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Biomedical subjects

A Toda

Publications and source records attributed to A Toda.

At least 19 recordsLinked to original sources
PubMed2006

Plasminogen activator inhibitor-1 aids nerve growth factor-induced differentiation and survival of pheochromocytoma cells by activating both the extracellular signal-regulated kinase and c-Jun pathways.

Astrocytes are thought to be critical to neurons' surviving damage caused by ischemic stroke or other injury. Plasminogen activator inhibitor-1 is one of the active soluble factors released by astrocytes and regulates plasminogen activator-plasmin proteolytic sequence in the CNS as a serpin. In this study, we show that plasminogen activator inhibitor-1 can promote neurite outgrowth and survival of rat pheochromocytoma cells in serum-deprived conditions, and that this neuroprotective activity is correlated with enhanced activation of both extracellular signal-regulated kinases following a direct phosphorylation of nerve growth factor receptor, Trk A, and of c-Jun. Our results suggest that plasminogen activator inhibitor-1 can act as a neurotrophic factor, protecting neurons from serum deprivation-induced neuron death not only by compensating for nerve growth factor functions, but also by activating the c-Jun/activating protein-1 pathway.

Animals↗
PubMed2005

Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds.

In order to clarify the onset mechanisms of drug-induced allergies, three fluorescent-labelled compounds were synthesized by subjecting sulfanilamide (SA), a base compound for sulfonamides, and its active metabolites, i.e. sulfanilamide hydroxylamine and sulfanilamide nitroso, to dansylation using dansylchloride. In other words, 5-dimethylamino-N-(4-aminobenzyl)-naphthalenesulfonamide (DNS-4ABA), 5-dimethylamino-N-(4-hydroxylaminobenzyl)-1-naphthalenesulfonamide (DNS-4HABA) and 5-dimethylamino-N-(4-nitrosobenzyl)-1-naphthalenesulfonamide (DNS-4NSBA) were synthesized as model haptens. When analysed by HPLC, a conjugate of DNS-4HABA and glutathione (GSH) with nucleophilic amino acids had two peaks (P-1 and P-2). FAB-MS and 1H-NMR revealed that the DNS-4HABA-GSH conjugate consisted of sulphinamide and semimercaptal. The reactivity of GSH to DNS-4ABA, DNS-4HABA and DNS-4NSBA was quantified by HPLC using an oxidization system (horseradish peroxidase/H2O2). The results show that production of DNS-4NSBA-GSH-conjugate was four to eight times higher than that of DNS-4HABA-GSH conjugate, but that DNS-4ABA did not bind with GSH. Skin reactions were assessed using guinea pigs, and strong delayed erythema was seen with DNS-4NSBA, which bound most strongly with GSH, whereas weak delayed erythema was seen with DNS-4ABA, which did not bind with GSH. This suggests a correlation between GSH conjugate production and skin reactions. DNS-4HABA enzymatically bound with proteins in rat and guinea pig liver cytosol and microsomal fractions. The proteins that bound to DNS-4HABA were purified by HPLC and then subjected to N-terminal amino acid analysis. Ubiquitin (10 kDa) and fatty acid binding protein (30 kDa) were detected in the rat liver cytosol fraction; retinol-dehydrogenase (35 kDa) in the rat microsomal fraction; and glutathione-S-transferase B (mmu) (25 kDa) in the guinea pig liver cytosol fraction. When DNS-4HABA or DNS-4NSBA binds to proteins that play important roles in the body, unexpected adverse reactions may occur. Furthermore, by utilizing our technique using model compounds, it may be possible to identify the carrier proteins of various compounds, including pharmaceutical agents.

Animals↗
PubMed2005

Nested polymerase chain reaction for detection of the avian leukosis virus causing so-called fowl glioma.

The complete nucleotide sequence of the avian leukosis virus causing so-called fowl glioma has been previously determined. Primers were designed for detection of the fowl glioma-causal virus (FGV) based on the 3' untranslated region of the viral genome. The provirus and viral RNA of FGV were specifically detected in various organs and tissues, including feather pulp, from experimentally infected birds using nested polymerase chain reaction (PCR) and reverse transcription nested PCR. The prevalence of FGV was evaluated in 131 Japanese fowls of a zoological garden in Japan based on the detection of the FGV genome in feather pulp using PCR and the detection of viral antigen in faeces by enzyme-linked immunosorbent assay. FGV proviral DNA was detected in feather pulp of 52 birds (39.7%) by nested PCR. Later, nine dead birds from among the 52 were histologically diagnosed as having fowl glioma and found to have the proviral DNA in the affected brain. These results demonstrated that the PCR-based detection of FGV in feather pulp is useful for epidemiological studies on fowl glioma.

Animals↗
PubMed2003

[Successful emergent replacement of ruptured aortic arch aneurysm in an inpatient waiting for surgery: report of a case].

A 71-year-old male was admitted to our hospital for examination of mediastinal abnormal shadow, which was diagnosed aortic arch aneurysm. Once he was discharged and stayed at home for 2 weeks, and then re-admitted for surgery. On the 3rd day of 2nd admission, he suddenly fainted away in the ward and was in shock by hemorrhagic cardiac tamponade. He was transferred to operation room within an hour from onset of rupture. Emergent aortic arch replacement was performed under circulatory arrest with deep hypothermia and retrograde cerebral perfusion. His postoperative course was uneventful without any neurological deficits. Prompt diagnosis and surgery may contribute to improvement of surgical result in patients with ruptured aortic arch aneurysms.

Aged↗
PubMed2002

Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients.

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.

Adolescent↗
PubMed2002

[Early and late survival of total aortic arch replacement in patients with dissecting or atherosclerotic aneurysm].

Forty-seven patients (pts) were underwent total aortic arch replacement (TAAR) were studied to compare the early and late results between atherosclerotic (AA) and dissecting aneurysm (DA). There were 23 pts with AA and 24 pts with 24 pts. Preoperative risk were observed with shock in 12 pts (26%), major organ ischemia in 2 pts (4%), rupture in 8 pts (17%), stroke in 8 pts (17%) and coronary artery disease in 4 pts (9%). Operative procedure was TAAR in 22 pts, TAAR with ascending aorta replacement in 14 pts, and TAA with descending aorta replacement in 11 pts. Hospital mortality was 21 pts (45%) and late mortality was a surgical death after thoracoabdominal aneurysm in 1 pts. There was no difference in early and late survival rate, however early mortality was higher in pts with ruptured AA and with DA suffered from preoperative shock. There were 19 of early death in recent pts without rupture in AA and preoperative shock in DA.

Adult↗
PubMed2001

A high-speed atomic force microscope for studying biological macromolecules.

The atomic force microscope (AFM) is a powerful tool for imaging individual biological molecules attached to a substrate and placed in aqueous solution. At present, however, it is limited by the speed at which it can successively record highly resolved images. We sought to increase markedly the scan speed of the AFM, so that in the future it can be used to study the dynamic behavior of biomolecules. For this purpose, we have developed a high-speed scanner, free of resonant vibrations up to 60 kHz, small cantilevers with high resonance frequencies (450-650 kHz) and small spring constants (150-280 pN/nm), an objective-lens type of deflection detection device, and several electronic devices of wide bandwidth. Integration of these various devices has produced an AFM that can capture a 100 x 100 pixel(2) image within 80 ms and therefore can generate a movie consisting of many successive images (80-ms intervals) of a sample in aqueous solution. This is demonstrated by imaging myosin V molecules moving on mica (see http://www.s.kanazawa-u.ac.jp/phys/biophys/bmv_movie.htm).

Animals↗
PubMed2001

Highly efficient oligosaccharide synthesis on water-soluble polymeric primers by recombinant glycosyltransferases immobilised on solid supports.

Recombinant beta-1,4-galactosyltranferase (beta 1,4-GalT) and alpha-2,6-sialytransferase (alpha 2,6-SiaT) immobilised covalently with activated Sepharose beads were employed for the practical synthesis of a trisaccharide derivative, Neu-5Ac alpha(2-->6)Gal beta(1-->4)GlcNAc beta-O-(CH2)6-NH2, on a water-soluble primer having GlcNAc residues through a alpha-chymotrypsin-sensitive linker.

Chymotrypsin↗
PubMed2001

Puromycin aminonucleoside induces apoptosis and increases HNE in cultured glomerular epithelial cells(1).

Puromycin aminonucleoside induces apoptosis and increases 4-hydroxy-2-nonenal (HNE) in cultured glomerular epithelial cells. We have previously reported the detachment of cultured glomerular epithelial cells (GECs) from their substrata by puromycin aminonucleoside (PAN) treatment. In this study we explored whether or not apoptosis was involved in the mechanisms of the detachment. DNA fragmentation on gel electrophoresis was clearly shown by 10(-3) M PAN treatment of GECs. Nuclear staining by Hoechst 33342 indicated the greatest number of apoptotic cells at 10(-3) M PAN for 48 h treatment. Similarly, TUNEL methods revealed maximal apoptotic cells at 10(-3) M PAN for 48 h treatment. Caspase-3 (like) protease activity increased at 10(-3) M PAN, and decreased at 2 x 10(-3) M PAN for 48 h treatment as well as at 10(-3) M PAN for 60 h treatment. Pretreatment with 2'-deoxycoformycin (DCF), inhibitor of adenosine deaminase, abolished these effects of PAN on cultured GECs. PAN treatment increased HNE, a lipid peroxide adduct, modified protein in cultured GECs, which was also prevented by pretreatment by DCF. These results for the first time indicate that the PAN-induced detachment of GECs from culture substrata is mediated at least in part through apoptosis via oxidative stresses by adenosine deaminase activity.

Adenosine Deaminase Inhibitors↗
PubMed2001

Stereoselective synthesis of 2-alkenylaziridines and 2-alkenylazetidines by palladium-catalyzed intramolecular amination of alpha- and beta-amino allenes.

Whereas palladium-catalyzed reaction of N-arylsulfonyl-alpha-amino allenes with an aryl iodide (4 equiv) in the presence of potassium carbonate (4 equiv) in DMF at around 70 degrees C affords the corresponding 3-pyrroline derivatives, the reaction in refluxing 1,4-dioxane under otherwise identical conditions yields exclusively or most predominantly the corresponding 2-alkenylaziridines bearing an aryl group on the double bond. Similarly, N-arylsulfonyl-beta-amino allenes can be also cyclized into the corresponding alkenylazetidines bearing a 2,4-cis-configuration under palladium-catalyzed cyclization conditions in DMF.

Journal Article↗
PubMed2001

Effect of bile acids on biliary excretion of cyclosporin A in the rat.

Cyclosporin A, a substrate of P-glycoprotein (P-gp), is known to cause cholestasis in humans and in rat experimental models. Tauroursodeoxycholate is reported to be effective in CyA-induced cholestasis in rats. In the present study, to investigate the mechanism of the inhibition of CyA induced cholestasis, effect of bile acids on biliary cyclosporin A excretion was studied in rats. Infusion of both taurocholate and tauroursodeoxycholate at the rate of 0.8 mmol/min per 100 g bodyweight increased bile flow and biliary cyclosporin A excretion, and the extent was more prominent with tauroursodeoxycholate. It was suggested that these findings were caused by the enhanced vesicular targeting of P-gp to the canalicular membrane by bile acids, thus increasing the numbers of P-gp in the canalicular membrane.

Journal Article↗
PubMed2001

Higher-order Laue zone line contrast in large-angle convergent-beam electron diffraction around a dislocation.

The physical picture of higher-order Laue zone (HOLZ) line contrast in a large-angle convergent-beam electron diffraction pattern around a dislocation, which is used for determining the Burgers vector, was examined. To evaluate the analytical expression of diffracted wave amplitude, we introduced an approximate form of the atomic displacement field of a dislocation. We showed that the four features of the HOLZ line contrast, that is, splitting, fading, bending and periodical contrast can be explained by analysis of the atomic displacement field. The localized lattice plane bending around a dislocation core made a HOLZ line split, fade and bend. However, we found that the periodical contrast of a HOLZ line was produced by the change of phase difference of the atomic displacement field between the crystals above and below the slip plane across the dislocation line.

Journal Article↗
PubMed1999

Cloning and characterization of rat leukotriene B(4) receptor.

Leukotriene B(4) (LTB(4)) is a potent chemoattractant for neutrophils and eosinophils. cDNAs for LTB(4) receptor (BLT) have been cloned from human, mouse, and guinea pig. Here we report the isolation of BLT from rat genomic library. Rat BLT consists of 351 amino acids with homologies of 80.2, 93.2, and 71.6%, to human, mouse, and guinea pig BLT, respectively. When expressed in human embryonic kidney (HEK)-293 cells, rat BLT showed a specific and high-affinity binding to LTB(4) with a Kd value of 0.68 nM (mean, n = 3). Northern blot analysis showed that BLT is exclusively expressed in polymorphonuclear leukocytes. Furthermore, the expression of BLT was high in proteosepeptone-activated peritoneal macrophages, while the resident macrophages did not show significant expression. The present results suggest important roles of LTB(4) in macrophage recruitment and activation.

Amino Acid Sequence↗
PubMed1999

Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron.

BACKGROUND: Leukotriene (LT) B4 is a well-known inflammatory mediator and is implied to play some roles in glomerulonephritis. Although LTA4 hydrolase, a final-step key enzyme to produce LTB4, is located in glomerular mesangial cells, as well as in leukocytes, platelets, and endothelial cells, its precise distribution in the kidney other than in mesangial cells remains unknown. Therefore, we have investigated the localization of mRNA, protein, and enzyme activity of LTA4 hydrolase in the rat kidney. METHODS: Microdissection reverse transcriptase-polymerase chain reaction was used for the determination of LTA4 hydrolase mRNA. The enzyme protein was detected by Western blot, and immunohistochemistry was performed. Finally, LTA4 hydrolase activity and LTB4 were assayed in kidney tissues. RESULTS: LTA4 hydrolase mRNA was detectable in all microdissected nephron segments of the cortex and outer medulla. The corresponding size of approximately 70 kDa protein was shown in descending order in the inner medullary > outer medullary >/= cortical homogenates. The immunohistochemical study demonstrated the ubiquitous presence of the enzyme in all nephron segments of cortex, outer medulla, and inner collecting tubules. LTA4 hydrolase activity was detected in the inner medullary >/= outer medullary >/= cortical tissue homogenates. LTB4 was demonstrated in the inner medullary > outer medullary >/= cortical tissues during the basal condition, and was time-dependently increased by stimulation with arachidonic acid and ionomycin in the cytosolic fraction from outer medulla and in the glomerular suspension. CONCLUSIONS: These results strongly suggest that renal tubular cells as well as glomerular cells have an LTB4-forming potency, which may participate in physiological and pathophysiological roles in the kidney.

Animals↗
PubMed1999

Hepatic heme metabolism in rats with fever induced by interleukin 1beta.

We have recently reported that the content of hepatic cytochrome P450 (CYP) apparently decreased in fever model rats, which were created by repeated injection of recombinant human interleukin-1beta (rhIL-1beta) into the cerebroventricle. To make clear the biochemical mechanism of the decreased CYP content, we examined the effect of fever on the activities of hepatic enzymes involved in the biosynthetic and degradative pathways of heme. The activities of delta-aminolevulinic acid synthase, a rate-limiting enzyme in the heme biosynthesis, and porphobilinogen synthase in the liver of rhIL-1beta-induced fevered rat were significantly lower than those in the control, whereas the activity of heme oxygenase, a key enzyme in the heme-degradative pathway, markedly increased in the fevered rat. Moreover, the heme saturation of tryptophan 2,3-dioxygenase in the fevered rat liver was decreased to 43% of the control. These results indicate that fever diminishes the hepatic heme content by decreasing the heme biosynthesis and by accelerating the heme degradation. The deficiency of hepatic heme pool may be one of the main mechanisms that cause the impairment of CYP synthesis.

5-Aminolevulinate Synthetase↗
PubMed1998

Gene cluster for creatinine degradation in Arthrobacter sp. TE1826.

The genes encoding creatininase (CrnA; 258 residues) and creatinase (CreA; 411 residues) from Arthrobacter sp. TE1826 were cloned and sequenced. The genes form a cluster with the sarcosine oxidase gene (soxA) and its regulator gene (soxR), which were cloned previously. The deduced amino acid sequences of CrnA and CreA show 35.9% and 63.1% identity, respectively to the corresponding Pseudomonas enzymes. CrnA and CreA were purified from the recombinant strains and characterized. Other open reading frames (creB and crnB), encoding proteins similar to several transporters, were found downstream of creA and crnA, respectively.

Amidohydrolases↗