Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

在免眼中进行经瞳孔阈值下温热疗法的组织学效应和蛋白表达

目的：研究阈值下经瞳孔温热疗法（TTT）对视网膜组织学的效应。方法：对正常视网膜色素的兔眼进行TTT，通过1个810nm激光二极管产生直径为1．2mm能量为50mW的光斑，持续时间为15、30和60秒。4周后进行荧光血管造影并摘除眼球，通过电子显微镜和免疫组化染色来检查。     

Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.

Glutathione transferase P (GST-P; glutathione transferase, EC 2.5.1.18) is known to be specifically expressed at high levels in precancerous lesions and in hepatocellular carcinomas from a very early phase of chemically induced hepatocarcinogenesis in the rat. The almost invariable occurrence of this phenotype in these lesions strongly suggests a mechanism by which GST-P gene is activated together with a crucial transforming gene of liver cells. To distinguish the two alternative possibilities--either the GST-P gene is coactivated with a closely located transforming gene by a cis mechanism or it is activated in trans by a common trans-acting factor--we carried out carcinogenesis experiments using transgenic rats harboring the bacterial chloramphenicol acetyltransferase reporter gene ligated to the upstream regulatory sequence of the GST-P gene. In each of three independent lines tested, liver foci and nodules produced by chemical carcinogens (Solt-Farber procedure) were found to express high levels of chloramphenicol acetyltransferase activity, indicating clearly that the GST-P gene is activated by a trans mechanism during hepatocarcinogenesis.     

Expression of classical protein kinase C subspecies in non-neoplastic lymphocytes and non-Hodgkin's lymphomas: an immunohistochemical study

It is generally accepted that phosphorylation plays a pivotal role in the cellular response of cell differentiation and proliferation. Immunohistochemical expression of classical protein kinase C (cPKC) subspecies (alpha, beta and gamma) in eight reactive lymphoid tissues, three normal spleens and 149 non-Hodgkin's lymphomas was examined. cPKC beta was observed primarily in the mantle zone B cells, but appeared as very faint staining in Ki-67 positive proliferated B cells in the germinal centers of secondary lymph follicles. In contrast to the reactive state, high levels of cPKC subspecies were recognized in the majority of 149 cases of non-Hodgkin's lymphoma, including those thought to have arisen from germinal center cells such as follicular lymphoma. The expression of cPKC alpha was found in higher frequency in T cell lymphomas than B cell lymphomas (P < 0.01) by the Chi-squared test. High levels of cPKC alpha were present only in high grade or highly aggressive lymphomas, showing the highest incidence in the small non-cleaved cell type, according to the International Working Formulation and National Cancer Institute (P < 0.01). cPKC gamma was not detected in normal lymphoid cells and was expressed in only four cases of non-Hodgkin's lymphomas. It is presumed that cPKC alpha and beta have a relationship to cell activation and proliferation of lymphoid cells of reactive and neoplastic states. It might be considered that the expression of cPKC alpha may have a relationship with aggressiveness in non-Hodgkin's lymphomas.     

Apoptosis and CD8-down-regulation in the thymus of chickens infected with Marek's disease virus

Summary Marek's disease virus (MDV)-infected chickens show thymic atrophy during the acute phase of infection. We examined whether the thymic atrophy by MDV-infection was mediated by apoptosis. Apoptosis-specific DNA ladderings were clearly observed in thymocytes one week after MDV-infection. Histological and flow cytometry studies revealed that immature CD4⁺CD8⁺ thymocytes underwent apototic cell death. In addition, the expression level of CD8 molecules on both CD4^–CD8⁺ and CD4⁺CD8⁺ thymocyte populations was down-regulated in the infected chickens. These thymic changes might be involved in the pathogenesis of Marek's disease.     

Bcl-2 gene prevents apoptosis in murine acth-secreting adenoma cells induced by bromocriptine

Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent for patients with prolactinomas and other pituitary adenomas. However, the mechanism by which bromocriptine decreases elevated serum levels of prolactin or growth hormone and shrinks tumors by diminishing tumor cell size is not clear. Recently, we obtained bromocriptine induced apoptosis in murine ACTH-secreting pituitary adenoma (AtT-20) cells, based on DNA fragmentation assay and cell cycle analysis (unpublished data). In this study, we demonstrate that enforced expression of bcl-2 gene in AtT-20 cells by the MPZenNeo(bcl-2) retroviral gene transfer increased resistance to apoptosis induced by bromocriptine.     

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11

 The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P<0.01 and P<0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy. Received: 6 October 1995/Accepted 29 June 1996     

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.