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Biomedical subjects

Toshio Tanaka

Publications and source records attributed to Toshio Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2005

All-trans-retinoic acid inhibits the development of mesangial proliferative glomerulonephritis in interleukin-6 transgenic mice.

All-trans-retinoic acid (ATRA), a vitamin A derivative, was reported to suppress the interleukin-6 (IL-6) production and to downregulate the IL-6 receptor (IL-6R) and/or its signal transducer glycoprotein 130. We investigated the in vivo antinephritic effect of ATRA on IL-6 transgenic mice which had developed mesangial proliferative glomerulonephritis (PGN) as well as its in vitro inhibitory effect on the proliferation of rat mesangial cells. In vivo experiments on IL-6 transgenic mice showed that ATRA administration suppressed proteinuria and hematuria and reduced the IL-6 concentrations; furthermore, histological examination demonstrated that it improved PGN. In vitro experiments using rat mesangial cells demonstrated that ATRA inhibited cell growth in a dose-dependent manner within a range from 10(-4) to 10(-6) M. This inhibition by ATRA was partially counteracted by the addition of IL-6. RT-PCR assay results showed that ATRA also reduced IL-6R, but not the glycoprotein 130 expression in mesangial cells. These findings indicate that, by blocking of the IL-6 function, ATRA may be therapeutically effective in PGN.

Animals↗
PubMed2005

Fulminant myocarditis demonstrating uncommon morphology--a report of two autopsy cases.

Two autopsy cases of fulminant myocarditis demonstrating uncommon morphology were studied. Subjects included two male patients: a 42-year-old (case 1) and a 39-year-old (case 2). Both cases had fever, chest or epigastric pain, electrocardiographic abnormalities, prominent elevation of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase and creatine phosphokinase. They were treated with intra-aortic balloon pumping and percutaneous cardiopulmonary support, and they died at 3 days and 4 days after admission (total course of 10 days and 9 days), respectively. Case 1 showed focal necrosis, severe myocardial dystrophic calcification positive for Kossa stain, inflammatory edema, lymphocyte and macrophage infiltration and extravasation of erythrocytes. Case 2 showed acute inflammation and severe myocardial necrosis with neutrophilic abscess, lymphocyte and macrophage infiltration, cell debris and purulent exudate. Calcified, degenerative and necrotic cardiac myocytes and macrophages were reacted with anti-Enterovirus antibody (clone 5-D8/1), which recognizes an epitope on the VP1 peptide of most Coxsackievirus, echovirus, poliovirus and enterovirus strains. Therefore, the present two cases may be compatible with fulminant enterovirus-associated myocarditis. Using reverse transcriptase-semi-nested polymerase chain reaction, picornaviral RNA was detected in the amplified products extracted from the paraffin-embedded myocardial sample of case 1 but not in case 2.

Adult↗
PubMed2005

Flocculating activity of cross-linked poly-gamma-glutamic acid against bentonite and Escherichia coli suspension pretreated with FeCl3 and its interaction with Fe3+.

Cross-linked poly-gamma-glutamic acid (C-L gamma-PGA) at 5 microg/ml flocculated bentonite suspension pretreated with polyaluminum chloride (PAC) at 2 microg/ml Al3+-PAC to a transparency of approximately 30% after 30 min and more than 90% after 4 h, while Al3+ concentration in the upper phase of the suspension decreased with incubation time. When pretreated with FeCl3 at 16 microg/ml Fe3+-FeCl3, similar results were obtained. In the case of Escherichia coli suspension, the combination of C-L gamma-PGA and FeCl3 demonstrated a more marked flocculating activity with a satisfactory transparency occurring after 30 min of treatment, accompanied by a decrease in residual Fe3+ concentration. In the above two suspensions pretreated with FeCl3, small visible floats appeared in the early stage of incubation. These floats were found to be due to the direct interaction between FeCl3 and C-L gamma-PGA, indicating the formation of a water-insoluble complex. After allowing the suspension to stand for a long time, elemental analysis and inductively coupled plasma spectroscopy of the precipitates produced suggested that not only the complex was formed due to the interaction between Fe3+ in FeCl3 and COO- in the C-L gamma-PGA molecule, but also Fe2O3 and Fe(OH)3 might be entrapped in this complex. This could be applied to scavenge metal ions including Fe3+ from polluted water.

Bentonite↗
PubMed2005

Biosynthesis of poly-gamma-glutamic acid in plants: transient expression of poly-gamma-glutamate synthetase complex in tobacco leaves.

Transient expression of genes coding for the poly-gamma-glutamate (gammaPGA) synthetase system (pgs) was investigated in tobacco plants. Three genes of the pgs, pgsA, pgsB and pgsC, were separately placed under the control of the CaMV 35S promoter and introduced into tobacco leaves via Agrobacterium infection. Synthesized gammaPGA in plant tissues was detected immunologically with mouse anti-gammaPGA antiserum which specifically reacts with gammaPGA on a nitrocellulose membrane. Confirmation of gammaPGA biosynthesis in the transient expression analysis in tobacco tissue indicates that subunits of pgs complex were expressed and reassembled in a functional form.

Genes, Plant↗
PubMed2005

Improved production of isoamyl acetate by a sake yeast mutant resistant to an isoprenoid analog and its dependence on alcohol acetyltransferase activity, but not on isoamyl alcohol production.

1-Farnesylpyridinium (FPy), an analog of isoprenoid farnesol, strongly inhibited the growth of sake yeast at 120 microM in YPD medium, whereas at 30 microM it reduced cellular production of isoamyl acetate to 20% of the control level despite the absence of inhibitory effect on CO2 evolution. The FPy-resistant mutant A1 was characterized by the high production of flavor compounds represented by a nearly threefold increase in the level of isoamyl acetate in YPD medium in which the level of isoamyl alcohol as its precursor remained almost unchanged. The FPy resistance phenotype of strain A1 was not accompanied by cellular resistance to either the L-leucine analog or L-canavanine, which alters yeast amino acid metabolism in favor of isoamyl alcohol production. Alcohol acetyltransferase (AATase) activity was high in strain A1, which further increased in response to isoamyl alcohol accumulation in medium. Flavor compound production in sake brewing could be improved using strain A1, resulting in a 1.4-fold increase in isoamyl acetate production in spite of a limited production of isoamyl alcohol.

Cell Proliferation↗
PubMed2005

Physicochemical properties of cross-linked poly-gamma-glutamic acid and its flocculating activity against kaolin suspension.

Cross-linked poly-gamma-glutamic acid (C-L gamma-PGA) was prepared with gamma-PGA irradiated with gamma-ray at various kGy values. The physicochemical properties including viscosity and water absorption capacity were compared between C-L gamma-PGA and several typical flocculating agents. The viscosity of C-L gamma-PGA increased with the dose of gamma-irradiation, although the water absorption capacity of C-L gamma-PGA did not, which showed a maximum of 1005.6 ml/g at 20 kGy. Flocculating activity against kaolin suspension was not observed for any of the test compounds when used singly. However, the activity of C-L gamma-PGA markedly increased following the addition of polyaluminum chloride. The activity increased with temperature up to 80 degrees C and remained at 80 degrees C of heat pretreatment for 1 h, but did not at more than 50 degrees C of heat pretreatment for 24 h. The activity was also observed within a pH range of 4.5-10.0. Both the water absorption capacity and flocculating activity of C-L gamma-PGA decreased in parallel with increasing NaCl concentration, suggesting that the flocculating activity of C-L gamma-PGA was associated with its water absorption capacity, rather than viscosity. An investigation of the effects of various cations on the flocculating activity of C-L gamma-PGA showed that only trivalent cations had a synergistic effect. The mechanism of C-L gamma-PGA flocculating activity is discussed based on the results of preliminary experiments.

Adsorption↗
PubMed2005

Proposals for wastewater treatment by applying flocculating activity of cross-linked poly-gamma-glutamic acid.

Cross-linked poly-gamma-glutamic acid (C-L gamma-PGA) markedly purified polluted water collected from rivers and ponds by flocculation and precipitation. This effect of C-L gamma-PGA occasionally required pretreatment with polyaluminum chloride (PAC). Components of polluted water in rivers or ponds are generally thought to be clay minerals, microorganisms and chemical compounds. In this study, the flocculating activities of C-L gamma-PGA against suspensions of bentonite, diatomaceous earth, Escherichia coli and Mycrocystis aeruginosa, and against solutions of crystal violet and bisphenol A were investigated. The mode of action of C-L gamma-PGA is thought to be based on electrostatic interaction between flocculants, C-L gamma-PGA and PAC, and the surface of polluted water components, which may lead to neutralization of the zeta-potential of those components.

Bacillus subtilis↗
PubMed2004

An unusual case of thrombocytosis associated with concurrent cytomegalovirus and respiratory syncytial virus infection in an immunocompetent infant: possible roles of thrombopoietin and interleukin-6.

This is the case study of concurrent cytomegalovirus and respiratory syncytial virus infection in an infant who showed thrombocytosis, liver dysfunction and bronchiolitis. The combination of thrombocytosis with this co-infection is causally related to elevated levels of thrombopoietin and interleukin-6. This study represents the first such case ever recorded.

Antibodies, Viral↗
PubMed2004

Potential role for heat shock protein 72 in antagonizing cerebral vasospasm after rat subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm can be defined as delayed-onset narrowing of the cerebral arteries that can occur after a spontaneous aneurysmal subarachnoid hemorrhage (SAH). Despite a large number of experimental and clinical investigations, the exact pathophysiology of vasospasm remains unknown. Using a fluorescence differential-display system, we have identified the gene encoding heat shock protein 72 (HSP72) as being highly upregulated by cerebral vasospasm. We therefore elucidated the role of the HSP72 gene in cerebral vasospasm in a rat experimental SAH model. METHODS AND RESULTS: By angiography, cerebral vasospasm was detected from day 1, with maximal narrowing detected on day 2. Intracisternal injection of antisense HSP72 oligodeoxynucleotide led to specific inhibition of HSP72 gene expression and significantly aggravated cerebral vasospasm on days 2 and 3 of the angiographic studies. Oral administration of geranylgeranylacetone (GGA), an antiulcer drug, enhanced HSP72 induction and reduced cerebral vasospasm. CONCLUSIONS: These results suggest HSP72 plays a novel role in antagonizing delayed cerebral vasospasm after SAH and that GGA provides protective effects against delayed cerebral vasospasm, at least partly via induction of HSP72.

Administration, Oral↗
PubMed2004

Upregulation of the transcript level of GTPase activating protein KIAA0603 in T cells from patients with atopic dermatitis.

We have analyzed transcription profiles in peripheral blood CD3(+) cells from patients with allergic diseases to better understand the genes that are involved. Transcription levels of the gene KIAA0603/AS160 in CD3(+) cells from patients with atopic dermatitis (AD) were significantly higher than in normal individuals. The KIAA0603 gene encodes a 1299 amino acid protein with two phosphotyrosine interaction domains at the N-terminal region and a TBC domain at the C-terminal region. The region containing the TBC domain has a 31% homology to human rab6 GTPase activating protein (GAP). When human primary CD3(+) cells were stimulated with anti-CD3 or calcium ionophore, the KIAA0603 transcript level was upregulated. The marked upregulation of KIAA0607 was accompanied by activation induced cell death of primary CD3+ cells. KIAA0603 is likely to be a Rab GAP that participates in the regulation of activated T cells, especially helper memory T cells. Expression of KIAA0603 in T cells may be involved in pathogenesis of AD.

Base Sequence↗
PubMed2004

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.

BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.

Animals↗
PubMed2004

TTV infection in children born to mothers infected with TTV but not with HBV, HCV, or HIV.

The TT virus (TTV) was isolated recently from the serum of a patient with post-transfusion hepatitis. TTV infection is widespread in the general population, and its prevalence increases continuously with age. The pathogenic role of TTV in liver disease remains controversial, and the source of transmission is still unclear. We investigated the pathogenicity and epidemiology of TTV infection in infants born to TTV DNA-positive mothers. Enrolled in this study were 22 mother-child pairs testing negative for antibodies to hepatitis B, hepatitis C, and the human immunodeficiency viruses (HIVs). The children were followed for 30 months after birth. Serum TTV DNA was detected by N22-PCR, and the PCR products were cloned and sequenced. The prevalence of TTV infection in children increased with age. Of the 22 children, 13 (59%) became positive for TTV DNA during the follow-up period. Of these 13 children, 6 (46%) had elevated levels of serum alanine aminotransferase (ALT), although the elevations were transient and mild. TTV viremia was not associated significantly with the abnormal ALT levels. Children with TTV viremia developed neither severe liver disease nor fulminant hepatitis. Phylogenetic analysis showed that, in 11 (85%) of the 13 pairs, the mother and child had the same genotype at the first PCR-positive time point. Among those 11 mother-child pairs, 6 (55%) had identical TTV nucleotide sequences. However, the genotype of predominant clones changed in 5 (50%) of 10 children who were positive for TTV DNA at two or more time points during the follow-up period. In conclusion, this study did not provide evidence that TTV infection is related to liver disease in children. Although the main source of TTV infection in children is presumed to be their mothers, transmitted via non-parenteral routes in the course of daily contact, intrafamilial carriers may also be sources of TTV infection.

Adult↗
PubMed2004

Changes in cyclic nucleotide phosphodiesterase activity and calmodulin concentration in heart muscle of cardiomyopathic hamsters.

Cyclic nucleotides (cAMP and cGMP) phosphodiesterase (PDE) activities and expression are altered in the cardiac muscle of cardiomyopathic heart failure, and PDE inhibitors improve the abnormal muscle condition through changing the cyclic nucleotide concentration. These observations prompted us to investigate the role of calmodulin (CaM) in the regulation of cyclic nucleotide PDE activities, and moreover to study the modulation of the PDE isozymes in heart failure, using cardiac muscles of cardiomyopathic hamster. The CaM concentrations in the heart muscle of the normal control and cardiomyopathic hamsters (each of three to four hamsters) varied with cell fraction and with the age of the animal. The CaM concentrations in the soluble fraction obtained from cardiomyopathic hamster tissue were significantly increased at 25 and 32 weeks of age (2.02 +/- 0.62 microg/mg protein (mean +/- S.E.), and 3.21 +/- 0.95) compared with that obtained from the control (0.60 +/- 0.04) or cardiomyopathic (0.95 +/- 0.12) hamsters at 8 weeks of age. The solubilized PDE isolated from the hamster heart muscle (three or four hamsters in each age) by column chromatography on diethylaminoethyl (DEAE)-cellulose revealed three peaks of activity, which may correspond to the isozymes of PDE classified recently, namely PDE I, II, and III. These three peaks of activity, particularly peak III, seen in the soluble fraction of cardiomyopathic hamster heart declined in proportion to the age of the animal compared with that of the control hamster heart. In the cGMP-PDE assay system, the concentration of CaM inhibitor W-7 required for 50% inhibition (IC(50)) of PDE I, II, and III peak activities was 140, 29, and 46 microM, respectively, suggesting that PDE II is more sensitive to W-7. These results suggest that alteration in these isozyme activities accompanied with changes of CaM concentration may influence the cardiac muscle contractility in cardiomyopathic hamster via changes of cyclic nucleotide concentration.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Oxidative stress-dependent inhibition of yeast cell growth by farnesylamine and its possible relation to amine oxidase in the mitochondrial fraction.

Among various analogs of the isoprenoid farnesol (FOH), farnesylamine (FNH2) inhibited the growth of the budding yeast Saccharomyces cerevisiae by accelerating cellular reactive oxygen species (ROS) generation. Unlike the case with FOH, however, FNH2 did not cause mitochondrial transmembrane potential (mtDeltaPsi) hyperpolarization so that FNH2-treated cells were not protected against ROS production by inhibiting the proton pumping function of mitochondrial F(O)F1-ATPase. FNH2 promoted ROS generation even in cells of a respiration-deficient mutant, indicating a yeast metabolic pathway other than mitochondrial electron transport as the origin of ROS. FNH2 oxidase activity was detected in the yeast mitochondrial fraction, which produces hydrogen peroxide (H2O2) in the reaction with either FNH2 or geranylgeranylamine (GGNH2), in addition to polyamine oxidase activity specific for spermine. GGNH2 also exhibited the growth inhibitory effect with the accompanying induction of ROS generation, while such an activity was not detected with any of the polyamines tested or geranylamine. FNH2 oxidase, which was sensitive to a typical copper-chelating agent, diethyldithiocarbamic acid (DDC), could be solubilized with Triton X-100, and detected as a single band upon activity staining with FNH2 but not with spermine in polyacrylamide gel electrophoresis. FNH2-treated cells were partly protected against ROS production by the additional supplementation of DDC in the medium. Our results suggest the involvement of H2O2 production due to direct oxidation of FNH2 by copper amine oxidase in oxidative stress-dependent inhibition of yeast cell growth.

Journal Article↗
PubMed2004

Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines.

The aim of this study was to investigate whether the suppressor of cytokine signalling (SOCS)-1 can act as a tumour suppressor when functioning as a negative regulator of the Janus family tyrosine kinases (JAKs), which have been reported to play important roles in leukaemogenesis. For this purpose, we carried out molecular analysis of the SOCS-1 gene in human acute myeloid leukaemia (AML) and human haematopoietic cell lines. Sequencing alterations in the coding region were found in two of 90 primary AML samples and one of 17 cell lines. Hypermethylation of the SOCS-1 gene was also observed in 72% of primary cases and 52% of cell lines and aberrant methylation strongly correlated with reduced expression. Transfection of SOCS-1 into Jurkat cells harbouring the mutation and methylation suppressed cell growth at a low serum concentration. These findings indicate that SOCS-1 is frequently silenced in haematopoietic malignancies, mainly as a result of hypermethylation, and suggest that SOCS-1 may be able to function as a tumour suppressor.

Acute Disease↗
PubMed2004

Screening for microtubule-disrupting antifungal agents by using a mitotic-arrest mutant of Aspergillus nidulans and novel action of phenylalanine derivatives accompanying tubulin loss.

The microtubule, which is one of the major targets of anthelmintics, anticancer drugs, and fungicides, is composed mainly of alpha- and beta-tubulins. We focused on a unique characteristic of an Aspergillus nidulans benA33 mutant to screen for microtubule-disrupting antifungal agents. This mutant, which has a beta-tubulin with a mutation of a single amino acid, undergoes mitotic arrest due to the formation of hyperstable microtubules at 37 degrees C. The heat sensitivity of the mutant is remedied by some antimicrotubule agents. We found that an agar plate assay with the mutant was able to distinguish three types of microtubule inhibitors. The growth recovery zones of the mutant were formed around paper disks containing microtubule inhibitors, including four benzimidazoles, ansamitocin P-3, griseofulvin, and rhizoxin, on the agar plate at 37 degrees C. Nocodazole, thiabendazole, and griseofulvin reversed the mitotic arrest of the mutant and promoted its hyphal growth. Ansamitocin P-3 and rhizoxin showed growth recovery zones around the growth-inhibitory zones. Benomyl and carbendazim also reversed mitotic arrest but produced weaker growth recovery than the aforementioned drugs. Other microtubule inhibitors, such as colchicine, Colcemid, paclitaxel, podophyllotoxin, TN-16, vinblastine, and vincristine, as well as some cytoskeletal inhibitors tested, did not show such activity. In our screening, we newly identified two mycotoxins, citrinin and patulin, two sesquiterpene dialdehydes, polygodial and warburganal, and four phenylalanine derivatives, arphamenine A, L-2,5-dihydrophenylalanine (DHPA), N-tosyl-L-phenylalanine chloromethylketone, and N-carbobenzoxy-L-phenylalanine chloromethyl ketone. In a wild-type strain of A. nidulans, DHPA caused selective losses of microtubules, as determined by fluorescence microscopy, and of both alpha- and beta-tubulins, as determined by Western blot analysis. This screening method involving the benA33 mutant of A. nidulans is useful, convenient, and highly selective. The phenylalanine derivatives tested are of a novel type of microtubule-disrupting antifungal agents, producing an accompanying loss of tubulins, and are different from well-known tubulin inhibitors affecting the assembly of tubulin dimers into microtubules.

Adenine↗
PubMed2004

Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisiae.

UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. C9-UK-2A, which has been prepared to improve the duration of the antifungal activity of UK-2A, shows durable fungicidal activities against various species of fungi and induces both membrane injury and the generation of cellular reactive oxygen species (ROS) against Rhodotorula mucilaginosa IFO 0001 cells. We found that C9-UK-2A inhibited the vegetative growth of Saccharomyces cerevisiae IFO 0203 cells accompanying cellular ROS generation in Sabouraud dextrose (SD) medium, which contained a fermentable carbon source. The ROS generation was completely restricted by pretreatment with a lipophilic antioxidant alpha-tocopherol. In addition, the pretreatment with the antioxidant protected against the growth inhibition induced by C9-UK-2A. C9-UK-2A also induced ROS generation in isolated mitochondria of the S. cerevisiae cells. The addition of both a complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated mitochondria. The addition of the inhibitors of complex III, AA or myxothiazol, or of complex IV, KCN, did not reduce ROS generation. These results suggest that C9-UK-2A induces ROS generation due to the blockade of electron flow at complex III, thereby inhibiting the growth of S. cerevisiae in SD medium.

Lactones↗