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Biomedical subjects

Hiroyuki Kojima

Publications and source records attributed to Hiroyuki Kojima.

At least 19 recordsLinked to original sources
PubMed2006

In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma and quantitative analysis of in vivo induction pathway.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors and key regulators of lipid metabolism and cell differentiation. However, there have been few studies reporting on a variety of environmental chemicals, which may interact with these receptors. In the present study, we characterized mouse PPARalpha and PPARgamma agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 11 acid amides, 7 triazines, 8 ureas and 44 others) by in vitro reporter gene assays using CV-1 monkey kidney cells. Three of the 200 pesticides, diclofop-methyl, pyrethrins and imazalil, which have different chemical structures, showed PPARalpha-mediated transcriptional activities in a dose-dependent manner. On the other hand, none of the 200 pesticides showed PPARgamma agonistic activity at concentrations <or =10(-5) M. To investigate the in vivo effects of diclofop-methyl, pyrethrins and imazalil, we examined the gene expression of PPARalpha-inducible cytochrome P450 4As (CYP4As) in the liver of female mice intraperitoneally injected with these compounds (< or =300 mg/kg). RT-PCR revealed significantly high induction levels of CYP4A10 and CYP4A14 mRNAs in diclofop-methyl- and pyrethrins-treated mice, whereas imazalil induced almost no gene expressions of CYP4As. In particular, diclofop-methyl induced as high levels of CYP4A mRNAs as WY-14643, a potent PPARalpha agonist. Thus, most of the 200 pesticides tested do not activate PPARalpha or PPARgamma in in vitro assays, but only diclofop-methyl and pyrethrins induce PPARalpha agonistic activity in vivo as well as in vitro.

Animals↗
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

Percutaneous vertebroplasty: relationship between vertebral body bone marrow edema pattern on MR images and initial clinical response.

PURPOSE: To prospectively investigate the relationship between initial clinical response and bone marrow edema pattern on preprocedural magnetic resonance (MR) images in vertebral bodies selected for percutaneous vertebroplasty (PVP). MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. PVP was performed for osteoporotic compression fractures in 80 consecutive patients (mean age, 72.4 years; range, 44-85 years; 67 women and 14 men; 157 vertebrae). Patients were divided into three groups according to the proportion of the vertebra in which the bone marrow edema pattern was observed on sagittal MR images: group 1, 50% or more of the vertebra; group 2, less than 50%; group 3, no edema pattern observed. By using Wilcoxon rank sum test, Fisher exact test, and Wilcoxon signed rank test, groups were examined for differences in treatment efficacy, which was defined as the difference between preprocedural and postprocedural pain as assessed by means of visual analog scale (VAS) score at 1-3 days after PVP. RESULTS: Forty-four patients were assigned to group 1, 14 to group 2, and 22 to group 3. No significant difference was seen between the groups with respect to age, sex, number of treated vertebrae, or preprocedural VAS score. In group 1, VAS score decreased from 7.5 before the procedure to 2.9 after (improvement of 4.6). In group 2, the score decreased from 6.8 to 3.1 (improvement of 3.7). In group 3, the score decreased from 7.0 to 4.3 (improvement of 2.7). Improvement was significantly greater in group 1 than in group 3 (P < .005). CONCLUSION: PVP resulted in significantly greater clinical improvement in patients with an extensive bone marrow edema pattern than in those without this pattern. (c) RSNA, 2006.

Adult↗
PubMed2006

[Basic experimental study of intraosseous venography using carbon dioxide contrast agent in percutaneous vertebroplasty].

PURPOSE: In percutaneous vertebroplasty (PVP), intraosseous venography is performed using water-soluble ionic iodinated contrast media (iodine contrast media) before injecting bone cement. However, because of contrast medium remaining in the fractured cleft, we experienced the persistence of intravertebral opacification that obscured visualization of the cement under X-ray fluoroscopy. To solve this problem, we examined carbon dioxide (CO(2)) as a contrast medium. METHODS: We measured the contrast of iodine contrast media and CO(2) and performed a subjective assessment of imaging by enforcing intraosseous venography by changing the tube voltage and image intensifier (I.I.) entrance dose in a bone sample of a cadaver using iodine contrast media and CO(2). In vivo study, we performed a subjective assessment of images obtained by intraosseous venography using CO(2) under two kinds of X-ray views. RESULTS: We determined that the contrast of CO(2) is 1/6-1/7.5 that of iodine contrast media, and that CO(2) fluctuates less in its contrast value with changes in tube voltage. In our assessment of the image of the bone sample, CO(2) performed worse that iodine contrast media. However, if the I.I. entrance dose is kept above 2.5 microGy/F, CO(2) is considered to be of clinical use. In the clinical image assessment, the best conditions were an image collection rate of 7.5 F/S and matrix of 1024 x 1024. CONCLUSIONS: CO(2) did not cause any obstacles when we injected bone cement, and its I.I. entrance dose, image collection rate, and matrix size indicate that it can be used for intraosseous venography.

Bone Cements↗
PubMed2006

A case of spontaneous regression of hepatocellular carcinoma with multiple lung metastases.

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We present herein the case of a patient with hepatocellular carcinoma with multiple lung metastases in whom malignancy spontaneously regressed after taking Pheliinus linteus Mycelium. A 79-year-old man consulted our hospital complaining of epigastric discomfort. Abdominal MRI and CT revealed a 3 cm diameter tumor in the liver, and chest CT showed numerous nodular lesions. The levels of alpha-fetoprotein (AFP) and protein induced by vitamin K deficiency or antagonist-II (PIVKA-II) were very high. We diagnosed HCC with multiple lung metastases, and no therapy was performed. Independently he took exact from Phellinus linteus Mycelium for one month, and 6 months later the tumors appeared to be in complete regression. The mechanism underlying this intriguing phenomenon remains unknown.

Aged↗
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

Efficient production of (2S)-flavanones by Escherichia coli containing an artificial biosynthetic gene cluster.

For the fermentative production of plant-specific flavanones (naringenin, pinocembrin) by Escherichia coli, a plasmid was constructed which carried an artificial biosynthetic gene cluster, including PAL encoding a phenylalanine ammonia-lyase from a yeast, ScCCL encoding a cinnamate/coumarate:CoA ligase from the actinomycete Streptomyces coelicolor A3(2), CHS encoding a chalcone synthase from a licorice plant and CHI encoding a chalcone isomerase from the Pueraria plant. The recombinant E. coli cells produced (2S)-naringenin from tyrosine and (2S)-pinocembrin from phenylalanine. When the two subunit genes of acetyl-CoA carboxylase from Corynebacterium glutamicum were expressed under the control of the T7 promoter and the ribosome-binding sequence in the recombinant E. coli cells, the flavanone yields were greatly increased, probably because enhanced expression of acetyl-CoA carboxylase increased a pool of malonyl-CoA that was available for flavanone synthesis. Under cultural conditions where E. coli at a cell density of 50 g/l was incubated in the presence of 3 mM tyrosine or phenylalanine, the yields of naringenin and pinocembrin reached about 60 mg/l. The fermentative production of flavanones in E. coli is the first step in the construction of a library of flavonoid compounds and un-natural flavonoids in bacteria.

Escherichia coli↗
PubMed2005

Targeted delivery of bone marrow mononuclear cells by ultrasound destruction of microbubbles induces both angiogenesis and arteriogenesis response.

OBJECTIVE: Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis. METHODS AND RESULTS: US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase, P<0.05) was observed compared with Bubble+US (25%). The ratio of capillary/muscle fiber increased by Bubble+US+BM-MNC-i.v (260%, P<0.01) than that in the Bubble+US group (172%), into which BM-MNCs were incorporated (angiogenesis). Smooth muscle alpha-actin-positive arterioles were also increased, and angiography showed augmented collateral vessel formation (arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble+US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow. CONCLUSIONS: This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.

Angiography↗
PubMed2005

Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor.

Some phthalates are suspected to disrupt the endocrine system, especially by mimicking estrogens. In this study, we characterized the activities of human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human androgen receptor (hAR) in the presence of 22 phthalates including 3 of their metabolites using highly sensitive reporter gene assays. Of the 22 compounds tested, several phthalate diesters with alkyl chains ranging in length from C3 to C6 exhibited not only hERalpha-mediated estrogenic activity, but also hERbeta-mediated antiestrogenic activity in a dose-dependent manner. In addition, we found that some phthalate diesters possess hAR-mediated antiandrogenic activity. However, the phthalates having side chains with very short length (diethyl) or very long length (diheptyl), and three metabolites (monoesters) were found to have no effect on the activities of the three receptors. These results indicate that several phthalate esters simultaneously act as agonists and/or antagonists via one or more hormonal receptors, and interaction of phthalate esters with the estrogen and androgen receptors requires certain size and bulkiness with alkyl groups.

Androgen Receptor Antagonists↗
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

Radiation exposure to operators during vertebroplasty.

PURPOSE: To measure the radiation received by physicians during percutaneous vertebroplasty with use of two types of injection devices with the interventional equipment guided by computed tomography (CT) and an angiographic/CT system. MATERIALS AND METHODS: Twenty consecutive patients who underwent percutaneous vertebroplasty were included in this study. The patients were divided into two groups, the 1-mL syringe group and the bone cement injector group. Percutaneous vertebroplasties were performed with the IVR-CT system, which combines angiographic and CT equipment with a single fluoroscopy table. Radiation dose to operators was measured as equivalent dose penetrating at a 10-mm tissue depth with use of electronic personal dosimeters attached outside and inside lead aprons. Effective radiation dose (HE) was estimated based on the radiation dose outside the lead apron (Ha) and the radiation dose inside the lead apron (Hb). Differences between the groups in doses and fluoroscopic duration were analyzed. RESULTS: In the 1-mL syringe group and bone cement injector group, mean Ha measurements were 320.8 microSv and 116.2 microSv, respectively. Mean Hb measurements were 14.5 microSv versus 7.8 microSv and mean HE measurements were 48.2 microSv versus 19.7 microSv. Significant differences were found in Ha, Hb, and HE. However, duration of fluoroscopy did not differ significantly between groups. CONCLUSIONS: Radiation dose was relatively high for operators performing percutaneous vertebroplasty. The bone cement injector was useful in reducing the level of radiation exposure to operators during vertebroplasty.

Fluoroscopy↗
PubMed2005

Radiofrequency ablation combined with CO2 injection for treatment of retroperitoneal tumor: protecting surrounding organs against thermal injury.

OBJECTIVE: The objective of this study was to separate target tumors from adjacent structures by injecting carbon dioxide (CO2) around the tumor to avoid thermal injury and the heat-sink effect from the blood vessel during percutaneous radiofrequency ablation. CONCLUSION: We successfully achieved complete ablation of a retroperitoneal tumor without thermal injury. Imaging-guided percutaneous CO2 injection is useful for preventing thermal injury while achieving complete ablation of the tumor during radiofrequency ablation.

Adrenal Gland Neoplasms↗
PubMed2005

Intraosseous venography with carbon dioxide contrast agent in percutaneous vertebroplasty.

OBJECTIVE: Our objectives were to ascertain whether CO2 can be used as a contrast agent in venography during percutaneous vertebroplasty and to evaluate whether it might be capable of replacing nonionic iodinated contrast agents. CONCLUSION: Intraosseous venography with CO2 contrast agent was slightly inferior to iodine venography in terms of its ability to visualize the vertebral bodies and perivertebral veins, but it remains a useful technique because no interference with optimal visualization of bone cement occurs during the cement injection when CO2 remains within the fracture cleft.

Aged↗
PubMed2005

Residual stenosis after conventional balloon angioplasty for hemodialysis shunt failure: treatment with metallic stent placement and post-balloon dilatation.

PURPOSE: The usefulness of metallic stent placement and post-balloon dilatation was investigated for patients with residual stenosis after conventional percutaneous transluminal balloon angioplasty (balloon PTA) of dialysis shunt vessels. MATERIALS AND METHODS: Among 92 patients who had received balloon PTA for dialysis shunt vessels, seven patients who showed a residual waist on the balloon even under maximum inflation were enrolled in this study. In these patients with residual stenosis after balloon PTA, we inserted a stent in the residual stenosis, and post-balloon dilatation was immediately applied using the same balloon catheter. RESULTS: After balloon PTA, the average percent diameter stenosis declined to 45.5 +/- 7.30%, and the stenosis was further improved to an average of 19.3 +/- 7.09% after the placement of a stent and the additional balloon PTA. The average percent diameter dilatation of the balloon before the placement of a stent was 65.8 +/- 12.7%, while the average dilatation increased to 84.1 +/- 8.96% after the placement of a stent. Dialysis became possible immediately after the procedure in all cases. CONCLUSION: Metallic stent placement and post-balloon dilatation was effective for patients with residual stenosis after conventional balloon PTA of dialysis shunt vessels.

Aged↗
PubMed2005

[Additive effect of intravenous prednisolone for acute severe asthma in infants and toddlers: a randomized controlled clinical trial].

BACKGROUND: The efficacy of systemic corticosteroids for infants and toddlers with acute severe asthma has been inadequately evaluated. OBJECTIVE: The purpose of this study was to evaluate the additive efficacy of intravenous prednisolone in a randomized controlled study in the management of infants and toddlers with acute severe asthma. METHODS: Sixty-two patients (aged 8 to 70 months) hospitalized with status asthmaticus were studied. They were randomized into two groups. One group received intravenous prednisolone treatment (1 approximately 3 mg/kg/day, 3 days); the other group served as a control. Each group received continuous aminophylline infusion and low-dose continuous isoproterenol inhalation by an Inspiron nebulizer. They were monitored their heart rate, respiratory rate and symptoms (Wood's clinical score). RESULTS: Each group showed rapid improvement in heart rate, respiratory rate and clinical score by low-dose continuous isoproterenol inhalation. There were no significant differences in the time course of these clinical indexes or the duration of aminophylline infusion, continuous isoproterenol inhalation and hospital stay. CONCLUSION: This study failed to confirm the additive benefit of intravenous prednisolone in the management of infants and toddlers with acute severe asthma.

Acute Disease↗
PubMed2004

Interparticle spacing control in the superlattices of carboxylic acid-capped gold nanoparticles by hydrogen-bonding mediation.

We have demonstrated that carboxylic acid-capped gold nanoparticles were self-assembled to form two-dimensional (2D) and/or three-dimensional (3D) superlattices at an air/water interface in the presence of a bifunctional hydrogen-bonding mediator such as 4-pyridinecarboxylic acid (PyC) or trans-3-(3-pyridyl)acrylic acid (PyA). Transmission electron microscopy revealed a hexagonal close-packed arrangement of nanoparticles in the superlattice with an extension of interparticle spacing. In the 2D superlattices, larger particles produced a higher-quality assembly having long-range translational ordering. Attenuated total reflectance IR (ATR-IR) spectroscopy revealed the presence of hydrogen bonds between the mediator used and the capping agents of carboxylic acid on nanoparticle surfaces. Since the experimentally obtained interparticle separation distance agreed approximately with that obtained by the geometrical model calculations, we conclude that the hydrogen-bonding mediation controlled the interparticle spacing or structure by monomolecular incorporation between adjacent nanoparticles in the superlattices.

Journal Article↗
PubMed2004

Membrane-associated prostaglandin E synthase-1 is required for neuropathic pain.

It is widely accepted that prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid and plays an important role in inflammatory pain. However whether PGE2 is involved in neuropathic pain remains unknown. PGE2 is produced from arachidonic acid via PGH2 by at least three PGE synthases (PGES), cytosolic PGES (cPGES), and membrane-associated PGES (mPGES)-1 and -2. In the present study, to clarify the involvement of PGE2 and identify PGES mediating neuropathic pain, we applied a neuropathic pain model prepared by L5 spinal nerve transection to mPGES-1 knockout (mPGES-1-/-) mice. Whereas they retained normal nociceptive responses, mPGES-1-/- mice did not exhibit mechanical allodynia and thermal hyperalgesia over a week. These results demonstrate that PGE2 produced by mPGES-1 is involved in neuropathic pain.

Animals↗