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K Mori

Publications and source records attributed to K Mori.

At least 235 records · Page 13Linked to original sources
PubMed2000

Doxorubicin, an RNA synthesis inhibitor, prevents vasoconstriction and inhibits aberrant expression of endothelin-1 in the cerebral vasospasm model of the rat.

A vasoconstrictor peptide, endothelin-1 (ET-1), has been identified as one of the causative substances in cerebral vasospasm after subarachnoid hemorrhage. We investigated whether doxorubicin, an RNA synthesis inhibitor, effectively suppresses induction of ET-1 in the rat vasospasm model. Blood was injected around the right femoral artery and the left one was used as an internal control. Seven days later (day 7), diameters of the right femoral arteries narrowed to about 60% and this vasoconstriction was prevented by clinical dose (0.6 mg/kg) or one third of its dose of doxorubicin injected on day 1. Reverse transcriptase-polymerase chain reaction analysis demonstrated that expression of ET-1 mRNA in the vasospastic artery was not detected in doxorubicin-treated rats. It is concluded that doxorubicin effectively inhibits aberrant expression of ET-1 in the vasospasm-destined artery in the rat.

Animals↗
PubMed2000

Molecular cloning of the full-length cDNA encoding mouse neutral ceramidase. A novel but highly conserved gene family of neutral/alkaline ceramidases.

We report here the molecular cloning, sequencing, and expression of the gene encoding the mouse neutral ceramidase, which has been proposed to function in sphingolipid signaling. A full-length cDNA encoding the neutral ceramidase was cloned from a cDNA library of mouse liver using the partial amino acid sequences of the purified mouse liver ceramidase. The open reading frame of 2,268 nucleotides encoded a polypeptide of 756 amino acids having nine putative N-glycosylation sites. Northern blot analysis revealed that the mRNA of the ceramidase was expressed widely in mouse tissues, with especially strong signals found in the liver and kidney. The ceramidase activity of lysates of CHOP cells increased more than 900-fold when the cells were transformed with a plasmid containing the cDNA encoding ceramidase. We also cloned the ceramidase homologue from the cDNA library of mouse brain and found that the sequence of the open reading frame, but not the 5'-noncoding region, was identical to that of the liver. Interestingly, phylogenetic analysis of various ceramidases clearly indicated that neutral/alkaline ceramidases form a novel but highly conserved gene family that is evolutionarily different from lysosomal acid ceramidases.

Amidohydrolases↗
PubMed2000

Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent.

The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 microg/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca(2+), similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187, histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G(i) subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.

Animals↗
PubMed2000

Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRP receptor: cloning and upregulation in obstructive nephropathy.

Adrenomedullin (AM) is a potent vasorelaxing peptide originally isolated pheochromocytoma. Recently, a family of receptor-activity-modifying proteins (RAMPs 1-3) were identified in humans. Associated with the calcitonin receptor-like receptor (CRLR), RAMP2 or RAMP3 may function as the AM receptor. Here we cloned rat RAMP family, analyzed their distribution in rat tissues, and examined regulation of their expression in the kidney using an obstructive nephropathy model. Northern blot analyses revealed that the RAMP family genes are expressed in various tissues with different tissue specificity; RAMP1 is abundantly expressed in the brain, fat, thymus, and spleen, RAMP2 in the lung, spleen, fat, and aorta, while RAMP3 is most abundant in the kidney and lung. After ureteral obstruction, RAMP1, RAMP2, and CRLR gene expressions in the obstructed kidney were markedly upregulated, whereas RAMP3 expression was unchanged. Thus, RAMPs are regulated differently in obstructive nephropathy, suggesting their distinct roles in renal pathophysiology.

Amino Acid Sequence↗
PubMed2000

Assessment of gastric carcinoma risk associated with Helicobacter pylori may vary depending on the antigen used: CagA specific enzyme-linked immunoadsorbent assay (ELISA) versus commercially available H. pylori ELISAs.

BACKGROUND: Previous epidemiologic studies produced inconsistent results when examining the relation between Helicobacter pylori infection and the risk of gastric carcinoma by measuring various anti-H. pylori antibodies. This study investigated the increased risk of cancer by examining different antibodies, including the specific anti-CagA antibody and antibodies from two commercially available kits. METHODS: An ELISA for the detection of serum anti-CagA was established using a recombinant CagA protein that the authors previously reported. Serum anti-CagA titer was determined for 80 patients with gastric carcinoma and 80 gender- and age-matched controls. Two anti-H. pylori antibodies from the commercially available kits HEL-p (Amrad, Kew Vic, Australia) and HM-CAP (Enteric Product Inc., Westbury, NY) were also evaluated. RESULTS: Anti-CagA seropositivity differed significantly between gastric carcinoma patients and controls (92.5% vs. 55.0%; P = 0. 0001), showing an odds ratio of 10.4 (95% confidence interval [CI]: 4.23-29.74). The difference was less prominent for the seropositivity of HEL-p (77.5% vs. 58.8%; P = 0.0139; odds ratio: 2. 38; 95% CI: 1.20-4.82) and insignificant for that of HM-CAP (65.0% vs. 57.5%; P = 0.4325; odds ratio: 1.30; 95% CI: 0.68-2.49). CONCLUSIONS: The current study revealed that the antibody assay system used could be one important factor in the assessment of gastric carcinoma risk for patients with H. pylori.

Adult↗
PubMed2000

Argatroban, a thrombin inhibitor, decreased mortality after 10 min of forebrain ischemia in the gerbil.

We investigated whether anticoagulant therapy with heparin or a selective thrombin inhibitor, argatroban, may ameliorate the postischemic cerebral circulation and attenuate mortality after 10 min of forebrain ischemia. Postischemic subcutaneous injection of argatroban (5 mg/kg) significantly attenuated mortality (9.1%) compared with non-treatment (45.5%) during 14 days' observation period. This effect coincided with: (1) increased cortical CBF after reperfusion; (2) attenuation of brain edema; and (3) less severe cell damages in the cerebral cortex. In contrast, nine of the 22 gerbils treated with heparin (830 IU/kg) were found dead on the next day due to massive bleeding in the surgical wound and 13 bleeding-avoided gerbils did not show significant amelioration in mortality (30.8%). These findings suggest that argatroban is an effective anticoagulant for prevention of cell damage after a relatively long forebrain ischemia.

Animals↗
PubMed2000

Positive charge intrinsic to Arg(37)-Arg(38) is critical for dopamine inhibition of the catalytic activity of human tyrosine hydroxylase type 1.

Tyrosine hydroxylase (TH), which converts L-tyrosine to L-3, 4-dihydroxyphenylalanine, is a rate-limiting enzyme in the biosynthesis of catecholamines; its activity is regulated by the feedback inhibition of the catecholamine products including dopamine. To rationalize the significant role of the N-terminal sequence Arg(37)-Arg(38) of human TH type 1 (hTH1) in determining the efficiency of feedback inhibition, we produced mutants of which the positively charged Arg(37)-Arg(38) site was replaced by electrically neutral Gly and/or negatively charged Glu and analyzed the degree of inhibition of these mutant enzymes by dopamine. The replacement of Arg by Gly reduced the inhibitory effect of dopamine on the catalytic activity measured in the basic pH range and the replacement of Arg by Glu was enough to abolish the inhibitory effect, although these mutations brought no significant changes to the circular dichroism spectrum. The prediction of the secondary structure of N-terminal residues 1-60 by computer software specified the location of the Arg(37)-Arg(38) sequence in the turn intervening between the two alpha-helices (residues 16-29 and residues 41-59). These results suggest that the positive charge of the amino acid residues at positions 37 and 38 is one of the main factors that maintains the characteristic of the turn and is responsible for the enzyme inhibition by dopamine.

Amino Acid Sequence↗
PubMed2000

Differences in water diffusion and lactate production in two different types of postinfectious encephalopathy.

We compared two different types of postinfectious encephalopathy using magnetic resonance imaging (MRI), including diffusion-weighted images and MR spectroscopy. Acute disseminated encephalomyelitis (ADEM) and acute necrotizing encephalopathy (ANE) showed different distribution of abnormal intensity areas and different diffusion of water measured by diffusion-weighted imaging (DWI). Proton MR spectroscopy (MRS) showed lactate production in both cases, which returned to a normal range; the rate of increased lactate production was much lower in the ANE case. Water diffusion showed a difference in pathophysiological background between the two encephalopathies, but the lactate elevation observed by proton MRS did not correlate with clinical severity.

Body Water↗
PubMed2000

Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a/CD18.

Intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a member of the immunoglobulin superfamily expressed on telencephalic neurons, and serves as a ligand for the leukocyte integrin CD11 a/CD18. We studied here the binding site in ICAM-5 for CD11a/CD18. Protein constructs containing the first immunoglobulin domain of ICAM-5 were able to support CD11a/CD18 interaction, while deletion of the first domain abolished binding. Monoclonal antibodies reacting with the first domain of ICAM-5 also completely blocked the interaction. The soluble first domain of ICAM-5 inhibited the binding of T cells to immobilized ICAM-5 at concentrations of 50 nM and higher. Interestingly, the sixth domain of ICAM-5 was also able to support leukocyte binding, but this binding activity may not involve leukocyte integrins. To test the involvement of ICAM-5 in leukocyte-neuron interactions, an assay using human T cells binding to rat hippocampal neurons was established. This binding was blocked by monoclonal antibodies against CD11a/CD18 and ICAM-5. Thus ICAM-5 may act as a major adhesion molecule for leukocyte binding to neurons in the central nervous system.

Animals↗
PubMed2000

Inhibitory effects of ovoglobulins on bacillary necrosis in larvae of the pacific oyster, Crassostrea gigas.

In order to develop an alternative method to antibiotics for preventing bacillary necrosis in bivalve mollusc larvae, we examined the effects of ovoglobulins (proteins derived from the whites of hens' eggs) on the survival of larvae of the Pacific oyster Crassostrea gigas. The pathogenic Vibrio tubiashii (ATCC 19106) was used to infect larvae of the Pacific oyster. V. tubiashii showed strong pathogenicity to oyster larvae, causing 100% mortality after experimental exposure for 24 h at a concentration of 10(5) cfu (colony-forming units)/ml. In contrast, the addition of ovoglobulins at a concentration of 10 microg/ml to larval oysters, challenged with V. tubiashii at 10(5) cfu/ml, led to a marked increase in larval survival of 96.5% at 24 h after infection. The V. tubiashii culture supernatant was also shown to be pathogenic to larval oysters; however, its pathogenicity was completely inhibited by the addition of 10 microg/ml of ovoglobulins. Larval oysters infected by V. tubiashii showed typical symptoms of bacillary necrosis including anomalous swimming and detachment of cilia and/or vela. In contrast, live larvae were actively motile, and their cilia and vela were not necrotized in the ovoglobulins-added group. The addition of ovoglobulins clearly suppressed the growth of V. tubiashii in gelatin-sea water broth, but the number of viable V. tubiashii 24 h after incubation did not decrease to the initial dose level. Findings obtained in this study indicate that ovoglobulins almost completely protect larval oysters from V. tubiashii infection by nonbactericidally inhibiting the growth of V. tubiashii without affecting survival of the oysters.

Animals↗
PubMed2000

Urinary trypsin inhibitor reduces C-X-C chemokine production in rat liver ischemia/reperfusion.

BACKGROUND AND AIM: Protease inhibitors attenuate ischemia/reperfusion injury. However, the underlying mechanisms by which protease inhibitors prevent reperfusion injury remain obscure. Neutrophils play an important role in reperfusion injury. We studied the effects of urinary trypsin inhibitor (UTI) on production of the C-X-C chemokine, cytokine-induced neutrophil chemoattractant (CINC), by Kupffer cells during ischemia/reperfusion of the liver. METHODS: Liver ischemia was induced in rats by occlusion of the portal vein for 30 min. UTI (50,000 U/kg) was injected intravenously 5 min before vascular clamping. Serum CINC concentrations were measured by enzyme-linked immunosorbent assay. Levels of CINC mRNA in the liver were determined by Northern blot analysis. We also examined the inhibitory effects of UTI on in vitro CINC production by peritoneal macrophages in response to neutrophil elastase (NE). RESULTS: Serum CINC concentrations increased and peaked 6 h after reperfusion. However, pretreatment of animals with UTI blunted this increase in CINC and significantly reduced CINC mRNA levels in the liver after ischemia/reperfusion. UTI also decreased neutrophil accumulation in the liver 24 h after reperfusion. In vitro CINC production by Kupffer cells from rats pretreated with UTI 3 h after ischemia/reperfusion was significantly decreased compared to those from untreated animals. UTI reduced NE activity in vitro in a dose-dependent manner, and UTI significantly reduced in vitro CINC production by peritoneal macrophages stimulated with NE. CONCLUSION: UTI reduces the production of CINC by Kupffer cells stimulated with NE, attenuating ischemia/reperfusion injury of the liver.

Alanine Transaminase↗
PubMed2000

Molecular cloning and expression of a novel klotho-related protein.

Klotho protein is a novel beta-glucosidase-like protein produced predominantly in the kidney. The klotho mouse, which genetically lacks klotho gene expression, manifests various systemic phenotypes resembling aging. In the present study we succeeded in isolating a novel human protein structurally related to klotho protein. The protein possesses one beta-glucosidase-like domain and is 42% identical with klotho protein at the amino acid level. Unlike klotho protein, it possesses neither a signal sequence nor a transmembrane domain, suggesting that it is a cytosolic protein, and thus was termed cytosolic beta-glucosidase-like protein-1 (cBGL1). By Northern blot analysis cBGL1 mRNA was expressed most abundantly in the liver, followed by the small intestine, colon, spleen, and kidney. When klotho and cBGL1 gene expression was examined in renal cell carcinoma tissues, both klotho and cBGL1 mRNA levels in tumors were lower than those in nontumor regions, suggesting that renal epithelial cells may lose klotho and cBGL1 gene expression during the course of malignant transformation. In conclusion, we describe the primary structure and gene expression of a novel protein related to klotho protein.

Aged↗
PubMed2000

The congenital anastomoses between hepatic arteries: angiographic appearance.

The purpose of this study was to evaluate congenital anastomoses between hepatic arteries demonstrated on angiography in ten patients and to correlate the anastomosis with types of hepatic arterial anatomy. We evaluated the types of the hepatic arterial anatomy based on Michels' classification for 720 patients and compared the anatomic types between the patients with the anastomoses (ten patients) and without the anastomoses (710 patients). The diameter of the anastomoses ranged from 1.5 to 3.0 mm (mean, 2.4 mm). Five anastomoses were classified as tortuous type and five as straight type. Based on Michels' classification for types of hepatic arterial anatomy, eight (80%) of ten patients with the congenital anastomoses were classified as type III (replaced right hepatic artery from superior mesenteric artery). The remaining two patients were classified as type IV (replaced right hepatic artery from superior mesenteric artery and replaced left hepatic artery from left gastric artery) and type VIIIa (replaced right hepatic artery from superior mesenteric artery and accessory left hepatic artery from left gastric artery). Eight (16%) of 48 patients who were classified as type III have the anastomoses. In conclusion, the congenital anastomoses were observed especially in patients with replaced right hepatic artery from superior mesenteric artery.

Aged↗
PubMed2000

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients.

PURPOSE: [corrected] Capecitabine (Xeloda) is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumors. The purpose of this study was to demonstrate the preferential activation of capecitabine, after oral administration, in tumor in colorectal cancer patients, by the comparison of 5-FU concentrations in tumor tissues, healthy tissues and plasma. METHODS: Nineteen patients requiring surgical resection of primary tumor and/or liver metastases received 1,255 mg/m2 of capecitabine twice daily p.o. for 5-7 days prior to surgery. On the day of surgery, samples of tumor tissue, adjacent healthy tissue and blood samples were collected simultaneously from each patient, 2 to 12 h after the last dose of capecitabine had been administered. Concentrations of 5-FU in various tissues and plasma were determined by HPLC. The activities of the enzymes (CD, TP and DPD) involved in the formation and catabolism of 5-FU were measured in tissue homogenates, by catabolic assays. RESULTS: The ratio of 5-FU concentrations in tumor to adjacent healthy tissue (T/H) was used as the primary marker for the preferential activation of capecitabine in tumor. In primary colorectal tumors, the concentration of 5-FU was on average 3.2 times higher than in adjacent healthy tissue (P = 0.002). The mean liver metastasis/healthy tissue 5-FU concentration ratio was 1.4 (P = 0.49, not statistically different). The mean tissue/plasma 5-FU concentration ratios exceeded 20 for colorectal tumor and ranged from 8 to 10 for other tissues. CONCLUSIONS: The results demonstrated the preferential activation of capecitabine to 5-FU in colorectal tumor, after oral administration to patients. This is explained to a great extent by the activity of TP in colorectal tumor tissue, (the enzyme responsible for the conversion of 5'-DFUR to 5-FU), which is approximately four times that in adjacent healthy tissue. In the liver, TP activity is approximately equal in metastatic and healthy tissue, which explains the lack of preferential activation of capecitabine in these tissues.

Aged↗
PubMed2000

In vitro DNA fragmentation of mitochondrial DNA caused by single-stranded breakage related to macroplasmodial senescence of the true slime mold, Physarum polycephalum.

We found that mitochondrial DNA (mtDNA) isolated from Physarum polycephalum fragmented itself in weak ionic solutions. The mtDNA was dissolved in STE (saline Tris-EDTA: 150 mM NaCl, 10 mM Tris-HCl, 1 mM EDTA), TE (10 mM Tris-HCl, 1 mM EDTA) and DW, and then electrophoresed in an agarose gel. The intact 86-kbp mtDNA band was seen in STE, but several novel bands appeared in TE and DW. In TE, two discrete bands appeared at 6.7-kbp (alpha-band) and 5.0-kbp (beta-band), whereas at least 17 discrete bands were observed in distilled water (DW). These fragmentation patterns were not stoichiometric, as seen when using restriction endonucleases, but were clearly different from the degradation of DNA caused by a physical shearing force or a contaminating nuclease. In this paper, we characterize this in vitro fragmentation of mtDNA from P. polycephalum. We located 19 fragments, including the alpha and beta fragments, on a mtDNA restriction map, and demonstrated that these cleavage sites were S1 nuclease-sensitive regions, which are single-stranded DNA regions such as nicks and gaps in the mtDNA. The alpha and beta fragments are derived from the region encoding ribosomal RNAs (rRNAs) and the ATP synthase (atpA) gene, while the other 17 fragments are not derived from any specific region, but the cleavage sites are located throughout the mtDNA molecule. In P. polycephalum, it is well known that the growth rate of macroplasmodia decreases with aging. Equal amounts of mtDNA from juvenile and aged macroplasmodia were electrophoresed and the frequency of the beta fragment in each sample was measured. The ratio of the beta band to the total signal including background was estimated to be 3.3-4.0% in juvenile macroplasmodia, whereas it increased to 8.3-28.2% in aged macroplasmodia. This result suggests that the in vitro fragmentation of mtDNA is associated with macroplasmodial senescence. The single-stranded breakage of mtDNA of P. polycephalum may accumulate with age.

Aging↗
PubMed2000

Aberrant expression of neurotrophic factors in the ventricular progenitor cells of infant congenitally hydrocephalic rats.

OBJECTS: This study was conducted to investigate the roles of neurotrophic factors in the development of hydrocephalus in HTX rats. METHODS: Expressions of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and fibroblast growth factor (FGF)-1 were examined immunohistochemically in the cerebral cortex and ventricular zone of 6-day-old rats with congenital hydrocephalus (HTX rats). In the ventricular zone of hydrocephalic rats, potent BDNF-like immunoreactivity (-LI) and weak but significant signals for NT-3- and FGF-1-LIs were observed. However, no significant signals were detected in non-HTX rats. A small subpopulation of ventricular cells was positive for microtubule-associated protein 2 in HTX and non-HTX rats. The positive cells in the HTX rats had neurites much longer than those in the non-HTX animals, suggesting that some ventricular cells of the hydrocephalics had ectopically differentiated into mature neurons. CONCLUSIONS: This abnormal differentiation may have been responsible for the aberrant expressions of neurotrophic factors. In contrast, the cerebral neuronal layers did not show such prominent alterations in neurotrophic factor expression.

Animals↗