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Biomedical subjects

Tomoko Suzuki

Publications and source records attributed to Tomoko Suzuki.

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

Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.

Apoptosis of distal lung epithelial cells plays a pivotal role in the pathogenesis of acute lung injury. In this context, proteinases, either circulating or leukocyte-derived, may contribute to epithelial apoptosis and lung injury. We hypothesized that apoptosis of lung epithelial cells induced by leukocyte elastase is mediated via the proteinase activated receptor (PAR)-1. Leukocyte elastase, thrombin, and PAR-1-activating peptide, but not the control peptide, induced apoptosis in human airway and alveolar epithelial cells as assessed by increases in cytoplasmic histone-associated DNA fragments and TUNEL staining. These effects were largely prevented by a specific PAR-1 antagonist and by short interfering RNA directed against PAR-1. To ascertain the mechanism of epithelial apoptosis, we determined that PAR-1AP, thrombin, and leukocyte elastase dissipated mitochondrial membrane potential, induced translocation of cytochrome c to the cytosol, enhanced cleavage of caspase-9 and caspase-3, and led to JNK activation and Akt inhibition. In concert, these observations provide strong evidence that leukocyte elastase mediates apoptosis of human lung epithelial cells through PAR-1-dependent modulation of the intrinsic apoptotic pathway via alterations in mitochondrial permeability and by modulation of JNK and Akt.

Apoptosis↗
PubMed2005

Erythromycin increases bactericidal activity of surface liquid in human airway epithelial cells.

Macrolide antibiotics have clinical benefits in patients with diffuse panbronchiolitis and in patients with cystic fibrosis. Although many mechanisms have been proposed, the precise mechanisms are still uncertain. We examined the effects of erythromycin on bactericidal activity of airway surface liquid secreted by cultured human tracheal epithelial cells. Airway surface liquid was collected by washing the surface of human tracheal epithelial cells with a sodium solution (40 meq/l). Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were incubated with airway surface liquid, and the number of surviving bacteria was examined. The number of bacteria in airway surface liquid from the cells cultured in medium alone was significantly lower than that in the sodium solution. Furthermore, the number of bacteria in airway surface liquid from the cells treated with erythromycin was significantly lower than that in airway surface liquid from the cells treated with solvent alone. The production of mRNA and protein of human beta-defensin-1 and human beta-defensin-2 was significantly increased by erythromycin. Bactericidal activity of airway surface liquid was observed at low concentrations (40 meq/l) of sodium but not at higher concentrations (> or =80 meq/l). Airway surface liquid did not contain significant amounts of antibiotics supplemented in the culture medium. Erythromycin at the levels in airway surface liquid and in culture medium did not inhibit bacterial growth. These results suggest that erythromycin may increase bactericidal activity of airway surface liquid in human airway epithelial cells through human beta-defensins production and reduce susceptibility of the airway to bacterial infection.

Anti-Bacterial Agents↗
PubMed2005

Anticoagulant therapy for idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: To evaluate the effect of anticoagulant therapy on the survival of patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Prospective study. SETTING: Five hospitals located in the Miyagi prefecture in Japan, including a university hospital, a Red Cross hospital, two public general hospitals, and a municipal hospital. PATIENTS: Fifty-six patients with IPF (mean age, 69.4 years; range, 47 to 89) admitted to the hospitals from April 2001 to April 2004. INTERVENTIONS: Patients were assigned to receive prednisolone alone or prednisolone plus anticoagulant therapy. The anticoagulants included oral warfarin in an outpatient setting and low-molecular-weight heparin for rehospitalized patients with severely progressive respiratory failure. MEASUREMENTS AND RESULTS: There was no difference in baseline characteristics, including age, gender, clinical condition, pulmonary function, and plasma d-dimer level between the non-anticoagulant group and the anticoagulant group. The overall survival and hospitalization-free periods were assessed. There was a significant difference between survival curves of the non-anticoagulant group and the anticoagulant group, with a 2.9 hazard ratio (p = 0.04, Cox regression model). There was no significant difference in the probability of a hospitalization-free period between groups. The major cause of clinical deterioration was acute exacerbation during follow-up in the present study. Therefore, the mortality and plasma d-dimer levels in patients with an acute exacerbation were also assessed. The mortality associated with acute exacerbations of IPF in the anticoagulant group was significantly reduced compared to that in the non-anticoagulant group (18% vs 71%, respectively; p = 0.008, Fisher Exact Test). Furthermore, the plasma d-dimer levels in patients who died were significantly higher than those in survivors during acute exacerbation of IPF (3.3 +/- 2.3 microg/mL vs 0.9 +/- 0.7 microg/mL, p < 0.0001). Histologic analysis performed in three patients who died due to an exacerbation of IPF in the non-anticoagulant group demonstrated the features of usual interstitial pneumonia and acute lung injury. CONCLUSIONS: Our data suggested that plasma d-dimer levels are associated with mortality in patients with an acute exacerbation of IPF, and that anticoagulant therapy has a beneficial effect on survival in patients with IPF.

Aged↗
PubMed2005

Inflammatory and bronchospastic factors in asthma exacerbations caused by upper respiratory tract infections.

It is still uncertain how viral respiratory infections cause acute exacerbations of bronchial asthma, although several mechanisms have been proposed. We studied the relationship between the airway narrowing and the inflammatory and bronchospastic factors in peripheral venous blood and urine, in 30 patients with asthma at the exacerbations caused by upper respiratory tract infections (URTIs). Acute exacerbations caused decreases in peak expiratory flow rate (PEFR) in all 30 patients with asthma. Asthma exacerbations caused the rises in serum levels of interleukin-6, soluble intercellular adhesion molecule-1 and eosinophil cationic protein, concentrations of urinary leukotriene E4 and plasma histamine, compared with those in patients with asthma at a stable condition and those in 30 control subjects (p < 0.05). The values of PEFR at the exacerbations correlated with the levels of these factors. Treatment with oral glucocorticoids reversed the decreases in PEFR and the increases in these factors. At the onset of URTIs, rhinovirus and influenza type A virus were identified in 13 and 7 patients, respectively. Each of parainfluenza virus, adenovirus, and enterovirus was identified in one patient. These findings suggest that respiratory viral infections may cause acute asthma exacerbations via the production of mediators that induce inflammation and bronchospasm.

Acute Disease↗
PubMed2005

Comparison of a small volume of hypertonic saline solution and dextran 40 on hemodynamic alternations in conscious calves.

The hemodynamic effects of rapid intravenous (IV) administration of 10% dextran 40 in saline solution (D40) and 7.2% hypertonic saline solution (HSS) in calves were compared. Calves received isotonic saline solution (ISS), HSS or D40 (3 calves/group) and were monitored of blood pressure, and cardiac output (CO) for 180 min. HSS and D40 infusions induced a significant increase in relative plasma volume reaching 134.9+/-2.8 and 125.0+/-1.9%, respectively at the end of fluid infusion. In the HSS group, CO, cardiac index (CI) and stroke volume (SV) remained constant at low levels after 90 minutes despite the maximal values of CO, CI and SV at the end of infusion, reaching 21.0+/-6.3 l/min (p<0.05), 177.8+/-14.2 ml/min/kg (p<0.001) and 0.20+/-0.03 l/beat (at t=10 min, p<0.001), respectively. In contrast, CI and SV in the D40 group showed significant increases to 14.7+/-2.9 l/min and 153.5+/-17.2 ml/min/kg, respectively, at the end of fluid infusion. And those values remained constant at higher levels than those of the before infusions values throughout the experimental periods. Positive effects for hemodynamic alternations of D40 in calf practice were milder and longer than those of HSS. Therefore, the D40 infusion should be explored as a possible treatment for dehydrated calves, since rapid infusion of D40 may be safe and more beneficial for rehydrating more than HSS treatment.

Animals↗
PubMed2004

Highly stereoselective synthesis of functionalized beta,beta-di- and trisubstituted vinylic sulfoxides by Cu-catalyzed conjugate addition of organozinc reagents.

beta,beta-Disubstituted chiral vinylic sulfoxides bearing functionalities have been synthesized via Cu-catalyzed conjugate addition of organozinc reagents to chiral 1-alkynyl sulfoxides. Due to the availability of functionalized organozinc reagents and high syn-selectivity of the reaction, both geometric beta,beta-disubstituted vinylic sulfoxides were selectively synthesized. Furthermore, 1-alkynyl sulfoxides were derivatized into trisubstituted vinylic sulfoxides by trapping the resulting alpha-sulfinyl vinylic carbanion with electrophiles. Highly diastereoselective THF and THP ring formations were accomplished by means of this methodology followed by an intramolecular Michael addition.

Journal Article↗
PubMed2004

Apoptosis induced by 5-(N,N-hexamethylene)-amiloride in regenerating liver after partial hepatectomy.

The effects of a specific inhibitor of the Na+/H+ exchanger, 5-(N,N-hexamethylene)-amiloride (HMA), on liver regeneration after partial hepatectomy were investigated. A single injection of HMA inhibited DNA synthesis and caused apoptosis in regenerating liver. Characteristic DNA fragmentation was observed at 4 h after partial hepatectomy with HMA-injection. The activity of Jun N-terminal kinase (JNK) increased to a maximal level at 15 min after partial hepatectomy in HMA-injected rats, while it was not detected until 30 min in the control. Western blot analysis revealed that the injection of HMA markedly increased c-Jun and phosphorylated c-Jun protein levels at 30 min after partial hepatectomy. An increase in p53 was also observed at 30 min after the HMA-injection and was followed by the upregulation of p21WAF1/CIP1 protein expression at 1 h after partial hepatectomy. These results suggested that HMA induced apoptosis accompanied by the activation of JNK and the upregulation of c-Jun, p53 and p21WAF1/CIP1 expression at an early stage of liver regeneration.

Amiloride↗
PubMed2004

Asymmetric intramolecular michael addition of alpha-sulfinyl vinylic carbanion to enoates.

The first example of an asymmetric intramolecular Michael addition reaction with use of alpha-lithiated vinylic sulfoxide as a Michael donor is reported. Michael addition of the alpha-lithiated vinylic sulfoxide to (Z)-enoates proceeds with high diastereoselectivity to give the adducts with (R)-configuration at the beta-position of the ester in the five-membered-ring formation. The selectivity was reversed in the six-membered-ring formation. The resulting ester enolates were reacted with alkyl halides or benzaldehyde with high diastereoselectivity.

Journal Article↗
PubMed2004

Pharmacobezoar complicating treatment with sodium alginate.

We encountered a gastric bezoar that had developed in a 9-year-old girl treated with sodium alginate (Alloid G) for acute gastritis associated with systemic lupus erythematosus. A hard mass palpated in the left upper abdomen proved, upon gastric endoscopy, to be an intragastric foreign body. Sodium alginate was detected in an analysis of a sample from this bezoar. In an in vitro simulation, sodium alginate solidified when mixed with the patient's other medicines. The bezoar caused no complications, and disappeared spontaneously after discontinuation of the medications. This case indicates that this sodium alginate preparation, Alloid G, can be a cause of pharmacobezoar.

Alginates↗
PubMed2004

Optical coherence tomographic findings of dissociated optic nerve fiber layer appearance.

PURPOSE: To examine the features of optical coherence tomographic (OCT) findings of dissociated optic nerve fiber layer (DONFL) appearance. DESIGN: Case-control study. METHODS: Twenty-four eyes undergoing vitrectomy for idiopathic epiretinal membrane or macular hole were examined postoperatively using OCT. RESULTS: Thirteen of the 24 eyes exhibited the DONFL appearance. In these 13 eyes, the OCT images indicated dimples in the retinal nerve fiber layer (RNFL) corresponding to each stria. The RNFL thickness (mean +/- SD) at the dimple site was 38.1 +/- 9.3 microm. The depth of each dimple was 28.6 +/- 8.0 microm. The depths of all the dimples were limited to the RNFL thickness. In the other 11 eyes without the DONFL appearance, OCT images showed no distinct dimples. CONCLUSIONS: The DONFL appearance is caused by dimples the depths of which are limited to the RNFL thickness.

Case-Control Studies↗
PubMed2004

Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients.

The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.

Antineoplastic Agents↗
PubMed2004

Is there any "free" choice? Self and dissonance in two cultures.

Four experiments provided support for the hypothesis that upon making a choice, individuals justify their choice in order to eliminate doubts about culturally sanctioned aspects of the self, namely, competence and efficacy in North America and positive appraisal by other people in Japan. Japanese participants justified their choice (by increasing liking for chosen items and decreasing liking for rejected items) in the standard free-choice dissonance paradigm only when self-relevant others were primed, either by questionnaires (Studies 1-3) or by incidental exposure to schematic faces (Study 4). In the absence of these social cues, Japanese participants showed no dissonance effect. In contrast, European Americans justified their choices regardless of the social-cue manipulations. Implications for cognitive dissonance theory are discussed.

Choice Behavior↗
PubMed2004

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt.

During acute inflammation, neutrophil-mediated injury to epithelium may lead to disruption of epithelial function, including the induction of epithelial apoptosis. Herein, we report the effects of neutrophil transmigration and of purified leukocyte elastase on epithelial cell survival. Neutrophil transmigration induced apoptosis of epithelial cells [control monolayers: 5 +/- 1 cells/25 high-power fields (HPF) vs. neutrophil-treated monolayers: 29 +/- 10 cells/HPF, P < 0.05, n = 3 as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay] as did low concentrations (0.1 U/ml) of purified leukocyte elastase (control monolayers: 6.4 +/- 2.5% apoptotic vs. elastase: 26.2 +/- 2.9% apoptotic, P < 0.05, as determined by cytokeratin 18 cleavage). Treatment with elastase resulted in decreased mitochondrial membrane potential, release of cytochrome c to the cytosol, and cleavage of caspases-9 and -3 as determined by Western blot analysis, implicating altered mitochondrial membrane permeability as a primary mechanism for elastase-induced apoptosis. Additionally, incubation of epithelial cells with leukocyte elastase resulted in an early increase followed by a decrease in the phosphorylation of epithelial Akt, a serine/threonine kinase important in cell survival. Inhibition of epithelial Akt before elastase treatment potentiated epithelial cell apoptosis, suggesting that the initial activation of Akt represents a protective response by the epithelial cells to the proapoptotic effects of leukocyte elastase. Taken together, these observations suggest that epithelial cells exhibit a dual response to cellular stress imposed by leukocyte elastase with a proapoptotic response mediated via early alterations in mitochondrial membrane permeability countered by activation of the survival pathway involving Akt.

Apoptosis↗
PubMed2004

[Relationship between the effects of word emotionality and the consciousness of retrieval process in memory].

Two experiments were carried out to examine the effects of word emotionality on explicit and implicit memory. In Experiment 1, 46 undergraduates studied a word list followed by free recall or word-stem completion test. The list was consisted of 36 nouns with pleasant, neutral, and unpleasant words. In free recall test, both the pleasant and unpleasant words were more recalled than the neutral words. In word-stem completion test, there were no significant effects of emotional value. Experiment 2 reexamined the result of word-stem completion test in Experiment 1. A process-dissociation procedure was used to estimate two components of conscious and automatic retrieval process in implicit memory. The results suggest that the emotionality of words had a facilitative effect on conscious component but no effect on unconscious component.

Adult↗
PubMed2003

Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells.

To examine the effects of rhinovirus (RV) infection on the adherence of Streptococcus pneumoniae to human tracheal epithelial cells, cells were infected with RV-14, and S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to epithelial cells increased after RV infection. Y-24180, a specific inhibitor of the platelet-activating factor receptor (PAF-R); PAF; and the pyrrolidine derivative of dithiocarbamate, an inhibitor of transcription factor nuclear factor-kappaB (NF-kappaB), decreased the number of S. pneumoniae adhering to cells after RV-14 infection. RV-14 infection increased PAF-R expression and the activation of NF-kappaB and promoter-specific transcription factor 1. These findings suggest that RV-14 infection stimulates S. pneumoniae adhesion to airway epithelial cells via increases in PAF-Rs that are partly mediated through activation of transcription factors. Increased adherence of S. pneumoniae may be one of the reasons that pneumonia develops after RV infection.

Bacterial Adhesion↗
PubMed2003

Pd-catalyzed sulfinylzincation of activated alkynes with 1-alkynyl sulfoxides as a sulfinyl source.

Unprecedented Pd-catalyzed sulfinylzincation with 1-alkynyl sulfoxide as a sulfinyl source was developed. Bis-sulfinyl alkenes were formed in good yields on treatment of 1-alkynyl sulfoxides with Et(2)Zn in the presence of a Pd-catalyst, wherein zinc sulfenate (or sulfinylzinc) species would be generated in situ to undergo highly syn-selective conjugate addition to the 1-alkynyl sulfoxides. By using 3,3-dimethyl-1-butynyl sulfoxides, formation of the bis-sulfinyl alkenes was completely suppressed and the sulfinylzincation of activated alkynes was accomplished. The reaction tolerates various functionalities, and was promoted considerably by the neighboring group participation of the heteroatom at the delta-position in the alkynoates. Stereodivergent synthesis of two diastereomeric vinylic sulfoxides and reaction of the resulting vinylzinc species with electrophiles were also described.

Journal Article↗
PubMed2003

Carbon nanowire made of a long linear carbon chain inserted inside a multiwalled carbon nanotube.

A new type of one-dimensional (1D) carbon structure, carbon nanowires (CNWs), was discovered in the cathode deposits prepared by hydrogen arc discharge evaporation of carbon rods. Observation of high-resolution transmission electron microscopy (HRTEM) indicates that a CNW consists of a multiwalled carbon nanotube (MWNT) with a long 1D linear carbon chain (C chain) inserted into its innermost tube of 0.7 nm in diameter. The characteristic Raman peaks of CNWs appeared at around 1850 cm(-1). Raman scattering and HRTEM studies show the formation of a long linear C chain involving more than 100 carbon atoms inside a MWNT. This novel 1D carbon allotrope has potential applications in nanoelectronics, nanomechanics, and nanomaterials.

Journal Article↗