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   

G9a selectively represses a class of late-replicating genes at the nuclear periphery

We have investigated the role of the histone methyltransferase G9a in the establishment of silent nuclear compartments. Following conditional knockout of the G9a methyltransferase in mouse ESCs, 167 genes were significantly up-regulated, and no genes were strongly down-regulated. A partially overlapping set of 119 genes were up-regulated after differentiation of G9a-depleted cells to neural precursors. Promoters of these G9a-repressed genes were AT rich and H3K9me2 enriched but H3K4me3 depleted and were not highly DNA methylated. Representative genes were found to be close to the nuclear periphery, which was significantly enriched for G9a-dependent H3K9me2. Strikingly, although 73% of total genes were early replicating, more than 71% of G9a-repressed genes were late replicating, and a strong correlation was found between H3K9me2 and late replication. However, G9a loss did not significantly affect subnuclear position or replication timing of any non-pericentric regions of the genome, nor did it affect programmed changes in replication timing that accompany differentiation. We conclude that G9a is a gatekeeper for a specific set of genes localized within the late replicating nuclear periphery.     

Usefulness of the hyperechoic rim for assessing the therapeutic efficacy of radiofrequency ablation in hepatocellular carcinoma patients

Aim:  During radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), a hyperechoic rim develops around the HCC nodules. The usefulness of the hyperechoic rim to guide treatment was assessed.
Methods:  RFA was first performed in pig livers to determine the significance of the hyperechoic rim. Fifty-five patients with 75 HCC nodules had received RFA for the treatment of HCC. For those patients, we evaluated whether conventional ultrasonography (US) could be used instead of contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS) using virtual imaging. Finally, 31 patients with 45 HCC nodules received RFA, and the degree of ablation was assessed based on the hyperechoic rim. Repeated RFA was done when ablation appeared incomplete.
Results:  In the pig livers, the hyperechoic rim was found to be related to the presence of dead cells. The preliminary study showed that US could be used instead of CECT and CEUS to evaluate the degree of ablation caused by RFA. Because hepatic vessels in the back side of the hyperechoic rim were not clear by the artifact, we used the distance from the surface of the liver to the hyperechoic rim for evaluation. By analyzing the extent of the hyperechoic rim, it was noted that incomplete ablation was achieved in 17 of 31 patients (21 of 45 HCC nodules). These patients were re-treated with RFA within 5–15 min of the first RFA.
Conclusion:  This study shows that the hyperechoic rim is related to the presence of dead and necrotic tissues. Thus, assessment of the hyperechoic rim's characteristics allows one to evaluate the efficacy of RFA.     

Portal vein thrombosis in a patient with hepatitis C virus-related cirrhosis complicated with antiphospholipid syndrome

We report a rare case of portal vein thrombosis (PVT) associated with antiphospholipid syndrome (APS) and hepatitis C virus-related cirrhosis. A 59-year-old woman with hepatitis C virus (HCV) infection was admitted because of coma. The blood test showed a typically cirrhosis pattern including an elevated serum ammonia level. Abdominal computed tomography showed liver cirrhosis and thrombus in the right branch of the portal vein. To elucidate the cause of PVT, antiphospholipid antibodies were examined. Both IgG anti-cardiolipin antibody (ELISA) and IgG anti-cardiolipin-β2 -glycoprotein I complex antibody (ELISA) were positive. When PVT is detected in a patient with cirrhosis, it might be necessary to examine antiphospholipid antibodies to clarify the cause of PVT.     

Nuclear receptor DAX1 in human prostate cancer: a novel independent biological modulator

The orphan nuclear receptor DAX1 (dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1; NR0B1) has been known for its various roles in human development, specifically sex determination and steroidogenesis. Its expression has been reported in endocrine and sex steroid-dependent neoplasms such as human adrenocortical, pituitary, endometrial, and ovarian tumors. Prostate cancer is also sex steroid-dependent tumor in which androgens play important roles in the pathogenesis and development via androgen receptor (AR). DAX1 is also reported to repress AR activity in human prostate cancer cell line (LNCaP) but its biological roles have remained unclear in the human prostate cancer. The aim of this study is to examine the expression of DAX1 in human prostate cancer using immunohistochemistry in order to evaluate its possible biological and/or clinical significance. In this study, we examined the DAX1 immunoreactivity in human prostate cancer obtained from surgery (n = 40), and correlated the findings with clinicopathological features of the patients. Twenty-one cases were defined as positive cases for DAX1 immunoreactivity (53%). Immunoreactivity for DAX1 was inversely and significantly correlated with Gleason score (P<0.05). However, DAX1 immunoreactivity was not significantly correlated with the status of sex steroid receptors we examined. DAX1 immunoreactivity is considered a new biological modulator of human prostate cancer, but independent to the status of sex steroid receptors in human prostate cancer tissues.     

Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders

We investigated the role of therapeutic dose monitoring (TDM) in the treatment of fungal infections with voriconazole through 49 analyses of 34 patients who received treatment for hematologic diseases. Voriconazole concentration was highly variable among patients regardless of renal, liver functions, or age, and the effect of dose enhancement was not constant. This indicates the difficulty of predicting voriconazole concentration without TDM. We evaluated the outcome with the composite assessment system where patients were assumed non-responders when they failed to show improvement in at least 2 of the following 3 criteria: clinical, radiologic, and mycologic. We showed that concentration–response relationship depended on the status of underlying hematologic diseases; this relationship was observed only in cases without refractory hematologic diseases, but not in those with refractory diseases. In the former group, cases with >2 mg/L of concentration were associated with good response to voriconazole. On the other hand, elevation of hepatic enzyme was frequently observed when voriconazole concentration was >6 mg/L. From these results, we concluded that TDM should be executed and targeted to 2–6 mg/L to improve efficacy and to avoid side effects.     

Effects of indomethacin on the rat small intestinal mucosa: immunohistochemical and biochemical studies using anti-mucin monoclonal antibodies

Background  The luminal surface of the gastrointestinal tract is covered by a viscoelastic gel layer that acts as a protective barrier against the intraluminal environment. Because the situation of the small intestine has not been elucidated to the same degree as other sections, in this study, we investigated the effects of indomethacin on the rat small intestinal mucosa. Methods  Male Wistar rats were given indomethacin 10 mg/kg s-c and sacrificed 1, 3, 7, or 14 days later. The small intestine was opened along the anti-mesenteric side, and examined macroscopically. Total mucin content in the small intestinal epithelium was measured and immunoreactivity was examined using anti-mucin monoclonal antibodies HCM31 and PGM34. Results  Indomethacin caused punched out and linear ulcers located mostly along the mesenteric margin of the distal jejunum with sparing of the ileum. Histological examination showed sialomucin recognized by HCM31 increased on day 3 especially in the regenerating epithelium around the ulcer edge. Furthermore, the surface mucous gel layer displayed a multilaminated pattern, consisting of non-sulfated sialomucin-rich layers and sulfated mucin-rich layers, where both mucins had the common core protein, MUC2. Biochemical measurements also showed the total mucin content of the jejunum increased transiently and HCM31-positive mucin increased approximately 4 times greater than baseline on day 3, but no marked changes were observed in the ileum, with few ulcers observed. Conclusions  Indomethacin administration causes quantitative and qualitative change in jejunal mucin. In particular, sialomucin plays an important role in regenerating epithelium during the healing process following indomethacin-induced mucosal damage.     

Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology

We performed a systematic immunohistochemical study on 378 brain tumors using 37 antibodies and tissue microarray (TMA) technology. The aim of this study was to find new diagnostic biomarkers using antibodies established in our laboratory. Our TMA consisted of a grid of 1.5-mm cores that were extracted from individual donor blocks. Staining for each antibody was scored using a three-point system. We used hierarchical clustering analysis to interpret these data, which resulted in separation of all the brain tumors into seven groups. Although there were some exceptions, cases with the same histological diagnosis were generally grouped together. We then carried out statistical analyses to find the most useful antibodies for grouping of brain tumors. Ten antibodies [glial fibrillary acidic protein (GFAP), Olig2, vimentin, epithelial membrane antigen (EMA), cytokeratin (AE1/AE3), alpha-internexin, nestin, pinealocytes PP5, aquaporin-4 (AQP4) M13d and AQP4M13e] discriminated between astrocytomas and oligodendroglial tumors. Six antibodies [EMA, AE1/AE3, TUJ1, nestin, neurofilament protein-MH (NF-MH) and perivascular cells GP-1] showed significant differences between high-grade and low-grade gliomas. Our data have revealed new antibodies with potential diagnostic utility (Olig2, PP5, GP-1) and demonstrate that TMA technology is highly useful for evaluating newly established antibodies in brain-tumor research.