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41.
Growth of aerobic mesophilic bacteria in mixed salad without dressing, containing cooked sweet corn and raw endive, was similar to that of raw endive alone. At 9°C, sweet corn permitted the growth of the lactic acid bacterium Leuconostoc mesenteroides , whenever the bacterium was present on raw endive, whereas no growth of lactic acid bacteria was recorded on raw endive alone. Listeria monocytogenes , artificially inoculated in the samples, grew more in the mixed salad than in the raw endive alone, for products stored at 6°C and 9°C. Acidification of sweet corn to pH 5.0 was proposed to reduce the development of L. monocytogenes in the mixed salad to a level similar to that recorded in the raw endive alone. Acidification with citric acid reduced spoilage of sweet corn, whereas acetic acid caused necrosis on the leaves of raw endive.  相似文献   
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Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.  相似文献   
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Clustering is an important data analysis tool for discovering structure in data sets. Although research on conceptual clustering has produced algorithms showing significant advantages over earlier numerical ones, existing methods still present some limitations regarding applicability to biomedical domains. In this paper we describe ADAGIO, a conceptual clustering algorithm combining a low-cost preordering process with a breadth-first incremental control strategy that incorporates merging and splitting operators. Experimental evaluation indicated that the algorithm achieves a good balance between structure discovery performance and computational efficiency, and demonstrated the comparative effectiveness of its missing information handling process. ADAGIO is able to handle qualitative, quantitative and mixed-type data. An application example to a cancer domain is given, where the algorithm was able to suggest interesting epidemiological interpretations.  相似文献   
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To investigate the biochemical requirements for in vivo L-DOPA production by cells genetically modified ex vivo in a rat model of Parkinson's disease (PD), rat syngeneic 9L gliosarcoma and primary Fischer dermal fibroblasts (FDFs) were transduced with retroviral vectors encoding the human tyrosine hydroxylase 2 (hTH2) and human GTP cyclohydrolase I (hGTPCHI) cDNAs. As GTPCHI is a rate-limiting enzyme in the pathway for synthesis of the essential TH cofactor, tetrahydrobiopterin (BH4), only hTH2 and GTPCHI cotransduced cultured cells produced L-DOPA in the absence of added BH4. As striatal BH4 levels in 6-hydroxydopamine (6-OHDA)-lesioned rats are minimal, the effects of cotransduction with hTH2 and hGTPCHI on L-DOPA synthesis by striatal grafts of either 9L cells or FDFs in unilateral 6-OHDA-lesioned rats were tested. Microdialysis experiments showed that those subjects that received cells cotransduced with hTH2 and hGTPCHI produced significantly higher levels of L-DOPA than animals that received either hTH2 or untransduced cells. However, animals that received transduced FDF grafts showed a progressive loss of transgene expression until expression was undetectable 5 weeks after engraftment. In FDF-engrafted animals, no differential effect of hTH2 vs hTH2 + hGTPCHI transgene expression on apomorphine-induced rotation was observed. The differences in L-DOPA production found with cells transduced with hTH2 alone and those cotransduced with hTH2 and hGTPCHI show that BH4 is critical to the restoration of the capacity for L-DOPA production and that GTPCHI expression is an effective means of supplying BH4 in this rat model of PD.  相似文献   
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Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.  相似文献   
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This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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