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Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.  相似文献   
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n = 25) and node-negative ( n = 81) groups. Among several pathologic factors, the diameter of the tumor and lymphatic involvement were significantly correlated with nodal involvement. Within the submucosal layer the depth of invasion and the horizontal cancerous expansion also correlated with lymph node disease ( p < 0.05). The size of the tumor did not correlate with the length of submucosal infiltration ( r = 0.12, p = 0.1). Patients with both slight invasion into the submucosa and less than 5 mm of horizontal expansion were often negative for lymph node involvement and thus may benefit from local surgery as an alternative to gastrectomy.  相似文献   
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OBJECTIVE: In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. METHOD: The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated. RESULTS: Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF. CONCLUSION: These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.  相似文献   
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To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.  相似文献   
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Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). TheN-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700±4300 IU/day), and recovered on days 9–15 (48,000±8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440±260 IU/day) and BT-PABA test results were low (45±17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient,rs=0.715,P<0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.  相似文献   
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BACKGROUND: Angiogenic therapy for ischemic tissues using angiogenic growth factors has been reported on an experimental and a clinical level. Electroporation enhances the efficiency of plasmid-based gene transfer in a variety of tissues. The purpose of this study was to evaluate the angiogenic effects of plasmid-based gene transfer using basic fibroblast growth factor (bFGF) in combination with electroporation. MATERIALS AND METHODS: The transfection efficiency of in vivo electroporation in rabbit skeletal muscles was evaluated using pCAccluc+ encoding luciferase. To evaluate the angiogenic effects of bFGF gene in ischemic limb, we constructed a plasmid, pCAcchbFGFcs23, containing human bFGF cDNA fused with the secretory signal sequence of interleukin (IL)-2. Then, 500 microg of pCAcchbFGFcs23 or pCAZ3 (control plasmid) was injected into the ischemic thigh muscles in a rabbit model of hind limb ischemia with in vivo electroporation (bFGF-E(+) group and LacZ-E(+) group). Other sets of animals were injected with pCAcchbFGFcs23 (bFGF-E(-) group) or pCAZ3 (LacZ-E(-) group) without electroporation. Then 28 days later, calf blood pressure ratio, angiographic score, in vivo blood flow, and capillary density in the ischemic limb were measured. RESULTS: Gene transfer efficiency increased markedly with the increase in voltage up to 100 V. Regarding angiogenic responses, calf blood pressure ratio, in vivo blood flow, and capillary density only in the bFGF-E(+) group were significantly higher than those in LacZ-E(-) group. Angiographic scores in the bFGF-E(+) and bFGF-E(-) groups were significantly higher than that in the LacZ-E(-) group. CONCLUSION: These data suggest that in vivo electroporation enhances bFGF gene transfer for the treatment of ischemic limb muscles.  相似文献   
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Background: Lymphatic invasion is a risk factor for lymph node metastases in patients with gastric cancer. No studies have been reported, however, on the correlation between lymphatic invasion and lymph node metastasis in early gastric cancer invading into the submucosa.Methods: We performed a retrospective analysis of lymphatic invasion in 170 patients with early gastric cancer invading into the submucosa.Results: Lymphatic invasion was found in 76 patients. Lymphatic invasion correlated significantly with the presence of lymph node metastasis and vascular invasion (P < .05) and with the degree of cancerous submucosal involvement (P < .05). The presence of lymph node metastasis also correlated with the grade of submucosal invasion and lymphatic invasion. The 5-year survival of patients with lymphatic invasion was poorer than that of patients without lymphatic invasion (P < .05). Node-negative patients had similar survival, regardless of the presence of lymphatic invasion. All patients with severe lymphatic invasion had sm3 invasion and lymph node metastases.Conclusion: Although lymphatic invasion is the first stage of lymph node metastasis, lymphatic invasion in itself does not have clinical importance except for severe invasion in early gastric cancer. It is possible to predict lymph node metastases from the combined evaluation of degree of lymphatic invasion and submucosal involvement of the tumor in patients with early gastric cancer invading into the submucosa.  相似文献   
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Background/Purpose: Given that the prognosis of patients with hepatocellular carcinoma (HCC) complicating severe cirrhosis remains uncertain, particularly with regard to various therapeutic strategies, we have evaluated the prognosis in a series of patients with homogeneous diagnostic and therapeutic histories. Methods: From 1990 to 1998, 411 consecutive HCC patients associated with Child class B and class C cirrhosis who did not have lymph node or distant metastasis were treated by partial hepatectomy (PH; n = 48), percutaneous ethanol injection (PEI; n = 105), transcatheter arterial chemoembolization (TACE; n = 189), chemotherapy, or supportive care (chemo/supportive; n = 69). Univariate survival curves were estimated. The Cox model, stratified by the treatment groups, was used for multivariate analysis. Results: As of January 1999, 305 patients (74.2%) had died. Overall median survival was 23.4 months. There were statistically significant differences between the survival times of patients receiving PH or PEI and TACE, as compared with those receiving chemo/supportive care. According to multivariate analysis, the independent predictive survival factors were: albumin level (≥3.0 g/dl), esophageal varices (i.e., absence), tumor size (≤3.0 cm), tumor number (solitary), and α-fetoprotein (AFP) level (<400 ng/ml). According to the total number of risk factors and the median survival, all patients were divided into four subgroups. For the score 0 group (no risk factor group), 3- and 5-year survival rates were 83.1% and 68.0% for PH, and 87.5% and 62.3% for PEI, respectively. In the score 1–2 group (one or two risk factors), survival rates at 3 and 5 years were 53.1% and 40.3% for PH, 54.8% and 33.2% for PEI, and 35.4% and 22.8% for TACE, respectively. For patients with a score of 3 or more, there were no differences among the treatment groups, excluding those with chemo/supportive care. Conclusions: These findings indicate that, in HCC patients with complicating Child B and C cirrhosis, PEI and PH should be considered first for subgroups of patients with scores (risk factors) of 0–2, as an acceptable survival rate was obtained in such patients. Therefore, the advantages and disadvantages of these therapies regarding tumor size and location should be counterbalanced. In patients with a score of 3 or more, TACE, when possible, could be a first choice because of its applicability and its adjuvant nature with respect to other therapies such as liver transplantation. Received: February 6, 2002 / Accepted: May 22, 2002 Offprint requests to: S. Ueno  相似文献   
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