Antibacterial activity of carbapenems against clinically isolated respiratory bacterial pathogens in Japan between 2005 and 2006

The current status of the susceptibility of the main respiratory bacterial pathogens was evaluated by analysing the antibacterial activity of 21 drugs, including four carbapenems, against five species of the pathogens isolated between January 2005 and January 2006. A total of 157 strains were studied. Carbapenems inhibited the growth of all of the tested strains of Moraxella catarrhalis, Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus strains at concentrations that were below the breakpoints set by the Japanese Society of Chemotherapy (2 and 1mug/mL for pneumonia and chronic respiratory tract infection, respectively). However, the majority of methicillin-resistant Staphylococcus aureus strains were resistant to carbapenems. Meropenem, but not the other carbapenems, inhibited the growth of all of the tested strains of Haemophilus influenzae isolates, including beta-lactamase-non-producing ampicillin-resistant strains, at concentrations of 相似文献   

Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study

STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to lung cancer, we investigated the association between a family history of lung cancer and subsequent risk of lung cancer in a large-scale, population-based cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791 cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A family history of lung cancer in a first-degree relative was associated with a significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.31 to 2.88). The association was stronger in women than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78, respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI, 1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition, family history was more strongly associated with the risk of squamous cell carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68), while no clear increase in risk was observed in adenocarcinoma and small cell carcinoma. A family history of overall cancer was not associated with an increased risk of lung cancer. CONCLUSIONS: These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves.     

RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4

Chemokines are now known to play an important role in cancer growth and metastasis. Here we report that differentiating osteoclasts constitutively produce CCL22 (also called macrophage-derived chemokine) and potentially promote bone metastasis of lung cancer expressing its receptor CCR4. We first examined expression of chemokines by differentiating osteoclasts. CCL22 was selectively upregulated in osteoclast-like cells derived from RAW264.7 cells and mouse bone marrow cells upon stimulation with RANKL (receptor activator of nuclear factor-κB ligand). In addition, a human lung cancer cell line SBC-5 that efficiently metastasized to bone when intravenously injected into NK cell-depleted SCID mice was found to express CCR4. Stimulation of SBC-5 cells with CCL22 induced cell migration and also enhanced phosphorylation of protein kinase B/Akt and extracellular signal-regulated kinase (ERK). Furthermore, immunohistochemical analysis of bone metastasis lesions demonstrated close co-localization of tartrate-resistant alkaline phosphatase (TRAP)-positive osteoclasts expressing CCL22 and SBC-5 cells expressing CCR4. Collectively, these results suggest that osteoclasts may promote bone metastasis of cancer cells expressing CCR4 in the bone marrow by producing its ligand CCL22.This study was supported in part by a Grant-in-Aid for Young Scientists (B) (No. 15790089), Grant-in-Aids for Cancer Research (No. 16022224 and 16023225) and a Grant-in-Aid for the 21st Century COE Program from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Solution Oriented Research for Science (SORST) of Japan Science and Technology Corporation (JST) and High-Tech Research Center Project for Private Universities: matching fund subsidy from MEXT, 2002–2006.     

Elevation of IL-12 p40 and its antibody in myasthenia gravis with thymoma

We examined the serum levels of cytokines, interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-4, IL-12 p40, and IL-12 p70; those that affect the T helper 1 and 2 balance in patients with myasthenia gravis (MG). Among the cytokines tested, only IL-12 p40, together with the serum titer of anti-IL-12 p40 antibody, was significantly elevated in MG with thymoma. Their elevation was independent of the histopathology of thymoma. Thymectomy decreased the levels of IL-12 p40 accompanied by the anti-acetylcholine receptor antibody, but not anti-IL-12 p40 antibodies. These data strongly suggest the association of IL-12 p40 and its autoantibody with the immunopathology of MG with thymoma.     

Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice

Aim of the study

Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na₂S), a hydrogen sulfide (H₂S) donor, markedly improved the neurological outcome and survival rate at 24 h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na₂S and its impact on the long-term survival after CA/CPR in mice.

Methods

Adult male mice were subjected to potassium-induced CA for 7.5 min at 37 °C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na₂S (0.55 mg kg⁻¹ i.v.) or vehicle 1 min before CPR.

Results

Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24 h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na₂S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P < 0.05 vs. Vehicle) after CA/CPR.

Conclusion

These results suggest that administration of Na₂S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation.     

Differential roles of spatial frequency on reading processes for ideograms and phonograms: a high-density ERP study

The neural substrate of the dissociation between reading Japanese ideograms (Kanji) and phonograms (Kana) is currently unclear. To test whether spatial frequency (SF) information is responsible for this phenomenon, we recorded high-density event-related potentials (ERPs) with unfiltered or spatially filtered word stimuli in Japanese-speaking subjects. Kanji (early-learned, late-learned), Kana (word, non-word), and scrambled characters served as stimuli. Fourier analysis revealed that Kanji and Kana were characterized by high-SF (HSF) and low-SF (LSF) information, respectively. In ERPs with unfiltered stimuli, bilateral occipital P100, left occipitotemporal N170 and fronto-central N400 were elicited. Scrambled characters did not evoke left-lateralized N170 or clear N400. Under the LSF condition, P100 and N170 latencies for Kanji were significantly longer than those for Kana. In the HSF condition, P100 and N170 latencies for late-learned Kanji were significantly longer than those for early-learned Kanji. There was no significant difference in the N400 between Kanji and Kana in both SF conditions. These results suggest that early visual responses, but not the semantic component, are influenced by SF. This indicates a close link between Kana and LSF information, and between Kanji and HSF information. The differential effects of SF could underlie the neural basis of the differences between Kanji and Kana reading.     

Evolution and virulence of Panton-Valentine leukocidin-positive ST30 methicillin-resistant Staphylococcus aureus in the past 30 years in Japan

Methicillin-resistant Staphylococcus aureus (MRSA) includes hospital-acquired MRSA (HAMRSA) and community-acquired MRSA (CA-MRSA). Panton-Valentine leukocidin (PVL)-positive multilocus sequence type 30 (ST30) MRSA is one of worldwide CA-MRSA, which has also persisted in Japan since the 1980s. However, unexpectedly, it was not the same ST30 clone throughout. Before 2000, it was HA-MRSA with spa43 and ψSa3sea (phage Sa3 carrying the sea gene) and only one PVL-positive MRSA in Japan; in the 1980s, ST30 MRSA accounted for 23.5% of HA-MRSA, showed multidrug resistance, had high MICs for oxacillin and imipenem, and caused decubitus and pneumonia in hospitalized patients. A dynamic clonal change (spa43/ψSa3sea→ spa19) occurred around 2000-2002. A rare spa43/ψSa3sea/SCCmecI-IE25923 genotype also emerged. After 2002, the prevalent spa19 clone was CA-MRSA; it accounted for only 0.3% (or less) of MRSA in hospitals but 7.6% of CA-MRSA. Since 2007, PVL-positive CA-MRSA with other ST types (such as ST8, ST22, and ST59) also emerged in Japan, albeit at a low frequency. ST30/spa19 CA-MRSA occasionally caused severe invasive infections and a novel ST1335/spa19 genotype emerged. These ST30/spa19 CA-MRSA and variants were identified by pulsed field gel electrophoresis. Further analysis revealed that PVL-positive ST30/spa19 CA-MRSA is a highlyvirulent, successful clone, having a potential of clonal expansion.