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Takeshi Shimizu

Publications and source records attributed to Takeshi Shimizu.

At least 19 recordsLinked to original sources
PubMed2026

Rop-Mediated Suppression of RpoS Production Increases Resistance to Nitric Oxide.

We identified the RNA-binding protein Rop, encoded on the pOSAK1 plasmid of enterohaemorrhagic Escherichia coli (EHEC), as a novel factor that enhances nitric oxide (NO) resistance, although it has previously been reported to regulate plasmid copy number. The Rop-induced increase in NO resistance was significantly reduced in several small noncoding RNA (sRNA) gene-deficient EHEC mutants. Among these sRNAs, DsrA, ArcZ, and RprA were directly involved in the translational regulation of rpoS expression, suggesting that Rop modulates rpoS expression through sRNAs. To examine this mechanism, we generated sRNA gene-deficient mutants with an additional deletion of the 5' untranslated region (5' UTR) of rpoS, which is required for translational regulation. The increase in NO resistance by Rop was restored in the double mutant, suggesting that this phenotype is mediated by Rop-dependent interactions between sRNAs and the 5' UTR of rpoS mRNA. Furthermore, Rop promoted rpoS mRNA degradation, an effect that likely suppresses RpoS production and may thereby enhance NO resistance. Finally, an hfq-deficient EHEC mutant exhibited no increase in NO resistance in the presence of Rop, indicating that Hfq is essential for Rop-mediated NO resistance.

Nitric Oxide↗
PubMed2006

Immunohistochemical and ultrastructural abnormalities in muscle from a patient with sensorineural hearing loss related to a 1555 A-to-G mitochondrial mutation.

Genetic studies indicate that hereditary susceptibility of the inner ear to aminoglycoside antibiotic toxicity is caused by a nucleotide 1555 A-to-G mutation in the mitochondrial 12S rRNA gene. Although the phenotype associated with this mutation is nonsyndromic hearing loss, the possibility remains that there could be effects on other tissues that, like the inner ear, contain numerous mitochondria, particularly muscle. We obtained a temporalis muscle specimen from a deaf patient with the A1555G mutation and found informative pathologic features, including mosaic activity of cytochrome c oxidase immunoreactivity and mitochondrial ultrastructure. These findings suggest that mitochondrial dysfunction from the A1555G mutation extends beyond the inner ear.

Electron Transport Complex IV↗
PubMed2006

Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.

Recent studies have suggested that dendritic cell (DC)-based immunotherapy is one promising approach for the treatment of cancer. We previously studied the clinical toxicity, feasibility, and efficacy of cancer vaccine therapy with peptide-pulsed DCs. In that study, we used granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood monocytes as a cell source of DCs. However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. These T helper (Th)-1-type cytokines are thought to promote antitumor immune response. In this study, we assessed the functional abilities of DCs generated from G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers. Peripheral blood mononuclear cells were obtained from leukapheresis products collected before and after systemic administration of G-CSF (subcutaneous administration of high-dose [5-10 microg/kg] human recombinant G-CSF for five consecutive days). In vitro cytokine production profiles after stimulation with lipopolysaccharide (LPS) were compared between monocytes with and without G-CSF mobilization. DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptide-specific T cell responses. Administration of G-CSF was found to efficiently mobilize peripheral blood monocytes. Although G-CSF-mobilized monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored the same level of IL-12 production as that seen in DCs generated from C/Mo. T cell induction assay using recall antigen peptide and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated from C/Mo. Our results suggest that G-CSF mobilization can be used to collect monocytes as a cell source for the generation of DCs for cancer immunotherapy. DCs generated in this fashion were pulsed with HLA-A24-restricted CEA epitope peptide and administered to patients safely; immunological responses were induced in some patients.

Adult↗
PubMed2006

Different susceptibility to peroxisome proliferator-induced hepatocarcinogenesis in rats with polymorphic glutathione transferase genes.

Although peroxisomal bifunctional enzyme (enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase; BE) is a positive marker for peroxisome proliferation, it is completely absent or expressed very weakly in rat hepatic preneoplastic and neoplastic lesions induced by peroxisome proliferators (PP). After administration of PP for 8-15 weeks, some rats exhibit BE-negative preneoplastic foci but other rats do not. In the present study, to investigate the involvement of glutathione S-transferase (GST) M1 gene polymorphism in interindividual differences in susceptibility to PP, we developed a method to determine the genotypes of rats. We then examined whether rats with one type encoding 198Asn-199Cys (NC-type) or another encoding 198Lys-199Ser (KS-type) exhibit differences in clofibrate (CF) susceptibility. After administration of 0.3% CF for 6 weeks or more, BE-negative foci were found immunohistochemically in KS/KS-type rats, but not in NC/NC-type rats. The number of BE-negative foci in KS/KS rats was 15.3 +/- 9.0 foci/cm2 of liver section after 6 weeks of CF administration, and the values did not alter thereafter. The mean areas of BE-negative foci in KS/KS rat livers increased during the period from 6 to 60 weeks. At weeks 30 and 60, almost all BE-negative foci exhibited a clear cell phenotype, a type of preneoplastic hepatic lesion. BE-negative foci were devoid of peroxisome proliferator-activated receptor alpha, whereas surrounding tissues were positive for the receptor. These results indicate that rats that are polymorphic for the GST M1 gene exhibit different susceptibilities to CF in vivo.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2006

Plasma atrial natriuretic Peptide and brain natriuretic Peptide levels after radiofrequency catheter ablation of atrial fibrillation.

It has been reported that plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels are elevated in patients with atrial fibrillation (AF). The aim of this study was to investigate the change in these patients after pulmonary vein isolation (PVI). In 66 patients with paroxysmal AF (PAF) and without any structural heart disease, plasma ANP and BNP levels were measured before and 3 months after successful PVI. At baseline, in 14 patients, ANP and BNP levels were elevated, and in 52 patients, only BNP levels were elevated. There were no significant relations between the attack frequency or the duration of PAF episodes and ANP or BNP levels. Neither ANP nor BNP level at baseline was a valid predictor of AF recurrence. Even in 31 patients (47%) with recurrent PAF, attacks of PAF were significantly reduced. In 66 patients with elevated ANP and/or BNP levels at baseline, levels were significantly reduced after PVI independent of PAF recurrence (ANP: 69.0+/-23.0 vs 25.0+/-7.7 pg/ml, p<0.0001; BNP: 58.4+/-50.7 vs 22.5+/-27.1 pg/ml, p<0.0001). In 42 patients without AF recurrences, ANP and BNP levels were reduced to within the normal range. In conclusion, in patients with PAF without any structural heart disease, ANP and/or BNP levels were elevated. In those patients, relief of the AF burden by successful PVI significantly reduced elevated plasma ANP and BNP levels.

Atrial Fibrillation↗
PubMed2006

Usefulness of esophageal leads for determining the strategy of pulmonary vein ablation to avoid complications associated with the esophagus.

To avoid fatal complications after extensive pulmonary vein (PV) ablation, it has been proved important to comprehend the anatomic relation between the PVs and the esophagus. In 42 consecutive patients with atrial fibrillation, PV ostial isolation was performed using a basket catheter. The shortest distance and anatomic relation between the esophageal lead and PV ostium, determined by successful PV ostial isolation, was analyzed in biplane fluoroscopic views. In 18 left superior PVs (LSPVs) (43%), 13 left inferior PVs (32%) (LIPVs), and all the right PVs (group A), the shortest distance was > 10 mm in > or = 1 of the biplane fluoroscopic views. In 4 LSPVs (10%) and 2 LIPVs (5%) (group B), the shortest distance was < or = 5 mm in the fluoroscopic views. In the remaining PVs (group C), the esophagus was situated directly behind 10 LSPVs (24%) and 12 LIPVs (29%) (group C1), posteromedial to 1 LSPV (2%) and 9 LIPVs (22%) (group C2), and medial to 9 LSPVs (21%) and 5 LIPVs (12%) (group C3). The risk of esophagus-associated complications with ablation around the left PV ostia was suggested to be high in group B, very low in group A, and relatively low in group C. In group C3, extensive PV ablation might increase the risk of that complication. In conclusion, esophageal leads are useful for determining strategies for PV ablation to avoid esophagus-associated complications, because they enable comprehension of the anatomic relation between the PVs and the esophagus.

Atrial Fibrillation↗
PubMed2006

Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARalpha, promotes energy consumption and reduces visceral fat deposition in rats.

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in beta-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) alpha as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

Animals↗
PubMed2006

Incidence, location, and cause of recovery of electrical connections between the pulmonary veins and the left atrium after pulmonary vein isolation.

AIMS: The aim of this study was to reveal the incidence, location, and cause of recovery of the electrical connections (ECs) between the left atrium and the pulmonary veins (PVs) after the segmental ostial PV isolation (PVI). METHODS AND RESULTS: Pulmonary vein mapping and successful PVI were performed using a computerized three-dimensional mapping system (QMS2trade mark) with a basket catheter in 167 PVs in 53 consecutive patients with atrial fibrillation (AF). In 14 patients with recurrent AF after PVI, the same PV mapping and isolation as in the first procedure were performed, and the PV potential maps constructed by QMS2 in two different procedures were compared. Forty-nine recovered ECs were observed in 27 PVs, and all were eliminated by a few local radiofrequency (RF) applications. Thirty-four (69%) of those ECs recovered at the edge of original ECs, and another 15 (31%) recovered at the mid-portion of the continuous broad original ECs. CONCLUSION: Electrical connection recovery occurred most commonly at the edges of original ECs and occasionally at the mid-portion of continuous broad original ECs after PVI probably due to tissue oedema neighbouring the segmental RF lesions. Further RF lesions at the edge of original ECs and linear ablation to the continuous broad ECs may help reduce AF recurrence.

Atrial Fibrillation↗
PubMed2006

Direct evidence that ventral forebrain cells migrate to the cortex and contribute to the generation of cortical myelinating oligodendrocytes.

Cortical neuroepithelial cells generate neurons, astrocytes, and oligodendrocytes (OLs) in vitro. However, whether cortical OLs are derived from the cortical neuroepithelium or migrate from the ventral forebrain is under severe debate yet. This is due to the fact that OL progenitor cells (OPCs), as marked by the expression of PDGFRalpha or NG2, are generated at around embryonic day (E) 11 or 12 in the mouse ganglionic eminences, but the myelinating OLs appear during the second week postnatally in the cortex. There has been no labeling method for long-term glial cell-lineage tracing. Thus, we developed a new strategy: plasmid DNA encoding Cre recombinase was introduced into the Cre/loxP reporter forebrain in ventral- or dorsal-specific manner by in utero DNA electroporation. The reporter gfp gene is expressed permanently owing to the chromosomal DNA recombination. The GFP-labeled myelinating OLs were detected in the adult cortex when electroporation was targeted to the ventral neuroepithelium, demonstrating at least some of the myelinating OLs are derived from the ventral forebrain. However, when electroporation was targeted to the dorsal, we could not find GFP-labeled myelinating OLs. This suggests that the progenitors of cortical OPCs are absent or located at restricted regions in the dorsal forebrain (cortex) at E12.

Animals↗
PubMed2006

Electrophysiological pulmonary vein antrum isolation with a multielectrode basket catheter is feasible and effective for curing paroxysmal atrial fibrillation: efficacy of minimally extensive pulmonary vein isolation.

BACKGROUND: How extensive should an appropriate pulmonary vein (PV) ablation be is a matter of controversy. OBJECTIVE: The study's aim was to investigate the efficacy of minimally extensive PV ablation for isolating the PV antrum (PVA) with the guidance of electrophysiological parameters. METHODS: Fifty-five consecutive symptomatic paroxysmal atrial fibrillation (PAF) patients underwent PV mapping with a multielectrode basket catheter (MBC). A 31-mm MBC was deployed in 3-4 PVs as proximally as possible without dislodgement, and the longitudinal PV mapping enabled us to recognize single sharp potentials formed by the total fusion of the PV and left atrial potentials around the PV ostium or the transverse activation patterns that were observed. Those potentials were defined as PVA potentials. Radiofrequency ablation was performed circumferentially targeting PVA potentials with the end point being their elimination. RESULTS: After circumferential PVA ablation, electrical disconnection was achieved in 77% and residual PVA conduction gaps were observed in 23% of all targeted PVs. Those residual conduction gaps were mainly located at the border between ipsilateral PVs (42%) and between the left PVs and left atrial appendage (33%) and were eliminated by a mean of 3 +/- 2 minutes of local radiofrequency deliveries. During the follow-up period (11 +/- 5 months), 46 (84%) patients were free of symptomatic PAF without any anti-arrhythmic drugs. No PV stenosis or spontaneous left atrial flutter occurred. CONCLUSIONS: Electrophysiological PVA ablation with an MBC is feasible and effective for curing PAF because this minimally extensive PVA isolation technique targets the optimal sites, achieving both high efficacy and safety.

Aged↗
PubMed2006

The effects of orbital frontal cortex damage on the modulation of defensive responses by rats in playful and nonplayful social contexts.

In a series of 3 experiments on rats, 2 hypotheses were tested: (a) that damage to the orbital frontal cortex (OFC) would alter the socially relevant context for executing defensive responses but not their performance and (b) that damage done to the OFC in early infancy would produce more deficits in social behavior than similar damage occurring in adulthood. Bilateral or unilateral OFC damage in adult males did not impair their ability to defend themselves during play fighting and when protecting their food but did impair their ability to modify the pattern of defense in response to different partners. Rats that sustained bilateral damage at 3 days of age not only had deficits in partner-related modulation of defense but also exhibited hyperactivity in their play. The findings thus supported the proposed hypotheses.

Age Factors↗
PubMed2006

The distal protection during primary percutaneous coronary intervention alleviates the adverse effects of large thrombus burden on myocardial reperfusion.

BACKGROUND: The presence of intracoronary large thrombus burden (LTB) in the infarct-related artery increases the risk of distal embolization and no-reflow during percutaneous coronary intervention (PCI). Evaluation of whether the distal protection (DP) during primary PCI reduces adverse effects of LTB on myocardial reperfusion and infarct size was investigated. METHODS AND RESULTS: A consecutive series of 88 patients with acute myocardial infarction undergoing primary PCI using DP were compared with 81 consecutive patients treated by primary PCI alone. The DP use showed similar post-procedural myocardial blush grade (MBG)-3 and infarct size, but improved corrected thrombolysis in myocardial infarction frame count (cTFC) (29+/-11 vs 35+/-20, p=0.011) and the incidence of ST-segment resolution (80.7% vs 66.7%, p=0.038). In patients with LTB present, however, the DP use reduced occurrences of no-reflow (0% vs 11.8%, p=0.036) and distal embolization (4.8% vs 17.6%, p=0.129), resulting in higher occurrences of MBG-3 (61.9% vs 35.3%, p=0.021) and ST-segment resolution (78.6% vs 50.0%, p=0.009), lower cTFC values (30+/-8 vs 40+/-22, p=0.012) and smaller infarct size (12.2+/-11.2 vs 18.7+/-11.1, p=0.015). CONCLUSIONS: With an improved myocardial reperfusion and smaller infarct size in patients with LTB, the DP during primary PCI might be a better strategy in this particular setting compared with conventional strategy.

Acute Disease↗
PubMed2006

Can segmental pulmonary vein ablation reduce the recurrence of atrial fibrillation when using a higher RF power, larger tip electrode catheter, and additional RF deliveries?: the limitations of point-by-point RF ablation.

The aim of this study was to investigate whether segmental ostial catheter ablation (SOCA) designed to prevent the electrical connections (ECs) between the left atrium and pulmonary veins (PVs) might help increase the efficacy of SOCA in paroxysmal atrial fibrillation (PAF). PV mapping and successful SOCA were performed with a basket catheter in 108 consecutive patients with PAF. Radiofrequency energy was delivered using a maximum output of 30 W with a 4 mm tip catheter (group I; 47) or 40 W with an 8 mm tip catheter (group II; 61). Only in the group II patients were additional radiofrequency deliveries to the specific sites where the ECs tended to recover performed after successful SOCA. After the first procedure, PAF recurred in 47% of the group I patients and 32% of the group II patients. In all 27 patients who underwent repeat procedures, EC recoveries were observed more frequently in group I than in group II (69% versus 49%; P < 0.05). After multiple procedures, there was more freedom from PAF in group II (84%) than in group I (66%) (P < 0.05). SOCA with a higher RF power, larger tip catheter, and additional RF deliveries could achieve a more effective SOCA.

Aged↗
PubMed2006

Dietary 5-campestenone (campest-5-en-3-one) enhances fatty acid oxidation in perfused rat liver.

The effect of dietary 5-campestenone (campest-5-en-3-one), a chemical modification product of a naturally-occurring plant sterol, campesterol, on lipid metabolism was examined using a rat liver perfusion system. Male Sprague-Dawley rats weighing about 140 g were fed a diet supplemented with or without 0.2% 5-campestenone for 14 d. 5-Campestenone feeding resulted in a marked reduction in the concentrations of serum lipids, such as triacylglycerol (TG), cholesterol, phospholipid, and free fatty acid, without influencing food intake or growth. Then, isolated livers from both groups were perfused for 4 h in the presence of an exogenous linoelaidic acid substrate. Dietary 5-campestenone markedly elevated hepatic ketone body production, while cumulative secretions of TG, cholesterol, and phospholipid by the livers of rats fed 5-campestenone were all significantly lowered as compared to those fed without the compound: the extent of the reduction was more prominent in the secretion of TG than other lipid components. In addition, the reduction of TG secretion was concomitantly accompanied by the reduced incorporation of both exogenous and endogenous fatty acids into this lipid molecule. These results suggest that dietary 5-campestenone exerts its hypotriglyceridemic effect, at least, in part through an enhanced metabolism of endogenous and exogenous fatty acids to oxidation at the expense of esterification in rat liver.

Animal Feed↗
PubMed2006

[Endoscopic ligation of maxillary and sphenopalatine artery for intractable epistaxis].

We report the endoscopic ligation of the maxillary and sphenopalatine arteries for the treatment of intractable epistaxis. From March 2003 to February 2005, 17 patients (12 men, 5 women) with epistaxis were hospitalized in our department. Patient age ranged from 25 to 83 years, with an average age of 62 years. 8 patients were successfully treated using the conventional packing method, 2 patients were treated using electrocauterization, and 1 patient with macroglobulinemia was treated using plasma exchange therapy. 6 patients underwent endoscopic ligation of the maxillary and sphenopalatine arteries while under general anesthesia. The post operative courses were uneventful, and no recurrent bleeding has been noted. Endscopic ligation of the maxillary and sphenopalatine arteries is safer than intraarterial embolization and less invasive than conventional surgical approach for the ligation of maxillary artery. This technique appears to be a safe and effective surgical treatment for patients with intractable epistaxis.

Adult↗
PubMed2006

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Antigen-Presenting Cells↗
PubMed2006

[Promising efficacy of the sirolimus-eluting stent in patients with acute myocardial infarction].

OBJECTIVES: This study investigated the safety and efficacy of sirolimus-eluting stents (SESs) on early and late outcomes in patients with acute myocardial infarction. METHODS: A series of 100 consecutive patients (September 2004 to November 2005)with acute myocardial infarction undergoing primary stenting using SES ptember 24 hr) was compared with 100 consecutive patients (September 2003 to August 2004) treated with bare metal stent (BMS). The frequency of major adverse cardiac events (MACE) and stent thrombosis, and status of ticlopidine administration were assessed at 270 days. RESULTS: The rates of premature discontinuation of ticlopidine (SES group <3 months: 11%, BMS group <1 month: 11%, p = NS) and stent thrombosis (SES group: 1%, BMS group: 0%, p = NS) were similar in the two groups. At follow-up, restenosis rate and target vessel revascularization rate were lower in the SES group(4% vs 19%, p < 0.001 and 4% vs 10%, p = 0.149, respectively). Furthermore, the occurrence of MACE at 270 days was significantly less frequent in the SES group compared with the BMS group (6% vs. 17%, p = 0.038). Multivariate analysis showed SES use tended to predict 270-day MACE (hazard ratio 0.37, 95% confidence interval 0.14-1.02, p = 0.055). Culprit lesion located in the left main trunk was identified as an independent predictor of 270-day MACE (hazard ratio 5.43, 95% confidence interval 1.07-27.59, p = 0.041). CONCLUSIONS: The use of a SES was not associated with increased risk of stent thrombosis compared with a BMS. With lower rates of restenosis and subsequent target vessel revascularization, SES placement could provide superior outcomes in patients with acute myocardial infarction.

Aged↗