Naoki Tsumura

Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site

Influenza virus RNA polymerase is a multifunctional enzyme that catalyses both transcription and replication of the RNA genome. The function of the influenza virus RNA polymerase PA subunit in viral replication is poorly understood, although the enzyme is known to be required for cRNA → vRNA synthesis. The protease related activity of PA has been discussed ever since protease‐inducing activity was demonstrated in transfection experiments.

Inhibition of influenza virus replication in cultured cells by RNA‐cleaving DNA enzyme

Influenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the AUG initiation codon of PB2 mRNA. We designed RNA‐cleaving DNA enzymes from 10‐23 catalytic motif to target PB2‐AUG initiation codon and measured their RNA‐cleaving activity in vitro. Although the RNA‐cleaving activity was not optimal under physiological conditions, DNA enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucleotides. Our data indicated that DNA enzymes could be useful for the control of viral infection.

Catheter-related infections by Hansenula anomala in children.

During August and September, 1992, we experienced 4 cases of Hansenula anomala (H. anomala, synonym Pichia anomala) fungemia in immunocompromised patients. Two patients had been suffering from a malignant disease, 3 of them had received broad-spectrum antibiotics and a central venous catheter (CVC) had been inserted in all of them. H. anomala was isolated as the sole pathogen from all 4 patients. Three of them responded favorably to fluconazole after withdrawal of the catheter, but one failed. H. anomala should be considered as a possible cause of catheter-related infections.

Outbreak of Chlamydia pneumoniae infection in a Japanese nursing home, 1999-2000.

OBJECTIVE To identify risk factors for infection and severe illness due to Chlamydia pneumoniae. METHODS To identify risk factors for infection, we conducted a case-control study among nursing home residents who had onset of symptoms during December 1, 1999, to February 20, 2000. To identify risk factors for severe illness among nursing home residents, we conducted a retrospective cohort study. SETTING A nursing home providing long-term and day care services for elderly patients in Japan.Participants. Fifty-nine residents and 41 staff members of a nursing home. RESULTS The attack rates for respiratory illness were 53% (31 of 59) among residents and 22% (9 of 41) among staff. Infection was confirmed in 15 resident and 2 staff case patients by isolation of C. pneumoniae from nasal swab specimens. Fifteen resident case patients developed severe illness (ie, bronchitis, pneumonia, and hypoxia); one case patient died. The median age of resident case patients was 87 years. We could identify neither the source of the outbreak nor significant risk factors for infection and severe illness in residents. However, residents with a higher level of physical activity were more likely to become infected, whereas older residents (aged more than 85 years) and those with a lower level of physical activity were more likely to develop severe illness (P>.05). Contact with residents was a risk factor for infection in staff (relative risk, undefined; P=.04). CONCLUSIONS C. pneumoniae can cause large outbreaks of infection and severe illness among elderly persons, and its transmission is likely to be enhanced by close contacts among people in nursing homes. Therefore, early detection of an outbreak by means of better surveillance, and subsequent isolation of patients, may be effective control measures.

Antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae in southwestern Japan and correlation of penicillin-binding protein 2b and 2x mutations in susceptibilities of penicillin G and cefotaxime

MICs of penicillin G and other drugs and serotypes were determined for 218 strains of Streptococcus pneumoniae isolated from children in southwestern Japan. Twenty-one (9.6%) and 81 (37.2%) isolates were penicillin-resistant (MIC >/=2.0 microg/ml) and intermediate (MIC 0.13-1.0 microg/ml), respectively. Panipenem was most active parenteral agent against penicillin-intermediate (MIC(90) 0.125 microg/ml) and -resistant strains (MIC(90) 0.25 microg/ml). Among oral beta-lactam agents, cefditoren had good activity against penicillin-intermediate and resistant strains (MIC(90) 0.5/1.0 microg/ml). Serogroup 6 was the most prevalent (65/218) among all strains and 19F (44 strains) was the most prevalent among penicillin-intermediate and -resistant strains. Both pbp2b resistant and susceptible genes were found in penicillin-intermediate strains. Pbp2x resistant genes were found in 33 of 80 (41.3%) cefotaxime-susceptible strains. These results suggest that possible resistance mechanisms may occur even in drug susceptible strains and that drug susceptibility survey should be updated carefully in Japan.

Comparison of serological tests for detection of immunoglobulin M antibodies to Chlamydophila pneumoniae

Background and objective:  To evaluate an enzyme immunoassay (EIA) (AniLab C. pneumoniae) for detecting anti‐Chlamydophila pneumoniae‐specific IgM antibody, by comparing it with an ELISA, Hitazyme C. pneumoniae, and a micro‐immunofluorescence (MIF) test.

Rapid and Simple Diagnosis of Chlamydophila pneumoniae Pneumonia by an Immunochromatographic Test for Detection of Immunoglobulin M Antibodies

ABSTRACT To evaluate a newly developed immunochromatographic test (the MySet test) for the detection of Chlamydophila pneumoniae-specific immunoglobulin M antibodies, the results obtained by the MySet test were compared with those obtained by two serological tests. The sensitivity and specificity of the MySet test were 100% and 92.9%, respectively. The MySet test is rapid and simple to use and is thought to be a useful tool for the selection of appropriate antibiotic therapy.

Molecular Evolution of Human Echovirus 9 Isolated from Patients with Aseptic Meningitis in Northern Kyushu during the Summer of 1997

An epidemic of aseptic meningitis caused by human echovirus 9 (E‐9) occurred in the summer of 1997 in northern Kyushu, Japan. Sequences of genome position 2504–3358, which encoded a part of VP1, of the nine isolated viruses were determined. An RGD motif and B‐C loop were found in all. They were almost identical and closely related to the virulent strain Barty.

Sepsis in children.

Abstract Background: Sepsis remains lethal to children. At our institution, we have noted that approximately 2% of all hospitalized patients have had sepsis. In the present study, we analyzed episodes of sepsis that occurred in our ward.

Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs

A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.