Search PubMed⌕ Search

Biomedical subjects

Jun Okuda

Publications and source records attributed to Jun Okuda.

At least 19 recordsLinked to original sources

Intracellular replication of Edwardsiella tarda in murine macrophage is dependent on the type III secretion system and induces an up-regulation of anti-apoptotic NF-kappaB target genes protecting the macrophage from staurosporine-induced apoptosis.

Edwardsiella tarda is a pathogen with a broad host range that infects both animals and humans. Resistance to phagocytic killing may be involved in the pathogenicity of this bacterium. Here we show that intracellular replication of E. tarda in murine macrophages is dependent on the type III secretion system and induces an anti-apoptotic effect by up-regulating anti-apoptotic NF-kappaB target genes. The wild-type strain replicates within the phagosomal membrane of macrophages; whereas the type III mutant does not. Microarray analysis shows the mRNA expression level of NF-kappaB target genes (e.g. pro-inflammatory cytokines and anti-apoptotic genes) in macrophages infected with the wild-type strain were up-regulated compared to macrophages infected with the type III mutant. Up-regulation of Bcl2a1a, Bcl2a1b, cIAP-2, and TRAF1 genes induced expression of anti-apoptotic proteins to protect macrophages from apoptosis induced by staurosporine. Further, this protection was inhibited by adding kamebakaurin, an inhibitor of NF-kappaB activation and was confirmed using an NF-kappaB reporter gene assay. Up-regulation of anti-apoptotic NF-kappaB target genes is responsible for the anti-apoptotic activity of E. tarda and is required for intracellular replication in murine macrophages.

Animals↗

Hafnocene catalysts for selective propylene oligomerization: efficient synthesis of 4-methyl-1-pentene by beta-methyl transfer.

A series of hafnocene complexes (eta5-C5Me4R1)(eta5-C5Me4R2)HfCl2 with [R1, R2] = [H, H] (1), [Me, H] (2), [Me, Me] (3), [Et, Me] (4), [(i)Pr, Me] (5), [SiMe(3), Me] (6), [(t)Bu, Me] (7), [(n)Bu, Me] (8), [(i)Bu, Me] (9), [Et, Et] (10), [(n)Bu, (n)Bu] (11), [(i)Bu, (i)Bu] (12) was tested as catalyst precursors for propylene oligomerization. Upon activation with methylaluminoxane or [Ph(3)C][B(C(6)F(5))(4)]/Al(i)Bu(3), complexes 2-4 and 8-12 catalyzed the dimerization of propylene to produce 4-methyl-1-pentene with selectivities ranging from 23.9 to 61.6 wt % in the product mixture. The selectivity was dependent on the nature of the substituents R(1) and R(2), with the highest value found for (eta5-C5Me4(i)Bu)2HfCl2 (12). Rapid deactivation was observed for 5-7, whereas (eta5-C5Me4H)2HfCl2 (1) polymerized propylene. 4-Methyl-1-pentene is proposed to form by repeated 1,2-insertion of propylene into the hafnocene methyl cation, followed by selective beta-methyl elimination. Detailed analysis of the byproduct distribution (isobutene, 1-pentene, 2-methyl-1-pentene, 2,4-dimethyl-1-pentene, 4-methyl-1-heptene, 4,6-dimethyl-1-heptene), determined by gas chromatography, was performed with the aid of a stochastic simulation involving rate constants for the propagation by insertion, beta-hydride elimination, and beta-methyl elimination. The rate of termination is dependent on the structure of the growing chain of the active species as well as on the bulkiness of the cyclopentadienyl ligands. The selectivity highly depends on the reaction conditions (pressure, temperature, concentration of methylaluminoxane). The rates of beta-methyl elimination leading to 4-methyl-1-pentene were proportional to propylene pressure for 2-4 and 8-10 but practically independent from propylene pressure for the sterically bulkier derivatives 11-12.

Journal Article↗

Synthesis, structure and hydrosilylation activity of neutral and cationic rare-earth metal silanolate complexes.

Rare-earth metal alkyl tri(tert-butoxy)silanolate complexes [Ln{mu,eta2-OSi(O(t)Bu)3}(CH2SiMe3)2]2 (Ln = Y (1), Tb (2), Lu (3)) were prepared via protonolysis of the appropriate tris(alkyl) complex [Ln(CH2SiMe3)3(thf)2] with tri(tert-butoxy)silanol in pentane. Crystal structure analysis revealed a dinuclear structure for with square pyramidal geometry at the yttrium centre. The silanolate ligand coordinates in an eta2-bridging coordination mode giving a 4-rung truncated ladder and non-crystallographic inversion centre. Addition of two equiv. of 12-crown-4 to a pentane solution of 1 or 3 respectively gave [Ln{OSi(O(t)Bu)(3)}(CH2SiMe3)2(12-crown-4)].12-crown-4 (Ln = Y (4), Lu (5)). Crystal structure analysis of 5 showed a slightly distorted octahedral geometry at the lutetium centre. The silanolate ligand adopts an eta(1)-terminal coordination mode, whilst the crown ether unit coordinates in an unusual kappa3-fashion. Reaction of 1-3 with [NEt3H]+[BPh4]- in thf yielded the cationic derivatives [Ln{OSi(O(t)Bu)3}(CH2SiMe3)(thf)4]+[BPh4]- (Ln = Y (6), Tb (7) and Lu (8)); coordination of crown ether led to compounds of the form [Ln{OSi(O(t)Bu)3}(CH2SiMe3)(L)(thf)n]+[BPh4]- (Ln = Y, Lu, L = 12-crown-4, n = 1 (9,10); Ln = Y, Lu, L = 15-crown-5, n = 0 (11,12)). Reaction of 1 with [NMe2PhH]+[B(C6F5)4]-, [Al(CH2SiMe3)3] or BPh3 in thf gave the ion pairs [Y{OSi(O(t)Bu)3}(CH2SiMe3)(thf)4]+[A]- ([A]- = [B(C6F5)4]- (13), [Al(CH2SiMe3)4]- (14), [BPh3(CH2SiMe3)]- (15)), whilst two equiv. [NMe2PhH]+[BPh4]- with 1 in thf produced the dicationic ion triple [Y{OSi(O(t)Bu)3}(thf)6]2+[BPh4]-2 (16). Crystal structure analysis revealed that 16 is mononuclear with pentagonal bipyramidal geometry at the yttrium centre. The silanolate ligand coordinates in an eta(1)-terminal fashion. All diamagnetic compounds have been characterized by NMR spectroscopy. 1, 3, 4, 6 and 13 were tested as olefin hydrosilylation pre-catalysts with a variety of substrates; 1 was found to be highly active in 1-decene hydrosilylation.

Journal Article↗

Cationic rare-earth metal trimethylsilylmethyl complexes supported by THF and 12-crown-4 ligands: synthesis and structural characterization.

To expand the limited range of rare-earth metal cationic alkyl complexes known, a series of mono- and dicationic trimethylsilylmethyl complexes supported by THF and 12-crown-4 ligands with [BPh4]-, [BPh3(CH2SiMe3)]-, [B(C6F5)4]-, [B(C6F5)3(CH2SiMe3)]-, and [Al(CH2SiMe3)4]- anions were prepared from corresponding neutral precursors [Ln(CH2SiMe3)3Ln] (Ln = Sc, Y, Lu; L = THF, n = 2 or 3; L = 12-crown-4, n = 1) as solvent-separated ion pairs. The syntheses of the monocationic derivatives [Ln(CH2SiMe3)2(12-crown-4)n(THF)m]+[A]- are all high yielding and proceed rapidly in THF solution at room temperature. A "one pot" procedure using the neutral species directly for the syntheses of a number of lutetium and yttrium dicationic derivatives [Ln(CH2SiMe3)(12-crown-4)n(THF)m]2+[A]-2 with a variety of different anions, a class of compounds previously limited to just a few examples, is presented. When BPh3 is used to generate the ion triple, the presence of 12-crown-4 is required for complete conversion. Addition of a second equiv of 12-crown-4 and a third equiv of [NMe2PhH]+[B(C6F5)4]- abstracts a third alkyl group from [Ln(CH2SiMe3)(12-crown-4)2(THF)x]2+[B(C6F5)4]-2 (Ln = Y, Lu). X-ray crystallography and variable-temperature (VT) NMR spectroscopy reveal a structural diversity within the known series of neutral 12-crown-4 supported tris(trimethylsilylmethyl) complexes [Ln(CH2SiMe3)3(12-crown-4)] (Ln = Sc, Y, Sm, Gd-Lu) in the solid and solution states. The X-ray structure of [Sc(CH2SiMe3)3(12-crown-4)] exhibits incomplete 12-crown-4 coordination. VT NMR spectroscopy indicates fluxional 12-crown-4 coordination on the NMR time scale. X-ray crystallography of only the second structurally characterized dicationic rare-earth metal alkyl complex [Y(CH2SiMe3)(12-crown-4)(THF)3]2+[BPh4]-2 shows exocyclic 12-crown-4 coordination at the 8-coordinate metal center with well separated counteranions. 11B and 19F NMR spectroscopy of all mono- and dicationic rare-earth metal complexes reported demonstrate that the anions are symmetrical and noncoordinating on the NMR time scale. A series of trends within the 1H and 13C{1H} NMR resonances arising from the Ln-CH2 groups and, in the case of yttrium, the 1JYC coupling constants at the Y-CH2 group and the 89Y chemical shift values are discussed.

Journal Article↗

Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses.

Shigella effectors injected into the host cell via the type III secretion system are involved in various aspects of infection. Here, we show that one of the effectors, IpaH9.8, plays a role in modulating inflammatory responses to Shigella infection. In murine lung infection model, DeltaipaH9.8 mutant caused more severe inflammatory responses with increased pro-inflammatory cytokine production levels than did wild-type Shigella, which resulted in a 30-fold decrease in bacterial colonization. Binding assays revealed that IpaH9.8 has a specific affinity to U2AF(35), a mammalian splicing factor, which interferes with U2AF(35)-dependent splicing as assayed for IgM pre-mRNA. Reducing the U2AF(35) level in HeLa cells and infecting HeLa cells with wild-type caused a decrease in the expression of the il-8, RANTES, GM-CSF, and il-1beta genes as examined by RT-PCR. The results indicate that IpaH9.8 plays a role in Shigella infection to optimize the host inflammatory responses, thus facilitating bacterial colonization within the host epithelial cells.

Animals↗

Aluminium alkyl complexes supported by [OSSO] type bisphenolato ligands: synthesis, characterization and living polymerization of rac-lactide.

Aluminium alkyl complexes [(OSSO)AlR](1-3: R = Me, Et) were isolated in good yields from the protonolysis reaction of AlR3 with the corresponding tetradentate 1,omega-dithiaalkanediyl-bridged bisphenols (1,4-dithiabutanediyl-bis(6-tert-butyl-4-methylphenol), etbmpH2; ortho-xylylenedithio-bis(6-tert-butyl-4-methylphenol), xytbmpH2). The monomeric structures of all three complexes were confirmed by X-ray diffraction studies. Complexes 1 and 2 have an isotypic packing arrangement. The aluminium center is coordinated by the etbmp ligand and one alkyl group with distorted trigonal bipyramidal geometry. Complex 3 shows Cs symmetry with square pyramidal geometry around the metal center. Substitution reaction of complex 1 with trityl alcohol gave the monomeric alkoxide complex [(etbmp)Al(OCPh3)] 4, which has a similar trigonal bipyramidal geometry around the aluminium atom as complex 1. In the presence of isopropanol, complexes 1-3 initiated the living ring-opening polymerization of rac-lactide (PDI = 1.03-1.06, Mw/Mn). The ligand structure influenced the tacticity of the obtained polymer, with complex 3 giving heterotactic-enriched polylactides.

Aluminum Compounds↗

Clinical implications of intermediate QRS prolongation in the absence of bundle-branch block in patients with ST-segment-elevation acute myocardial infarction.

BACKGROUND: In the reperfusion era the clinical characteristics of intermediate QRS prolongation without bundle-branch block (BBB) remain unclear in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 465 patients with STEMI within 24 h of onset were classified into 3 groups according to QRS duration on presenting electrocardiograms: 338 patients had QRS duration <100 ms (group N), 71 had QRS duration >or=100 ms without BBB (group W), and 56 had BBB (group B). The frequency of Killip class >1 was higher in group W (28%) than in group N (12%), but lower than in group B (47%) (p<0.05, respectively). The percentages of patients with non-anterior infarction (69% vs 42%, 47%), 3-vessel disease (30% vs 9%, 16%), and coronary artery bypass graft surgery (24% vs 4%, 13%) were higher in group W than in groups N and B (all p<0.05). In group W, 6-month-mortality was similar to that in group N, but lower than that in group B (4%, 3% vs 25%, p<0.05 respectively). CONCLUSIONS: In the reperfusion era, although patients with intermediate QRS prolongation without BBB have more severe coronary disease, 6-month-mortality is similar to those with normal conduction, but lower than those with BBB.

Adult↗

Intravascular ultrasound predictors of side branch occlusion in bifurcation lesions after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) of bifurcation lesion has been associated with a low success rate and a high incidence of procedural complications, including side branch occlusion and myocardial infarction. It remains controversial whether preintervention intravascular ultrasound (IVUS) findings can help to identify side branches likely to occlude after PCI of bifurcation lesions. METHODS AND RESULTS: From our IVUS database we identified 81 bifurcation lesions in 72 patients. Side branches were classified into 2 groups: group 1 had ostial side branch stenosis due to atherosclerotic plaque only in the main vessel (n=61), and group 2 had plaque truly involved in the side branch ostium (n=20). There was no significant difference between the 2 groups in the extent of ostial stenosis as assessed by angiography. After PCI, 7 side branches occluded in group 2, compared with 5 side branches occluded in group 1 (35% vs 8%, p=0.003). CONCLUSION: Ostial plaque distribution as assessed by IVUS may be one of the consistent predictors of side branch occlusion after PCI.

Aged↗

[Medical pots of Yakushi Buddha in Japan].

The origin of Yakushi buddha (Bhaisajyaguru in Sanscrit, buddha of healing) is not clearly known. It has been proposed the original statue of Yakushi buddha may have been conceived from Varna, a god in Brahminism, believed to be a god of justice who possessed medicines and prolonged life. It is believed that Yakushi buddha appeared in Japan when the buddhism was imported from Korea and China in VI century, Yakushi buddha was believed more profoundly in Japan, compared with Korea and China.The reasons are probably as follows: Yakushi buddha is buddha of healing, Emperor Temmu (672-685) built Yakushi-ji temple in Nara, Emperor Shomu (724-749) built Kokubun-ji temples at principal towns. The principal statues of buddha in these temples are Yakushi buddha. In Japan, there are 252 Yakushi Buddha statues in Buddhistical Temples, which are listed in Important Cultural Property including 14 National Treasures. Belief in Yakushi Buddha was especially prevalent from the 7th to the 13th centuries in Japan. The oldest wooden Yakushi Buddha statue is in the Horin-ji temple in Nara. Among the 252 Yakushi Buddha statues, 224 are in wood, 15 are in copper, 6 are in picture and etc. 212 (84,1%) have medicinal pots (or rarely, a bowl) on the palm of left hand. However, these medicinal containers are wooden blocks. Very recently, it was found that Yakushi Buddha statue in the Suho-Kokubun-ji temple (Yamaguchi Prefecture, Japan) has a medicinal pot on the palm of the left hand in which an offering (220 g materials) was found. The date on the reverse side of lid places the offering at October 12, 1699. The offering is composed of five cereals (rice, barley, wheat, soybean, adzuki bean), five medicinal plants (Acori Graminei, Acori Calami, Radix Ginseng, Flos Caryophylli, Lignum Santali Albi), and five minerals (rock crystals, purple and blue glasse, CaCO3, particles, silver and golden foils). DNA analysis proved those three randomly selected seeds of rice all belongs to the template japonica, which is predominant in the present variety of Japan.

Buddhism↗

[Preparation of a "chronological table of main diseases in Japanese history" for pharmacy students of the 6-year program].

A chronological table of the main diseases that have appeared throughout Japanese history was prepared for pharmacy students, especially for students of clinical pharmacy in the new 6-year system. In ancient times (even in the 8th century), smallpox and measles prevailed in Japan. Japanese people prayed to gods and Buddha to cure the sick. New infectious diseases, like ruebella, pest, typhoid fever, dysentery, cholera, leprosy, etc., prevailed with the increasing exchange of culture from foreign countries. After the vaccines and the toxides were prepared, these infectious diseases were gradually stamped out in Japan early in the Meiji Era. While, public nuisances like the Minamata disease (CH3HgCl), Itaiitai disease (Cd), and atmospheric pollution with sulfurous acid gas, drug-induced suffering (Thalidomide, Sumon, AIDS, etc.) and toxin contaminations in foods have recently increased and produced new diseases. However, these diseases can be prevented if the workers in factories and government officers keep in mind the medical ethics and the ethics for pharmacists to protect the health of people from diseases. Today, cancer, diseases of cerebral vessels, heart diseases, and pneumonia are the four most important causes of death related to aging.

Chronology as Topic↗

Hydrosilylation of dienes by yttrium hydrido complexes containing a linked amido-cyclopentadienyl ligand.

The dimeric hydrido complex [Y(L)(THF)(mu-H)](2)() containing the CH(2)SiMe(2)-linked amido-cyclopentadienyl ligand L = C(5)Me(4)CH(2)SiMe(2)NCMe(3)(2-) catalyzed the hydrosilylation of 1,5-hexadiene, 1,7-octadiene and vinylcyclohexene by PhSiH(3). As demonstrated for 1,7-octadiene, the product distribution of the hydrosilylation strongly depends on the molar ratio of the reagents. In the absence of PhSiH(3), the stoichiometric reaction of with 1,5-hexadiene gave the isolable crystalline cyclopentylmethyl complex [Y(L)[CH(2)CH(CH(2))(4)](THF)]. Internal olefins such as trans-stilbene and alkynes such as tert-butylacetylene were not hydrosilylated by. trans-Stilbene was inserted into the yttrium-hydride bond of to give the 1,2-diphenylethyl complex [Y(L)[CH(CH(2)Ph)Ph](THF)]. tert-Butylacetylene reacted with to give the dimeric acetylide [Y(L)(C[triple bond]CCMe(3))](2). In an attempt to detect the monomeric hydrido species as a DME adduct [Y(L)H(DME)], complex was reacted with DME to form the sparingly soluble, dimeric 2-methoxyethoxy complex [Y(L)(mu-OCH(2)CH(2)OMe-kappaO)](2) under C-O splitting.

Journal Article↗

Different clinical and coronary angiographic findings according to ratios of total cholesterol to high-density lipoprotein cholesterol during the acute phase of myocardial infarction.

OBJECTIVES: Several pathological studies have shown that a higher ratio of the serum total cholesterol concentration to the high-density lipoprotein cholesterol concentration (TC/HDL-C ratio) is associated with plaque rupture in patients with acute coronary syndromes. We examined the relationship between the serum total cholesterol concentration and the TC/HDL-C ratio, and clinical and angiographic findings in patients with first acute myocardial infarction. METHODS: Two hundred eighty patients were classified into quartiles according to the TC/HDL-C ratio measured within 24 hr from symptom onset: 70 patients in the first quartile (group L: mean TC/HDL-C ratio, 3.0), 140 in the second and third quartiles (group M: mean TC/HDL-C ratio, 4.6), and 70 in the fourth quartile (group H: mean TC/HDL-C ratio, 7.5). RESULTS: There were no differences among the three groups with regard to sex, diabetes mellitus or hypertension. Patients in group L were older (66 +/- 9 vs 60 +/- 11, 56 +/- 10 years, p < 0.01) and had a higher incidence of stable angina before acute myocardial infarction (26% vs 14%, 10%, p < 0.05) than in patients groups M and H. Although coronary angiograms revealed no difference in the number of diseased vessels among the three groups, extent index indicating the proportion of each coronary segment that appears angiographically abnormal was lowest in group L (0.7 +/- 0.5), followed by group M (1.3 +/- 0.6), and high- est in group H ( 1.7 +/- 0.6, p < 0.01). The number of segments with calcification and the incidence of calcification in the culprit lesion were higher in group L than in groups M and H. CONCLUSIONS: Our findings suggest that the clinical presentations and angiographic appearances differ according to the TC/HDL-C ratio in the acute phase of acute myocardial infarction.

Acute-Phase Reaction↗