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Biomedical subjects

T Nagano

Publications and source records attributed to T Nagano.

At least 73 records · Page 4Linked to original sources
PubMed2000

Lactoferrin protects against UV-B irradiation-induced corneal epithelial damage in rats.

PURPOSE: Lactoferrin supplementation suppresses ultraviolet light B (UV-B)-induced oxidation of cultures of human corneal epithelial cells. To investigate the protective effect of lactoferrin containing eyedrops against UV-B-induced corneal damage in vivo, we examined lactoferrin efficacy in a rat UV-B keratitis model. METHODS: Sprague-Dawley rats were irradiated with >10 kJ/m2 after anesthetization, and then corneal epithelial defect was observed at 24 h postirradiation. The pre- or postapplication of vehicle or lactoferrin-containing eyedrops was performed, and then corneal epithelial damage was scored based on fluorescein staining. RESULTS: Posttreatment with lactoferrin did not inhibit the extent of corneal damage and did not affect wound healing. However, pretreatment by topical application of lactoferrin suppressed development of a corneal epithelial defect induced by UV-B irradiation in rats. CONCLUSION: These results suggest that the presence of lactoferrin in human tear fluid may inhibit UV-induced corneal epithelial damage.

Animals↗
PubMed2000

Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism.

Adrenomedullin, which was discovered as a vasodilating peptide, has been reported to be produced in various organs, in which adrenomedullin regulates not only vascular tone but also cell proliferation and differentiation in an autocrine/paracrine manner. We evaluated the effect of adrenomedullin on endothelial cell apoptosis. Human umbilical vein endothelial cells underwent apoptosis when cultured in serum-free medium. Treatment with adrenomedullin reduced the number of cells with pyknotic nuclei (Hoechst 33258 staining) and inhibited cell death (dimethylthiazol-diphenyltetrazolium bromide assay) in a dose-dependent manner. The administration of adrenomedullin did not alter the expression levels of Bcl-2 family proteins. Experiments with analogs of cAMP or a cAMP-elevating agonist demonstrated that elevation of the intracellular cAMP concentration does not mediate the antiapoptotic effect of adrenomedullin. The coadministration of N-nitro-L-arginine methyl ester (2 mmol/L), an inhibitor of nitric oxide synthase, abrogated the effect of adrenomedullin. Lower doses of sodium nitroprusside (1 to 10 micromol/L), a nitric oxide donor, mimicked the antiapoptotic effect of adrenomedullin. The antiapoptotic effect of sodium nitroprusside was not attenuated by the inhibition of soluble guanylyl cyclase with 1 micromol/L oxadiazolo-quinoxalin-1-one nor could apoptosis be inhibited by the incubation of human umbilical vein endothelial cells with 1 mmol/L 8-bromo-cGMP, a cell-permeant cGMP analog. These results indicate that adrenomedullin and nitric oxide inhibit endothelial cell apoptosis via a cGMP-independent mechanism.

Adrenomedullin↗
PubMed2000

Effects of Dai-kenchu-to on levels of 5-hydroxytryptamine (serotonin) and vasoactive intestinal peptides in human plasma.

We examined the effects of Dai-kenchu-to (DKCT) on the levels of vasoactive intestinal peptide (VIP) and 5-hydroxytryptamine (serotonin; 5-HT) in plasma taken from 6 healthy subjects. A single oral administration of 7.5 g DKCT caused significant increases in plasma VIP at 30, 60 to 90 and 120 min (3.5-5.5 pg/ml), compared with the response in a placebo group (about 1.0 pg/ml). DKCT also caused significant increases in plasma 5-HT at 30 (121.8+/-7.3 ng/ml) and 60 (156.5+/-8.0 ng/ml) min, compared with the response in the placebo group (about 101 ng/ml). These results indicate that the stimulatory effect of DKCT on VIP-immunoreactive substance (VIP-IS) secretion is due, at least in part, to increased 5-HT levels in the abdomen. As a consequence, increased VIP-IS may improve feelings of coldness in the abdomen.

Adult↗
PubMed2000

Superoxide dismutase activity of iron(II)TPEN complex and its derivatives.

Superoxide is involved in the pathogenesis of various diseases, such as inflammation, ischemia-reperfusion injury and carcinogenesis. Superoxide dismutases (SODs) catalyze the disproportionation reaction of superoxide to produce oxygen and hydrogen peroxide, and can protect living cells against the toxicity of free radicals derived from oxygen. Thus, SODs and their functional mimics have potential value as pharmaceuticals. We have previously reported that Fe(II)tetrakis-N,N,N',N'-(2-pyridylmethyl)ethylenediamine (Fe(II)TPEN) has an excellent SOD activity (IC50 = 0.5 microM) among many iron complexes examined (J. Biol. Chem., 264, 9243-9249 (1989)). Fe(II)TPEN can act like native SOD in living cells, and protect Escherichia coli cells from free radical toxicity caused by paraquat. In order to develop more effective SOD functional mimics, we synthesized Fe(II)TPEN derivatives with electron-donating or electron-withdrawing groups at the 4-position of all pyridines of TPEN, and measured the SOD activities and the redox potentials of these complexes. Fe(II) tetrakis-N,N,N',N'-(4-methoxy-2-pyridylmethyl)ethylenediamine (Fe(II)(4MeO)4TPEN) had the highest SOD activity (IC50 = 0.1 microM) among these iron-based SOD mimics. In addition, a good correlation was found between the redox potential and the SOD activity of 15 Fe(II) complexes, including iron-based SOD mimics reported in the previous paper (J. Organometal. Chem., in press). Iron-based SOD mimics may be clinically applicable, because these complexes are generally tissue-permeable and show low toxicity. Therefore our findings should be significant for the development of clinically useful SOD mimics.

Ethylenediamines↗
PubMed2000

Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine.

The superoxide dismutase (SOD) activity of iron(II) tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 microM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 10(6) M-1 S-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 10(5) M-1 S-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN-superoxide complex.

Antioxidants↗
PubMed2000

High expression of the second lysine decarboxylase gene, ldc, in Escherichia coli WC196 due to the recognition of the stop codon (TAG), at a position which corresponds to the 33th amino acid residue of sigma38, as a serine residue by the amber suppressor, supD.

Escherichia coli WC196, which was obtained from the strain W3110 by nitrosoguanidine mutagenesis as an overproducer of lysine, produced approximately twenty times more cadaverine than did W3110, and had a twenty fold higher level of rpoS gene product, sigma38, than in W3110. Both WC196 and W3110 had a stop codon (TAG) in rpoS at position which corresponds to the 33th residue of sigma38 protein. In addition, WC196 but not W3110 had a mutation in the gene encoding Ser-tRNA (SerU), called, supD. Analysis of the amino acid sequence of a sigma38 preparation from WC196 showed that the 33th residue of sigma38 is a serine residue. The deltarpoS deltacadA mutant of E. coli W3110 harboring the plasmid containing rpoS, in which the TAG codon was converted to a TCG codon for serine-33 residue of sigma38, expressed a significant amount of Ldc and accumulated a large amount of sigma38. However, the deltarpoS deltacadA mutant of W3110 with the plasmid containing the intact rpoS from W3110 could synthesize neither sigma38 nor Ldc significantly.

Amino Acid Sequence↗
PubMed2000

[Giant osteoma of the temporal bone with otitis media: a case study].

A 71-year-old female presented with a giant osteoma of the right temporal bone and otitis media. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the giant osteoma. An operation was performed to alleviate the difficult-to-treat otitis media and to address the related cosmetic problem. During the operation, three-dimensional CT (3D-CT) was very helpful in understanding the relationship between the tumor and the peripheral structures. Removal of the tumor improved the patient's otitis media. Osteoma of the temporal bone is rare. Only twenty-one cases of mastoid osteoma have been reported in Japan. In the present study, we review osteomas of the temporal bone and discuss their management.

Aged↗
PubMed2000

[Malignant pheochromocytoma with remarkable response to CVD chemotherapy--a case report].

A 60-year-old man was admitted to our hospital with the chief complaint of a left upper abdominal mass. 131I-MIBG scintiscan revealed a left upper abdominal mass, and the patient's serum catecholamine level was very high. Our diagnosis was pheochromocytoma of the left adrenal gland. On Oct. 19, 1995, a left nephrectomy and adrenectomy were performed. The serum catecholamine level then decreased and blood pressure was normalized. Two years later, it became difficult to control the patient's hypertension, and multiple metastatic liver cancer was found by an abdominal CT scan. The diagnosis of malignant pheochromocytoma was confirmed by the accumulation of 131I-MIBG in the liver. We started CVD chemotherapy. After 10 cycles of this chemotherapy, the serum catecholamine level was almost normalized and the metastatic liver cancer was reduced to one-third in size.

Adrenal Gland Neoplasms↗
PubMed2000

ICTS, an interventional cardiology training system.

In this article, we present an Interventional Cardiology Training System developed by the Medical Application Group at Mitsubishi Electric in collaboration with the Center for Innovative Minimally Invasive Therapy. The core of the ICTS is a computer simulation of interventional cardiology catheterization. This simulation integrates clinical expertise, research in learning, and technical innovations to create a realistic simulated environment. The goal of this training system is to augment the training of new cardiology fellows as well as to introduce cardiologists to new devices and procedures. To achieve this goal, both the technical components and the educational content of the ICTS bring new and unique features: a simulated fluoroscope, a physics model of a catheter, a haptic interface, a fluid flow simulation combined with a hemodynamic model and a learning system integrated in a user interface. The simulator is currently able to generate--in real-time--high quality x-ray images from a 3D anatomical model of the thorax, including a beating heart and animated lungs. The heart and lung motion is controlled by the hemodynamic model, which also computes blood pressure and EKG. The blood flow is then calculated according to the blood pressure and blood vessel characteristics. Any vascular tool, such as a catheter, guide wire or angioplasty balloon can be represented and accurately deformed by the flexible tool physics model. The haptics device controls the tool and provides appropriate feedback when contact with a vessel wall is detected. When the catheter is in place, a contrast agent can be injected into the coronary arteries; blood and contrast mixing is computed and a visual representation of the angiogram is displayed by the x-ray renderer. By bringing key advances in the area of medical simulation--with the real-time x-ray renderer for instance--and by integrating in a single system both high quality simulation and learning tools, the ICTS opens new perspectives for computer based training systems.

Angioplasty, Balloon, Coronary↗
PubMed1999

Potential role of hepatocyte growth factor, a novel angiogenic growth factor, in peripheral arterial disease: downregulation of HGF in response to hypoxia in vascular cells.

BACKGROUND: Although hepatocyte growth factor (HGF), a novel angiogenic growth factor, plays an important role in angiogenesis, regulation of local HGF production under hypoxia has not yet been clarified in vascular smooth muscle cells (VSMC) and endothelial cells (EC). Thus, we have studied the role of HGF in hypoxia-induced endothelial injury and the regulation of local vascular HGF expression in response to hypoxia. METHODS AND RESULTS: HGF attenuated hypoxia-induced endothelial cell death. Importantly, hypoxic treatment of EC resulted in a significant decrease in local HGF production according to the severity of hypoxia and increased VEGF. Similarly, hypoxia significantly decreased in mRNA and protein of HGF and increased VEGF production in VSMC. In organ culture system, local HGF production was also significantly decreased by hypoxia (P<0.01). Downregulation of HGF by hypoxia is due to a significant decrease in cAMP, as hypoxic treatment decreased cAMP, a stimulator of HGF. Although active TGF-beta, a suppressor of HGF, was increased at 72 hours after hypoxic treatment, treatment of anti-TGF-beta antibody did not attenuate decreased HGF production. Finally, rHGF was intra-arterially administered into unilateral hind limb ischemia rabbits, to evaluate in vivo angiogenic activity. Of importance, a single intra-arterial administration of rHGF reduced severe necrosis due to ischemia in rabbit muscle, accompanied by a significant increase in angiographic score (P<0.01). CONCLUSIONS: Overall, these data demonstrated that hypoxic treatment of vascular cells significantly downregulated HGF production due to decreased cAMP, suggesting their potential roles in the pathophysiology of ischemic diseases. Moreover, administration of rHGF induced therapeutic angiogenesis, accompanied by improvement of necrotic changes in the ischemic hind limb model, as cytokine supplement therapy for peripheral arterial disease.

Animals↗
PubMed1999

Fluorescent Indicators for Imaging Nitric Oxide Production.

The membrane-permeating indicator DAF-FM DA is transformed by intracellular esterases into the highly water-soluble dye DAF-FM, which traps NO produced by NO synthase (NOS) to yield a highly fluorescent triazole compound in cells (see schematic diagram). Monitoring with a fluorescence microscope should allow direct identification of intracellular production and location of NO.

Journal Article↗
PubMed1999

Positive and negative regulation of the human heme oxygenase-1 gene expression in cultured cells.

To elucidate the regulation of the human heme oxygenase-1 (hHO-1) gene expression, we assessed approximately 4 kb of the 5'-flanking region of the hHO-1 gene for basal promoter activity and sequenced approximately 2 kb of the 5'-flanking region. A series of deletion mutants of the 5'-flanking region linked to the luciferase gene was constructed. Basal level expression of these constructs was tested in HepG2 human hepatoma cells and HeLa cervical cancer cells. By measuring luciferase activity, which was transiently expressed in the transfected cells, we found a positive regulatory region at position -1976 to -1655 bp. This region functions in HepG2 cells but not in HeLa cells. A negative regulatory region was also found at position -981 to -412 bp that functions in both HepG2 cells and HeLa cells.

5' Untranslated Regions↗
PubMed1999

Inhibition of E. coli growth by fullerene derivatives and inhibition mechanism.

Cationic ammonium fullerene derivatives (C60-bis(N, N-dimethylpyrrolidinium iodide) and C60-bis(N-methylpiperazinium iodide)) suppressed E. coli growth, whereas an anionic derivative (C60-dimalonic acid) did not. Both cationic derivatives inhibited E. coli dioxygen consumption. Inhibition of energy metabolism is concluded to be a mechanism of the growth inhibition effect of fullerene derivatives.

Anti-Bacterial Agents↗
PubMed1999

Novel Fluorescent Probes for Singlet Oxygen.

The first fluorescent chemical traps for (1)O(2) have been developed. DPAXs react specifically with (1)O(2) to yield the corresponding endoperoxides, DPAX-EPs (see scheme; X = H, Cl, F). DPAXs scarcely fluoresce, while DPAX-EPs are strongly fluorescent. Since the fluorescence of these probes is unaffected by H(2)O(2), superoxide, and nitric oxide, they are useful for the selective detection of (1)O(2) in biological systems.

Journal Article↗
PubMed1999

Imaging of caspase-3 activation in HeLa cells stimulated with etoposide using a novel fluorescent probe.

Microscopic visualization of intracellular enzyme activity can provide information about the physiological role of the enzyme. Caspases are cysteine proteases that have critical roles in the execution of apoptosis. General fluorometric substrates of caspase-3, such as DEVD-MCA, are unsuitable for imaging because they are excited at short wavelength, so we designed and synthesized novel fluorescent probes that are excited at suitable wavelengths for detecting caspase-3 activity in living cells. Using one of these probes, we succeeded in microscopic visualization of caspase-3-like activity within HeLa cells treated with etoposide. The caspase-3-like activity was increased in the cytosol at first, then expanded to the whole cell.

Apoptosis↗
PubMed1999

Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney.

BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of </=10(-10) mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10(-10) mol/L: -10.3+/-0. 6% versus 11.2+/-1.5%, R versus S; P<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10(-10) mol/L: 10.7+/-0.7 versus 3.1+/-0.4 fmol/min per gram of kidney, R versus S; P<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced diabetic rats and diet-induced hypercholesterolemic rats. Expression of endothelial NO synthase decreased in S rats but not in diabetic or hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was decreased in all 3 disease models compared with that in the vascular smooth muscle cell. CONCLUSIONS: These results suggest that impaired NO release in response to stimulation of ETBR is due, at least in part, to a decrease in endothelial ETBR and may play a role in vascular dysfunction usually associated with arteriosclerosis-related diseases.

Animals↗