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Biomedical subjects

Tomoko Suzuki

Publications and source records attributed to Tomoko Suzuki.

At least 19 recordsLinked to original sources
PubMed2006

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Prime-boost immunization with DNA followed by a recombinant vaccinia virus expressing P50 induced protective immunity against Babesia gibsoni infection in dogs.

A heterologous prime-boost immunization regime with priming DNA followed by recombinant vaccinia virus expressing relevant antigens has been shown to induce effective immune responses against several infectious pathogens. In this study, we constructed a recombinant plasmid and vaccinia virus, both of which expressed P50 of Babesia gibsoni, to investigate the immunogenicity and protective efficacy of a heterologous prime-boost immunization against canine babesiosis. The dogs immunized with the prime-boost regime developed a significantly high level of specific antibody against P50 when compared with the control groups, and the antibody level was strongly increased after a booster immunization with a recombinant vaccinia virus. The prime-boost immunization regime induced a specific IgG2 antibody response and IFN-gamma production in dogs. Two weeks after the booster immunization with a recombinant vaccinia virus expressing P50, the dogs were challenged with B. gibsoni patasites. The dogs immunized with the prime-boost regime showed partial protection, manifested as a significantly low level of parasitemia and a 2-day delay of the peak parasitemia. These results indicated that such a heterologous prime-boost immunization approach might be useful against B. gibsoni infection in dogs.

Animals↗
PubMed2006

A homologue of the 3-oxoacyl-(acyl carrier protein) synthase III gene located in the glycosylation island of Pseudomonas syringae pv. tabaci regulates virulence factors via N-acyl homoserine lactone and fatty acid synthesis.

Pseudomonas syringae pv. tabaci 6605 possesses a genetic region involved in flagellin glycosylation. This region is composed of three open reading frames: orf1, orf2, and orf3. Our previous study revealed that orf1 and orf2 encode glycosyltransferases; on the other hand, orf3 has no role in posttranslational modification of flagellin. Although the function of Orf3 remained unclear, an orf3 deletion mutant (Deltaorf3 mutant) had reduced virulence on tobacco plants. Orf3 shows significant homology to a 3-oxoacyl-(acyl carrier protein) synthase III in the fatty acid elongation cycle. The Deltaorf3 mutant had a significantly reduced ability to form acyl homoserine lactones (AHLs), which are quorum-sensing molecules, suggesting that Orf3 is required for AHL synthesis. In comparison with the wild-type strain, swarming motility, biosurfactant production, and tolerance to H2O2 and antibiotics were enhanced in the Deltaorf3 mutant. A scanning electron micrograph of inoculated bacteria on the tobacco leaf surface revealed that there is little extracellular polymeric substance matrix surrounding the cells in the Deltaorf3 mutant. The phenotypes of the Deltaorf3 mutant and an AHL synthesis (DeltapsyI) mutant were similar, although the mutant-specific characteristics were more extreme in the Deltaorf3 mutant. The swarming motility of the Deltaorf3 mutant was greater than that of the DeltapsyI mutant. This was attributed to the synergistic effects of the overproduction of biosurfactants and/or alternative fatty acid metabolism in the Deltaorf3 mutant. Furthermore, the amounts of iron and biosurfactant seem to be involved in biofilm development under quorum-sensing regulation in P. syringae pv. tabaci 6605.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed2006

Arsenite induces apoptosis in hepatocytes through an enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy.

To investigate the effects of arsenite on cell proliferation and the signal transduction in hapatocytes in vivo, rats received a single injection of sodium arsenite immediately after partial hepatectomy. Characteristic DNA fragmentation was observed at 4h after the arsenite-injection in partially hepatectomized liver, while it was not detected either in the control (partial hepatectomy only) or arsenite-injected normal (without partial hepatectomy) liver. The effect of the arsenite-injection on the activation of extracellular signal-regulated kinase (ERK) was not observed in the normal or the partially hepatectomized liver. The activity of p38 mitogen-activated protein kinase (MAPK) markedly increased after 15min to 2h after the arsenite-injection in partially hepatectomized liver while no or a less increase was observed in the arsenite-injected normal or the control, respectively. The Jun N-terminal kinase (JNK) was activated to a maximal level, about six-fold the maximum of the control, at 15min after the injection with partial hepatectomy. The arsenite-injection markedly increased the phosphorylated forms of c-Jun and ATF-2 and the protein levels of c-Jun, p53 and p21(WAF1/CIP1) in the partially hepatectomized liver. These results suggested that arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy and the p53-dependent p21(WAF1/CIP1) protein expression.

Animals↗
PubMed2006

Enhancement of antibacterial activity of beta-lactam antibiotics by [P2W18O62]6-, [SiMo12O40]4-, and [PTi2W10O40]7- against methicillin-resistant and vancomycin-resistant Staphylococcus aureus.

The enhancement of antibacterial activity of beta-lactam antibiotics by polyoxometalates against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) was investigated by using K6[P2W18O62] . 14H2O (P2W18), K4[SiMo12O40] . 3H2O (SiMo12), and K7[PTi2W10O40] . 6H2O (PTi2W10). Susceptibility test by a beta-lactam-disk method showed the synergistic effect of the polyoxometalates in combination with oxacillin against both MRSA and VRSA. Energy dispersive X-ray analysis of the strain treated with P2W18 revealed localization of the polyoxometalate-tungsten atoms at the periphery of the cell, and the biological reduction of P2W18 and SiMo12 proceeded within both cells of MRSA and VRSA as far as they keep alive. These results indicate that the polyoxometalates can penetrate through the cell wall consisting of peptidoglycan layers and reach cytoplasmic membrane. The inhibitory effect of the polyoxometalates on both mecA- and pbp-induced mRNA expression of both MRSA and VRSA cells, verified by the RT-PCR-electrophoresis analysis, is observed, and the mechanism of the synergistic effect by the polyoxometalates is discussed in terms of the depression of penicillin-binding protein 2' (PBP2') coded by mecA gene.

Anti-Bacterial Agents↗
PubMed2006

Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer.

PURPOSE: To investigate the efficacy and safety of nitroglycerin plus vinorelbine and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell lung cancer (NSCLC) as the experimental arm for the next phase III trial. PATIENTS AND METHODS: One hundred twenty patients with stage IIIB/IV NSCLC were randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5 days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four cycles in a double-blind and controlled trial. Primary efficacy end points were the best confirmed response rate and time to disease progression (TTP). RESULTS: The response rate in arm A (72%; 43 of 60 patients) was significantly higher than that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm A was longer than that in arm B (327 v 185 days). No severe adverse effect was recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of 60 patients) was significantly higher than that in arm B (2%; one of 60 patients; P < .001, chi(2) test). CONCLUSION: Use of nitroglycerin combined with vinorelbine and cisplatin may improve overall response and TTP in patients with stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III trial.

Adult↗
PubMed2006

Tyrosine phosphatase SHP-2 regulates IL-1 signaling in fibroblasts through focal adhesions.

Interleukin-1beta (IL-1beta) mediates destruction of matrix collagens in diverse inflammatory diseases including arthritis, periodontitis, and pulmonary fibrosis by activating fibroblasts, cells that interact with matrix proteins through integrin-based adhesions. In vitro, IL-1beta signaling is modulated by focal adhesions, supramolecular protein complexes that are enriched with tyrosine kinases and phosphatases. We assessed the importance of tyrosine phosphatases in regulating cell-matrix interactions and IL-1beta signaling. In human gingival fibroblasts plated on fibronectin, IL-1beta enhanced the maturation of focal adhesions as defined by morphology and enrichment with paxillin and alpha-actinin. IL-1beta also induced activation of ERK and recruitment of phospho-ERK to focal complexes/adhesions. Treatment with the potent tyrosine phosphatase inhibitor pervanadate, in the absence of IL-1beta, recapitulated many of these responses indicating the importance of tyrosine phosphatases. Immunoblotting of collagen bead-associated complexes revealed that the tyrosine phosphatase, SHP-2, was also enriched in focal complexes/adhesions. Depletion of SHP-2 by siRNA or by homologous recombination markedly altered IL-1beta-induced ERK activation and maturation of focal adhesions. IL-1beta-induced tyrosine phosphorylation of SHP-2 on residue Y542 promoted focal adhesion maturation. Association of Gab1 with SHP-2 in focal adhesions correlated temporally with activation of ERK and was abrogated in cells expressing mutant (Y542F) SHP-2. We conclude that IL-1beta mediated maturation of focal adhesions is dependent on tyrosine phosphorylation of SHP-2 at Y542, leading to recruitment of Gab1, a process that may influence the downstream activation of ERK.

Actinin↗
PubMed2006

Interaction of non-adherent suspended neutrophils to complement opsonized pathogens: a new assay using optical traps.

Phagocytosis of opsonized pathogens by circulating non-adherent neutrophils is an essential step in host defense, which when overwhelmed contributes to sepsis. To investigate the role played by ligation of complement receptors CR3 and CR4 in non-adherent neutrophils, we designed a novel assay system utilizing dual optical traps, respectively, holding a suspended unactivated cell and presenting a specific ligand-coated bead to the cell surface. We chose anti-CD18 as an example ligand, mimicking the bacterial opsonizing complement fragment iC3b. Presentation of anti-CD18-coated beads elicited both pseudopodial protrusion and subsequent phagocytosis. This is in sharp contrast to previously reported responses of adherent neutrophils, which phagocytize opsonized particles without pseudopod formation. We used this same new assay to probe actomyosin pathways in the neutrophil's pseudopodial and phagocytic response. Disruption of actin or inhibition of myosin light-chain kinase dose-dependently reduced pseudopod formation and phagocytosis rates. In summary, i) the new dual trap assay can be used to study the responses of suspended neutrophils to a variety of ligands, and ii) in a first application of this technique, we found that local ligation of CR3/4 in unactivated neutrophils in suspension induces pseudopod formation and phagocytosis at that site, and that these events occur via an actomyosin-dependent pathway.

Adult↗
PubMed2006

Neonatal myocardial infarction due to thrombotic occlusion.

Neonatal myocardial infarction is rare and its prognosis is poor. We describe the clinical course and autopsy findings of a newborn female with myocardial infarction. Her clinical course was rapidly progressive, becoming fatal before we could detect the cause. Autopsy demonstrated significant occlusion of the left coronary artery as well as evidence of new infarction, suggesting that the event occurred at birth. This case illustrates myocardial infarction as a possible cause of early neonatal death.

Autopsy↗
PubMed2006

Identification of glycosylation genes and glycosylated amino acids of flagellin in Pseudomonas syringae pv. tabaci.

A glycosylation island is a genetic region required for glycosylation. The glycosylation island of flagellin in Pseudomonas syringae pv. tabaci 6605 consists of three orfs: orf1, orf2 and orf3. Orf1 and orf2 encode putative glycosyltransferases, and their deletion mutants, Deltaorf1 and Deltaorf2, exhibit deficient flagellin glycosylation or produce partially glycosylated flagellin respectively. Digestion of glycosylated flagellin from wild-type bacteria and non-glycosylated flagellin from Deltaorf1 mutant using aspartic N-peptidase and subsequent HPLC analysis revealed candidate glycosylated amino acids. By generation of site-directed Ser/Ala-substituted mutants, all glycosylated amino acid residues were identified at positions 143, 164, 176, 183, 193 and 201. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) analysis revealed that each glycan was about 540 Da. While all glycosylation-defective mutants retained swimming ability, swarming ability was reduced in the Deltaorf1, Deltaorf2 and Ser/Ala-substituted mutants. All glycosylation mutants were also found to be impaired in the ability to adhere to a polystyrene surface and in the ability to cause disease in tobacco. Based on the predicted tertiary structure of flagellin, S176 and S183 are expected to be located on most external surface of the flagellum. Thus the effect of Ala-substitution of these serines is stronger than that of other serines. These results suggest that glycosylation of flagellin in P. syringae pv. tabaci 6605 is required for bacterial virulence. It is also possible that glycosylation of flagellin may mask elicitor function of flagellin molecule.

Amino Acid Sequence↗
PubMed2006

Skewed Th1 responses caused by excessive expression of Txk, a member of the Tec family of tyrosine kinases, in patients with Behcet's disease.

Behcet's disease (BD) is characterized by recurrent attacks of uveitis, oral aphtha, genital ulcers and skin lesions. The etiology and pathogenesis of BD are largely unknown. It has been reported that excessive Th1 cell function is involved in the pathogenesis of BD. Previously, we found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell-specific transcription factor that is involved in the effector function of Th1 cells. Thus, we studied Th1 cytokine production and Txk expression of T-lymphocytes in patients with BD. Peripheral blood lymphocytes produced excessive Th1-associated cytokines including interferon-gamma (IFN-gamma) and interleukin (IL)-12 in patients with BD. Circulating CD3+ and purified CD4+ T cells expressed excessive Txk protein. The extent of IFN-gamma production by the lymphocytes correlated with the expression of Txk protein in the immunoblotting analysis. The majority of cells infiltrating into the skin lesions of patients with BD expressed IFN-gamma. IL-12 and IL-18 were found in the mononuclear cell aggregates in the skin and intestinal lesions of those with BD. Lymphocytes accumulating in the skin and intestinal lesions expressed higher levels of Txk as compared with other Th2-associated diseases. IFN-gamma, IL-18 and IL-12 detected in skin lesions may induce preferential development of Th1 cells in patients with BD. Collectively, Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with BD. This review may serve as a reminder of the importance of excessive Th1 cell function in the pathogenesis of BD and may contribute to the discovery of new molecular targets for the development of a specific therapeutic strategy for BD.

Behcet Syndrome↗
PubMed2006

[Features of emotional voices: focus in differences between expression and recognition].

This study investigated the relationship between expressed emotions through voices and emotions judged from the voices. In Study 1, to prove the judgment of emotions in speech, 21 participants evaluated emotions expressed by an actress. The average accuracy rate was 67.6%. Some emotions are more likely to be interpreted incorrectly than other emotions. The similarities of emotional categories caused some misjudgments. In Study 2, verifying the universality of judgment, 25 participants judged emotions expressed by 23 speakers. The average accuracy rate was 48.6%. Similar to the result of the study 1, there were some misjudgments on specific emotions; between sadness and relax, joy and relax, fear and sadness, and surprise and anger. To prove the role of acoustic cues, we examined the similarities of physical features in emotions using speech-analysis. Some emotions have similarities of vocal features and some have similarities of emotional categories. In conclusion, this study suggests that the similarities of vocal features and emotional categories lead to the judgments of emotions.

Emotions↗
PubMed2006

Beneficial effect of erythropoietin administration on murine infection with Trypanosoma congolense.

The effect of erythropoietin treatment on Trypanosoma congolense infection in mice was studied. Survival rates of mice were dramatically improved by treatment with recombinant human erythropoietin (r-hu-EPO; 5,000 U/kg) when infected with 1,000 cells of T. congolense IL3000 (P < 0.05). All the untreated mice infected with T. congolense IL3000 died by day 9 of infection; however, 100%, 50%, and 25% of the mice treated with r-hu-EPO for 8 days survived to day 20, day 40, and day 60 of the parasitical infection, respectively. Anti-8-hydroxy-2'-deoxyguanosine antibody, a biomarker for oxidative damage of DNA, yielded positive reactions in the cytoplasm of the parasites recovered from the mice treated with r-hu-EPO. These results, taken together, indicate that erythropoietin administration is effective for the treatment of T. congolense infection.

Anemia↗
PubMed2005

Substitution of the N-glycan function in glycosyltransferases by specific amino acids: ST3Gal-V as a model enzyme.

The sialyltranferase ST3Gal-V transfers a sialic acid to lactosylceramide. We investigated the role of each of the N-glycans modifying mouse ST3Gal-V (mST3Gal-V) by measuring the in vitro enzyme activity of Chinese hamster ovary (CHO) cells transfected with ST3Gal-V cDNA or its mutants. By examining mutants of mST3Gal-V, in which each asparagine was replaced with glutamine (N180Q, N224Q, N334Q), we determined that all three sites are N-glycosylated and that each N-glycan is required for enzyme activity. Despite their importance, N-glycosylation sites in ST3Gal-V are not conserved among species. Therefore, we considered whether the function in the activity that is performed in mST3Gal-V by the N-glycan could be substituted for by specific amino acid residues selected from the ST3Gal-V of other species or from related sialyltransferases (ST3Gal-I, -II, -III, and -IV), placed at or near the glycosylation sites. To this end, we constructed a series of interspecies mutants for mST3Gal-V, specifically, mST3Gal-V-H177D-N180S (medaka or tetraodon type), mST3Gal-V-N224K (human type), and mST3Gal-V-T336Q (zebrafish type). The ST3Gal-V activity of these mutants was quite similar to that of the wild-type enzyme. Thus, we have demonstrated here that the N-glycans on mST3Gal-V are required for activity but can be substituted for specific amino acid residues placed at or near the glycosylation sites. We named this method SUNGA (substitution of N-glycan functions in glycosyltransferases by specific amino acids). Furthermore, we verified that the ST3Gal-V mutant created using the SUNGA method maintains its high activity when expressed in Escherichia coli thereby establishing the usefulness of the SUNGA method in exploring the function of N-glycans in vivo.

Amino Acid Sequence↗
PubMed2005

Manganese-induced apoptosis in hepatocytes after partial hepatectomy.

To investigate the apoptosis induced by manganese (Mn) in hepatocytes in vivo, rats received a single injection of manganese chloride immediately after partial hepatectomy. Characteristic DNA fragmentation was observed at 4 h after partial hepatectomy with Mn-injection. The activation of caspase-3 by Mn-injection was detected as early as 30 min and peaked at 1 h after partial hepatectomy. The activity of Jun N-terminal kinase (JNK) increased to a maximal level, which was about 10-fold the maximal level of the control, at 15 min after partial hepatectomy and this increase was maintained for 4 h in Mn-injected rats, while a transient increase was observed at 1 h in the control. No effect of the Mn-injection on the activation of p38 mitogen-activated protein kinase (MAPK) was observed. Western blot analysis revealed that the injection of Mn markedly increased c-Jun and phosphorylated c-Jun protein levels at 1 h after partial hepatectomy. An increase in p53 was also observed at 30 min after the Mn-injection and followed by the upregulation of p21(WAF1/CIP1) protein expression at 2 h after partial hepatectomy. These results suggested that the activation of JNK and the upregulation of c-Jun, p53 and p21(WAF1/CIP1) were involved in the apoptosis of hepatocytes induced by partial hepatectomy with manganese.

Animals↗