Under normal growth conditions, there was more PBZ1 protein in gid1 than in the wild type. In addition, gid1 showed increased tolerance to cold stress and resistance to blast fungus infection. The entcopalyl diphosphate synthase (OsCPS) genes, which encode enzymes at the branch point between GA and phytoalexin biosynthesis, were expressed differentially in gid1 relative to the wild type. Specifically, OsCPS1, which encodes an enzyme in the GA biosynthesis pathway, was down-regulated and OsCPS2 and OsCPS4, which encode enzymes in phytoalexin biosynthesis, were up-regulated in gid1. These results suggest that the expression of PBZ1 is regulated by GA signalling and stress stimuli, and that gid1 is involved in tolerance to cold stress and resistance to blast fungus.

Abscisic Acid↗

PubMed2006

Laparoscopic findings in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH. METHODS: Twenty-four patients were enrolled. The degrees of hepatomegaly, color and irregularity of the liver surface, and the presence of depressions, patches, and vesicles were investigated. These laparoscopic findings were compared among NASH, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH). RESULTS: Mild hepatomegaly, dullness of the liver edge, increased fat accumulation of the round ligament, and whitish markings were found in most of the patients with NASH. Small depressions were observed in approximately 70% of the patients. As fibrosis developed, the liver surface became whiter and more uneven. Compared with patients with ALD and AIH, increased fat accumulation of the round ligament and dullness of the liver edge were observed more frequently in those with NASH. However, coarse and groove-like depressions were rare in NASH patients. CONCLUSIONS: Several findings, including mild hepatomegaly, increased fat accumulation of the round ligament, rounded liver edge, whitish markings, and small depressions were common in patients with NASH. However, coarse and groove-like depressions were rare. These findings may be helpful for confirming a diagnosis of NASH.

Adult↗

PubMed2006

Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population.

BACKGROUND/AIMS: As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH. METHODS: First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory examination and US were enrolled. These patients were histologically divided into NASH and non-NASH groups, and their clinical features were compared. Second, the diagnostic accuracy of predictors of NASH was examined prospectively. RESULTS: Fifteen patients (28%) were histologically diagnosed as having NASH with mild steatosis. Multivariable analysis revealed that body mass index (BMI) and serum ferritin level were independent predictors of NASH. The best cutoff values to detect NASH were assessed by using receiver-operating characteristic curves: BMI>25.2 kg/m(2) and serum ferritin level >142 ng/ml. When both markers were concomitantly negative, the negative predictive value to detect NASH was 100%. CONCLUSIONS: In cases of mild steatosis, US is not a perfect tool for the accurate diagnosis of NASH. BMI and serum ferritin level are useful discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful markers for diagnosing NASH more accurately in Japanese patients.

Adolescent↗

PubMed2006

Nasopharyngeal decolonization of methicillin-resistant Staphylococcus aureus can reduce PEG peristomal wound infection.

OBJECTIVES: The aim of this study is to determine whether nasopharyngeal decolonization of methicillin-resistant Staphylococcus aureus (MRSA) can reduce peristomal wound infection shortly after percutaneous endoscopic gastrostomy (PEG) placement. METHODS: Of the 84 hospitalized patients referred for PEG, 72 were enrolled in a one-third observation (Group A) and two-thirds in a randomized trial (Groups B and C). Nasopharyngeal swabs were taken from a consecutive series of patients prior to PEG insertion. Based upon these results, they were classified into three groups: Group A, MRSA-negative (n = 24), Group B, MRSA-positive, but not eradicated (n = 24), Group C, MRSA-positive and eradicated with intranasal application of mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim (n = 24). The standard PEG pull-through insertion technique was performed on all 72 patients. All patients received prophylactic and concomitant antibiotics. Infections at the peristomal site were prospectively evaluated and defined as having at least two of the following conditions: peristomal erythema, induration, and purulent discharge. Bacterial culture using purulent discharge was performed. RESULTS: There was significant difference in the peristomal infection rates among the groups: Group A, 0% (0/0); Group B, 100% (24/24); Group C, 8% (2/24) (p < or = 0.0001). In Group C, nasopharyngeal decolonization of MRSA, which was achieved by the combination of intranasal mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim in all 24 patients, significantly reduced peristomal infections. Eighteen (16 in Group B and 2 in Group C) of these 26 infected patients had cellulitis and developed purulent discharge from which MRSA was isolated. CONCLUSIONS: Nasopharyngeal decolonization of MRSA can reduce peristomal infection shortly after the pull-through PEG insertion. MRSA appears to be a major pathogen in PEG peristomal infection while prophylactic and concomitant antibiotics are being used.

Aged↗

PubMed2006

Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities.

A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.

Adult↗

PubMed2006

[PPAR and NASH].

The nuclear receptor peroxisome proliferator-activated receptor (PPAR) plays important roles in maintaining the homeostasis of lipids and glucose. Among three isoforms of PPAR, PPARa and PPARgamma are localized mainly in hepatocytes and adipocytes, respectively. Recently, it has been recognized that PPAR also modulates inflammatory responses, regulates cell division and associates with liver fibrogenesis and tumorigenesis. Although the roles of PPAR for the pathogenesis of nonalcoholic steatohepatitis (NASH) remain unclear, several data suggest the relationship between PPAR and the occurrence or progression of NASH. For example, in mice lacking acyl-CoA oxidase gene, which developed NASH spontaneously, the absence of PPARalpha prevented the development of NASH. Long term administration of PPARgamma activator pioglitazone ameliorated the activity of NASH. In this review, we summarize the evidences concerning NASH and PPAR in this time.

Acyl-CoA Oxidase↗

PubMed2005

Suppression of expression of muscle-associated proteins by PPARalpha in brown adipose tissue.

Peroxisome proliferator-activated receptor alpha (PPARalpha) belongs to the steroid/nuclear receptor superfamily. Two-dimensional (2D) SDS-PAGE analysis of brown adipose tissue (BAT) unexpectedly revealed six spots that were present only in PPARalpha-null mice. Proteomic analysis indicated that these proteins were tropomyosin-1 alpha chain, tropomyosin beta chain, myosin regulatory light chain 2, myosin light chain 3, and parvalbumin alpha. Analyses of mRNA have revealed that PPARalpha suppressed the genes encoding these proteins in a synchronous manner in adult wild-type mice. Histological and physiological analyses of BAT showed in adult wild-type mice, a marked suppression of BAT growth concurrent with a prominent decrease in lipolytic and thermogenesis activities. These results suggest that in adult mice, PPARalpha functions to suppress the expression of the proteins that may be involved in the architecture of BAT, and thus may function in keeping BAT in a quiescent state.

Adipose Tissue, Brown↗

PubMed2005

Effects of R-102444 and its active metabolite R-96544, selective 5-HT2A receptor antagonists, on experimental acute and chronic pancreatitis: Additional evidence for possible involvement of 5-HT2A receptors in the development of experimental pancreatitis.

The effects of R-102444 ((2R, 4R)-4-lauroyloxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine hydrochloride) and its active metabolite R-96544 ((2R, 4R)-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-4-hydroxy-1-methylpyrrolidine hydrochloride), potent and selective 5-hydroxytryptamine 2A (5-HT2A) receptor antagonists, on development of pancreatitis were investigated in experimental models of acute and chronic pancreatitis. Rat acute pancreatitis was induced by caerulein (20 microg/kg) intraperitoneal injection and by pancreatic duct ligation. In both the models, serum amylase and lipase activities were markedly increased. R-102444 dose-dependently reduced these enzyme activities at a dose range of 10 to 100 mg/kg (p.o.) for the caerulein model and 0.3 to 10 mg/kg (p.o.) for the ligation model. In a mouse model of acute pancreatitis induced by a choline-deficient, ethionine (0.5%)-supplemented diet, subcutaneous administration of R-96544 (10-100 mg/kg, bid) reduced serum amylase activity. Histological analysis showed that R-96544 dose-dependently attenuated pancreatic necrosis, inflammation and vacuolization. The effect of R-102444 was further examined in male Wistar Bonn/Kobori rats (4-9 months of age) which spontaneously show pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis. In Wistar Bonn/Kobori rats (from 3 to 9 months of age) fed a diet containing 0.017% and 0.17% of R-102444, pancreatic weight, pancreatic protein and amylase content were higher compared to those in non-treated pancreatitis control rats. Histological analysis showed that R-102444 suppressed parenchymal destruction and replacement with adipose tissue, indicating inhibition of pancreatic atrophy. These results clearly indicate that R-102444 and R-96544 inhibit the progression of acute and chronic pancreatitis and support the contention of possible involvement of 5-HT2A receptors in the progression of experimental pancreatitis.

Acute Disease↗

PubMed2005

Expression and function of proteins during development of the basal region in rice seedlings.

A differential display of proteins with a two-dimensional polyacrylamide gel electrophoresis approach was used to analyze protein expression changes during development of the basal region in rice seedlings (Oryza sativa L. cv. Nipponbare). The proteins were detected as 700 Coomassie Brilliant Blue-stained spots with pI values from around 3.5 to 9.0. A proteome reference map was established for the basal region of two-week-old seedlings. The basal region proteome map was used to analyze quantitative variations in the tissue during development from 2-, 4-, 6-, 8-, and 10-week-old seedlings. During development, 31 proteins were up-regulated, and 30 proteins were down-regulated compared with the 2-week-old basal region proteome map. The main functions of these proteins were primary metabolism and protein synthesis or maintenance. Calreticulin precursor, enolase, and voltage-dependent anion channel were identified among the up- and down-regulated proteins. The twin spots of calreticulin precursor and enolase with different pI values are possibly due to post-translational modifications such as phosphorylation. In addition, seven proteins showed developmental stage-specific expression. All of the developmentally regulated proteins of the basal region were clustered by the S-system, a differential equation that fit to time course of cluster and analyzed for cluster relationships. Proteins with unknown functions were tentatively assigned to functional groups based on cluster relationships. Basal region development proteome data will be valuable for resolving questions in functional genomics. In addition, cluster analysis of the basal region proteome during development will be useful for the assessment of functional proteins.

Electrophoresis, Gel, Two-Dimensional↗

PubMed2005

Genome-wide identification of the rice calcium-dependent protein kinase and its closely related kinase gene families: comprehensive analysis of the CDPKs gene family in rice.

In plants, calcium acts as a universal second messenger in various signal transduction pathways. The plant-specific calcium-dependent protein kinases (CDPKs) play important roles regulating downstream components of calcium signaling. We conducted a genome-wide analysis of rice CDPKs and identified 29 CDPK genes and eight closely related kinase genes, including five CDPK-related kinases (CRKs), one calcium and calmodulin-dependent protein kinase (CCaMK) and two phosphoenolpyruvate (PEP) carboxylase kinase-related kinases (PEPRKs). The mRNA splicing sites of the rice CDPKs, CRKs and PEPRKs (but not OsCCaMK) are highly conserved, suggesting that these kinases are derived from a common ancestor. RNA gel blot analyses revealed that the majority of rice CDPK genes exhibited tissue-specific expression. Expression of OsCPK9 was elevated in seedlings infected by rice blast, indicating that this gene plays an important role in signaling in response to rice blast treatment. Our genomic and bioinformatic analyses will provide an important foundation for further functional dissection of the rice CDPK gene family.

Alternative Splicing↗