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Biomedical subjects

Toru Takahashi

Publications and source records attributed to Toru Takahashi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Transport of bacteria across and along the large intestinal lumen of guinea pigs.

Flow cytometry was used to observe the transport of fluorescently labelled viable bacteria in the large intestinal lumen of guinea pigs after the injection of the bacteria into the proximal colon. Bacteria were transported along the radial and longitudinal axes of the intestine and were separated from dietary residue, accumulated, and then transported back to the caecum. These observations, together with the heterogeneous distribution of bacterial species and chemical composition across and along the large intestine, suggest that there are several different microenvironments within the intestinal lumen between which bacteria and/or dietary residues move. The existence of different microenvironments within the intestinal lumen is consistent with poor mixing of the digesta within the large intestine of pigs and chickens.

Animals↗
PubMed2005

Cloning of the bovine antiapoptotic regulator, BCL2-related protein A1, and its expression in trophoblastic binucleate cells of bovine placenta.

This report studied the identification and sequence of a full-length cDNA for the bovine BCL2 antiapoptotic family member, BCL2-related protein A1 (BCL2A1), and its localized and quantitative expression in the placenta to clarify the regulatory mechanism of trophoblast cell proliferation and differentiation during implantation and placental development. We cloned a full-length bovine BCL2A1 cDNA with 725 nucleotides and an open-reading frame corresponding to a protein of 175 amino acids. The predicted amino acid sequence shared 78% homology with human BCL2A1. All BCL2 homology domains (BH1, BH2, BH3, and BH4) in bovine BCL2A1 were conserved as well as in other mammalian BCL2A1. In the placentomes, in situ hybridization demonstrated that the BCL2A1 was limited in binucleate cells expressing various pregnancy-specific molecules like placental lactogen. BCL2-associated X protein (BAX) was also expressed in binucleate cells. Quantitative real-time RT-PCR detection exhibited a high-level expression of BCL2A1 in the conceptus at Day 21 of gestation, and it was expressed and increased in the extraembryonic membrane, cotyledon, and intercotyledon from implantation to term. BAX expression intensity increased with progression of gestation and remained elevated in postpartum. Caspase-3 protein (CASP3) and mRNA (CASP3) were detected from late gestation to postpartum in placenta as well as in the results of TUNEL detection. We believe that the apoptosis of binucleate cells may be regulated by the balance of the BCL2A1 and BAX. BCL2A1 genes produced a BCL2A1 protein in the mammalian cell-expression system. This molecule is a new candidate for antiapoptotic maintenance of the binucleate cells that support placental functions throughout gestation in bovine.

Amino Acid Sequence↗
PubMed2005

Increased heme catabolism in critically ill patients: correlation among exhaled carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IXalpha concentrations.

It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IXalpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.

Aged↗
PubMed2005

Doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

To determine if doxapram stimulates the carotid body through the same mechanism as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose-dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia stimulated the carotid body. Although, doxapram had an additive effect on the carotid body chemosensory response to hypercapnia, a synergistic effect was not observed. Also, we investigated the various K(+) channel activators on the response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator; and halothane as a TASK-like background K(+) channel activator. The hypoxic response was partially reduced by halothane only, while pinacidil, levcromakalim and NS-1619 had no effect. Interestingly, the effect of doxapram was partially inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

Anesthetics, Inhalation↗
PubMed2005

Prevention of hemorrhagic shock-induced lung injury by heme arginate treatment in rats.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress, which leads to acute lung injury. Heme oxygenase (HO)-1 (EC 1.14.99.3), the rate-limiting enzyme in heme catabolism, is inducible by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. In this study, we examined expression of HO-1 as well as tissue injuries in the lung, liver, and kidney after HSR in rats. We also pretreated animals with heme arginate (HA), a strong inducer of HO-1, and examined its effect on the HSR-induced lung injury. HO-1 expression significantly increased in the liver and kidney following HSR, while its expression in the lung was very low and unchanged after HSR. In contrast to HO-1 expression, tissue injury and tumor necrosis factor-alpha (TNF-alpha) gene expression was more prominent in the lung compared with those in the liver and kidney. HA pretreatment markedly induced HO-1 in pulmonary epithelial cells, and ameliorated the lung injury induced by HSR as judged by the improvement of histological changes, while it decreased TNF-alpha and inducible nitric oxide synthase gene expression, lung wet weight to dry weight ratio, and myeloperoxidase activity. In contrast, inhibition of HO-1 by tin-mesoporphyrin administration abolished the beneficial effect of HA pretreatment. These findings suggest that tissues with higher HO-1 may be better protected than those with lower HO-1 from oxidative tissue injury induced by HSR. Our findings also indicate that HA pretreatment can significantly suppress the HSR-induced lung injury by virtue of its ability to induce HO-1.

Animals↗
PubMed2005

Cloning and expression of a new member of prolactin-related protein in bovine placenta: bovine prolactin-related protein-VII.

This study reports the identification and sequence of a full-length cDNA for a new member of bovine prolactin-related protein (bPRP-VII) and its quantitative and localized expression in the placenta. A full-length bPRP-VII cDNA was cloned with a 929-nucleotide open-reading-frame corresponding to a protein of 238 amino acids. The predicted amino acid sequence shares 63% homology with bPRP-I and 70% with bPRP-VI. bPRP-VII has eight cysteine residues with four disulfide bonds, which is more abundant than that of other bPRPs. RT-PCR detected bPRP-VII only in the placenta. In the placenta, mRNA was expressed in the cotyledon and intercotyledonary tissues throughout gestation. Quantitative real-time RT-PCR analysis exhibited a high expression of bPRP-VII mRNA in the fetal membrane at Day 27 of gestation. In the placentome on Day 60 of gestation, in situ hybridization analysis evidenced bPRP-VII mRNA in binucleate cells. bPRP-VII gene produced a mature protein in mammalian cell expression system. Approximately 29kDa protein was confirmed in this by the Western blot analysis with FLAG epitope tag. Expression profiles and localization were similar to those of bPRP-I. Although the functional data remain to be examined, a new member of the bPRP-VII gene was cloned. In addition to bPRP-I, bPRP-VII may take on an important functional role in implantation.

Amino Acid Sequence↗
PubMed2005

Crystalline cellulose reduces plasma glucose concentrations and stimulates water absorption by increasing the digesta viscosity in rats.

Although cellulose is generally considered not to affect the viscosity of the digesta in the upper gastrointestinal tract, we found previously that the ingestion of cellulose elevated the viscosity of the gastric, small intestinal, and cecal contents when particulate matter was included in the measurements. We hypothesized that the digesta viscosity influences absorption. Here, we examined the effects of crystalline cellulose on plasma glucose concentrations by infusing control and cellobiose- and cellulose-containing artificial digesta of approximately 30 mL into the small intestine of rats. Cellulose, but not cellobiose, decreased the postinfusion plasma glucose concentration (P < 0.05), although cellulose did not cause adsorption or dilution of glucose. Among the physical properties of the artificial digesta, only viscosity was responsible for the decrease in the plasma glucose concentration, whereas water content, free water, bound water, and osmotic pressure were not. The cellulose-induced increase in digesta viscosity may delay glucose diffusion in the lumen, as found in our previous study. Cellulose also stimulated water absorption from the small intestine (P < 0.05), which may be attributable to increases in the water potential of the digesta moving through the small intestine. The ingestion of cellulose with meals, which increases digesta viscosity, is likely to modulate the postprandial plasma glucose concentration and to reduce the incidence of diarrhea associated with enteral nutrition.

Animals↗
PubMed2005

The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury.

OBJECTIVE: The aim of the present study was to investigate whether glutamine pretreatment improves intestinal injury in rats with endotoxemia by its heme oxygenase-1 induction in the lower intestinal tract. DESIGN: Randomized, blinded, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 220-250 g (n = 201). INTERVENTIONS: Rats were treated with glutamine (0.75 g/kg) dissolved in lactated Ringer's solution via the tail vein. Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (10 mg/kg or 20 mg/kg for survival study). Lipopolysaccharide-treated animals were pretreated with glutamine or lactated Ringer's solution 9 hrs before lipopolysaccharide treatment. Some of the glutamine-pretreated animals further received tin mesoporphyrin (1 micromol/kg), a specific inhibitor of heme oxygenase activity, 1 hr before lipopolysaccharide treatment. MEASUREMENTS AND MAIN RESULTS: Glutamine treatment markedly induced heme oxygenase-1 messenger RNA and protein in the mucosal epithelial cells as well as in the lamina propria cells in the ileum and the colon, whereas its expression in the duodenum and the jejunum was not influenced by the treatment. Glutamine treatment before lipopolysaccharide administration significantly ameliorated lipopolysaccharide-induced mucosal injury, inflammation, and apoptotic cell death in the ileum and the colon, as judged by significant decreases in tumor necrosis factor-alpha gene expression, histologic damage scores, and expression of activated caspase-3 and by an increase in gene expression of Bcl-2. In addition, glutamine treatment markedly decreased lipopolysaccharide-induced mortality. In contrast, treatment with tin mesoporphyrin abolished the beneficial effect of glutamine pretreatment. CONCLUSIONS: Glutamine pretreatment significantly ameliorated intestinal tissue injury of rats following lipopolysaccharide treatment. The same treatment also improved the survival of animals from endotoxemia. The protective effect of glutamine is mediated by its lower intestine-specific induction of heme oxygenase-1, since its inhibition by tin mesoporphyrin completely abolished the beneficial effect of glutamine.

Animals↗
PubMed2005

The fungal hydrophobin RolA recruits polyesterase and laterally moves on hydrophobic surfaces.

When fungi grow on plant or insect surfaces coated with wax polyesters that protect against pathogens, the fungi generally form aerial hyphae to contact the surfaces. Aerial structures such as hyphae and conidiophores are coated with hydrophobins, which are surface-active proteins involved in adhesion to hydrophobic surfaces. When the industrial fungus Aspergillus oryzae was cultivated in a liquid medium containing the biodegradable polyester polybutylene succinate-coadipate (PBSA), the rolA gene encoding hydrophobin RolA was highly transcribed. High levels of RolA and its localization on the cell surface in the presence of PBSA were confirmed by immunostaining. Under these conditions, A. oryzae simultaneously produced the cutinase CutL1, which hydrolyses PBSA. Pre-incubation of PBSA with RolA stimulated PBSA degradation by CutL1, suggesting that RolA bound to the PBSA surface was required for the stimulation. Immunostaining revealed that PBSA films coated with RolA specifically adsorbed CutL1. Quartz crystal microbalance analyses further demonstrated that RolA attached to a hydrophobic sensor chip specifically adsorbed CutL1. Circular dichroism spectra of soluble-state RolA and bound RolA suggested that RolA underwent a conformational change after its adsorption to hydrophobic surfaces. These results suggest that RolA adsorbed to the hydrophobic surface of PBSA recruits CutL1, resulting in condensation of CutL1 on the PBSA surface and consequent stimulation of PBSA hydrolysis. A fluorescence recovery after photobleaching experiment on PBSA films coated with FITC-labelled RolA suggested that RolA moves laterally on the film. We discuss the novel molecular functions of RolA with regard to plastic degradation.

Adipates↗
PubMed2005

Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis in relation to the basic core promoter and precore mutations.

BACKGROUND: The clinicopathological profiles and outcome of chronic hepatitis B can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are two major HBV genotypes. The basic core promoter and precore mutations are other known viral factors for disease activity, although the relationship between HBV genotypes and these mutations is not fully understood. METHODS: The HBV genotypes in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained data were correlated with clinicopathological parameters, basic core promoter, precore and the nucleotide 1858 mutations of the HBV genome. RESULTS: Among 90 cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B patients were older than genotype C patients (44.0 +/- 13.9 vs 34.7 +/- 11.0 P = 0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008) while anti-HBe was more common in genotype B than C patients (P = 0.0002). Serum aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 +/- 612.8/257.0 +/- 498.0 IU/L vs C: 111.3 +/- 122.8/201.6 +/- 229.4 IU/L, P = 0.16/0.48) and HBV viral loads in blood (B: 6.1 +/- 3.1 log genome equivalent [LGE]/mL vs C: 6.7 +/- 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion from HBeAg to anti-HBe occurred significantly earlier in genotype B than C patients (62 +/- 53 months vs 136 +/- 54 months, P = 0.0028) during the mean observation period of 149 +/- 82 months even under various therapeutic modalities. The categories III and IV of the histological activity index in genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B patients whereas category II was higher in genotype B than C patients (P < 0.05). The double mutation (1762T/1764A) in the basic core promoter was more frequently found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of 1858C that was complementary to the precore mutation site in the stem-loop structure in, was equally rare in both genotype B and C HBV. CONCLUSIONS: Genotype B patients were older, had earlier HBeAg seroconversion and exhibited more severe lobular necroinflammation, less portal inflammation and fibrosis than genotype C patients. This genotypic difference is related to the basic core promoter and precore mutations irrespective of 1858C. (c) 2004 Blackwell Publishing Asia Pty Ltd.

Adult↗
PubMed2005

Autografting followed by a reduced-intensity conditioning unrelated donor cord blood transplantation for a patient with refractory multiple myeloma: successful engraftment with minimal toxicity.

We report on a 59-yr-old man with recurrent multiple myeloma. To reduce treatment-related mortality, while retaining the cytoreductive effects of high-dose chemotherapy, as well as graft vs. myeloma effect, we used a reduced-intensity conditioning umbilical cord blood (CB) transplantation following high-dose chemotherapy with autologous stem cell transplantation support. This patient was engrafted rapidly and extramedullary toxicities were acceptable. Although he had local recurrence in the right calf on day +130 after the CB transplantation, the tumor was successfully treated with radiation therapy, and he is alive and well at present (day +480).

Cord Blood Stem Cell Transplantation↗
PubMed2005

Cytoprotective effects of heme oxygenase in acute renal failure.

Following ischemia, superoxide is produced during the reperfusion phase in various organs. In renal pathophysiology, excess of free heme, which is released from hemeproteins under these conditions, catalyzes the formation of further reactive oxygen species to accelerate cellular injuries. There is accumulating evidence suggesting that transcriptional activation of heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation as well as the 32-kDa heat shock protein, participates in the defense against oxidative tissue injuries. Ischemia followed by reperfusion of the rat kidney accompanies significant induction of HO-1 mRNA, protein and enzyme activity, which is in part mediated through a rapid and transient increase in microsomal heme concentration. Inhibition of HO activity by tin mesoporphyrin results in a sustained and enhanced increase in microsomal heme content, and significantly exacerbates renal function. In contrast, SnCl2 treatment, which specifically induces HO-1 mRNA and protein in the proximal tubular epithelial cells, prevents the ischemia-reperfusion-mediated increase in microsomal heme concentration, and ameliorates the ischemic renal injury. In addition to these findings, recent evidence on the role of HO-1 in the kidney pathophysiology is summarized, with a particular emphasis on its protective role in the ischemic acute renal failure.

Acute Kidney Injury↗
PubMed2005

The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy.

We investigated whether perioperative extensive epidural block (C3-L) affects postoperative immune response in patients undergoing radical esophagectomy. Patients undergoing radical esophagectomy were randomly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia (group E, n = 15) or intraoperative general anesthesia and postoperative IV morphine analgesia (group G, n = 15). Plasma levels of stress hormones, cytokines, C-reactive protein (CRP), leukocyte counts, and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days (PODs) 1 and 3. In comparison with group E, significant increases in plasma epinephrine level at the end of surgery (P < 0.05) and norepinephrine level at the end of surgery (P < 0.01) and on POD1 (P < 0.01) and POD3 (P < 0.01) and significant decrease in cluster of differentiation (CD4/CD8 ratio) at the end of surgery (P < 0.05) were observed in group G. However, there were no significant differences in other variables between groups. In both groups, plasma cortisol, adrenocorticotropic hormone, interleukin (IL)-1beta, IL-6, IL-10, and CRP levels were increased after surgery (each group P < 0.01) and IL-1beta, IL-6, IL-10, and CRP were still increased on POD1 and POD3 (each change, each group P < 0.01). Leukocyte counts were increased on POD1 (each group P < 0.05) and POD3 (each group P < 0.01). The proportion of lymphocytes decreased from the end of surgery to POD3 (each group P < 0.01). The proportion of B cells was increased on POD1 (each group P < 0.01); that of natural killer cells was decreased at POD1 and POD3 (each group P < 0.01). We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy.

Aged↗
PubMed2005

Mitral regurgitation with an isolated anterior mitral leaflet cleft: a case report.

A 20-year-old man was admitted to hospital because of general fatigue during exercise. He had had a heart murmur since the age of 6 years. Echocardiography showed severe mitral regurgitation (MR, IV), probably caused by an anterior leaflet cleft or tendon rupture. During surgery, a cleft measuring 9 mm in length was found in the center of the anterior leaflet of the mitral valve. The cleft was closed directly, together with annuloplasty using the bilateral Kay's method. A Cosgrove ring (32 mm) was added because the mitral valve annulus was dilated. The patient's postoperative course was uneventful and echocardiography after surgery demonstrated no MR. An isolated cleft of the anterior mitral leaflet is a rare cause of MR and in this case, direct closure of the cleft with additional annuloplasty gave a good functional result.

Adult↗