Clinical Significance of Extramural Tumor Deposits in the Lateral Pelvic Lymph Node Area in Low Rectal Cancer: A Retrospective Study at Two Institutions.

BACKGROUND: The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer. METHODS: This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses. RESULTS: Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001). CONCLUSIONS: The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

Diversities and similarities in pH dependency among bacterial NhaB-like Na+/H+ antiporters.

NhaB-like antiporters were the second described class of Na(+)/H(+) antiporters, identified in bacteria more than 20 years ago. While nhaB-like gene sequences have been found in a number of bacterial genomes, only a few of the NhaB-like antiporters have been functionally characterized to date. Although earlier studies have identified a few pH-sensitive and -insensitive NhaB-like antiporters, the mechanisms that determine their pH responses still remain elusive. In this study, we sought to investigate the diversities and similarities among bacterial NhaB-like antiporters, with particular emphasis on their pH responsiveness. Our phylogenetic analysis of NhaB-like antiporters, combined with pH profile analyses of activities for representative members of several phylogenetic groups, demonstrated that NhaB-like antiporters could be classified into three distinct types according to the degree of their pH dependencies. Interestingly, pH-insensitive NhaB-like antiporters were only found in a limited proportion of enterobacterial species, which constitute a subcluster that appears to have diverged relatively recently among enterobacterial NhaB-like antiporters. Furthermore, kinetic property analyses of NhaB-like antiporters at different pH values revealed that the degree of pH sensitivity of antiport activities was strongly correlated with the magnitude of pH-dependent change in apparent Km values, suggesting that the dramatic pH sensitivities observed for several NhaB-like antiporters might be mainly due to the significant increases of apparent Km at lower pH. These results strongly suggested the possibility that the loss of pH sensitivity of NhaB-like antiporters had occurred relatively recently, probably via accumulation of the mutations that impair pH-dependent change of Km in the course of molecular evolution.

Determinants and risk factors for central corneal thickness in Japanese persons: the Funagata Study.

PURPOSE: To examine the association between glucose metabolism and central corneal thickness (CCT) in Japanese adults. METHODS: A sub-sample of 322 Japanese adults participating in the Funagata Study was included in this analysis. CCT was measured using a specular microscope. Glucose metabolism was examined using 75-g oral glucose tolerance test. Mean differences in CCT (µm) and 95% confidence intervals were estimated with univariate, age-sex-adjusted and multivariate models using multiple linear regression. RESULTS: The mean (± standard deviation) age of the study sample was 63.7 ± 11.4 years and 44% were men. The mean fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG) and haemoglobin A1c (HbA1c) concentrations were 96.8 ± 12.6mg/dl, 123.6 ± 41.2mg/dl and 5.3 ± 0.4%, respectively. CCT was normally distributed in the study sample, and the mean CCT was 544.7 ± 34.6µm. After multivariate adjustment, characteristics associated with increased CCT were 2hPG and HbA1c concentrations, impaired glucose tolerance, diabetes, body weight or body mass index and current smoking. CONCLUSION: Impaired glucose tolerance, diabetes, obesity and current smoking are associated with increased CCT. Additional studies are required to examine whether interventions to affect these characteristics may reduce CCT.

Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.

Bone marrow cell implantation (BMI) has been utilized to treat patients with limb and heart ischemia. BMI provides angiogenic precursors and angiogenic cytokine-producing cells, especially erythroid cells. In this study, we induced in vitro angiogenesis cultures and in vivo BMI simulation using a murine limb ischemia model to examine the role of erythroid cells and the effect of erythropoietin (EPO). Human erythroid colonies (BFU-e) induced capillary networks around the colonies in vitro. Erythroid cells in human bone marrow produced vascular endothelial growth factor and placental growth factor. The angiogenic effects of erythroid cells were further amplified in the presence of EPO. Limb-ischemic mice were treated with BMI +/- EPO, and limb survival, blood flow recovery, and muscle histology were analyzed. Treatment with whole bone marrow cells + EPO significantly improved limb survival and blood flow. The cumulative effects of EPO on BMI induced and increase in capillary number and artery enlargement. Erythroid cells were essential for the in vivo effects of BMI, and CD14-positive cells supported the biological effects. In addition to the direct effect of EPO on angiogenesis, EPO showed indirect effect on angiogenesis through amplifying the angiogenic effects by erythroid cells supported by CD14-positive cells.

Liver-type fatty acid-binding protein is highly expressed in intestinal metaplasia and in a subset of carcinomas of the stomach without association with the fatty acid synthase status in the carcinoma.

OBJECTIVE: To investigate the relation of liver-type fatty-acid-binding protein (L-FABP) expression to the clinicopathological characteristics or the fatty acid synthase status of gastric cancers. METHODS: L-FABP expression was examined immunohistochemically in 667 gastric cancers, 60 gastric adenomas, and non-neoplastic epithelium contiguous with cancer tissue including normal foveolae, intestinal metaplasia, regenerative epithelium, and gastric glands. RESULTS: L-FABP was positive in 38% (high in 9% and low in 29%) of gastric cancers. It occurred preferentially in papillary carcinomas, female cases, and in patients under 50 years. In gastric cancers, L-FABP expression had no intimate correlation with the FAS status, and it showed no relationship with prognosis and cancer progression as indicated by venous and lymphatic permeation, and nodal or hepatic metastasis. Gastric tubular adenomas mainly revealed low (22%) expression of L-FABP while intestinal metaplasia showed the most frequent (>95%) and intense L-FABP expression. Normal foveolae and gastric glands showed no or less L-FABP expression. CONCLUSIONS: L-FABP is highly and intensely expressed in metaplasia and in a subset of gastric adenocarcinomas, without association with progression, prognosis and fatty acid synthase status of the carcinoma.