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Biomedical subjects

Toru Takahashi

Publications and source records attributed to Toru Takahashi.

At least 19 recordsLinked to original sources
PubMed2007

A neutrophil elastase inhibitor, sivelestat, ameliorates lung injury after hemorrhagic shock in rats.

Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play a pivotal role in the pathogenesis of ALI. This study investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI induced by HSR in rats. Male Sprague-Dawley rats were subjected to hemorrhagic shock by withdrawing blood so as to maintain a mean arterial blood pressure of 30+/-5 mm Hg for 60 min followed by resuscitation with the shed blood. HSR-treated animals received a bolus injection of sivelestat (10 mg/kg) intravenously at the start of resuscitation followed by continuous infusion for 60 min (10 mg/kg/h) during the resuscitation phase, or the vehicle. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, myeloperoxidase (MPO) activity, gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), DNA binding activity of nuclear factor (NF)-kappaB, and immunohistochemical analysis of intercellular adhesion molecule (ICAM)-1. HSR treatment induced lung injury, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment significantly ameliorated the HSR-induced lung injury, as judged by the marked improvement in all these indices. These results indicate that sivelestat attenuated HSR-induced lung injury at least in part through an inhibition of the inflammatory signaling pathway, in addition to the direct inhibitory effect on NE.

Animals↗
PubMed2006

Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts.

Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91(phox)-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase-dependent ROS generation.

Animals↗
PubMed2006

Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer.

PURPOSE: This retrospective study evaluated the effects of neoadjuvant chemotherapy in advanced gastric cancer. METHODS: Between 2002 and 2005, we treated 14 patients with advanced gastric cancer (involvement of more than five nodes or tumor invasion into pancreas) and 25 patients with Stage III gastric cancer. The group of 14 patients with advanced gastric cancer received combination chemotherapy with S-1 and cis-diamminedichloroplatinum (CDDP) as a neoadjuvant chemotherapy (NAC). This regimen was repeated every 5 weeks for a total of 2-5 cycles. The 25 patients with Stage III gastric cancer was carried surgery alone (SA). All patients underwent extensive surgery, including gastrectomy, and D2 lymphadenectomy. The rate of response and overall survival in the two groups were compared. RESULTS: All patients of NAC group completed the planned regimens of chemotherapy and surgery. Patients of the NAC group had a response rate of 78.6% (95% confidence interval 57.1-100.0%). The most common adverse effect was leukocytopenia (42.9%). However, only four patients (28.6%) had upper Grade 2 leukocytopenia, and all recovered promptly. Postoperative complications were not significant differentiated between NAC and SA group of patients (7.2 vs. 4.0%). Patients in the NAC group had a significantly better survival than those in the SA group (P = 0.03). The median survival has not been reached after 26.9 months of median follow-up for patients in the NAC group. 1-, 2-, and 3-year survival rates were 92.3, 92.3, and 61.5%, respectively. NAC was identified as an independent prognostic factor in all patients (P = 0.018). CONCLUSION: Neoadjuvant chemotherapy with TS-1 + CDDP improves the survival in patients with advanced gastric cancer.

Aged↗
PubMed2006

Effect of unpleasant loud noise on hippocampal activities during picture encoding: an fMRI study.

The functional link between the amygdala and hippocampus in humans has not been well documented. We examined the effect of unpleasant loud noise on hippocampal and amygdaloid activities during picture encoding by means of fMRI, and on the correct response in humans. The noise reduced activity in the hippocampus during picture encoding, decreased the correct response and increased the activity of the amygdala. A path diagram using structural equation modeling suggested that hippocampus activity might be depressed by high amygdala activity. Therefore, noise should diminish memory by reducing hippocampal activity, which might be depressed by high amygdala activity.

Adult↗
PubMed2006

Surgical treatment with deep hypothermia for thoracic aortic aneurysm in a patient with renal transplantation.

An increasing number of patients have undergone aortic reconstruction, exposing the transplanted kidney to ischemic injury. A 58-year-old male underwent renal transplantation previously. A thoracic aortic aneurysm (TAA) of the distal aortic arch was identified. His renal function was poor due to chronic rejection. The TAA was exposed by a left anterolateral thoracotomy through the 4th intercostal space, and cardiopulmonary bypass established with canulation of the left femoral artery and vein. Deep hypothermic circulatory arrest with retrograde cerebral perfusion was adopted at a rectal temperature of 20 degrees C, and distal arch replacement was successfully performed. Prednisolone was administered intravenously for perioperative immunosuppression. Poor renal function recovered to the preoperative level. No other complications occurred. Perioperative renal graft protection, immunosuppression and infection control are mandatory for surgical treatment in patients with TAA after renal transplantation.

Aortic Aneurysm, Thoracic↗
PubMed2006

Developmental aberrations of liver gene expression in bovine fetuses derived from somatic cell nuclear transplantation.

Cloning by somatic cell nuclear transfer (NT) has been accomplished. However, the process itself is inefficient since most clones die before birth and survivors often display various anomalies. In an effort to determine global expression profiles of developmentally regulated liver genes in NT bovine fetuses, we employed a custom-made bovine liver complementary DNA (cDNA) microarray. The NT fetuses in early pregnancy were derived from cumulus cells as the nuclear donor cells. Normal fetuses were derived from in vitro fertilization (IVF) and artificial insemination (AI). Gene expression levels in NT, IVF, and AI fetal livers were obtained by comparing individual fetal liver samples with that of adult liver of nonpregnant cycling cows. Statistical analyses of the expression data showed widespread dysregulation of developmentally important genes in the three NT fetuses examined. It was found that the number of dysregulated genes was within a range of 3.5-7.7% of the tested genes in the NT fetal livers. The analyses revealed that one NT fetus was markedly different in liver gene expression profile from the other two NT fetal livers in which the expression profiles were highly correlated. Thus, our findings demonstrate that widespread dysregulation of liver genes occurs in the developing liver of NT bovine fetuses. It is possible that inappropriate genomic reprogramming after NT is a key factor associated with abnormal gene expressions in the livers of NT fetuses, whereas distinct expression patterns between the fellow cloned fetuses likely have resulted from variable epigenetic status of the donor nuclei.

Animals↗
PubMed2006

Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis.

OBJECTIVE: Circulating levels of KL-6, a high MW glycoprotein (MUC1 mucin), are elevated in a majority of patients with a number of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). However, KL-6 levels vary from patient to patient. The aim of the present study was to determine whether the serum KL-6 level at the time of diagnosis predicts prognosis in IPF. METHODS: The relationship between clinical variables and prognosis in 27 patients with IPF were analysed retrospectively. The diagnosis was made by histological examination (n = 16) or on clinical findings including high-resolution CT scanning (n = 11). All patients were followed up for at least 3 years. Variables such as age, FVC%, PaO(2) at rest, initial LDH level, C-reactive protein and KL-6 were used for analysis. RESULTS: At the cut-off level determined by receiver operating characteristic curves, LDH and KL-6 showed a significant correlation with the patient's prognosis by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of prognosis. The patients were categorized by their serum KL-6 levels (as above or below the cut-off level of 1000 U/mL) and their survival estimated using the Kaplan-Meier method. The difference in median survival between the two groups was significant. The median survival of patients with low KL-6 was more than 36 months, whereas that of patients with high KL-6 was only 18 months. CONCLUSION: These results suggest that initial evaluation of serum KL-6 level can predict survival in patients with IPF.

Antigens, Neoplasm↗
PubMed2006

Novel hydrophobic surface binding protein, HsbA, produced by Aspergillus oryzae.

Hydrophobic surface binding protein A (HsbA) is a secreted protein (14.5 kDa) isolated from the culture broth of Aspergillus oryzae RIB40 grown in a medium containing polybutylene succinate-co-adipate (PBSA) as a sole carbon source. We purified HsbA from the culture broth and determined its N-terminal amino acid sequence. We found a DNA sequence encoding a protein whose N terminus matched that of purified HsbA in the A. ozyzae genomic sequence. We cloned the hsbA genomic DNA and cDNA from A. oryzae and constructed a recombinant A. oryzae strain highly expressing hsbA. Orthologues of HsbA were present in animal pathogenic and entomopathogenic fungi. Heterologously synthesized HsbA was purified and biochemically characterized. Although the HsbA amino acid sequence suggests that HsbA may be hydrophilic, HsbA adsorbed to hydrophobic PBSA surfaces in the presence of NaCl or CaCl(2). When HsbA was adsorbed on the hydrophobic PBSA surfaces, it promoted PBSA degradation via the CutL1 polyesterase. CutL1 interacts directly with HsbA attached to the hydrophobic QCM electrode surface. These results suggest that when HsbA is adsorbed onto the PBSA surface, it recruits CutL1, and that when CutL1 is accumulated on the PBSA surface, it stimulates PBSA degradation. We previously reported that when the A. oryzae hydrophobin RolA is bound to PBSA surfaces, it too specifically recruits CutL1. Since HsbA is not a hydrophobin, A. oryzae may use several types of proteins to recruit lytic enzymes to the surface of hydrophobic solid materials and promote their degradation.

Adipates↗
PubMed2006

Early positive biomarker in relation to myocardial necrosis and impaired fatty acid metabolism in patients presenting with acute chest pain at an emergency room.

BACKGROUND: Measurement of circulating biomarkers has enabled early diagnosis and risk assessment of acute coronary syndrome. This study sought diagnostic values of the first single-point data of biomarkers obtained soon after patient arrival by comparing with scintigraphically quantified myocardial injury in patients presenting with acute chest pain at an emergency room. METHODS AND RESULTS: Serial blood samples were taken soon after arrival in an emergency department in 74 patients with suspected acute coronary syndrome to quantify blood levels of troponin-T (TnT), heart-type fatty acid-binding protein (H-FABP), myocardial-bound creatine kinase (CK-MB), and myoglobin. Myocardial perfusion and metabolic defects were scintigraphically quantified. The first single-point data had high positive predictive values for detecting the defects (80-100%) but low negative predictive values (15-41%). CK-MB and TnT had higher specificities (73-100%) but significantly lower positive rates (22-27%) than the others (61-68%), resulting in greater sensitivities of H-FABP and myoglobin (75-80%) than those of CK-MB and TnT (29-35%). Among biomarkers, TnT peak concentrations most closely correlated with scintigraphic abnormalities. CONCLUSION: H-FABP can contribute to early detection of myocardial injury and TnT is most likely to correlate with injured myocardial mass. The differential features of biomarkers are complementary in patients with acute chest pain presenting at an emergency room.

Acute Disease↗
PubMed2006

Effectiveness of a spot urine method in evaluating daily salt intake in hypertensive patients taking oral antihypertensive drugs.

Kawasaki et al. developed a spot urine method (SUM) for evaluating daily salt intake using one pre-breakfast sample obtained after initial voiding upon arising. Their subjects were healthy persons who were not taking any regular medications. To determine whether SUM can be successfully used for patients taking antihypertensive drugs, we estimated daily salt intake in 73 hypertensive patients by SUM and by a food consumption method (FCM) when they were at home, and also by SUM in the hospital with a defined intake of 7 g of sodium chloride (NaCl). Forty-one patients took oral antihypertensive medications once daily, while 32 patients took none. Mean daily salt intakes by SUM during admission were 7-8 g of NaCl in both groups (95% confidence intervals: 5.0-10.6 g in the medication group; 5.2-11.1 g in the no-medication group), which corresponded well to the diet. In contrast, ambulatory daily salt intake by SUM varied widely (95% confidence intervals: 5.5-20.7 g in the medication group; 7.6-22.8 g in the no-medication group). However, the daily salt intakes determined by SUM and FCM correlated significantly with each other in the medication group (r=0.69, p<0.01) and the no-medication group (r=0.66, p<0.01). SUM is therefore a reliable method for evaluating daily salt intake in patients taking antihypertensive medication as well as unmedicated patients.

Administration, Oral↗
PubMed2006

Separation of V(V)-4-(2-pyridylazo)resorcinolato complex from a large excess reagent using an ODS cartridge for high-performance liquid chromatography.

A selective off-line preconcentration technique for the V(V) complex with 4-(2-pyridylazo)resorcinol has been developed and successfully applied to the determination of V(V) in an air-borne sample. The target complex was separated from excess reagent using an ODS cartridge and water as the eluent. The complex was then concentrated on another ODS cartridge using tetrabutylammonium bromide and eluted with methanol; the eluate was applied to a one-drop concentration/HPLC. A detection limit as low as (6.05 +/- 0.82)x 10(-11) M (5 ppt) was achieved.

Journal Article↗
PubMed2006

Estrogenic activity of phthalate esters by in vitro VTG assay using primary-cultured Xenopus hepatocytes.

Estrogenic activity of phthalate esters in dental soft resins was evaluated with an amphibian system consisting of a vitellogenin (VTG)-detecting Enzyme-Linked Immunosorbent Assay and a primary-cultured hepatocyte assay using adult male Xenopus laevis. In particular, phthalate esters--Di-n-butyl phthalate (DBP), Butyl phthalyl butyl glycolate (BPBG), Benzyl butyl phthalate (BBP), and Benzyl benzoate (BB)--were investigated. Bisphenol A (BPA) was prepared for comparison with these chemicals, and 17beta-estradiol (E2) was used as a positive control. The chemicals were diluted in dimethyl sulfoxide (DMSO) to obtain final concentrations ranging from 10(-11) to 10(-4) mol/l. BPA induced estrogenic activity at a concentration of 1.1x10(-6) mol/l, while E2 showed at 4.1x10(-11) mol/l. DBP, BBP, BB, and BPBG showed no estrogenic activity at concentrations between 4x10(-7) mol/l and 1x10(-4) mol/l. The latter result indicated that these phthalate esters might be metabolically transformed into non-estrogenic substances in Xenopus hepatocytes. Furthermore, this study demonstrated that through in vitro metabolism assessment, the estrogenic activity of chemical substances could be directly detected in terms of VTG secretion in primary-cultured Xenopus hepatocytes.

Animals↗
PubMed2006

Bovine trophoblast cell culture systems: a technique to culture bovine trophoblast cells without feeder cells.

Bovine trophoblastic cells are the first cells to differentiate during embryogenesis and play pivotal role in morphological and physiological development of the placenta. We have developed culture systems for bovine trophoblast stem cells isolated from in vitro fertilized blastocysts in the absence of feeder cells. These cells continuously proliferate in Dulbecco's modified Eagle's/F12 culture medium supplemented with bovine endometrial fibroblast-conditioned medium. The cells possess epithelial morphology, express cytokeratin, and form dome-like structures (vesicles). Methods for the maintenance, subculture, storage, and measurement of bovine trophoblast stem cell growth are described. The cells exhibit characteristics of bovine trophoblastic stem cells and possess the ability to differentiate into binucleate cells and express placental lactogen, prolactin-related protein-1, pregnancy-associated glycoprotein-1, and interferon tau.

Animals↗
PubMed2006

[Successful platelet recovery after the second eradication of Helicobacter pylori with metronidazole in two patients with chronic idiopathic thrombocytopenic purpura].

There are many reports on the efficacy of Helicobacter pylori (H. pylori) eradication therapy in patients with H. pylori-positive chronic idiopathic thrombocytopenic purpura (ITP). We administrated metronidazole (MNZ), amoxicillin (AMPC), and a proton-pump inhibitor (PPI) as the second eradication therapy for two patients who failed in the first eradication therapy consisting of PPI, AMPC, and clarithromycin (CAM). Successful eradication and the rapid recovery of platelet counts within one month were achieved in both patients. Recently, H. pylori eradication is considered as the first-line therapy for H. pylori-positive chronic ITP patients. In Japan, the PPI + AMPC + CAM regimen is recognized as the standard eradication therapy for H. pylori. However, the PPI + AMPC + MNZ regimen is also useful for eradication and should be tried as the re-treatment regimen after failure of the first-line CAM-containing regimen.

Aged↗
PubMed2006

Highly liver-specific heme oxygenase-1 induction by interleukin-11 prevents carbon tetrachloride-induced hepatotoxicity.

Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, can be induced in response to various oxidative stimuli, and its induction is thought to be critical in the cellular defense against oxidative tissue injuries. Carbon tetrachloride (CCl(4)) treatment of rats causes lipid peroxidation of cell membranes and produces massive hepatic injury. We previously demonstrated that HO-1 induction following CCl(4) treatment is an essential part of the cellular defense against the CCl(4)-inducible toxic changes. As recombinant human interleukin-11 (rhIL-11) has been shown to induce HO-1 in cultured hepatoma cells, we examined the effect of rhIL-11 in vivo in rats on the CCl(4)-induced tissue injury. rhIL-11 treatment of animals by itself markedly induced HO-1 mRNA and its functional protein principally in the liver. rhIL-11 treatment (150 microg/kg) of the CCl(4)-administered (1 ml/kg) animals led to a further increase in HO-1 mRNA, while it markedly suppressed CCl(4)-induced serum alanine transaminase, hepatic malondialdehyde formation, tumor necrosis factor-alpha mRNA, nitric oxide synthase mRNA, nuclear factor-kappaB DNA-binding activity, as well as inflammatory changes of hepatocytes. In contrast, inhibition of HO activity by tin-mesoporphyrin, a competitive specific inhibitor of HO, entirely abolished the cytoprotective effect of rhIL-11. These findings thus demonstrate that rhIL-11 confers significant protection against CCl(4)-induced hepatic injury by virtue of its liver-specific HO-1 induction.

Animals↗
PubMed2005

Cloning and expression of two new prolactin-related proteins, prolactin-related protein-VIII and -IX, in bovine placenta.

BACKGROUND: Prolactin-related proteins (PRPs) are specific proteins of the growth hormone/prolactin (GH/PRL) family in bovine placenta. This study reports the identification and sequencing of a full-length cDNA for two new members of bovine PRPs, bPRP-VIII and -IX, and their localization and quantitative expression in bovine placenta. METHODS: New bPRP-VIII and -IX were identified from bovine placentome. Localization and quantitative gene expression in the placenta were respectively investigated by in situ hybridization and real-time RT-PCR methods. Recombinant proteins of these genes were produced by a mammalian HEK293 cell expression system. RESULTS: Full-length bPRP-VIII and -IX cDNA were respectively cloned with 909 and 910 nucleotide open-reading-frames corresponding to proteins of 236 and 238 amino acids. The predicted bPRP-VIII amino acid sequence shared about 40 to 70% homology with other bPRPs, and bPRP-IX had about 50 to 80% homology of others. The two new bPRPs were detected only in the placenta by RT-PCR. mRNA was primarily expressed in the cotyledon and intercotyledonary tissues throughout gestation. An in situ hybridization analysis revealed the presence of bPRP-VIII and -IX mRNA in the trophoblastic binucleate and/or trinucleate cells. bPRP-VIII mRNA was observed in the extra-embryonic membrane on Day 27 of gestation, however, no bPRP-IX mRNA was observed in the extra-embryonic membrane in the same stage of pregnancy by quantitative real-time RT-PCR analysis. Both new bPRP genes were possible to translate a mature protein in a mammalian cell expression system with approximately 28 kDa in bPRP-VIII and 38 kDa in bPRP-IX. CONCLUSION: We identified the new members of bovine prolactin-related protein, bPRP-VIII and -IX. Localization and quantitative expression were confirmed in bovine placenta by in situ hybridization or real-time PCR. Their different temporal and spatial expressions suggest a different role for these genes in bovine placenta during gestation.

Amino Acid Sequence↗