Clinical significance of human neutrophil antigen-1 antibodies in children with neutropenia.

Primary autoimmune neutropenia in young children is characterized by chronic neutropenia and positivity for antibodies against human neutrophil antigens (HNAs). This study analyzed the clinical characteristics of 402 children with neutropenia to identify differences between those with and without HNA-1 antibodies (HNA1abs). HNAabs in sera were detected by granulocyte immunofluorescence testing using flow cytometry. Relative fluorescence intensity (RFI) values were used to divide patients into positive (PG, n = 302), borderline (BG, n = 34), and negative (NG, n = 66) groups. The antibodies reacted to HNA-1a alone (59%), HNA-1b alone (1%), and HNA-1a/1b (40%). The PG had a significantly lower absolute neutrophil count before definitive diagnosis and a 1.6- to 2-times greater risk of hospitalization during neutropenia than the other groups. The median duration of neutropenia was longest in the PG at 25 months, followed by 20 months in the BG and 14 months in the NG. This large-scale cohort characterizes clinically distinct groups using the RFI value for HNA1abs in young children with neutropenia. Detection of HNA1abs may aid in understanding the clinical characteristics of children with neutropenia.

Cross-wire assist suit concept, for mobile and lightweight multiple degree of freedom hip assistance.

In this paper, we present our cross-wire assist concept, for assisting a single joint in multiple degrees of freedom. It is comprised of four motor driven Bowden cable actuators (wires) per assisted joint, with the wires crossed over each other at the front and rear. Simulation results show that selectively actuating a subset of these wires allows torque to be generated in 6 directions, with the torque magnitude dependent on joint angle. We have built a fully wearable prototype of our assistance device for both hip joints, with 8 high-speed and independently controllable actuators each providing force up to 100 N. The prototype has a total mass of 9.3 kg, and is shown in motion capture testing to generate movement in 6 directions around the users joint, including internal and external rotation. Mobile, multi-degree of freedom assistance cross-wire system will enable assistive devices to better match human movement, allowing support and rehabilitation in tasks beyond straight line walking.

Twelve-year survey (2001-2012) of the antimicrobial susceptibility of Streptococcus pneumoniae isolates from otorhinolaryngology clinics in Miyagi Prefecture, Japan.

INTRODUCTION: Streptococcus pneumoniae is one of the most common bacteria causing otorhinolaryngological infections, such as acute otitis media and upper respiratory tract infection. Our group surveyed the drug susceptibility profile of S. pneumoniae isolates from otorhinolaryngology patients. MATERIALS AND METHODS: A total of 41,069 S. pneumoniae isolates were detected at Miyagi Medical Association Health Center between May 2001 and December 2012. Specimens were obtained from patients at 40 otorhinolaryngology outpatient clinics in Miyagi Prefecture, Japan. The minimum inhibitory concentrations (MICs) of 8 antimicrobial agents were measured using the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines. RESULTS: In children aged 0-2 years old, the MIC50 values of penicillins decreased after 2010 (PCG: 1 µg/ml (2010) to 0.06 µg/ml (2012); ABPC: 1 µg/ml (2010) to 0.25 µg/ml (2012)). The prevalence of penicillin-resistant S. pneumoniae (PRSP) decreased from 35.2% (2010) to 14.6% (2012) in rhinorrhea specimens and from 43.4% (2010) to 14.3% (2012) in otorrhea specimens. Susceptibility to cephems (ceftriaxone and cefditoren) and carbapenems (panipenem) also showed improvement after 2010. For macrolides (clarithromycin) and lincosamides (clindamycin), MIC50 values increased in all age groups during the study period, and a high level of resistance was seen until 2012. There were no marked changes of susceptibility to fluoroquinolones (LVFX) during the study period. CONCLUSION: Improvement of susceptibility of S. pneumoniae to ß-lactams occurred after 2010 in Miyagi Prefecture, Japan.

Molecular characteristics of extended-spectrum ß-lactamase-producing Escherichia coli in Japan: emergence of CTX-M-15-producing E. coli ST131.

We investigated the molecular characteristics of ESBL-producing Escherichia coli in Japan. A total of 101 clinical isolates of ESBL-positive E. coli collected in Japan between June 2008 and November 2009 were studied. Among the 101 strains, 97 were positive for CTX-M, while 47 and two were positive for TEM and SHV, respectively. Sequencing revealed that CTX-M-14 was most common (49/101), followed by CTX-M-27 (22/101) and CTX-M-15 (8/101). Based on MLST data, seven of eight CTX-M-15 producers belonged to ST131. This is the first report about clinical isolates of E. coli ST131 possessing CTX-M-15 in Japan.

Estimating the burden of acute gastroenteritis and foodborne illness caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus by using population-based telephone survey data, Miyagi Prefecture, Japan, 2005 to 2006.

Most cases of acute gastroenteritis and foodborne disease are not ascertained by public health surveillance because the ill person does not always seek medical care and submit a stool sample for testing, and the laboratory does not always test for or identify the causative organism. We estimated the total burden of acute gastroenteritis in Miyagi Prefecture, Japan, using data from two 2-week cross-sectional, population-based telephone surveys conducted in 2006 and 2007. To estimate the number of acute gastroenteritis illnesses caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus in Miyagi Prefecture, we determined the number of cases for each pathogen from active laboratory-based surveillance during 2005 to 2006 and adjusted for seeking of medical care and submission of stool specimens by using data from the population-based telephone surveys. Monte Carlo simulation was used to incorporate uncertainty. The prevalence of acute gastroenteritis in the preceding 4 weeks was 3.3% (70 of 2,126) and 3.5% (74 of 2,121) in the winter and summer months, yielding an estimated 44,200 episodes of acute gastroenteritis each year in this region. Among people with acute gastroenteritis, the physician consultation rate was 32.0%, and 10.9% of persons who sought care submitted a stool sample. The estimated numbers of Campylobacter-, Salmonella-, and V. parahaemolyticus -associated episodes of acute gastroenteritis were 1,512, 209, and 100 per 100,000 population per year, respectively, in this region. These estimates are significantly higher than the number of reported cases in surveillance in this region. Cases ascertained from active surveillance were also underrepresented in the present passive surveillance, suggesting that complementary surveillance systems, such as laboratory-based active surveillance in sentinel sites, are needed to monitor food safety in Japan.

[Drug susceptibility of bacteria isolated from pediatric respiratory infections at general practitioners' clinics to pediatric antibiotics].

Four major causative bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes) of pediatric respiratory infections, 295 clinical isolates in total, were isolated at general practitioners' clinics in Sendai city, and evaluated the drug susceptibility to seven antibiotics for pediatric. Penicillin-resistant S. pneumoniae and penicillin-intermediate S. pneumoniae (PRSP-PISP) were 55.8% of all S. pneumoniae isolates. The MIC90 of penicillin and cephalosporin antibiotics in S. pneumoniae were good, 0.5-1 microg/mL, however, macrolide-resistant strains remarkably increased. As for H. influenzae, 50.0% of all isolates were ampicillin-intermediate and -resistant (MIC: > or = 2 microg/mL), the MIC90s of cephalosporin antibiotics had large differences between 0.5 to 8 microg/mL, and generally less susceptibility was shown to other antibiotics. M. catarrhalis showed less susceptibility to amoxicillin which behaved unstably to penicillinase, on the other hand, the MIC90s of other antibiotics were relatively good, 0.25-1 microg/mL. S. pyogenes remarkably tend to be resistant to macrolide antibiotics, however, the MIC90s of penicillin and cephalosporin antibiotics were very good, 0.03-0.06 microg/mL. Pediatric respiratory infections are required a treatment which results in inhibition of drug-resistant bacteria. Based on the results of drug susceptibility testing, we should make a proper selection of antibiotics by reference to disposition such as drug concentration in serum and transfer into cells.

The human health burden of foodborne infections caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus in Miyagi Prefecture, Japan.

To estimate the human health burden of foodborne infections caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus in Japan, an epidemiological study was conducted in Miyagi Prefecture. Laboratory-confirmed infections among patients with diarrhea caused by the three pathogens were ascertained from two clinical laboratories in the prefecture from April 2005 to March 2006. To estimate the number of ill persons who were not laboratory-confirmed, we estimated physician-consultation rates for patients with acute diarrhea by analyzing foodborne outbreak investigation data for each pathogen and the frequency at which stool specimens were submitted from a physician survey. Each factor was added to a Monte-Carlo simulation model as a probability distribution, and the number of laboratory-confirmed cases was extrapolated to estimate the total number of ill persons. The estimated incidence of foodborne infections per 100,000 per year in this region estimated by this model was 237 cases for Campylobacter, 32 cases for Salmonella, and 15 cases for V. parahaemolyticus. Simulated results indicate a significant difference between our estimated incidence and the reported cases of food poisoning in this region. An enhanced surveillance system is needed to complement the present passive surveillance on foodborne illnesses in Japan to identify food safety issues more precisely, and to monitor the effectiveness of risk management options.

In vitro efficacy of imipenem in combination with six antimicrobial agents against Mycobacterium abscessus.

Antimicrobial therapy of Mycobacterium abscessus infection is difficult because there are relatively few effective treatment regimens and single-agent therapy frequently fails clinically. In light of the lack of data on the susceptibility profile of M. abscessus strains recovered from infections in Japan, the in vitro activity of imipenem in combination with clarithromycin, levofloxacin, moxifloxacin, minocycline, amikacin or tobramycin was investigated by the checkerboard method and compared with the combination amikacin and cefoxitin. The combination of imipenem with moxifloxacin, levofloxacin or clarithromycin had a higher synergistic and/or additive effect than amikacin and cefoxitin. A decrease in the MIC(90) value (minimum inhibitory concentration for 90% of the organisms) was observed in the presence of imipenem for clarithromycin, minocycline, levofloxacin and moxifloxacin. The data suggest that a combination regimen including imipenem may be a good choice in empirical treatment of M. abscessus infection.

Novel carbohydrate-binding activity of bovine liver beta-glucuronidase toward lactose/N-acetyllactosamine sequences.

Beta-glucuronidase is a lysosomal enzyme that plays an essential role in normal turnover of glycosaminoglycans and remodeling of the extracellular matrix components in both physiological and inflammatory states. The regulation mechanisms of enzyme activity and protein targeting of beta-glucuronidase have implications for the development of a variety of therapeutics. In this study, the effectiveness of various carbohydrate-immobilized adsorbents for the isolation of bovine liver beta-glucuronidase (BLG) from other glycosidases was tested. Beta-glucuronidase and contaminating glycosidases in commercial BLG preparations bound to and were coeluted from adsorbents immobilized with the substrate or an inhibitor of beta-glucuronidase, whereas beta-glucuronidase was found to bind exclusively with lactamyl-Sepharose among the adsorbents tested and to be effectively separated from other enzymes. Binding and elution studies demonstrated that the interaction of beta-glucuronidase with lactamyl-Sepharose is pH dependent and carbohydrate specific. BLG was purified to homogeneity by lactamyl affinity chromatography and subsequent anion-exchange high-performance liquid chromatography (HPLC). Lactose was found to activate beta-glucuronidase noncompetitively, indicating that the lactose-binding site is different from the substrate-binding site. Binding studies with biotinyl glycoproteins, lipids, and synthetic sugar probes revealed that beta-glucuronidase binds to N-acetyllactosamine/lactose-containing glycoconjugates at neutral pH. The results indicated the presence of N-acetyllactosamine/lactose-binding activity in BLG and provided an effective purification method utilizing the novel carbohydrate binding activity. The biological significance of the carbohydrate-specific interaction of beta-glucuronidase, which is different from the substrate recognition, is discussed.