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1.  Autopsy-Proven Intravascular Lymphoma Presenting as Rapidly Recurrent Strokes 
Case Reports in Oncology  2016;9(1):148-153.
We present a 79-year-old Japanese woman diagnosed with cerebral infarction. In spite of enough antiplatelet and anticoagulant therapy, she presented rapidly recurrent strokes three times for 3 months. Magnetic resonance imaging showed progression of bilateral cerebral infarcts, and chest-abdominal computed tomography showed multiple bilateral nodular lesions in the lung and multiple tumor lesions in the liver. Autopsy revealed diagnosis of intravascular lymphoma (IVL). This case indicates that IVL is rare and usually goes undiagnosed until time of autopsy because of its protean neurological manifestations; hence, it should be considered as a possible etiology if multiple strokes occur in a short period of time.
PMCID: PMC4821140  PMID: 27065845
Intravascular lymphoma; Rapidly recurrent strokes; Autopsy
2.  Validation of a B-type natriuretic peptide as a prognostic marker in pneumonia patients: a prospective cohort study 
BMJ Open  2016;6(2):e010440.
To validate a B-type natriuretic peptide (BNP) as a prognostic marker in pneumonia patients.
A prospective cohort study.
Kanazawa Medical University Himi Municipal (a 250-bed community hospital in Himi-shi, Toyama-ken, Japan).
All patients diagnosed with pneumonia by the physician and admitted to our hospital between 1 January 2012 and 31 March 2015 whose BNP levels had been determined in the first 24 h of admission. A total of 673 patients were enrolled. Of these, BNP levels were measured for a total of 369 patients on admission.
After enrolment, baseline, demographic, clinical and laboratory characteristics including levels of suspected prognostic markers for pneumonia proposed in previous papers, were collected. All patients were followed up until discharge. During analysis, they were divided into categories as follows: community-acquired pneumonia (CAP), aspiration pneumonia (AP), healthcare-associated pneumonia (HCAP) and pneumonia with acute heart failure (PAHF). A univariate and multivariable Cox-regression analysis were applied to each parameter to identify predictors of death. Three cut-off points, namely 40, 100 and 200 pg/mL, as well as the mean, were applied when comparing BNP levels.
Main outcome measures
30-day mortality.
Of the 369 patients finally included, 137 were diagnosed with CAP, 122 with AP, 74 with HCAP, and 36 with PAHF. In the univariate analysis, BNP levels (mean, cut-off points 100 pg/mL and 200 pg/mL, p<0.01, respectively) were associated with death in CAP, and similar situation was found for BNP (cut-off points 200 pg/mL, p<0.05) in AP, but not for HCAP, or PAHF. In multivariable Cox-regression analysis, BNP remained an independent mortality predictor (HR 10.01, 95% CI 1.32 to 75.7, p=0.03) in CAP.
BNP levels may be a useful single prognostic marker for CAP. Further research for validation is warranted.
PMCID: PMC4769382  PMID: 26908529
3.  Changes in Surgical Site Infections after Living Donor Liver Transplantation 
PLoS ONE  2015;10(8):e0136559.
Surgical site infections (SSIs) are a major threat for liver transplant recipients. We prospectively studied SSIs after living donor liver transplantation (LDLT) at Kyoto University Hospital from April 2001 to March 2002 (1st period) and from January 2011 to June 2012 (2nd period). We investigated the epidemiology of SSIs after LDLT and determined the differences between the two periods. A total of 129 adult recipients (66 during the 1st period and 63 during the 2nd period) and 72 pediatric recipients (39 and 33) were included in this study. The SSI rates for each period were 30.3% (1st period) and 41.3% (2nd period) among the adult recipients and 25.6% and 30.3% among the pediatric recipients. The overall rates of 30-day mortality among adult transplant recipients with SSIs were 10.0% (1st period) and 3.9% (2nd period). No pediatric recipient died from SSIs after LDLT in either period. The incidence of Enterococcus faecium increased from 5.0% to 26.9% in the adults and from 10.0% to 40.0% in the pediatric patients. Extended-spectrum β-lactamase-producing Enterobacteriaceae were emerging important isolates during the 2nd period. For this period, a univariate analysis showed that ABO incompatibility (P = 0.02), total operation duration (P = 0.01), graft-to-recipient body weight ratio (GRWR [P = 0.04]), and Roux-en-Y biliary reconstruction (P<0.01) in the adults and age (P = 0.01) and NHSN risk index (P = 0.02) in the children were associated with SSI development. In a multivariate analysis, lower GRWR (P = 0.02) and Roux-en-Y biliary reconstruction (P<0.01) in the adults and older age (P = 0.01) in the children were independent risk factors for SSIs during the 2nd period. In conclusion, SSIs caused by antibiotic resistant bacteria may become a major concern. Lower GRWR and Roux-en-Y biliary reconstruction among adult LDLT recipients and older age among pediatric LDLT recipients increased the risk of developing SSIs after LDLT.
PMCID: PMC4556480  PMID: 26322891
4.  Antimicrobial Ointments and Methicillin-Resistant Staphylococcus aureus USA300 
Emerging Infectious Diseases  2011;17(10):1917-1920.
We tested 259 methicillin-resistant Staphylococcus aureus isolates and 2 USA300 ATCC type strains for susceptibility to bacitracin and neomycin contained in over-the-counter antibacterial ointments. Resistance to both bacitracin and neomycin was found only in USA300. The use of over-the counter antimicrobial drugs may select for the USA300 clone.
PMCID: PMC3310646  PMID: 22000371
bacteria; antimicrobial drug resistant; methicillin-resistant Staphylococcus aureus; MRSA; over-the-counter; community acquired infections; nonprescription drugs; ointments; bacitracin; neomycin; polymyxin B; drug resistance; USA300; dispatch
5.  Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes 
The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes.
Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined.
Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3) β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes.
In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.
PMCID: PMC3073915  PMID: 21439061
6.  Necrotizing Fasciitis Caused by Haemophilus influenzae Type b in an Elderly Patient▿  
Journal of Clinical Microbiology  2008;47(3):852-854.
Necrotizing fasciitis caused by Haemophilus influenzae type b is a rare infection of the skin and soft tissues. The only previously reported case involved a healthy infant. We report herein the case of an 81-year-old Japanese woman with diabetes mellitus who developed necrotizing fasciitis caused by H. influenzae type b.
PMCID: PMC2650905  PMID: 19116357
7.  Genotypes and Related Factors Reflecting Macrolide Resistance in Pneumococcal Pneumonia Infections in Japan▿  
Journal of Clinical Microbiology  2007;45(5):1440-1446.
Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR] = 11.1; 95% confidence interval [CI] = 1.30 to 95.0; P = 0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR = 14.2; 95% CI = 4.27 to 46.9; P < 0.0001 and P < 0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.
PMCID: PMC1865875  PMID: 17344362
8.  Infection by Chlamydophilia avium in an Elderly Couple Working in a Pet Shop 
Journal of Clinical Microbiology  2005;43(6):3011-3013.
Psittacosis infection is usually reported in adults aged around 30 to 60 years. We report here two cases of psittacosis in an elderly couple (76 and 77 years old) who jointly ran a pet shop. Psittacosis was diagnosed from a history of exposure to birds and from serological testing for Chlamydophilia avium.
PMCID: PMC1151884  PMID: 15956448
9.  Isothermal RNA Sequence Amplification Method for Rapid Antituberculosis Drug Susceptibility Testing of Mycobacterium tuberculosis 
Journal of Clinical Microbiology  2005;43(5):2489-2491.
RNA transcript quantification by an isothermal sequence amplification reaction was evaluated for susceptibility testing of 15 Mycobacterium tuberculosis strains. Agreement with the proportion method on Ogawa egg medium and the BACTEC MGIT 960 system was 100 and 87% for rifampin, 93 and 100% for isoniazid, 60 and 53% for ethambutol, and 80 and 80% for streptomycin, respectively.
PMCID: PMC1153809  PMID: 15872291
10.  Whole-Blood Counting Immunoassay as a Short-Turnaround Test for Detection of Hepatitis B Surface Antigen, Anti-Hepatitis C Virus Antibodies, and Anti-Treponema pallidum Antibodies 
Journal of Clinical Microbiology  2004;42(9):4250-4252.
Whole-blood samples were used for a counting immunoassay (CIA) with the aim of developing a short- turnaround test. After optimization of the CIA, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV), and anti-Treponema pallidum antibodies (anti-TP) were detected as efficiently as by an enzyme immunoassay (EIA) with serum samples. The correlations between whole-blood CIA and serum EIA were 99.8, 97.1, and 99.4% for HBsAg, anti-HCV, and anti-TP, respectively. Whole-blood CIA may be of value when rapid screening of many samples is required.
PMCID: PMC516346  PMID: 15365019
11.  Characterization of Group C and G Streptococcal Strains That Cause Streptococcal Toxic Shock Syndrome 
Journal of Clinical Microbiology  2004;42(1):186-192.
Twelve strains (the largest number ever reported) of group C and G1 streptococci (GCS and GGS, respectively) that caused streptococcal toxic shock syndrome (STSS) were collected and characterized. Eleven strains were identified as Streptococcus dysgalactiae subsp. equisimilis, and one strain was identified as Streptococcus equi subsp. zooepidemicus. We found that it was the first reported case of STSS caused by S. equi subsp. zooepidemicus. Cluster analysis according to the 16S rRNA gene (rDNA) sequences revealed that the S. dysgalactiae strains belonged to clusters I and II, both of which were closely related. The emm types and the restriction patterns of chromosomal DNA measured by pulsed-field gel electrophoresis were highly variable in these strains except BL2719 and N1434. The 16S rDNA sequences and other characteristics of these two strains were indistinguishable, suggesting the clonal dissemination of this particular S. dysgalactiae strain in Japan. As the involvement of superantigens in the pathogenesis of group A streptococcus-related STSS has been suggested, we tried to detect known streptococcal superantigens in GCS and GGS strains. However, only the spegg gene was detected in seven S. dysgalactiae strains, with none of the other superantigen genes being detected in any of the strains. However, the sagA gene was detected in all of the strains except Tokyo1291. In the present study no apparent factor(s) responsible for the pathogenesis of STSS was identified, although close genetic relationships of GCS and GGS strains involved in this disease were suggested.
PMCID: PMC321656  PMID: 14715751
12.  Molecular Analysis of Mycobacterium kansasii Isolates from the United States 
Journal of Clinical Microbiology  2004;42(1):119-125.
We studied the population genetics of Mycobacterium kansasii isolates from the United States by PCR restriction enzyme analysis (PRA) of the 441-bp Telenti fragment of the hsp-65 gene and pulsed-field gel electrophoresis (PFGE) of genomic DNA with the restriction endonucleases AseI, DraI, and XbaI, and we compared the patterns to those previously reported from France and Japan. By PRA, 78 of 81 clinical isolates (96%) from the United States belonged to subspecies I. With PFGE, 28 AseI patterns, 32 DraI patterns, and 35 XbaI patterns were produced. PFGE showed marked clonality of the U.S. isolates, with differences between genotypes involving only one or two bands. Isolates within Texas showed lower pattern diversity than those from different states. With DraI, 31 of 71 isolates (44%) had the same common PFGE pattern, which matched the predominant pattern in France (pattern Ia), determined by Picardeau et al. (M. Picardeau, G. Prod'hom, L. Raskine, M. P. LePennec, and V. Vincent, J. Clin. Microbiol. 35:25-32, 1997), and in Japan (type M), determined by Iinuma et al. (Y. Iinuma, S. Ichiyama, Y. Hasegawa, K. Shimokata, S. Kawahara, and T. Matsushima, J. Clin. Microbiol. 35:596-599, 1997). With AseI, 42% of isolates produced a common pattern indistinguishable from the common pattern seen in French isolates (Ia) and with only one band difference from the common pattern (type M) in Japan. This study demonstrates that subspecies I is the predominant subspecies of M. kansasii among clinical isolates in the United States, as it is in Europe and Japan, and that genotype I is highly clonal worldwide, with the same major genotype responsible for human infection. The fact that a single clone of M. kansasii is responsible for most cases of human disease suggests that specific virulence factors may be associated with this specific genotype.
PMCID: PMC321655  PMID: 14715741
13.  Apoptotic Signaling Pathway Activated by Helicobacter pylori Infection and Increase of Apoptosis-Inducing Activity under Serum-Starved Conditions 
Infection and Immunity  2001;69(5):3181-3189.
The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.
PMCID: PMC98275  PMID: 11292739
14.  Effect of Subinhibitory Concentrations of Macrolides on Expression of Flagellin in Pseudomonas aeruginosa and Proteus mirabilis 
Antimicrobial Agents and Chemotherapy  2000;44(10):2869-2872.
In the present study we showed by molecular analysis that the inhibition of motility by macrolides in Proteus mirabilis and Pseudomonas aeruginosa was well correlated with the loss of the expression of flagellin. Erythromycin, clarithromycin, and azithromycin at subinhibitory concentrations (sub-MICs) suppressed the expression of flagellin dose dependently. Azithromycin had the strongest inhibitory effect on the expression of P. aeruginosa flagellin, whereas 16-membered rokitamycin had only a weak inhibitory effect. These results indicate the potential effectiveness of sub-MICs of erythromycin, clarithromycin, and azithromycin for the treatment of patients with P. mirabilis and P. aeruginosa infections.
PMCID: PMC90167  PMID: 10991876

Results 1-14 (14)