Search PubMed⌕ Search

Biomedical subjects

Akira Watanabe

Publications and source records attributed to Akira Watanabe.

At least 109 records · Page 6Linked to original sources
PubMed2002

Antioxidant action of 2,2,4,6-tetra-substituted 2,3-dihydro-5-hydroxybenzofuran against lipid peroxidation: effects of substituents and side chain.

With increasing evidence suggesting the involvement of oxidative stress in various disorders and diseases, the role of antioxidants in vivo has received much attention. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) was designed, synthesized and has been evaluated as a novel antiatherogenic drug. In order to further understand the action of BO-653 and also radical-scavenging antioxidants in general, the dynamics of inhibition of oxidation by BO-653 were compared with those of the related compounds, 2,3-dihydro-5-hydroxy-2,2-dimethyl-4,6-di-tert-butylbenzofuran (BOB), 2,3-dihydro-5-hydroxy-2,2,4,6-tetramethylbenzofuran (BOM), alpha-tocopherol and 2,2,5,7,8-pentamethyl-6-chromanol (PMC), aiming specifically at elucidating the effects of substituents and side chain length of the phenolic antioxidants. These five antioxidants exerted substantially the same reactivities toward radicals and antioxidant capacities against lipid peroxidation in organic solution. When compared with di-methyl side chains, the di-pentyl side chains of BO-653 reduced its inter-membrane mobility but exerted less significant effect than the phytyl side chain of alpha-tocopherol on the efficacy of radical scavenging within the membranes. Di-tert-butyl groups at both ortho-positions made BO-653 and BOB more lipophilic than di-methyl substituents and reduced markedly the reactivity toward Cu(II) and also the synergistic interaction with ascorbate. The results of the present study together with those of the previous work on the effect of substituents on the stabilities of aryloxyl radicals suggest that tert-butyl group is more favorable than methyl group as the substituent at the ortho-positions and that di-pentyl side chains may be superior to a phytyl side chain.

Antioxidants↗
PubMed2002

In vitro activity of rifampicin against Helicobacter pylori isolated from children and adults.

Antibiotic resistance in Helicobacter pylori has been a growing problem with current treatment regimens. However, second-line therapy for cases with eradication failure remains to be established. The aim of this study was to evaluate (in vitro) the potential use of rifampicin for H. pylori eradication. The susceptibility of 52 H. pylori strains isolated from children and adults to amoxicillin, clarithromycin, metronidazole and rifampicin was determined. Forty H. pylori isolates susceptible to these antibiotics were investigated for in vitro inducement of resistance. All isolates were susceptible to rifampicin. None of the H. pylori isolates tested acquired rifampicin resistance during prolonged exposure in in vitro inducement experiments. It is suggested that rifampicin has stable activity against H. pylori.

Adolescent↗
PubMed2002

Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappa B transcription factors.

Erythromycin and other macrolides are effective for the treatment of chronic inflammatory airway diseases such as diffuse panbronchiolitis (DPB) and chronic sinusitis. The effect of macrolides in DPB is suggested to be anti-inflammatory rather than antibacterial. We investigated the effects of clarithromycin on interleukin-8 (IL-8) production using human peripheral monocytes and the human monocytic leukaemia cell line, THP-1. Bacterial extracts from Escherichia coli, Pseudomonas aeruginosa and Helicobacter pylori, as well as E. coli-derived lipopolysaccharide (LPS), induced IL-8 production. Clarithromycin suppressed this production in a dose-dependent manner in both monocytes and THP-1 cells (49.3-75.0% inhibition at 10 mg/L). A luciferase reporter gene assay with plasmids containing a serially deleted IL-8 promoter fragment showed that both the activator protein-1 (AP-1) and/or the nuclear factor-kappa B (NF-kapp aB) binding sequences were responsible for the LPS and clarithromycin responsiveness of the IL-8 promoter. Consistently, in an electromobility shift assay, LPS increased the specific binding of both AP-1 and NF-kappaB, whereas clarithromycin suppressed it. Moreover, LPS and clarithromycin regulated three other promoters that have either the NF-kappa B or the AP-1 binding sequences: two synthetic (pAP-1-Luc and pNF-kappa B-Luc) and one naturally occurring (ELAM-Luc). Our results indicate that clarithromycin modified inflammation by sup-pressing IL-8 production and that clarithromycin may affect the expression of other genes through AP-1 and NF-kappa B. In addition to treatment of airway diseases, the anti-inflammatory effect of macrolides may be beneficial for the treatment of other inflammatory diseases such as chronic gastritis caused by H. pylori.

Anti-Bacterial Agents↗
PubMed2002

Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate.

OBJECTIVE: Accumulating data have demonstrated that macrolide antibiotics suppress Pseudomonas aeruginosa virulence, which may explain the efficacy of macrolides in clinical settings. We examined the virulence of macrolide-treated bacteria in vivo. METHODS: P. aeruginosa PAO-1 was grown for 24 h on agar containing sub-MIC antibiotics, and then mice were challenged intranasally with 10(7) cfu of bacteria. RESULTS AND CONCLUSIONS: The mortality rate of mice inoculated with bacteria grown in the presence of clarithromycin (10 mg/L), erythromycin (10 mg/L) or azithromycin (5 mg/L) was 80%, 80% and 100%, respectively. In contrast, none of the mice inoculated with non-treated bacteria or bacteria treated with other antibiotics died. Lung weight and protein concentration in bronchoalveolar lavage fluid (BALF) were significantly higher in the clarithromycin group between 3 and 9 h. Moreover, we detected higher levels of tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the BALF of these mice. These data demonstrate that macrolide-treated P. aeruginosa induced paradoxically strong responses, such as elevation of TNF-alpha, NO and permeability in the lungs.

Animals↗
PubMed2002

Activation of the promoters of Arabidopsis genes for the branched-chain alpha-keto acid dehydrogenase complex in transgenic tobacco BY-2 cells under sugar starvation.

Sugar starvation exerted by sub-10 mM levels of sucrose on Arabidopsis T87 suspension-cultured cells triggered marked accumulation of the transcripts of genes for E1beta and E2 subunit of the branched-chain alpha-keto acid dehydrogenase complex. Similar levels of sugar starvation increased the luciferase activity in transgenic tobacco BY-2 lines expressing the Arabidopsis E1beta- or E2-promoter-luciferase fusion gene. These results indicate that sugar levels tightly regulate the E1beta and E2 promoter activity in the heterologous plant system. We further showed in the transgenic tobacco BY-2 lines that sugar-starvation-induced activation of the E1beta and E2 promoters was prevented by K-252a, an inhibitor of Ser/Thr protein kinase, and was enhanced by okadaic acid, an inhibitor of protein phosphatases. By contrast, the cauliflower mosaic virus 35S promoter activity in sugar-starved BY-2 cells was not significantly affected by K-252a and only slightly enhanced by okadaic acid. Taken together, we propose that transcriptional activation of genes for the branched-chain alpha-keto acid dehydrogenase complex and its modulation by specific protein kinases/phosphatases are of critical importance in branched-chain amino acid catabolism in plant cells under sugar starvation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2002

Acute eosinophilic pneumonia following cigarette smoking: a case report including cigarette-smoking challenge test.

A 21-year-old woman presented with acute progressive dyspnea. Chest computed tomography (CT) revealed diffuse bilateral infiltrates. Based on the results of transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid (BALF) and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspected that the disease was related to smoking because she had started smoking ten days before the onset of symptoms. Therefore, a cigarette-smoking challenge test was done with the patient's informed consent. After the challenge, eosinophilic pneumonia was documented by BALF and TBLB findings, which were similar to those detected on admission, without significant radiographic findings.

Acute Disease↗
PubMed2002

Humidifier lung: possible contribution of endotoxin-induced lung injury.

A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest computed tomography demonstrated bilateral diffuse ground-glass opacities predominantly in the upper lungs. Subpleural non-segmental consolidation was observed in the late phase. Hypersensitivity pneumonitis was suspected, and an environmental provocation test with the incidental use of a home ultrasonic humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6 levels were normal. Although several microorganisms were isolated from the humidifier water, there was no evidence for immune sensitization. We detected high amounts of endotoxin in the humidifier water, which may have contributed to the lung injury of this patient.

Alveolitis, Extrinsic Allergic↗
PubMed2002

Community-acquired Chlamydia pneumoniae pneumonia in Japan: a prospective multicenter community-acquired pneumonia study.

OBJECTIVE: To investigate the clinical features of Chlamydia pneumoniae pneumonia in Japan and to evaluate the newly created Japanese community-acquired pneumonia (CAP) guidelines. PATIENTS AND METHODS: A multicenter CAP surveillance study was carried out in 20 hospitals between December 1999 and March 2000. The diagnosis of C. pneumoniae infection was based on isolation in cell culture, the polymerase chain reaction and serologic testing of antibodies by the microimmunofluorescence test. RESULTS: Among 232 CAP cases, C. pneumoniae was identified as the etiologic agent in 15 cases (6.5%). C. pneumoniae was the only pathogen identified in nine of these cases, while one or more additional etiological agents were found in the other six cases. Of the present and previously reported single agent C. pneumoniae pneumonia cases, about 50% were more than 60 years old and had underlying diseases. A relatively slow pulse rate in relation to fever was not seen in these patients. The mean WBC count of all patients was normal. No patient required respiratory support or admission to an intensive care unit and no deaths occurred among these patients. CONCLUSION: The clinical pictures of C. pneumoniae pneumonia as a single agent were mild to moderate and were remarkably different from those of cases of C. pneumoniae pneumonia concomitant with other bacteria. If the patient is less than 60 years old and some guideline headings are excluded, we think it would be possible to distinguish between C. pneumoniae and bacterial pneumonia.

Adolescent↗
PubMed2002

Gross total removal of gliomas in the pulvinar and correlative microsurgical anatomy.

Tumors in the pulvinar tend to present as circumscribed lesions with exophytic growth into the lateral and third ventricles. These lesions may be best explored via a parietal-transcortical-transventricular approach. If the tumor extends posteriorly or inferiorly, a posterior-interhemispheric-transtentorial approach may provide a good angle of access. Gross total removal of the tumors in the pulvinar of two patients was achieved by surgical sectioning of the unilateral crus of the fornix or the splenium via a transventricular or interhemispheric approach with acceptable risk. These patients are now doing well as students about 6 years following the first operations. During tumor removal, a posterior-interhemispheric-transtentorial approach combined with above-mentioned approaches was useful for orientation of the critical structures in the posterior incisural space. Knowledge of the anatomical relationships of the pulvinar to the crus of the fornix and the choroid plexus, and to the critical structures located in the posterior incisural space is extremely important for neurosurgeons.

Adolescent↗
PubMed2002

[Culture filtrate of Aspergillus fumigatus and its cytotoxic activity against leukocytes].

Aspergillosis has become the biggest cause of death among mycoses in Japan. The main causative agent is Aspergillus fumigatus and its virulence factors have been variously investigated, yet much remains to be clarified. We recently found that the culture filtrate of A. fumigatus has potent anti-leukocyte activity. It seriously damages macrophages and hampers the function of polymorphonuclear neutrophils. The filtrate is also active in vivo: when injected intraperitoneally, the culture filtrate lowered the survival of mice infected with A. fumigatus. This activity becomes overt within 24 hours of culture of the fungus. Although the mechanism of pathogenicity of A. fumigatus is believed to be somewhat complex, we suggest the activities shown in the culture filtrate may play a crucial role in the development of the infection.

Animals↗
PubMed2002

Cytotoxicity of Aspergillus fumigatus culture filtrate against macrophages.

Aspergillus fumigatus causes serious, life-threatening human infection, and is one of the most important pathogenic fungi. Little is known, however, about its mechanism of infection or its virulence factors. To learn about its virulence factors, the effect of the culture filtrate of A. fumigatus on macrophages was studied. When cocultured with A. fumigatus in 96-well microplates, murine peritoneal macrophages showed significant morphological changes indicating serious cellular damage, even when the macrophages were not in direct contact with the fungus. Then culture filtrates of Aspergillus spp., A. fumigatus, A. flavus, A. terreus and A. niger, were prepared by culturing the fungus in 96-well or 24-well microplates for 24 h, and the effect of the culture filtrates was determined by culturing macrophages with or without culture filtrate. When cultured with the culture filtrate of A. fumigatus at a concentration of 1% or higher, macrophages demonstrated significant morphological changes, leading to their death. Treatment with heat greatly lowered the activity of the culture filtrate. In contrast, culture filtrates of A. terreus and A. flavus showed no detectable effect on macrophages, whereas A. niger did display a similar, but much weaker effect. Our study strongly suggests that A. fumigatus releases a toxic product (s) in the medium very rapidly, and this may be critically involved as the virulence factor in human infection, at least in part, by causing serious injury to macrophages.

Animals↗
PubMed2002

[beta-lactamase-producing activity and antimicrobial susceptibility of major pathogenic bacteria isolated from clinical samples. Japan beta-lactamase Research Group].

beta-Lactamase production and susceptibility to an assortment of antimicrobial agents were examined in 9,483 strains of organisms isolated from clinical materials obtained from inpatients and outpatients at 104 institutions throughout Japan from December 1999 to February 2000. The organisms were Staphylococcus aureus, 1,369 strains, including 847 methicillin-resistant (MRSA) strains; Enterococcus faecalis, 735 strains; Enterococcus faecium, 302 strains; Moraxella (Branhamella) catarrhalis, 730 strains; Haemophilus influenzae, 1,142 strains; Escherichia coli, 1,276 strains; Klebsiella pneumoniae, 1,058 strains; Enterobacter cloacae, 772 strains; Serratia marcescens, 847 strains; and Pseudomonas aeruginosa, 1,252 strains. The 23 antimicrobial agents used were ampicillin, sulbactam/ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefazolin, cefotiam, cefmetazole, cefoperazone, sulbactam/cefoperazone, cefotaxime, ceftazidime, cefepime, cefpodoxime, imipenem, gentamicin, arbekacin, clarithromycin, minocycline, chloramphenicol, vancomycin, teicoplanin, and levofloxacin. Antimicrobial agents appropriate for each organism were used. Among S. aureus strains, 61.9% were MRSA, and 62.3% were positive for beta-lactamase. Among the MRSA strains, none was resistant to vancomycin or teicoplanin, and only 3% were resistant to arbekacin. There was no vancomycin resistance in the Enterococcus strains. Only 0.1% of E. faecalis strains were ampicillin-resistant. Among the M. catarrhalis strains, 97.5% produced beta-lactamase, while among the H. influenzae strains, 8.5% produced beta-lactamase and 14.5% were beta-lactamase-negative and ampicillin-resistant (BLNAR). Among the Enterobacteriaceae and P. aeruginosa strains, there were 20 (E. coli; 7/1,276, K. pneumoniae; 13/1,058) that produced extended-spectrum beta-lactamases (ESBLs), and 11 that produced class B beta-lactamases. Multiple drug resistance was advanced in every species, and organisms resistant to 7 or more common antimicrobial agents were isolated. The best combination of antimicrobial agent and beta-lactamase inhibitor was sulbactam/cefoperazone. Sulbactam/cefoperazone, cefepime, and imipenem still have excellent antimicrobial activity. Rates of resistance to each antimicrobial agent differed more among institutions than among geographical regions.

Bacteria↗
PubMed2002

[Antibiotic susceptibility and beta-lactamase activity of pathogenic microbes isolated in Miyagi Prefecture between December in 1999 and February in 2000].

We determined beta-lactamase activity and antimicrobial susceptibility of 556 strains consisting of 10 species isolated in four medical institutions and one microbiological laboratory of Miyagi Prefecture in Japan between December in 1999 and February in 2000. beta-Lactamase determined by nitrocefin method was positive in 68% of S. aureus, in 15% of H. influenzae and in 100% of M. catarrhalis. Penicillinase/cephalosporinase determined by acidometry was positive in 9%/10% of E. coli, in 17%/2% of K. pneumoniae, in 16%/58% of E. cloacae, in 43%/78% of S. marcescens, and in 4%/32% of P. aeruginosa, respectively. Of a total of 298 strains of Enterobacteriaceae and P. aeruginosa, 25 strains (14 strains of E. coli, 10 strains of K. pneumoniae and one strain of S. marcescens) produced class A beta-lactamase, two strains of E. cloacae produced class B beta-lactamase, and 12 strains (one strain of E. coli, four strains of E. cloacae, six strains of S. marcescens and one strain of P. aeruginosa) produced class C beta-lactamase. According to NCCLS standard, three strains (one strain of E. coli and two strains of K. pneumoniae) of ESBL-positive microbes were detected. beta-Lactamase-negative ampicillin-resistant (BLNAR) strains of H. influenzae were found in 10/40 (25.0%) of the strains tested.

Enterobacteriaceae↗
PubMed2001

Dark-inducible genes from Arabidopsis thaliana are associated with leaf senescence and repressed by sugars.

We have isolated 5 cDNA clones (din2, din6, din9, din10 and din11) corresponding to genes, the transcripts of which accumulated in leaves of Arabidopsis thaliana kept in the dark. These cDNA clones encode proteins similar to beta-glucosidase (EC 3.2.1.21, din2), asparagine synthetase (EC 6.3.5.4, din6), phosphomannose isomerase (EC 5.3.1.8, din9), seed imbibition protein (din10) and 2-oxoacid-dependent dioxygenases (din11). Accumulation of the transcripts from din6 and din10 occurred within 3 h after plants were transferred to darkness. The transcripts from din2, din9 and din11 were only detected after 24 h of dark treatment. We also observed the accumulation of the din transcripts in senescing leaves. Application of a photosynthesis inhibitor, 3-(3,4-dichlorophenyl)-1-1-dimethyl-urea, induced the expression of the din genes under illumination. Application of sucrose to detached leaves suppressed the accumulation of the din transcripts in the dark. These results indicate that expression of these genes partly depends on cellular sugar level. The sugar-modulated expression of the din genes suggests that dark-induced expression of these genes might be related to sugar starvation occurring in leaf cells in the dark, when the photosynthesis is hindered.

Journal Article↗
PubMed1999

Clinical evaluation methods for new antimicrobial agents to treat respiratory infections: Report of the Committee for the Respiratory System, Japan Society of Chemotherapy.

The present report constitutes an attempt to improve and modify the existing clinical evaluation method for new antimicrobial agents to treat respiratory infections. One year ago, a general guideline on the clinical evaluation of antimicrobial agents to treat respiratory infections was drafted in Japanese, leaving scope for critical discussion, and this has been translated into English, as there were no major changes. In this report, respiratory infections have been discussed under the headings "acute respiratory tract infection" and pneumonia and acute exacerbation of chronic pulmonary diseases. Standardized criteria were set for the assessment of severity of infection and effectiveness of the antimicrobial agent in question. Severity was evaluated on the basis of a combined assessment of the severity of infection and severity of the clinical condition of the patients. Clinical effectiveness of the antimicrobial agent used was evaluated on the basis of clinical outcome as well as microbiological outcome of the trial. Body temperature, local pain, cough, change in sputum quality, peripheral white blood cell count, C-reactive protein level, and chest radiograph were used as the parameters for the evaluation. To maintain the quality of specimens to be examined, Geckler's classification of specimens was used. This report was constructed based on the analysis of large amounts of material collected over the years, incorporating internal and external factors concerning the present evaluation methods. The newly suggested standardized criteria for clinical evaluation of the new antimicrobial drugs are expected to be practiced properly hereupon and subjected to further improvement if necessary.

Journal Article↗