Biomedical subjects

Akira Imaizumi

Publications and source records attributed to Akira Imaizumi.

13 recordsLinked to original sources

PubMed2007

Renal effects of beta2-adrenoceptor agonist and the clinical analysis in children.

The objectives of the present study were to define the contribution of beta2-adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether over-expression of renal beta2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of beta2-AR activation. The renal functional responses to the systemic injection of the beta2-AR agonist terbutaline in Wistar rats over-expressing renal beta2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal beta2-AR expression in 34 children (age 2-15 y) and the changes in serum creatinine levels of 99 children (age 1-15 y) who received beta2-AR agonists. The animal study showed that the suppression of glomerular function by terbutaline was associated with a reduction in systemic blood pressure and over-expression of renal beta2-ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal beta2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by beta2-AR agonists can be explained, at least partly, by enhanced beta2-AR expression in the kidney. This may have important implications for the use of beta2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.

Adolescent↗

PubMed2006

The effect of intracellular ppGpp levels on glutamate and lysine overproduction in Escherichia coli.

Although the enhancement of amino-acid synthesis by guanosine-3',5'-tetraphosphate (ppGpp) is well known, the effect of intracellular ppGpp levels on amino-acid overproduction in Escherichia coli has not been investigated. In this study, we demonstrate that overexpression of the relA gene, encoding ppGpp synthetase, increases the accumulation of amino acids, such as glutamate and lysine, in amino-acid-overproducing strains of E. coli. Elevation of intracellular ppGpp levels due to depletion of required amino acids also enhances glutamate overproduction. Moreover, the extent of overproduction is highly dependent on the intracellular ppGpp level. These results demonstrate that amino-acid overproduction in E. coli is closely connected to amino-acid auxotrophy via the accumulation of ppGpp.

Amino Acids↗

PubMed2006

Improved production of enzymes, which are expressed under the Pho regulon promoter, in the rmf gene (encoding ribosome modulation factor) disruptant of Escherichia coli.

Using a DNA macroarray, we investigated the effects of rmf gene (encoding ribosome modulation factor) disruption on gene expression profiles in Escherichia coli. This strain showed a phosphate-starvation-like response in gene expression even under phosphate sufficient conditions; significant upregulation of the Pho regulon genes was observed. Further, the production of alkaline phosphatase, a product of the Pho regulon gene, phoA, increased in the rmf disruptant under a Pi sufficient condition. Furthermore, production of PhoC acid phosphatase/nucleoside pyrophosphate phosphotransferase derived from Morganella morganii also increased significantly in the rmf disruptant. We concluded that host modification by the rmf gene disruption has potential benefit in industrial enzyme production using Escherichia coli.

Alkaline Phosphatase↗

PubMed2005

Improved production of L-lysine by disruption of stationary phase-specific rmf gene in Escherichia coli.

Growth and rate, at which fermentation products are formed in cells, generally decreases during the stationary phase as a result of changes in gene expression. We focused on the rmf gene, which encodes the ribosome modulation factor protein, as a target for strain modification in order to improve the rate of L-lysine production in Escherichia coli. Increased expression of the rmf gene during the stationary phase was confirmed under various cultivation conditions using DNA macroarray analysis. Mutants with disrupted rmf were then generated from an L-lysine-producing E. coli strain. The rates of L-lysine accumulation and production were significantly increased in disruptants that were cultivated with excess phosphate. By contrast, a higher biomass was generated in disruptants that were grown under limited phosphate conditions. These results demonstrate that disruption of the rmf gene significantly affects L-lysine production and growth in E. coli.

Base Sequence↗

PubMed2005

Adenoviral delivery of the beta2-adrenoceptor gene in sepsis: a subcutaneous approach in rat for kidney protection.

Successful gene therapy requires gene delivery that is efficient, has an optimal route of administration and has biosafety. The aims of the present study were to evaluate the safety and applicability of the subcutaneous delivery route for adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) and to investigate whether this approach prevented renal dysfunction in a rat model of endotoxaemic shock induced by LPS (lipopolysaccharide). Subcutaneous administration of adeno-beta(2)-AR (a total of 10(10) viral particles) significantly increased beta-AR density in the kidney, lung and liver, but was without effect on physiological and plasma biochemical parameters. Moreover, this dose of virus did not cause any of the potential toxic responses of viral administration, such as inflammation and tissue TNF (tumour necrosis factor)-alpha expression. Although the LPS challenge caused a decrease in glomerular filtration rate, fractional excretion of sodium and renal beta-AR density in all groups, the reduction in renal function was significantly less in the rats given adeno-beta(2)-AR compared with non-treated rats. Thus, although further evaluation will be required, this initial study demonstrated that the subcutaneous injection of adeno-beta(2)-AR was efficient, comparatively non-pathogenic and potentially therapeutic to deal with acute renal failure associated with sepsis.

Acute Kidney Injury↗

PubMed2004

ASIAN: a website for network inference.

UNLABELLED: We constructed a website for inferring a network by applying the graphical Gaussian model, from a large amount of data, including redundant information. The available tools on the website are based on a system, named ASIAN (Automatic System for Inferring A Network), in combination with the two methods in our previous papers, which were designed to analyze gene expression profiles on a genomic scale. One of the remarkable features of the website is its ability to infer a network, concomitant with hierarchical clustering and the following estimation of cluster boundaries. AVAILABILITY: http://eureka.ims.u-tokyo.ac.jp/asian

Computer Simulation↗

PubMed2004

beta(2)-Adrenoceptor activation attenuates endotoxin-induced acute renal failure.

Abnormalities in the beta(2)-adrenergic control of organ function have been implicated in the pathogenesis of several disease states, such as septic shock. The objectives of the present study were to define the contribution of beta(2)-adrenoceptors (beta(2)-AR) to normal renal physiology and to investigate whether overexpression of renal beta(2)-AR might be potentially beneficial in preventing progressive renal damage associated with endotoxemia. Adenoviral transgenes containing the human beta(2)-AR (Adeno-beta(2)-AR) were constructed and delivered into the rat kidney by means of intraparenchymal injections. Administration of 10(9) total viral particles of Adeno-beta(2)-AR induced an approximately threefold increase in beta(2)-AR density in the renal tissue, which 2 wk after delivery, enhanced GFR and sodium reabsorption compared with control rats. The enhanced GFR was abolished by the addition of the beta(2)-AR antagonist, ICI 118,551. Administration of lipopolysaccharide (LPS) caused a reduction in GFR, beta(2)-AR density, and cAMP together with enhanced TNF-alpha mRNA in the kidney. In rats overexpressing beta(2)-AR, the reduction in baseline GFR and elevation of TNF-alpha mRNA and leukocyte infiltration into the kidney associated with the endotoxin were blocked. These findings suggested the possibility that a renal-specific overexpression of beta(2)-AR preserves basal renal function in response to a ligand-independent beta(2)-AR activation and that the delivery of Adeno-beta(2)-AR gene is a potential novel therapeutic strategy for treatment of acute renal failure associated with sepsis.

Acute Kidney Injury↗

PubMed2004

[Beta 2-adrenoceptor function in the kidney].

The majority of beta(2)-adrenoceptor (beta(2)-AR) agonists is eliminated via the kidneys as an unchanged substance. It is likely that such agents will exert pharmacological effects during their passage through the nephron. However, these pharmacological effects have, to our knowledge, not been taken into consideration when using these compounds in clinical practice because the role of beta(2)-AR in the regulation of renal function remains unclear. Renal beta(2)-ARs are predominantly localized to the proximal tubular epithelia and the membranes of smooth muscle cells from renal arteries. From this morphologic evidence, it is proposed that beta(2)-AR activation may regulate glomerular function and thereby sodium and water balance in the nephron segments. Actually, beta(2)-AR agonists given acutely cause a marked decrease in glomerular filtration rate. On the other hand, beta(2)-AR agonists inhibit the renal production of inflammatory cytokines such as TNF-alpha. Furthermore, the administration of beta(2)-AR agonists is found to attenuate apoptosis associated with shigatoxin in the hemolytic uremic syndrome (HUS). Increased understanding of the pharmacological basis of beta(2)-AR function in the kidney provides important new information relevant to the clinical use of beta(2)-AR agonists in airway diseases and potential applications of these drugs in renal inflammation and injury associated with sepsis or HUS.

Adrenergic beta-Agonists↗

PubMed2004

Detection of inter-spread repeat sequence in genomic DNA sequence.

Various types of periodic patterns in nucleotide sequences are known to be very abundant in a genomic DNA sequence, and to play important biological roles such as gene expression, genome structural stabilization, and recombination. We present a new method, named "STEPSTONE", to find a specific periodic pattern of repeat sequence, inter-spread repeat, in which the tandem repeats of the conserved and the not-conserved regions appear periodically. In our method, at first, the data on periods of short repeat sequences found in a target sequence are stored as a hash data, and then are selected by application of an auto-correlation test in time series analysis. Among the statistically selected sequences, the inter-spread repeats are obtained by usual alignment procedures through two steps. To test the performance of our method, we examined the inter-spread repeats in Mycobacterium tuberculosis and Zamia paucijuga genomic sequences. As a result, our method exactly detected the repeats in the two sequences, being useful for identifying systematically the inter-spread repeats in DNA sequence.

Algorithms↗

PubMed2004

Causes for the large genome size in a cyanobacterium Anabaena sp. PCC7120.

Three possible causes responsible for the large genome size of a cyanobacterium Anabaena sp. PCC7120 are investigated: 1) sequential tandem duplications of gene segments, genes or genomic segments, 2) horizontal gene transfers from other organisms, and 3) whole-genome duplication. We evaluated the frequency distribution of angles between paralog locations for the possibility 1), the fraction of genes deviated in GC content, GC skew, AT skew and codon adaptation index for the 2) and the gene-configuration comparison of paralogs for the 3). As a result, the possibility 3), the whole-genome duplication, was more reasonable as a molecular cause than the other causes for the large genome size in Anabaena sp. PCC7120. In addition, the whole-genome duplication was supported by the analysis of distribution pattern of protein genes with respect to functional categories.

Anabaena↗

PubMed2003

Beta2-adrenoceptor activation inhibits Shiga toxin2-induced apoptosis of renal tubular epithelial cells.

Apoptosis is regulated by several pathways, such as caspases, mitogen activated protein kinase (MAPK) and cAMP/cAMP-dependent protein kinase A (PKA) cascade. This study investigated the effect of beta(2)-adrenoceptor activation on Shiga toxin (Stx)2-induced apoptosis in renal tubular cells and the contribution of these signalling pathways. Cultured human adenocarcinoma-derived tubular cells were exposed to Stx2 (64 pg/mL) for 2-24hr following the addition of the beta(2)-adrenoceptor agonist (terbutaline) to the incubation medium. Stx2-induced apoptosis and its amelioration by beta(2)-adrenoceptor activation was confirmed using DNA degradation assays and by flow cytometry for annexin V, mitochondrial membrane potential and caspase(-3 and -7) activity. Exposure of cells to Stx2 for 24hr increased the DNA fragmentation to 11.6+/-0.9%, compared to 3.3+/-0.2% in control cells (P<0.05) but was decreased to approximately 5-7% (P<0.05) in the presence of terbutaline. Furthermore, Stx2-stimulated apoptosis, detected by TUNEL, annexin V and mitochondrial potential, was inhibited by terbutaline (P<0.05) which was prevented by cAMP-PKA inhibitors and a beta(2)-adrenoceptor antagonist. However, inhibition of Stx2-mediated caspase activity by terbutaline was partially blocked by cAMP-PKA inhibitors. On the other hand, p38MAPK inhibition by terbutaline prevented Stx2-induced apoptosis and caspase activity through a cAMP-independent pathway via beta(2)-adrenoceptor. These data indicate that beta(2)-adrenoceptor activation can inhibit Stx2-induced apoptosis of the cells, which may be caused by a reduction in caspase activity through cAMP-PKA activation and the p38MAPK pathway.

Annexin A5↗

PubMed2002

Role of angiotensin II-induced cAMP in mesangial TNF-alpha production.

Previous findings indicated that cAMP had an inhibitory effect of on tumour necrosis factor (TNF)-alpha production. Angiotensin II (Ang II) may activate the cAMP-protein kinase A (PKA) pathway in renal mesangial cells through synthesis of prostaglandins (PGs) and the possibility arises that inhibition of Ang II-induced cAMP formation might result in the overproduction of TNF-alpha in the cell and this hypothesis was tested in the present study. Rat mesangial cells were exposed to Ang II in the presence or absence of cyclooxygenase inhibitor (indomethacin) or cAMP-PKA inhibitor (H-89). Exposure of mesangial cell to Ang II (10(-6)M-10(-8)M) significantly increased intracellular cAMP level through type 1 Ang II receptor but had no effect on TNF-alpha protein release, transcriptional activity, or mRNA. However, following the addition of indomethacin or H-89, Ang II significantly increased TNF-alpha release, transcriptional activity, and mRNA level. These data suggested that in mesangial cells after blockade of cAMP-PKA by PG inhibition, Ang II was capable of stimulating TNF-alpha transcription which subsequently increased TNF-alpha mRNA accumulation and protein release.

Angiotensin II↗

PubMed2001

Activation of beta(2)-adrenoceptor prevents shiga toxin 2-induced TNF-alpha gene transcription.

Exposure of renal tubular epithelial cells to shiga toxin 2 (Stx-2) causes cytotoxicity, and the potency of this toxin is enhanced in the presence of tumor necrosis factor-alpha (TNF-alpha). It has been shown that Stx-2 induces TNF-alpha production and that activation of beta(2)-adrenoceptors downregulates TNF-alpha. However, little is known about the signaling pathway by which beta(2)-adrenoceptor agonists suppress the Stx-2-induced TNF-alpha gene transcription. The possible signaling components involved in this pathway were investigated. Human adenocarcinoma-derived renal tubular epithelial cells (ACHN) were exposed to Stx-2 in the presence or absence of a beta(2)-adrenoceptor agonist. Mitogen-activated protein kinase (MAPK), activating protein-1 (AP-1), and nuclear factor-kappa B (NF-kappa B) were measured to evaluate the regulatory mechanisms involved in TNF-alpha gene transcription. Stx-2 (4 pg/ml) stimulated MAPK (p42/p44, p38) and AP-1 and increased TNF-alpha promoter activity by 2.4-fold. The increase in TNF-alpha was attenuated by both a p42/p44 inhibitor, PD098059 (10(-6) M), and a p38 inhibitor, SB203580 (10(-6) M), and AP-1-binding activity was inhibited by PD098059. Terbutaline (10(-6) M to 10(-8) M) suppressed MAPK (p42/p44, p38), NF-kappa B (p50, p65), and TNF-alpha promoter activity in a dose-dependent way that was prevented by the beta(2)-adrenoceptor antagonist, ICI118,551. However, inhibition of MAPK (p42/p44) and TNF-alpha promoter activity was partially prevented by the cAMP-protein kinase (PKA) inhibitors, H-89 (5 x 10(-6) M) and KT5720 (10(-5) M), whereas the suppression of p38 MAPK or NF-kappa B (p50) was not blocked by these inhibitors. The suppression of NF-kappa B (p65) was completely overcome by H-89 or KT5720. In summary, the downregulation of TNF-alpha transcription by terbutaline was mediated by an inhibitory effect of beta(2)-adrenoceptor activation on MAPK (p42/p44, p38) and NF-kappa B (p50/p65), which were exerted through a cAMP-PKA pathway and a cAMP-independent mechanism. It is likely that cAMP-PKA and MAPK (p42/p44, p38) may play a critical role in the regulation of the Stx-2-induced TNF-alpha transcription via beta(2)-adrenoceptor activation.

Adrenergic beta-Agonists↗