R-Y reconstruction seems superior to B-I reconstruction for preventing both bile reflux into the gastric remnant and postoperative complications. We consider R-Y reconstruction as a feasible and safe method for LADG.

SUMMARY:To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in mycobacterial inflammation, IL-1 ␣/␤ double-knockout (KO) mice were produced. These mice were infected with either Mycobacterium tuberculosis H37Rv by the airborne route using an airborne infection apparatus, and their capacities to control mycobacterial growth, granuloma formation, cytokine, and nitric oxide (NO) production were examined. The IL-1 ␣/␤ mice developed significantly larger (p Ͻ 0.01) granulomatous, but not necrotic, lesions in their lungs than wild-type (WT) mice after infection with H37Rv. Inflammatory lesions, but not granulomas, were observed in spleen and liver tissues from both IL-1 ␣/␤ KO and wild-type mice. Granulomatous lesion development in IL-1 ␣/␤ KO mice was not significantly inhibited by treatment with exogenous recombinant IL-1␣/␤. Compared with wild-type mice, splenic IFN-␥ and IL-12 levels were within the normal range. NO production by cultured alveolar macrophages from IL-1 ␣/␤ KO mice was lower than in wild-type mice but were increased by the addition of recombinant IL-1 ␣/␤. Our data clearly indicate that IL-1 is important for the generation of early-phase protective immunity against mycobacterial infection. (Lab Invest 2000, 80:759-767).

Activation of 5-fluorouracil into its nucleotides requires phosphorylation by three pathways involving orotate phosphoribosyltransferase (OPRT), uridine phosphorylase (UP), or thymidine phosphorylase (TP). In this study, we investigated the association between gene expressions of these three enzymes and antitumour effect. Gene expressions in primary colorectal tumours were analysed by a real-time reverse transcriptional -polymerase chain reaction method in 37 patients receiving oral treatment of tegafururacil and leucovorin for metastatic diseases. The median values of OPRT mRNA expressions were 1.39 and 0.85 for responding tumours and nonresponding tumours, respectively, showing a statistically significant difference (P ¼ 0.0008). Responding tumours had statistically lower expressions of TP mRNA than nonresponding tumours (P ¼ 0.006). However, there was no difference in UP mRNA expression between responding and nonresponding tumours. Patients with high OPRT (X1.0) gene expression survived longer than those with low OPRT (o1.0) expression. Dihydropyrimidine dehydrogenase (DPD) gene expressions were measured. Responding tumours had a statistically higher OPRT/DPD ratio than the nonresponding ones (P ¼ 0.003). When the median value of the OPRT/DPD ratio was selected as the cutoff value, patients with a high OPRT/DPD ratio survived statistically longer than those with a low ratio (P ¼ 0.0014). In conclusion, both the expression of OPRT gene and the OPRT/DPD ratio might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. An important anticancer agent widely used in the treatment of colorectal cancers, 5-fluorouracil (5-FU), is catabolised rapidly to the inactive metabolite dihydrofluorouracil (FUH 2 ) by the first and rate-limiting enzyme-dihydropyrimidine dehydrogenase (DPD) (Heggie et al, 1987). The main mode of action of 5-FU is thought to be through its active metabolite: 5-fluoro-uridine-5 0 -triphosphate (FUTP) or 5-fluoro-2 0 -deoxyuridine-5 0 -monophosphate (FdUMP) (Danenberg, 1977). Metabolites such as FUTP can be incorporated into RNA, while FdUMP suppresses thymidylate synthase (TS), an essential DNA de novo synthetic enzyme that catalyses the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) (Danenberg, 1977;Pinedo and Peters, 1988).With combined DPD and TS gene expressions, both response and survival could be predicted more precisely than on the bases of only one gene expression. No tumour with both high DPD and high TS expression responded to tegafur-uracil (UFT), an oral fluoropyrimidine, and leucovorin (LV) therapy, but not even all tumours with both low DPD and low TS expression responded to the therapy, such cases having a response rate of 75% (Ichikawa et al, 2003). Salonga et al (2000) reported that only one of 12 tumours with both low DPD and low TS expression was a nonresponder to 5-FU, but that case had a high thymidine phosphorylase (TP) expression. These data suggested that combined...

Abstract:To investigate the role of TLR in the development of murine tuberculosis in vivo, TLR2 and TLR6 knockout (KO) mice were infected with Mycobacterium tuberculosis by placing them in the exposure chamber of an airborne infection apparatus. Both TLR2 and TLR6 KO mice survived until sacrifice at 12 weeks after infection. Infected TLR2 KO mice developed granulomatous pulmonary lesions with neutrophil infiltration, which were slightly larger in size than those in wild-type mice. Pulmonary levels of the mRNAs for inducible nitric oxide synthase (iNOS), TNF-␣, TGF-␤, IL-1␤, and IL-2 were significantly lower, but levels of the mRNAs for IL-4 and IL-6 were higher, than in wild-type (WT) mice. No significant difference was recognized in cytokine mRNA expression between TLR2 KO and WT mice at 12 weeks after infection. DNA binding by NF-B was low in TLR2 KO mice. On the other hand, TLR6 KO mice were not different from WT mice in terms of pulmonary histopathology, mRNA expression and CFU assay. Therefore, TLR2 does not play an essential role in the pathogenesis of murine tuberculosis, although it is important for defense against mycobacterial infection.

Background: The role of human epidermal growth factor receptor (HER) 3 and HER4 has been elucidated in gastric cancer. HER1 and HER2 overexpression are regarded as prognostic factors and targets of treatment. The dimerization of the HER family receptors activates downstream signal pathways and promotes tumor progression. This study investigated the positive correlation between HER1and HER4 expression and the prognosis of patients with gastric cancers. Experimental Design: Tumor samples were obtained from gastric adenocarcinomas of 134 patients who underwent a gastrectomy from 1999 to 2002. The expression of each HER was analyzed in the tumor by immunohistochemical staining. Parametric correlations were done between HER expression and the clinicopathologic findings. A multivariate analysis was done with the overall survival. Results: HER3 expression was significantly associated with parameters involved with tumor progression, including the depth of tumor invasion (T 1 versusT 2 -T 4 ; P = 0.000), involved lymph nodes (P = 0.000), distant metastasis (P = 0.008), tumor stage (P = 0.000), and recurrent disease (P = 0.000). HER1was also significantly associated with those factors excluding distant metastasis. A significant relationship was observed between the expression of HER1 and HER3 (P = 0.000). HER3 overexpression was associated with a significantly worse survival (P = 0.0000) and was an independent prognostic factor in the multivariate analysis (hazard ratio, 2.382; 95% confidence interval, 1.009-5.625; P = 0.048). Conclusions: HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer. It may become a new prognostic factor and a target of treatment.