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Biomedical subjects

Hiroshi Sakata

Publications and source records attributed to Hiroshi Sakata.

14 recordsLinked to original sources
PubMed2006

Bactericidal activities of parenteral antibiotics and genotype of penicillin-binding protein in Streptococcus pneumoniae and Haemophilus influenzae isolated from children's blood.

A total of 16 isolates of Streptococcus pneumoniae and 18 isolates of Haemophilus influenzae were obtained from the blood of children admitted to the pediatric wards of hospitals in Hokkaido Kamikawa subprefecture between January 2003 and December 2005. The ages of the patients with S. pneumoniae or H. influenzae infection ranged from 2 months to 9 years and from 1 month to 4 years, respectively. The diagnoses of S. pneumoniae infection were as follows: pneumonia in 8 patients, occult bacteremia in 5 patients, and meningitis in 3 patients. The diagnoses of H. influenzae were: meningitis in 6 patients, pneumonia in 4 patients, occult bacteremia in 4 patients, epiglotitis in 2 patients, and facial cellulitis in 2 patients. Out of 16 S. pneumoniae isolates, penicillin-resistant strains with a mutation of 3 genes were observed in 7 children, and penicillin intermediate-resistant strains with a mutation of 1 or 2 genes were observed in 8 children. Out of 18 H. influenzae isolates, the beta-lactamase-negative ampicillin-resistant strain with a substitution of 2 points in the ftsI gene was revealed in 2 children, the beta-lactamase-negative ampicillin-resistant strain with a substitution of 1 point in the ftsI gene was observed in 4 children, the beta-lactamase-positive amoxicillin/clavulanic acid-resistant strain with blaTEM-1 and ftsI with 2 substitutions in the ftsI gene was observed in 3 children, and the beta-lactamase-positive ampicillin-resistant strain with blaTEM-1was not observed. The MBC90s of ampicillin, ceftriaxone, cefotaxime, meropenem, panipenem, and vancomycin against S. pneumoniae were 8 microg/ml, 1 microg/ml, 1 microg/ml 1 microg/ml, 0.25 microg/ml, and 0.5 microg/ml, respectively. Those of ampicillin, piperacillin, ceftriaxone, cefotaxime, meropenem, and panipenem against H. influenzae were >128 microg/ml, >128 microg/ml, 0.25 microg/mL, 1 microg/ml, 0.12 microg/ml, and 0.5 g/ml, respectively. It is suggest that the minimum bactricidal concentration (MBC) was dissociated from the minimum inhibitory concentration (MIC) in S. pneumoniae and H. influenzae with abnormal pbp genes.

Ampicillin Resistance↗
PubMed2006

[Serotype distribution and penicillin-binding protein genes of Streptococcus pneumoniae in children with invasive pneumococcal infection].

Between August 1998 and July 2005, we studied the serotypes and mutation of penicillin-binding protein (PBP) genes of 46 strains of Streptococcus pneumoniae isolated from children with invasive pneumococcal infection in Hokkaido. The clinical diagnosis was pneumonia in 16 cases, occult bacteremia in 15, meningitis in 8, upper respiratory infection in 6, and arthritis in 1. Patients ranged in age from 2 months to 9 years old. Prevalent serotypes were 6B (39.1%), 23F (17.4%) 6A (8.7%), and 19F (8.7%). The serotype coverage rate by the 7-valent pneumococcal vaccine was greater than 70% in children. Mutation of 3 genes (Penicillin-binding S. pneumoniae, PRSP) was detected in 18 isolates, mutation of 10 genes (pbp1a and pbp2x, or pbp2x and pbp2b) in 2, and of pbp2x alone in 15. PRSP was found in serotypes 6A, 6B, and 23F, and the rate of PRSP in 6A, 6B, and 23F was 75.0%, 62.5%, and 55.6%, respectively.

Bacteremia↗
PubMed2006

[Relationship between protein binding and antimicrobial activities of antibiotics against Streptococcus pneumoniae and Haemophilus influenzae].

Fifty isolates of Streptococcus pneumoniae and 42 isolates of Haemophilus influenzae were isolated from the blood of children admitted to pediatric wards of hospitals in subprefucture between January 1998 and December 2005. The susceptibilities were measured by a microbroth dilution method using a standard broth and a broth containing 4.5% albumin. Against S. pneumoniae, penicillin G, ampicillin, cefotaxime, ceftriaxone, panipenem, meropenem, vancomycin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used and against H. influenzae, ampicillin, piperacillin, cefotaxime, ceftriaxone, panipenem, meropenem, clavulanic acid/ amoxicillin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used. Against S. pneumoniae, tebipenem was the highest antimicrobial activity in oral antibiotics (MIC90; < or = 0.06 microg/ml) and panipenem showed the highest activity for intravenous antibiotics (MIC90; < or = 0.12 microg/ml). Against H. influenzae, cefditoren was the highest activity for oral antibiotics (MIC90; < or = 0.06 microg/ml) and meropenem showed the highest activity for intravenous antibiotics (MIC90; < or = 50.06 microg/ml). The MIC90s measured by albumin containing broth were higher than those measured by standard broth. Protein binding rates of ceftriaxone, cefditoren, and faropenem were greater than 90%, and the MIC90 of these antibiotics measured by albumin addition methods were over 4-fold higher than those measured by standard methods.

Administration, Oral↗
PubMed2005

Apoptosis under hypercytokinemia is a possible pathogenesis in influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy is reported to be frequent in Japan and East Asia. No evaluating markers except interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and no likely pathological mechanism for the disease have yet been elucidated. METHODS: In this study, influenza-associated encephalopathy was defined by clinical symptoms, and the use of an anti-influenza antibody test and/or influenza antigen detection kits, as well as computed tomography and/or magnetic resonance imaging. The levels of proinflammatory cytokines, acute phase proteins, endothelial markers and cytochrome c were compared in sera from 11 patients with and 42 without encephalopathy. RESULTS: Cytochrome c concentration in sera from patients with encephalopathy was markedly increased compared with that from patients without encephalopathy and normal controls. Although levels of several other proinflammatory cytokines and acute phase proteins such as TNF-alpha and IL-8 were also elevated in patients with influenza virus infection, the difference between those with and without encephalopathy, though significant, was less dramatic. The mean serum concentration of cytochrome c in 11 patients with encephalopathy, consisting of four deceased, four with and three without residual central nervous system sequelae, was 26.7 +/- 19.5 ng/mL on admission. In contrast, cytochrome c levels in 42 patients without encephalopathy were 0.3 +/- 0.7 ng/mL. CONCLUSION: The present results indicate that cytochrome c is a useful marker to follow patients with influenza-associated encephalopathy and suggest that an apoptosis of cells in several organs including the cerebrum and liver under the influence of hypercytokinemia is a possible mechanism of the disease.

Apoptosis↗
PubMed2005

[Study of Streptococcus pneumoniae bacteremia in children].

From July 1999 to June 2004, we evaluated Streptococcus pneumoniae bacteremia in 40 children in Kamikawa and Soya Subprefectures in Hokkaido by obtaining the patient's information from 7 out of 9 hospitals in the area. The incidences of S. pneumoniae bacteremia in children aged < 2 years and < 5 years were 79.1 and 63.4. Median age was 19.6 months with a range from 4 months to 4 years. Thirty-one (77.5%) of the total were less than 2 years old. All of the children were admitted. The diagnoses were occult bacteremia in 12 patients, pneumonia or bronchitis in 11, pharyngitis in 7, pneumonia and acute otitis media in 5, acute otitis media in 3, orbital cellulitis in 1, and arthritis in 1. All of the patients had fever and temperatures and 35 (87.5%) of them were more than 39 degrees C. Ten patients had a febrile convulsion. Twenty-nine had a high total white blood cell counts (> 15,000/microg/ml) and 31 had positive CRP values (> 0.6 mg/dl) on admission. Meningitis and poor prognosis did not occur after occult bacteremia in our patients. We studied the susceptibility to penicillin G in 22 strains of S. pneumoniae isolated from the children. One and 18 strains were penicillin-resistant (MIC > or = 2.0 microg/ml) and intermediate (MIC 0.1-1.0 microg/ml).

Bacteremia↗
PubMed2005

[A study of bacterial meningitis in Hokkaido between 1999 and 2003].

We evaluated 83 children with bacterial meningitis in 67 of 81 insitutions in Hokkaido, Japan between 1999 and 2003 by questionnaire. The incidence of bacterial meningitis in children aged < 5 years and 5 < or =, < 10 years was 6.3 and 0.7 cases per 100, 000 children/year. The incidences of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus agalactiae in children aged < 5 years were 3.7, 1.4 and 0.8. Median age was 13 months ranging from 0 day to 9 years. Seventy-four (89.1%) of the total were less than 5 years old with 39 (47.0%) less than 1 year old. Major causative organisms were H. influenzae in 51 patients, S. pneumoniae in 18, S. agalactiae in 9 and E. coli in 3. Four deaths occurred, giving an overall case mortality rate of 4.8%. Sequelae were seen at discharge in 25.3%, predominantly epilepsy, hearing loss, and developmental delay of varying severity. The frequency of poor prognosis was 55.6% for patients with meningitis due to S. pneumoniae compared with 21.6% for H. influenzae and 22.2% for S. agalactiae.

Child↗
PubMed2004

[Antimicrobial susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae isolated from children with meningitis].

Between April 2001 and March 2003, we studied minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 7 strains of Streptococcus pneumoniae and 8 strains of Haemophilus influenzae isolated from children with meningitis. The age range of the patients was from 4 months to 5 years. Susceptibilities of ampicillin (ABPC), cefotaxime (CTX), panipenem (PAPM), and vancomycin (VCM) in S. pneumoniae and those of ABPC, CTX, ceftriaxone (CTRX), and meropenem (MEPM) in H. influenzae were measured. MICs of ABPC, CTX, PAPM, and VCM to S. pneumoniae were < or = 0.06-2, < or = 0.06-0.5, < or = 0.06, and 0.25-0.5 microgram/ml and MICs of ABPC, CTX, CTRX, and MEPM to H. influenzae were 0.12-64, < or = 0.06-0.5, < or = 0.06-0.12, and < or = 0.06-0.25 microgram/ml, respectively. In 5 of all strains, difference between MIC and MBC to ABPC was observed. Four strains out of them had mutations of penicillin binding protein genes measured by PCR methods.

Ampicillin↗
PubMed2003

Can an arbitrary sequence evolve towards acquiring a biological function?

To explore the possibility that an arbitrary sequence can evolve towards acquiring functional role when fused with other pre-existing protein modules, we replaced the D2 domain of the fd-tet phage genome with the soluble random polypeptide RP3-42. The replacement yielded an fd-RP defective phage that is six-order magnitude lower infectivity than the wild-type fd-tet phage. The evolvability of RP3-42 was investigated through iterative mutation and selection. Each generation consists of a maximum of ten arbitrarily chosen clones, whereby the clone with highest infectivity was selected to be the parent clone of the generation that followed. The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein. This study therefore exemplifies the process of a random polypeptide generating a functional role in rejuvenating the infectivity of a defective bacteriophage when fused to some preexisting protein modules, indicating that an arbitrary sequence can evolve toward acquiring a functional role. Overall, this study could herald the conception of new perspective regarding primordial polypeptides in the field of molecular evolution.

Amino Acid Sequence↗
PubMed2003

[10-yearly monitoring of prevalence of MRSA and antibiotic usage in a neonatal intensive care unit].

From 1992 to 2001, we studied the prevalence of infants colonized MRSA and antibiotic usage for very-low-birth-weight infants in a neonatal intensive care unit at Asahikawa Kosei Hospital. We investigated nasopharyngeal swabs and stool samples every week after admission, and occasionally skin swabs, eye discharges and urines. Seventeen infants contracted nosocomial blood stream infection caused by MRSA which occurred between 1993 and 1996. Rate of infants colonized MRSA to all inpatients was 14.9% in 1992, which increased to 40.0% in 1994, and decreased to 7.1% in 2001. In each birth-weight group, rates of > or = 1,500 g, 1,000-1,499 g, and < 1,000 g infants were 6.5%, 45.0% and 60.0% in 1992, 24.5%, 100%, and 100% in 1994, 6.2%, 10.5%, and 21.4% in 2001. The longest period of antibiotic usage was 148.4 per 1000 patient-day in 1995 and decreased to 32.6 per 1,000 patient-day in 2001. The total value of antibiotics in 1995 was about yen 3,050,000, but in 2001 was about yen 470,000.

Anti-Bacterial Agents↗
PubMed2003

[Evaluation of rapid urinary antigen test kit for Streptococcus pneumoniae in children with pneumonia or meningitis].

We evaluated rapid urinary antigen test kit for Streptococcus pneumoniae (Binax NOW S. pneumoniae) in 85 inpatients between February 2002 and November 2002. Diseases of patients were pneumonia in 82 and meningitis in 3. The age range of the patients was from 4 months to 14 years. We studied urinary antigen assay and culture of nasopharyngeal swab in all patients. Three infants with meningitis were measured liquor by the kit. Two infants with meningitis due to S. pneumoniae showed positive reactions in urine and liquor, but result of 1 infant with meningitis due to Haemophilus influenzae was negative. Of 82 patients with pneumonia, S. pneumoniae was isolated from 52 patients and the urinary antigen test was positive in 39. Thirty-eight patients were isolated S. pneumoniae in 39 positive patients and 14 children were isolated it in 44 negative patients. Sensitivity in this test kit was 73.1% and specificity was 96.8%. This test is useful for children as well as adults.

Adolescent↗
PubMed2002

[Mutation of penicillin-binding protein genes and antimicrobial susceptibility of Haemophilus influenzae isolated from spinal fluid or blood in children].

Between September 1999 and August 2001, we studied serotypes to capsular antigen, beta-lactamase production, mutation of penicillin binding protein (PBP) genes by PCR method, and antimicrobial susceptibilities of 13 strains of Haemophilus influenzae isolated from spinal fluid or blood in children. Diseases of patients were meningitis in 11, pneumonia in 1, and laryngitis in 1. The age range of the patients was from 26 days to 5 years. The serotypes of all strains were b. Four of the 13 strains were beta-lactamase-positive. The mutation of genes of pbp3 was revealed from 4 isolates and 2 of the strains were beta-lactamase-positive. MICs of ampicillin to beta-lactamase-negative strains ranged from 0.125 to 1 microgram/ml and those to beta-lactamase-positive were more than 32 micrograms/ml. MICs of 2 strains of beta-lactamase-negative and mutation-positive were 0.5 and 1 microgram/ml. The excellent active antimicrobials in our study was cefotaxime (MIC90 0.06 microgram/ml), meropenem (MIC90 0.125 microgram/ml), ceftazidime (MIC90 0.25 microgram/ml), and cefepime (MIC90 0.25 microgram/ml).

Anti-Bacterial Agents↗
PubMed2002

[Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field].

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.

Anti-Bacterial Agents↗