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Noboru Yamanaka

Publications and source records attributed to Noboru Yamanaka.

35 records · Page 2Linked to original sources
PubMed2005

Increase of macrolide-resistant Streptococcus pneumoniae-expressing mefE or ermB gene in the nasopharynx among children with otitis media.

OBJECTIVE: To evaluate prevalence of macrolide resistant strains and the genotypes of the resistance among Streptococcus pneumoniae isolated from the nasopharynx of children with otitis media. STUDY DESIGN: Retrospective review. METHODS: A total of 858 S. pneumoniae isolates were collected from the nasopharynx of pediatric patients with acute otitis media at the clinics of Otolaryngology-Head and Neck Surgery, Wakayama Medical University Hospital and six affiliated hospitals in Wakayama prefecture between January 1998 and December 2002. The antibiotic susceptibility patterns were analyzed for penicillin, erythromycin, and clindamycin according to the National Committee for Clinical Laboratory Standards. Macrolide resistance genes of mefE and ermB were determined by polymerase chain reaction of all S. pneumoniae. RESULTS: Of 858 clinical isolates, 259 (30.1%) were strains without ermB or mefE gene, 279 (32.5%) carrying mefE, 292 (34.0%) carrying ermB, and 28 (3.4%) carrying both genes. There was a strong correlation between phenotypes and the presence of macrolide resistance genes. The macrolide resistance genes were especially frequently identified among penicillin-resistant S. pneumoniae. Strains carrying ermB gene gradually increased from 25% in 1998 to 45% in 2002, with a concurrent decrease in strains carrying mefE from 36% in 1998 to 1999 to 19% in 2002. Strains having mefE were frequently identified among children younger than 2 years old. The current finding suggested that high-level ermB-mediated macrolide resistance in S. pneumoniae is increasing at an alarming rate in pediatric patients with otitis media, especially among young children. Physicians should pay close attention to such macrolide-resistant bacterial pathogens in the antimicrobial treatment of pediatric patients with otitis media.

Bacterial Proteins↗
PubMed2004

Treatment and outcome of severe and non-severe acute otitis media.

UNLABELLED: To determine outcomes in acute otitis media (AOM) according to severity of disease and to assess different initial treatment regimens, 308 with AOM were enrolled and divided into severe (n = 277; 89.9%) and non-severe (n = 31; 10.1%) groups based on symptoms and tympanic membrane changes. Children in the severe group were initially managed with amoxicillin (AMPC) whereas children in the non-severe group were initially managed without antibiotics. Children were monitored on days 1, 5, 10, 14 and 28. Five outcome measures were assessed: disappearance of symptoms at day 5, resolution of tympanic membrane changes by day 28, disappearance of middle ear effusions by day 28, recurrence of acute symptoms prior to day 28, and need to change treatment regimens. Children with severe disease were more often male (57% versus 36%, P < 0.05) and more often colonized with pathogens (77% versus 55%, P < 0.05 than children with non-severe disease. The two groups were similar with respect to age and day care attendance. Despite differences in initial treatment regimens between the two groups, symptoms improved at the same rate for severe and non-severe disease, 94% by day 5. In contrast, tympanic membranes returned to normal in 69% of the severe and 81% of the non-severe groups by day 28; however, as early as day 5, 10% of the severe and 55% of the non-severe groups demonstrated normal tympanic membranes. Middle ear effusions similarly disappeared more slowly in the severe group, 52% versus 74% by day 14 and 76% versus 84% by day 28. Recurrence rates of acute symptoms occurred with equal frequency in the severe, 15%, and non-severe groups, 10%. Failure of the symptoms or the tympanic membranes to improve led to antibiotic changes in 59.9% of the severe group and to the addition of antibiotics in 51.6% of the non-severe group. Children in the severe group who failed to improve with an initial course of amoxicillin were younger (40.2 months versus 45.8 months, P < 0.05), had higher tympanic membrane scores (4.5 versus 4.1, P < 0.05), and were more often colonized with penicillin-resistant Streptococcus pneumoniae (33.8% versus 6.5%, P < 0.01) than children who responded to AMPC. In a similar manner, children with non-severe disease who failed to improve without antibiotics were younger (40.7 months versus 54.8 months, P < 0.05) and more often colonized with pathogens (75.0% versus 33.4%, P < 0.05). CONCLUSION: Severe disease occurred more often among males and among children colonized with pathogens. Response to treatment was impaired in younger children and in children colonized with pathogens, especially penicillin-resistant Streptococcus pneumoniae.

Acute Disease↗
PubMed2004

Macrolide-resistant genes of Streptococcus pyogenes isolated from the upper respiratory tract by polymerase chain reaction.

The growing number of macrolide-resistant strains of Streptococcus pyogenes is an increasing problem worldwide. This study evaluated 300 clinical isolates obtained from the upper respiratory tract. Minimal inhibitory concentrations (MICs) of erythromycin (EM), azithromycin (AZM), and clindamycin (CLDM), serotypes, and macrolide resistance genes of mefA, ermB, and ermTR were determined. The genetic relationship of EM-resistant and susceptible strains were also analyzed by pulsed-field gel electrophoresis (PFGE). Twenty-nine (9.7%) EM-resistant S. pyogenes were identified. Of the 29 strains showing resistance to EM, 22 isolates (7.3%, MIC 3.13-12.5 microg/ml) expressed the mefA gene. The predominant serotypes among the mefA-positive isolates were T12, emm9 or T25, emm75-1. The two isolates (0.1%) that possessed the ermB gene were highly resistant to EM (MIC > 100 microg/ml). The remaining five strains (1.6%) possessed the ermTR gene (MIC 3.13-100 microg/ml). Restriction fragment polymorphism analyzed by pulsed-field gel electrophoresis (PFGE) by SmaI and ApaI digestions showed several clones among the mefA-positive S. pyogenes. Our findings suggest that the mefA gene is the predominant mechanism for macrolide resistance and that this gene is horizontally transmitted among M phenotype strains of S. pyogenes. Consequently, macrolides would not be the first drug of choice for treatment of tonsillitis and other S. pyogenes-related diseases. Physicians and researchers need to take into consideration the macrolide resistance of some strains of S. pyogenes.

Adolescent↗
PubMed2004

Immunity of tonsil and IgA nephropathy--relationship between IgA nephropathy and tonsillitis.

Our study hypothesized that cytokines or chemokines induced in tonsils by infectious stimulations play an important role on the exacerbation of the glomerular injuries in patients with IgA nephropathy (IgAN). Tonsils from six patients with IgAN diagnosed by renal biopsy were studied after getting their written informed consents Tonsils from six patients with tonsil disorders with non-renal disorders were examined as controls. Tonsillar mononuclear cells (TMCs) were isolated and resuspended with RPMI 1640 with 10% FCS. These cells were incubated for 48 h with staphlococcus enterotoxin-B (SEB) or lipopolysaccaride (LPS). The levels of IL-6, IL-8, IL-12 and MCP-1 in the supernatants were measured by solid-phase enzyme-linked immunosorbent assay (ELISA) kits. The actual cytokine concentrations were calculated by determining the standard curves. The experiments were performed in duplicate, and the mean value was calculated. We found that tonsillar mononuclear cells of IgA nephropathy produced mesangial proliferative chemokines (MCP-1, IL-8) in higher amounts compared to tonsils from non-IgA nephropathy. This result suggests that upper respiratory tract infections such as tonsillitis may be one of the risk factors of the aggravation in patients with IgA nephropathy.

Cells, Cultured↗
PubMed2004

Genotyping of Streptococcus pneumoniae and Haemophilus influenzae isolated from paired middle ear fluid and nasopharynx by pulsed-field gel electrophoresis.

Twenty-eight isolates of Streptococcus pneumoniae and 30 isolates of Haemophilus influenzae from paired nasopharynx and middle ear fluids of 21 children with acute otitis media (AOM) were evaluated to determine genotypes by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE). Among the 28 isolates of S. pneumonaie, 21 isolates (75.0%) possessed mutations in the pbp1a,pbp2x, and pbp2b genes, and 7 isolates (25%) had mutations in the pbp2x gene. Nineteen isolates (67.9%) expressed the mefE gene, and 5 isolates (17.9%) possessed the ermB gene. Among the 30 isolates of H. influenzae, 5 isolates (16.7%) had mutations in pbp3 genes, 3 isolates (10.0%) produced beta-lactamase, and 2 (6.7%) isolates possessed mutations both in the pbp3 gene and the beta-lactamase gene. Ten out of the 14 pairs (71.4%) of the restriction fragment patterns of S. pneumoniae from paired nasopharynx and middle ear fluids were indistinguishable following PFGE analysis. The same patterns were identified among 5 children of unrelated families. The restriction fragment patterns of H. influenzae isolated by PFGE were also indistinguishable in 13 out of the 15 pairs (86.7%) of nasopharynx and middle ear fluids. The genetic similarity between nasopharyngeal and middle ear isolates suggests that the causative bacteria migrate from the nasopharynx into the middle ear cavity via the Eustachian tube. Some resistant strains might be prevalent. In children with AOM, the nasopharynx could have been colonized by a virulent strain of bacteria that replaced the benign, commensal bacteria and then progressed to the middle ear, where they caused AOM.

Bacterial Proteins↗
PubMed2004

Factors associated with clinical outcomes in acute otitis media.

Acute otitis media (AOM) is a common disease in childhood. If predictors of outcome in AOM were known, it would be possible to individualize therapy. Our aim was to identify factors that predict the outcome in AOM. We enrolled 368 children with AOM (ages, 10 to 86 months). The severity of symptoms and the severity of tympanic membrane changes were graded with a scoring system. Nasopharyngeal colonization with middle ear pathogens was determined on day 1. Three outcomes were assessed: persistence of symptoms at day 5, persistence of tympanic membrane changes at day 28, and recurrence of acute symptoms prior to day 28. Persistence of symptoms at day 5 was associated with younger age (35 versus 44 months; p < .001), higher symptom score on day 1 (3.5 versus 2.9; p < .05), and colonization with Streptococcus pneumoniae (61% versus 41%; p < .05). Persistence of tympanic membrane changes at day 28 was associated with younger age (39 versus 45 months; p < .01), higher tympanic membrane score on day 1 (4.1 versus 3.6; p < .01), and nasopharyngeal colonization with S. pneumoniae, especially drug-resistant S. pneumoniae (33% versus 13%; p < .05). Recurrence of acute symptoms prior to day 28 occurred in 14% of the children. Streptococcus pneumoniae was the only pathogen associated with an increased recurrence rate (23%) as compared to the group without pathogens (7%; p < .05). Age, severity of disease at presentation, and nasopharyngeal colonization patterns were proven to be important determinants of outcome in AOM.

Child↗
PubMed2003

[Roles of beta-catenin overexpression and adenomatous polyposis coli mutation in head and neck cancer].

Beta-catenin is an undercoat protein of cadherin, a cellular adhesion molecule. Beta-catenin also functions as a transcriptional activator downstream of the Wnt signaling pathway. Intracellular beta-catenin is regulated by the formation of a complex with APC (adenomatous polyposis coli) protein. The activation of this pathway by stabilization with beta-catenin has been shown to be an important step in the development of colorectal carcinoma, which is mainly caused by inactivating mutations in the APC tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. This study was conducted to clarify the contribution of beta-catenin accumulation and the mutation of the beta-catenin gene to the carcinogenesis of head and neck cancer. Beta-catenin accumulation was examined immunohistochemically in 49 frozen or formalin-fixed, paraffin-embedded samples of head and neck tumors. We also performed a direct sequence analysis of APC and beta-catenin to examine the cause of beta-catenin accumulation. Genomic DNA was extracted and purified from fresh tissue samples of head and neck cancers. We examined the APC mutation cluster region in 15 samples and analyzed beta-catenin exon 3 mutations in 31 cases. Twelve out of 49 (24.5%) cases exhibited beta-catenin accumulation in our histochemical study. The 5 year survival rate was 0% in the beta-catenin accumulation group, compared to 50% in the non-accumulation group, (p < 0.01). This finding strongly suggests that beta-catenin may play an important role in the carcinogenesis or progression of head and neck cancer. One of the 15 cases exhibited an APC missense mutation that led to the replacement of amino acids; this case died in 12 months. Regarding the beta-catein mutation, non of the 31 samples exhibited a gene mutation in beta-catenin exon 3. Thus, the rate of APC and beta-catenin mutation in head and neck cancer may be very low.

Adult↗
PubMed2003

[A questionnaire survey on the theory of postoperative infection prophylaxis in otorhinolaryngology].

A questionnaire survey on postoperative infection prophylaxis was conducted to achieve the consensus on the perioperative antimicrobial use among otolaryngologists in Japan during the period of time from April to July 2000. Fifty-two out of 84 otolaryngologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Pseudomonas aeruginosa and Bacteroides fragilis group; Use an AMP agent that achieves a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. Newer agents should be considered as therapeutics for postoperative infections. Therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations is cefazolin (CEZ), followed by cefotiam (CTM) and piperacillin (PIPC), in this order. For clean-contaminated operations, the most commonly used agent is CEZ, followed by flomoxef (FMOX) and CTM.

Antibiotic Prophylaxis↗
PubMed2003

[Susceptibility of major pathogens of acute pharyngitis and tonsillitis to levofloxacin and other oral antimicrobial drugs].

A total of 2865 strains of the causative organisms isolated from the patients with acute pharyngitis and tonsillitis at the primary medical institutions were used in this study. The MICs of levofloxacin (LVFX) and other oral antimicrobial drugs were determined and evaluated by the NCCLS guideline. LVFX, cefditoren (CDTR) and cefcapene (CFPN) were potently active against 773 isolates of Hemophilus influenzae, the MIC50S of LVFX being < or = 0.06 microgram/mL and also the same as the MIC90S of LVFX. LVFX was the most active against 496 isolates of Enterobacteriaceae. The MIC50S of LVFX were < or = 0.06 microgram/mL and were lower than those of CDTR, cefdinir (CFDN) and cefpodoxime (CPDX) (MIC50S: 0.5 microgram/mL). The MIC90S of these cephems were markedly higher than the respective MIC50S, whereas MIC50 of LVFX was 0.12 microgram/mL, only twice the MIC50. Against the majority of Streptococcus pyogenes (555 isolates) and Streptococcus spp. (495 isolates), CDTR, CFDN, CPDX and CFPN were highly active (MICs: < or = 0.06 microgram/mL), and clarithromycin (CAM) and azithromycin (AZM) were also active against these organisms (MICs: 0.12 to 0.25 microgram/mL). Against S. pneumoniae (92 isolates), CDTR and CFDN were active (MIC50S: 0.12 and 0.25 microgram/mL, respectively). However, the MIC90S of these drugs were 4-8 times the MIC50S. Against Moraxella (Branhamella) catarrhalis (454 isolates), LVFX was potently active, the MIC90 of LVFX being < or = 0.06 microgram/mL and MIC90S of the other cephems being 0.5 microgram/mL or more. When the susceptibility of these strains to LVFX was evaluated by the NCCLS guideline, about 3% of other Streptococcus spp. were resistant to the drug but no test strains resistant to LVFX were detected in H. influenzae, S. pyogenes or Enterobacteriaceae. On the other hand, the percentages of strains susceptible to the cephems tested were 60-90%, which were quite different according to kinds of drugs and species used. Furthermore, the strains of S. pneumoniae resistant to CFDN and CPDX, and those to CAM and AZM were 21-25% and 50% or more, respectively, whereas no LVFX-resistant strains were detected. The major pathogens isolated from patients with pharyngitis and tonsillitis in the primary institutions were highly susceptible to LVFX. These results suggest that LVFX is a useful drug which is potently active against the strains resistant to oral cephem and macrolide antibiotics.

Acute Disease↗
PubMed2002

Intranasal immunization with recombinant outer membrane protein P6 induces specific immune responses against nontypeable Haemophilus influenzae.

OBJECTIVE: Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative pathogens for otitis media. The outer membrane protein P6 of NTHi is highly conserved among the strains and is an attractive candidate for a preventive vaccine. However, for the production of a relatively small amount P6 containing lipopolysaccharides, the development of a recombinant version of this protein is required. This study was designed to investigate the specific mucosal immunity induced by intranasal immunization of recombinant P6 (rP6) with cholera toxin (CT). METHODS: BALB/c mice were immunized with of rP6 (30 microg) and CT (2 microg) intranasally every 2 days for 2 weeks. Anti-rP6 specific IgG, IgA and IgM antibodies and the subclass of anti-rP6 specific IgG antibody were determined by enzyme linked immunosorbent assay (ELISA). Anti-rP6 specific IgA in nasopharyngeal washings were also determined by ELISA. Nasopharyngeal clearance of inoculated NTHi after the intranasal immunization were assessed. All statistical differences between the two groups were assessed by ANOVA parametric test. RESULTS: Intranasal immunization with rP6 and CT evoked rP6-specific mucosal IgA immune response as well as the systemic IgG immune response against rP6 and enhanced nasopharyngeal clearance of inoculated live NTHi. CONCLUSION: These results indicate the good immunogenicities of rP6 to induce specific immune responses against NTHi. Intranasal immunization with rP6 will be an effective approach to protect infections of NTHi.

Analysis of Variance↗
PubMed2002

Nasopharyngeal carriage of drug-resistant Streptococcus pneumoniae in children with acute otitis media evaluated by polymerase chain reaction-based genotyping of penicillin-binding proteins.

A polymerase chain reaction (PCR)-based genotyping of the penicillin-binding protein (PBP) genes pbp1a, pbp2x and pbp2b was used to characterize Streptococcus pneumoniae isolated from the nasopharynx of children with acute otitis media (AOM). Mutations were observed in pbp1a, pbp2x and pbp2b genes in 36.5% of the strains. Decreased susceptibility to beta-lactam antibiotics was closely associated with the frequency of mutations in the three PBP genes. Of penicillin-intermediately-resistant S. pneumoniae strains, 54.5% appeared to be genetically similar to penicillin-resistant S. pneumoniae strains. Of penicillin-susceptible S. pneumoniae strains, 33.3% had mutations in the pbp2x gene and showed relatively high MICs to cephalosporins. Strains with mutations in the three PBP genes were often isolated from children < or = 2 years old. Evaluation of mutations in PBP genes using PCR will prove useful for studying the epidemiology of antibiotic resistance.

Acute Disease↗
PubMed2002

Household transmission of Streptococcus pneumoniae among siblings with acute otitis media.

Nasopharyngeal transmission of Streptococcus pneumoniae was evaluated among 23 siblings with acute otitis media (AOM). Restriction fragment length polymorphism revealed that the nasopharyngeal strains were identical between siblings in 12 of 13 clusters of AOM experienced in 11 families. This study demonstrated person-to-person transmission of S. pneumoniae, especially drug-resistant strains, among siblings with AOM.

Acute Disease↗
PubMed2002

An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin.

To date an increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Survivin was originally identified as a member of the inhibitor of apoptosis protein family. Expression of this gene is developmentally regulated. Although survivin is expressed during normal fetal development, the expression is barely detected in terminally differentiated adult tissues except for testis, thymus, and placenta. In contrast, it is abundantly expressed in a wide variety of malignant tissues. We examined the expression of survivin and the two splicing variants survivin-2B and survivin-DeltaEx3 in various cancer cells, immortalized cells, and normal adult tissues. It was demonstrated that two splicing variants were detected in various types of cancer cells as well as survivin, and their expression was more restricted to cancer cells as compared with survivin expression. To identify HLA-A24-restricted T-cell epitopes from survivin and the variant proteins, three peptides were selected from amino acid sequence of these proteins, based on the HLA-A24-binding motif. Peptide binding assay to HLA-A24 revealed that only one peptide designated as survivin-2B80-88 (AYACNTSTL) was capable of binding to HLA-A24. By stimulating peripheral blood lymphocytes with the peptide-pulsed antigen-presenting cells, CTLs were successfully induced in vitro from five of five HLA-A24-positive cancer patients. The CTLs showed significant cytotoxicity against HLA-A24-positive survivin-2B-positive cancer cells. These data suggest that survivin-2B80-88 may be a potent T-cell epitope eliciting CTL response against a splicing variant survivin-2B, which is specifically expressed in many kinds of cancer cells.

Amino Acid Sequence↗
PubMedDate not supplied

A fast placement technique for covered tracheobronchial stents in patients with complicated esophagorespiratory fistulas.

PURPOSE: To test an endotracheal placement procedure for malignant esophagorespiratory fistula when endoesophageal placement is inapplicable. METHODS: We report on patients with malignant esophagorespiratory fistula to which endoesophageal approaches were complicated with a complete obstruction of the hypopharynx, a collapsible tracheobronchus, or a previously placed endoesophageal stents. Gore-Tex membrane-covered Z-stents were deployed in the trachea using a coaxial introducer system in three patients. A Dumon tube was deployed in the bronchus over the bronchofiberscope in one patient. RESULTS: All fistula were completely sealed by the endotracheal or endobronchial stenting. Symptomatic and clinical improvements were immediate obtained. CONCLUSION: Endotracheal or endobronchial covered stent placement is thought to be an effective alternative method for sealing esophagorespiratory fistula.

Aged↗