Biomedical subjects

H Kido

Publications and source records attributed to H Kido.

At least 19 recordsLinked to original sources

PubMed2006

Sendai virus infection up-regulates trypsin I and matrix metalloproteinase-9, triggering viral multiplication and matrix degradation in rat lungs and lung L2 cells.

To elucidate the virus-host cell interaction, we analyzed quantitatively the expression of various cellular proteases and tumor necrosis factor-alpha (TNF-alpha) after Sendai virus infection in rat lungs and lung L2 cells. After infection, TNF-alpha mRNA levels increased rapidly to a peak on day one, and then trypsin I and matrix metalloproteinase (MMP)-9, but not MMP-2, were significantly up-regulated with a peak on day 2 in vivo. These up-regulations were confirmed in L2 cells. Up-regulation of proMMP-9 and its active convertase trypsin I seems to synergistically enhance virus multiplication and the destruction of lung matrix, resulting in the progression of pneumonia.

Animals↗

PubMed2005

Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy.

To assess the etiology of influenza-associated encephalopathy (IAE), a surveillance effort was conducted during 2000-2003 in South-West Japan. All fatal and handicapped patients except one (4/34 patients) exhibited a disorder of mitochondrial beta-oxidation evoked by the inactivated carnitine palmitoyltransferase II (CPT II) with transiently elevated serum acylcarnitine ratios (C(16:0) + C(18:1))/C(2) > 0.09 during high-grade fever. Analyses of genotypes and allele compositions of CPT II revealed a thermolabile phenotype of compound heterozygotes for [1055T > G/F352C] and [1102G > A/V368I], which shows a higher frequency in IAE patients than healthy volunteers (P < 0.025). The thermolabile phenotype of CPT II variations may be a principal genetic background of IAE in Japanese.

Adolescent↗

PubMed2002

A novel bioactive 31-amino acid ET-1 peptide stimulates eosinophil recruitment and increases the levels of eotaxin and IL-5.

OBJECTIVE AND DESIGN: Investigation of the role of a novel inflammatory mediator 31-amino acid endothelin-1 [ET-1 (1-31)], a major ET derivative in granulocytes, in eosinophil recruitment after its subcutaneous administration to mice. METHODS: Various ET-1 derivatives (100 pmol), with or without ET receptor antagonists (200 pmol), were administered subcutaneously to mice, and then the eosinophil migration into and chemokine levels in the injected loci were analyzed. RESULTS: ET-1 (1-31) and a 21-amino acid endothelin-1 (ET-1), but not big ET-1, induced eosinophil migration into the injected loci with a peak after administration for 12 h, and increased the levels of eotaxin and interleukin-5 with peaks at 6 and 24 h, respectively. These effects of ET-1(1-31) and ET-1 were significantly inhibited by an ETA receptor antagonist, BQ-123, but not by an ETB receptor antagonist, BQ-788. CONCLUSION: Novel bioactive ET-1 (1-31) induces local eosinophil migration, and increases in eotaxin and interleukin-5 through an ETA or ETA-like receptor.

Animals↗

PubMed2002

Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels.

The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release of pulmonary surfactant, against influenza-virus proliferation in the airway was investigated in mice. Ambroxol or the vehicle was administered intraperitoneally twice a day for 5-7 days to mice shortly after intranasal infection with a lethal dose of influenza A/Aichi/68 (H3N2) virus, and the survival rate, virus titre and levels of factors regulating virus proliferation in the airway fluid were analysed. Ambroxol significantly suppressed virus multiplication and improved the survival rate of mice. The effect of ambroxol reached a peak at 10 mg x kg(-1) x day(-1), higher doses being less effective. Ambroxol stimulated the release of suppressors of influenza-virus multiplication, such as pulmonary surfactant, mucus protease inhibitor, immunoglobulin (Ig)-A and IgG, although it stimulated the release of a trypsin-type protease that potentiates virus proliferation. In addition, ambroxol transiently suppressed release of the cytokines, tumour necrosis factor-alpha, interferon-gamma and interleukin-12, into airway fluid. Although ambroxol had several negative effects on the host defence system, overall it strikingly increased the concentrations of suppressors of influenza-virus multiplication in the airway.

Ambroxol↗

PubMed2001

Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs.

An effective method for determination of the levels of newly discovered 31-amino acid endothelins [ETs(1-31)] as well as big ETs and 21-amino acid ETs [ETs(1-21)], in human lungs has been developed. About 85% of ETs in human lung homogenates were recovered on acid extraction 8 times. Most of the published protocols for the determination of tissue ETs involve a reverse-phase minicolumn to separate proteins from peptides, after which the levels of ETs are directly determined by enzyme immunoassay. The levels determined, however, include fairly high amounts of non-bioactive ET metabolites in tissues and the data reported are diverse. We established an effective methods for the extraction and the separation of nine different muscle constricting ETs from their metabolites on a reverse-phase C18 column. Using this protocol, the levels of ETs in human lungs were determined by means of a sandwich-enzyme immunoassay specific for each ET derivative. The levels of ET-2(1-21) were the highest among those of ETs, and the levels of ETs(1-31) were in a similar range to those of big ETs but were lower than those of ETs(1-21). This method can be utilized to assess the pathophysiological roles of ETs(1-31) in various human organs.

Chromatography, High Pressure Liquid↗

PubMed2001

Cloning and expression of novel mosaic serine proteases with and without a transmembrane domain from human lung.

Two cDNAs encoding novel mosaic proteins with a serine protease domain and potential regulatory modules, consisting of a protein kinase substrate and a low-density lipoprotein receptor, were cloned from a human lung cDNA library by PCR. One with a transmembrane domain (MSPL) and the other without one (MSPS) comprise 581 and 537 amino acids, respectively. Except for the C-terminal ends, the two isoforms had an identical serine protease domain exhibiting 42, 39 and 43% identity with those of plasma kallikrein, hepsin and transmembrane protease serine 2, respectively. Both genes were predominantly expressed in human lung, placenta, pancreas and prostate.

Amino Acid Sequence↗

PubMed2001

Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.

BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

14-3-3 Proteins↗

PubMed2001

Assessment of air pollution in Nagasaki City: determination of polycyclic aromatic hydrocarbons and their nitrated derivatives, and some metals.

Air pollutants such as polycyclic aromatic hydrocarbons (PAHs), their nitrated derivatives (NPAHs), and some metals on airborne particles in Nagasaki city, Japan were determined over a period of 12 months by high-performance liquid chromatography with chemiluminescence, fluorescence and flameless atomic absorption spectrometry. The average concentrations (range) were 18.24 (4.07-41.54) ng/m3 for total PAHs, 0.91 (0.23-4.10) pg/m3 for NPAHs, 7.95 (1.71-16.31) ng/m3 for Pb, 11.56 (3.35-24.96) ng/m3 for Mn and 3.79 (0.97-14.71) ng/m3 for Ni (n = 136). The toxic equivalency factors adjusted concentration of total PAHs determined in Nagasaki city area was 2.33 ng/m3. Concentrations of total PAHs and NPAHs in winter were higher than those in summer. In a weekly variations study, total PAHs and NPAHs concentrations, as well as traffic volume showed a similar tendency with all values higher during weekdays and lower at the weekend. The correlation coefficients between total PAHs or NPAHs and traffic volume were 0.781 and 0.818, respectively. These results suggested that one of the main sources for NPAHs and PAHs in a city area might be motor vehicles.

Air Pollutants↗

PubMed2001

Reduction of white coat effect by cilnidipine in essential hypertension.

Stress elevates blood pressure (BP) by increased sympathetic nerve activity. Cilnidipine, a novel dihydropyridine calcium antagonist that has inhibitory actions on N-type as well as L-type voltage-dependent calcium channels, has been reported to attenuate the cold stress-induced increase in plasma norepinephrine and BP in rats. Because white coat effect is associated with an enhanced pressor response to mental stress, we postulated that cilnidipine would attenuate white coat effect in patients with essential hypertension. Sixty-one consecutive outpatients (50 men, 11 women) with essential hypertension were studied prospectively. Twenty-nine patients were treated with either cilnidipine (n = 15) or nifedipine, a representative L-type voltage-dependent calcium antagonist (n = 14). Gender, age, body mass index, duration of hypertension, target organ damage of hypertension, and BP and heart rate (HR) were not significantly different between cilnidipine and nifedipine groups, and both systolic (SBP) and diastolic BP (DBP) were significantly decreased after treatment in both groups. White coat effects on systolic and DBP and HR were not significantly different between groups before antihypertensive treatment. Cilnidipine, but not nifedipine, significantly reduced white coat effects on SBP and HR. Furthermore, white coat effects on systolic BP and HR were significantly lower after treatment in the cilnidipine group compared with the nifedipine group. These data suggest that cilnidipine may reduce white coat effect in hypertensive patients by N-type calcium channel antagonism.

Blood Pressure↗

PubMed2001

Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site.

BACKGROUND: Influenza virus RNA polymerase is a multifunctional enzyme that catalyses both transcription and replication of the RNA genome. The function of the influenza virus RNA polymerase PA subunit in viral replication is poorly understood, although the enzyme is known to be required for cRNA --> vRNA synthesis. The protease related activity of PA has been discussed ever since protease-inducing activity was demonstrated in transfection experiments. RESULTS: PA protein was highly purified from insect cells infected with the recombinant baculovirus carrying PA cDNA, and a novel chymotrypsin-type serine protease activity was identified with the synthetic peptide, Suc-LLVY-MCA, in the PA protein. [3H]DFP was crosslinked with PA and a mutational analysis revealed that serine624 was as an active site for the protease activity. CONCLUSIONS: These results constitute the demonstration of protease activity in PA subunit of the influenza virus RNA polymerase complexes.

Amino Acid Sequence↗

PubMed2001

Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus.

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. Here we report a protease present in the airway that, like tryptase Clara, can process influenza A virus haemagglutinin and Sendai virus envelope fusion glycoprotein. This protease was extracted from the membrane fraction of rat lungs, purified and then identified as a mini-plasmin. Mini-plasmin was distributed predominantly in the epithelial cells of the upward divisions of bronchioles and potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. In comparison with plasmin, its increased hydrophobicity, leading to its higher local concentrations on membranes, and decreased molecular mass may enable mini-plasmin to gain ready access to the cleavage sites of various haemagglutinins and fusion glycoproteins after expression of these viral proteins on the cell surface. These findings suggest that mini-plasmin in the airway may play a pivotal role in the spread of viruses and their pathogenicity.

Amino Acid Sequence↗

PubMed2001

New fabrication system for dental implant surgical stents: time-saving laboratory technique using a light-curing resin and transparent artificial teeth.

BACKGROUND: Surgical stents are a prerequisite for dental implant diagnosis. However, the traditional fabrication method including wax-up, investment, and resin polymerization is time consuming. PURPOSE: This article introduces a new fabrication system using a light-curing resin and transparent artificial teeth to reduce time spent in the laboratory. MATERIALS AND METHOD: The process of this system includes placing the light-curing resin and the artificial teeth on the partially edentulous dentition and alveolar ridge, making an appropriate pattern for the stent, light-curing for 5 minutes, briefly polishing, and making holes for titanium guide pins. RESULTS: This system requires only 30 to 40 minutes in the laboratory to complete a stent after mounting the casts on the articulator. Owing to the elasticity of the light-curing resin, this system eliminates the need for a blockout procedure on the undercuts of existing teeth on the casts, protects the casts from breakage, and provides the appropriate retention intraorally without any retainers. As well, titanium guide pins embedded in the stent were clearly identified by panoramic and computed tomographies. CONCLUSIONS: The new fabrication system proposed here can be time saving and, further, serve benefits for radiographic diagnosis.

Dental Implantation, Endosseous↗

PubMed2001

[Torasemide (LUPRAC): a review of its pharmacological and clinical profile].

Loop diuretics potently excrete water and electrolytes and therefore have been widely prescribed for the treatment of various kinds of edema for a long time. The potent diuretic action of loop diuretics, however, often causes hypokalemia, and therefore potassium sparing diuretics have also been supplied as a concomitant drug. Torasemide (LUPRAC), a novel diuretics, shows not only an effective loop diuretic action but also a potassium sparing action due to its anti-aldosteronergic effect. Torasemide also has a high bioavailability and is only slightly influenced by meals in humans. In addition, its pharmacodynamic features contribute to its stable diuretic action without any individual differences. In animal experiments, torasemide showed about a tenfold more potent diuretic action in comparison with furosemide, an authentic loop diuretic. On the one hand, the increase in the urinary potassium excretion by torasemide was relatively slight compared to the increase in urinary sodium excretion and, as a result, the urinary sodium to potassium (Na+/K+) ratio increased. The diuretic profile of torasemide was equal to that of the concomitant use of furosemide and an anti-aldosteronergic drug, spironolactone. Torasemide showed a significant efficacy and safety in comparison with furosemide in the patients with edema in both domestic and foreign clinical studies. Moreover, torasemide also showed a decreased rate of cardiac death in comparison to furosemide in patients with chronic heart failure in a large-scale clinical study (TORIC Study). The difference in cardiac death between these two diuretics has been suggested to depend on the anti-aldosteronergic effect of torasemide. In Japan, no new loop diuretics have been developed in over 10 years. Torasemide is therefore expected to be useful as an effective diuretic for diseases with edema.

Animals↗

PubMed2001

A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes.

Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca(2)(+) caused by ET-1(1-31) were significantly inhibited by BQ123, an ET(A) receptor antagonist, but not by BQ788, an ET(B) receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ET(A) or ET(A)-like receptor.

Calcium↗

PubMed2000

Hormonal control of mRNA expression of immunoglobulin binding factor in uterine cervix.

Uterine cervical mucus contains an immunoglobulin binding factor (IgBF). It may play a role in preventing antibody production against sperm in the female reproductive tract. To elucidate the mechanism involved in the production of activated IgBF, we determined the effects of hormones on the expression of mRNAs of IgBF and of protein disulfide isomerase (PDI), activating enzyme, in uterine cervix by quantitative RT-PCR. The uterine cervices of female rats were excised at preovulatory, ovulatory, and postovulatory phases. The human uterine cervical adenocarcinoma cells (TCO-2) were cultured for 24 h in serum-free medium containing 17beta-estradiol or progesterone. Expression of IgBF and PDI mRNAs was significantly highest during the ovulatory phase. 17beta-estradiol stimulated the expression of both mRNAs in TCO-2; whereas progesterone was ineffective. In conclusion, estrogen regulates the production of IgBF by the endocervix and PDI in vivo, thereby increasing the level of activated IgBF in the female reproductive tract during the ovulatory phase, allowing sperm to enter the uterine cavity.

Animals↗

PubMed2000

14-3-3tau associates with a translational control factor FKBP12-rapamycin-associated protein in T-cells after stimulation by pervanadate.

Proteins of the 14-3-3 family can associate with and/or modulate the activities of a variety of proteins, such as protooncogene and oncogene products, Cdc25 phosphatases and phosphatidylinositol 3-kinase, and thus are implicated in regulation of signaling pathways and the cell cycle. We report here that treatment of Jurkat T-cells with an inhibitor of protein tyrosine phosphatase, pervanadate, induces the association of 14-3-3tau with a translational control factor, FKBP12-rapamycin-associated protein (FRAP), with significant latter's autophosphorylation. Coimmunoprecipitation of various mutants of FRAP coexpressed with 14-3-3tau in COS-7 cells revealed that 14-3-3tau binds to the C-terminal side of FRAP at unknown site(s) different from the predicted binding motifs to date.

14-3-3 Proteins↗

PubMed2000

Chymase is a potent chemoattractant for human monocytes and neutrophils.

Chymase is a major chymotrypsin-like serine protease expressed in the secretory granules of mast cells in many mammalian species. In this study, we revealed the chemotactic activity of chymase for human mononuclear cells and neutrophils with a 48-well microchemotaxis chamber technique. Human chymase showed the potent chemotactic activity for monocytes and neutrophils dose-dependently in a concentration range from 0.1 to 10 microg/mL, corresponding to about 4-400 microM. The activity was as potent as that of N-formyl-methionyl-leucyl-phenylalanine. Chymase also stimulated cell migration of lymphocytes and purified T cells, but checkerboard analysis revealed that the effect was chemokinetic rather than chemotactic. Inhibition of chymase activities with chymase inhibitors, such as antileukoprotease and Bowman-Birk soybean trypsin inhibitor, significantly inhibited the chemotactic activity of chymase, suggesting that the proteolytic activity of chymase participates in the chemotactic activity. Our results suggest that mast cell chymase acts as a chemoattractant, and may play a role in the accumulation of inflammatory cells in development of the chronic inflammatory responses of allergic and nonallergic diseases.

Chemotactic Factors↗

PubMed2000

Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses. Purification and characterization.

A novel trypsin-type serine proteinase, which processes the precursors of the envelope fusion glycoproteins of pneumotropic Sendai and human influenza A viruses, was purified to homogeneity from pig lungs. On SDS/PAGE, the purified enzyme gave a protein band corresponding to about 32 kDa, and has an apparent molecular mass of 120 kDa, as determined by gel permeation chromatography. Immunohistochemical staining with antibodies against this enzyme revealed that the enzyme is located in pig lung mast cells. The N-terminal 44-amino-acid sequence of the enzyme exhibits about 80% identity with those of mast cell tryptases from other species. Of the inhibitors tested, di-isopropyl fluorophosphate, antipain, leupeptin, benzamidine and a few proteinaceous inhibitors, such as mucus protease inhibitor and aprotinin, inhibited this enzyme activity. Heparin stabilized the enzyme, but high-ionic-strength conditions did not, unlike for human mast cell tryptase. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and slowly processed hemagglutinin of human influenza A virus, and triggered the infectivity of Sendai virus in a dose-dependent manner, although human mast cell tryptase beta and rat mast cell tryptase (rat MCP-7) from lungs did not process these fusion glycoproteins at all. These results suggest that mast cell tryptase in pig lungs is the possible trigger of the pneumotropic virus infections.

Amino Acid Sequence↗