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Akira Watanabe

Publications and source records attributed to Akira Watanabe.

At least 55 records · Page 3Linked to original sources
PubMed2004

Dendritic cells pulsed with live and dead Legionella pneumophila elicit distinct immune responses.

Legionella pneumophila is the causative pathogen of Legionnaires' disease, which is characterized by severe pneumonia. In regard to the pathophysiology of Legionella infection, the role of inflammatory phagocytes such as macrophages has been well documented, but the involvement of dendritic cells (DCs) has not been clarified. In this study, we have investigated the immune responses that DCs generate in vitro and in vivo after contact with L. pneumophila. Heat- and formalin-killed L. pneumophila, but not live L. pneumophila, induced immature DCs to undergo similar phenotypic maturation, but the secreted proinflammatory cytokines showed different patterns. The mechanisms of the DC maturation by heat- or formalin-killed L. pneumophila depended, at least in part, on Toll-like receptor 4 signaling or on Legionella LPS, respectively. After transfer to naive mice, DCs pulsed with dead Legionella produced serum Ig isotype responses specific for Legionella, leading to protective immunity against an otherwise lethal respiratory challenge with L. pneumophila. The in vivo immune responses required the Ag presentation of DCs, especially that on MHC class II molecules, and the immunity yielded cross-protection between clinical and environmental strains of L. pneumophila. Although the DC maturation was impaired by live Legionella, macrophages were activated by live as well as dead L. pneumophila, as evidenced by the up-regulation of MHC class II. Finally, DCs, but not macrophages, exhibited a proliferative response to live L. pneumophila that was consistent with their cell cycle progression. These findings provide a better understanding of the role of DCs in adaptive immunity to Legionella infection.

Animals↗
PubMed2004

In vitro exposure to macrolide antibiotics in Helicobacter pylori strains isolated from children.

Clarithromycin resistance of Helicobacter pylori is a serious problem in eradication therapy. We investigated whether the use of maclorides (clarithromycin, erythromycin, and azithromycin) induces clarithromycin resistance in the organism. Twenty H. pylori strains were isolated from pediatric patients with gastrointestinal symptoms. The minimum inhibitory concentrations (MICs) of each macrolide antibiotic were determined by the Etest. Among these, 17 strains susceptible to macrolide antibiotics were used for the in vitro induction of drug resistance. In each of these 17 strains of H. pylori, 30-day exposure to clarithromycin in experiments for in vitro induction did not change the MIC of any antibiotic, nor did it induce either the A2143G or the A2144G mutation in the 23S rRNA gene. These results suggest that the use of macrolide antibiotics does not induce clarithromycin resistance in H. pylori by 23S rRNA gene mutation.

Adolescent↗
PubMed2004

Survey of methicillin-resistant Staphylococcus aureus from neonates and the environment in the NICU.

Methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor of nosocomial infection with compromised hosts including neonates. Currently, the prevalence of MRSA carriers among children is increasing in Japan. There are some reports of nosocomial infection caused by MRSA in a pediatric ward or neonatal intensive care unit (NICU). During 6 months (from January 2001 to June 2001), 37 MRSA strains were isolated from 37 neonates who were admitted in the NICU and 52 MRSA were strains isolated from NICU environments. We performed DNA typing of MRSA using an arbitrary primed-PCR method on these isolates. Thirty-seven clinical isolates were classified into four types (A type, 14; B type, 4; C type, 4; D type, 3; and others, 12). The A-type strains of MRSA continued to be isolated for more than 6 months. In the NICU environment, the detection rate of the A-type MRSA was 23.1% (12/52). The A-type strains were frequently isolated from environments around patients. The A-type strains of MRSA were prevalent in the NICU, probably due to nosocomial infection. Although none of the neonatal patients developed severe MRSA infection, the same genotype strains were persistently isolated during a period of more than 6 months from patients and the NICU environment around patients. Environmental control around neonatal patients is important to prevent nosocomial infection in the NICU.

Cross Infection↗
PubMed2004

Unprecedented mechanism of chain length determination in fungal aromatic polyketide synthases.

Fungal aromatic polyketides show remarkable structural diversity fundamentally derived from variations in chain length and cyclization pattern. Their basic skeletons are synthesized by multifunctional iterative type I polyketide synthases (PKSs). Recently, we have found that the C-terminal thioesterase (TE)-like domain of Aspergillus nidulans WA catalyzes Claisen-type cyclization to form the B-ring of naphthopyrone YWA1. Here we report the unprecedented mechanism of chain length determination by the C-terminal TE-like domain of Colletotrichum lagenarium PKS1, which, in addition to catalyzing Claisen-type cyclization, intercepts the polyketomethylene intermediate from the acyl carrier protein domain during the condensation reaction to produce shorter chain length products. This chain length determination system is novel among PKSs, including bacterial and plant PKSs. The functional diversity of the TE-like domain directly influences the structural diversity of aromatic polyketides in C. lagenarium PKS1.

Cyclization↗
PubMed2004

Prevalence of community-acquired respiratory tract infections associated with Q fever in Japan.

A multicenter prospective cohort study to assess the occurrence and characteristics of acute Q fever associated with community acquired respiratory infections was performed. Among the 400 patients enrolled for the study, 10 (2.50%) patients (5 out of 120 cases of pneumonia, 3 out of 131 cases of acute bronchitis, and 2 out of 149 cases of upper respiratory infections) were diagnosed as having acute Q fever. Contact with dogs or cats before the onset of the disease was confirmed in most of the patients. The clinical profiles of these 10 patients were generally similar to those reported from other countries, such as fever, general fatigue and liver dysfunction, except for the predominance of sporadic cases among the urban population. Our study demonstrates that Q fever is not uncommon cause of community-acquired respiratory infections even in Japan.

Adolescent↗
PubMed2004

Multiplex PCR for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila in community-acquired pneumonia.

A multiplex polymerase chain reaction (PCR) was developed for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. Oligonucleotide primers for the amplification of the DNA of these three organisms were optimized for use in combination in the same reaction. PCR products were detected by the Micro-Chip Electrophoresis Analysis System. Clinical samples were obtained from 208 community-acquired pneumonia (CAP) patients who were participants in a multicenter CAP surveillance study performed at seven medical schools and their affiliate hospitals in Japan. No significant differences in the sensitivity of each primer set were observed when tested in both the multiplex and monoplex PCR assays. Our multiplex PCR was able to reliably detect 10 copies/100 microl of each of the three pathogen DNAs. Of the panel of 208 samples, 14 of 15 C. pneumoniae, 10 of 10 M. pneumoniae, eight of eight L. pneumophila and 165 of 176 negative samples were correctly identified. Eleven cases who were the multiplex PCR positive and conventional method negative were observed. The PCR findings were of possible significance in at least four of these patients. Our multiplex PCR assay could potentially be used as a diagnostic and epidemiological tool. Further prospective studies are needed to establish its clinical usefulness.

Adolescent↗
PubMed2004

Cytotoxic substances from Aspergillus fumigatus in oxygenated or poorly oxygenated environment.

Aspergillus fumigatus often causes serious health problems. The airway of the human body, the most common initial site of damage, is always exposed to an oxygenated condition, and the oxygen concentration may play a critical role in the virulence of A. fumigatus. In this study, oxygen content, fungal growth, the production of cytotoxic substance(s) in the fungal culture, and their relationship were investigated. Two clinical strains of A. fumigatus were cultured under certain oxygen contents (10, 14 and 20%), and cytotoxicity of their culture filtrates on murine macrophages and their fungal growth were evaluated. The components of these filtrates were analyzed by gas chromatography-mass spectrometry. All culture filtrates contained gliotoxin and showed potent cytotoxicity on macrophages at very low concentration. The amount of gliotoxin in the culture filtrate prepared at 10% oxygen was markedly less, but diminutions in fungal growth and cytotoxicity of this culture filtrate were negligible. These results suggest that a well-oxygenated condition is suitable for the production of gliotoxin by A. fumigatus. A significant role of cytotoxic substances(s) other than gliotoxin is also suggested.

Animals↗
PubMed2004

Cerebrovascular response to cognitive tasks in patients with schizophrenia measured by near-infrared spectroscopy.

We assessed the cerebral hemoglobin oxygenation response in the left frontal area in 62 schizophrenia patients and 31 healthy subjects during a verbal fluency test (VF) and letter number span test (LN) measured by near-infrared spectroscopy (NIRS). Oxygenated hemoglobin (oxyHb) increased during VF and LN in both groups. Schizophrenia patients showed lower VF and LN performance and a smaller increase in oxyHb during VF than controls. A reduced oxyHb response during VF in schizophrenia patients was also observed even when their VF performance was matched with controls' performance. On the other hand, increase in oxyHb during LN in schizophrenia patients was comparable with that in controls. In addition, patients medicated with atypical antipsychotics showed a larger increase in oxyHb during VF and LN than those medicated with typical antipsychotics. The present study confirmed functional hypofrontality in schizophrenia patients reported by other modalities such as position emission tomography, single-photon emission tomography, and functional magnetic resonance imaging and suggested that the hypofrontality may be task dependent.

Adult↗
PubMed2004

In vitro activity of fluoroquinolone and the gyrA gene mutation in Helicobacter pylori strains isolated from children.

Resistance to antibiotics, especially clarithromycin, is the major cause of the failure to eradicate Helicobacter pylori. There are few studies in children concerning fluoroquinolone activity against H. pylori. Primary resistance to antibiotics including fluoroquinolones was studied in 55 H. pylori strains isolated from Japanese children. DNA sequences of the gyrA gene in fluoroquinolone-resistant strains were determined. Twelve strains (21.8%) were resistant to clarithromycin and three (5.5%) were resistant to both levofloxacin and ciprofloxacin. Out of 12 clarithromycin-resistant strains, 11 (91.7%) were susceptible to levofloxacin and ciprofloxacin. Sequence analysis in three fluoroquinolone-resistant strains showed point mutations of the gyrA gene at G271A, G271T and A272G, indicating mutations of the codon Asp91 in the fluoroquinolone-resistance-determining region of the DNA gyrase. The results suggest that fluoroquinolones should be considered as an option for second- or third-line H. pylori eradication therapy in children.

Adolescent↗
PubMed2004

Differences of satisfaction with medication between patients with schizophrenia treated with typical antipsychotics and atypical antipsychotics.

Many studies have demonstrated that atypical antipsychotics are superior to typical antipsychotics in that they have fewer side-effects and produce better improvement of cognitive deficits and quality of life in patients with schizophrenia. However, most of these studies dealt with objective indices assessed by researchers rather than subjective indices that are indeed important to patients themselves. In 126 patients with schizophrenia, annoyance of side-effects and psychotic symptoms, satisfaction with medication, wish to change medication, and knowledge of atypical antipsychotics were assessed using questionnaires. Patients treated with typical antipsychotics complained less of annoyance of poor attention and concentration than those treated with atypical antipsychotics, which can be explained by increased awareness of these symptoms by the patients due to the improvement of cognitive function. There were no significant differences between the two groups in other variables. The present results that satisfaction and annoyance were similar between patients treated with typical antipsychotics and those with atypical antipsychotics, may partly explain why patients hesitated and rejected changing or shifting from typical to atypical antipsychotics. But because 98 of 126 patients did not know about atypical antipsychotics, it is important to educate the patients on the merits of atypical antipsychotics.

Adult↗
PubMed2004

Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X).

PURPOSE: To describe the clinical characteristics of a Japanese male patient with enhanced S-cone syndrome (ESCS) and investigate the existence of mutations in the NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor. METHODS: Fundus examinations, fluorescein angiography, colour vision tests, spectral sensitivity, and full-field and spectral electroretinography were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction (PCR) amplification and direct sequencing. RESULTS: We identified a novel homozygous mutation (c.1048C > T), that converts glutamine (CAA) to a termination codon (TAA) at amino acid position 350. The subject's unaffected parents were heterozygous for the mutation, consistent with autosomal recessive transmission. The electroretinographic findings revealed that the patient had neither rod nor 30-Hz flicker responses but did have cone responses with large a-wave and low b-wave amplitudes, similar to the rod-plus-cone responses, and also substantial short wavelength-sensitive (S) cone and extremely diminished long/middle wavelength-sensitive (L/M) cone responses. In the right eye, spectral sensitivity in the fovea revealed both functional S-cone and remarkably reduced L- and M-cone sensitivities, which was compatible with the decreased visual acuity (VA) and red/green colour vision defects noted in this eye. In contrast, the patient had good VA and normal red/green colour vision in the left eye. CONCLUSION: The nonsense mutation results in a truncated NR2E3 protein lacking 61 amino acids within the ligand-binding domain (LBD) that consists of 190 amino acids of the C-terminus end. Therefore, null function of the LBD is likely to cause ESCS in the patient. The clinical findings for this patient suggest that his left eye, with its functional L/M- and S-cones, was at an earlier stage of the syndrome than his right eye.

Adolescent↗
PubMed2004

Mannose-binding lectin gene polymorphism is a modulating factor in repeated respiratory infections.

STUDY OBJECTIVE: To clarify how mannose-binding lectin (MBL) participates in the pulmonary defense system. DESIGN: Multicenter retrospective study. PARTICIPANTS: Sixty-two patients with unexplained recurrent respiratory infections, 50 patients with nontuberculous mycobacterial infection, 23 patients with aspergillosis, and 49 patients with diffuse panbronchiolitis (DPB). For controls, 52 blood samples were provided by the Blood Donation Center of the Japanese Red Cross Society. For BAL fluid (BALF) evaluation, there were five patients with acute phase pneumonia and five healthy volunteers. MEASUREMENT AND RESULTS: We demonstrated that MBL protein could be directly measured in the BALF from the lungs of patients with pneumonia by means of enzyme-linked immunosorbent assay. Furthermore, we demonstrated that the prevalence of the codon 54 mutation of the MBL gene in 62 patients having repeated respiratory infections was significantly higher compared with healthy control subjects (54.8% vs 32.7%). The prevalence of the MBL mutant genotype among patients with DPB was higher (51.1%) than in the rest of the patients. In contrast, the prevalence of the MBL mutant genotype among patients with nontuberculous mycobacteria or Aspergillus chronic infection was not significantly different from that in control subjects (44.0% and 34.8%). CONCLUSIONS: Our results suggest that MBL may play an important role in modulating the inflammatory response against repeated microbial infections.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate.

Gliotoxin, one of the mycotoxins produced by Aspergillus fumigatus, has various, potent bioactivities. However, it has not been considered to be a toxic (or virulence) factor because of its slow production. The aim of the present study was to investigate the effects of aeration on the cytotoxicity of A. fumigatus culture filtrate, and to determine the optimal condition for the rapid production of gliotoxin from this fungus. Fungal culture filtrates were made in three different containers under various conditions of aeration and O2 concentration. These filtrates were compared in terms of their cytotoxicity on murine macrophages and analyzed by gas chromatography. The culture filtrate showed high cytotoxicity when it was made under highly aerated conditions, but it was significantly less cytotoxic when prepared under non-aerated conditions. The cytotoxic activity became evident within 15 h of culture at 20% O2, when the fungus had already started producing gliotoxin. The culture filtrates also contained some other as yet unidentified substances that might also to some extent contribute to the cytotoxicity. In light of these results, the authors propose that a highly aerated condition is responsible for the rapid production of gliotoxin, and that gliotoxin might play an important role in the respiratory infection by A. fumigatus, with other toxic substances acting additively or synergistically.

Animals↗
PubMed2004

Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate.

Gliotoxin, one of the mycotoxins produced by Aspergillus fumigatus, has various, potent bioactivities. However, it has not been considered to be a toxic (or virulence) factor because of its slow production. The aim of the present study was to investigate the effects of aeration on the cytotoxicity of A. fumigatus culture filtrate, and to determine the optimal condition for the rapid production of gliotoxin from this fungus. Fungal culture filtrates were made in three different containers under various conditions of aeration and O2 concentration. These filtrates were compared in terms of their cytotoxicity on murine macrophages and analyzed by gas chromatography. The culture filtrate showed high cytotoxicity when it was made under highly aerated conditions, but it was significantly less cytotoxic when prepared under non-aerated conditions. The cytotoxic activity became evident within 15 h of culture at 20% O2, when the fungus had already started producing gliotoxin. The culture filtrates also contained some other as yet unidentified substances that might also to some extent contribute to the cytotoxicity. In light of these results, the authors propose that a highly aerated condition is responsible for the rapid production of gliotoxin, and that gliotoxin might play an important role in the respiratory infection by A. fumigatus, with other toxic substances acting additively or synergistically.

Aerobiosis↗
PubMed2004

[Case report of pentazocine dependence from a standpoint of the cognitive therapy].

Drug dependence is a social problem of over the world and resistant to medical intervention by psychiatrist as well as general clinicians. In Japan, methamphetamine dependence is one of the most critical social problems, but opioid dependence is relatively rare. Pentazocine was called the non-addictive opioid at the time of development and release and there are few reports of its dependence. We experienced a medical worker with pentazocine dependence. He started to use pentazocine to reduce serious migraine and felled into dependence by changing the purpose to relaxation of stammering fear and strain towards other people. He was successfully treated by cognitive therapy.

Adult↗