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Background  

Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum.  相似文献   
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BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known for its selective cytotoxic activity on tumour cells. We analysed the response of HT-29 human colon carcinoma cells to this cytokine. MATERIALS AND METHODS: After TNF-alpha treatment, cell proliferation, cell cycle, reactive oxygen species (ROS) production (flow cytometry), the amount of apoptotic cells (flow cytometry, fluorescence microscopy), cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 activity (Western blotting) were detected. RESULTS: TNF-alpha induced a decrease of cell growth and viability, an accumulation of cells in the S-phase of the cell cycle, an increase of subdiploid cell population and nuclear chromatin condensation and fragmentation, but not sooner than 96-120 hours. However, earlier events characteristic of apoptosis occurred, such as caspase-3 activation, PARP cleavage to 89 kDa fragment and changes in ROS production. CONCLUSION: We demonstrated that, in addition to being an early marker of apoptosis, activation of caspase-3 and degradation of PARP may play a causative role in HT-29 cell death induced by TNF-alpha.  相似文献   
55.
Vaccines that induce high numbers of sustained T cell responses are urgently needed for the treatment of numerous diseases including cancer. Antigen-presenting cells (APCs), the most important of which are dendritic cells, orchestrate antigen-dependent T cell responses in that they present antigens to T cells in an appropriate environment. Here we present evidence that after vaccination with a simple mixture of the cationic poly-amino acid poly-L-arginine and tumor antigen-derived peptide antigens, large numbers of antigen-specific T cells are induced and APCs mediate the generation of T lymphocytes. We observe that after s.c. injection, MHC class II(+) cells infiltrate injection sites and are loaded with large amounts of antigen in vivo under the influence of poly-L-arginine. Consequently, numerous antigen-charged APCs can be detected in draining lymph nodes of vaccinated animals. Antigen-specific T cell responses induced are systemic and were readily detected more than 4 months after the last vaccination, the latest time point we measured. By contrast, even after repeat injections, we were consistently unable to detect antibody responses against poly-L-arginine, allowing this compound to be used for numerous booster injections. Clinical trials in cancer patients using poly-L-arginine as immunostimulant will be carried out in the near future.  相似文献   
56.
AIMS: Beneficial effects of statin treatment on cardiovascular morbidity and mortality has been not entirely explained by the reduction in LDL-cholesterol level. We hypothesised that antioxidant activity of statins may contribute to their salutary cardiovascular effects. The aim of the present study was to examine effect of simvastatin treatment on some parameters of LDL oxidation and antioxidant protection in patients with hypercholesterolemia and combined hyperlipidemia. Furthermore, we were interested, whether the effect of treatment is related to the type of hyperlipidemia. PATIENTS AND METHODS: Fourty-two patients (12 males, 30 females, mean age 60+/-10 years) were included in the present study. Fourteen patients had hypercholesterolemia defined as total cholesterol>5.0 mmol/l. Twenty-eight patients had combined hyperlipidemia defined by total cholesterol>5.0 mmol/l and triglycerides>1.7 mmol/l. Simvastatin was administered to patients during 8-week period in a daily dose of 20mg. Oxidation of LDL was measured by assessment of circulating conjugated diene (CD) and malondialdehyde (MDA) level. Antioxidant properties of blood were assessed based on measurement of total antioxidant status (TAS) and glutathione peroxidase (GPx) activity. RESULTS: Besides expected significant decrease in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels, simvastatin treatment also reduced significantly circulating CD by 41% (p<0.0001) and MDA level non-significantly by 6% (p=0.078). Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS. Patients with combined hyperlipidemia had significantly higher baseline CD (p<0.01) and consequently significantly greater absolute and relative decrease (46% versus 23%) in circulating CD (DeltaCD), when compared with patients with hypercholesterolemia. The increase in GPx activity was significant only in patients with combined hyperlipidemia (p<0.0001). In the multiple stepwise linear regression analysis, both baseline triglyceride (r(2)=0.32; p=0.004) and LDL cholesterol (r(2)=0.08; p=0.05) levels were significant independent predictors of DeltaCD after simvastatin treatment. CONCLUSION: Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. These effects were more pronounced in patients with combined hyperlipidemia than in hypercholesterolemia. The results suggest that simvastatin possesses certain antioxidant properties, which may contribute to its beneficial cardiovascular effect.  相似文献   
57.
1. Mittels eines Antigens, das aus E. crescens E mmons et J ellison 1960 hergestellt wurde, ist es möglich, spezifische Antikörper und Überempfindlichkeit beim Menschen nach-zuweisen und spezifisdie Antikörper beim Versuchstier hervorzurufen.
2. Diese immunologiscben Reaktionen sind vom Alter, eventuell vom Gesdilecht und durchgemachten Krankheiten abhängig.
3. Es besteht keine Abhängigkeit dieser Reaktionen von den klinischen Symptomen, von der überstandenen Bronchitis und Pneumonie, oder von dem Kontakt der Menschen mit dem Boden und den Tieren.
4. Zwischen E. crescens E mmons et J ellison 1960, H. capsulatum, C. immitis, Blastomyces dermatitidis und Paracoccidioides brasiliensis könnte man wohl gemeinsame antigene Bestandteile, vielleicht Polysaccharide, voraussetzen. Diese sind jedoch mittels weiterer immunologischer Reaktionen nachzuweisen.

Summary


By means of an antigen prepared from E. crescens E mmons et J ellison , 1960, specific antibodies and hypersensitivity can be demonstrated in the human subject and specific antibodies can be induced in animals. These immunological reactions depend on the age, and possibly also on sex and previous diseases. There is no relation between these reactions and the clinical symptoms, bronchitis and pneumonia in the past history or contact of the subject with soil and animals. It may be postulated that E. crescens E mmons et J ellison 1960, H. capsulatum, C. immitis, Blastomyces dermatitidis and Paracoccidioides brasiliensis have antigenic components – possibly polysaccharides – in common. However, further immunological reactions are necessary to demonstrated these.  相似文献   
58.
Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.  相似文献   
59.
Diabetic nephropathy is the main cause of morbidity and mortality in patients with Type 1 diabetes mellitus. Microalbuminuria has been established as a risk factor for the development and the progression of diabetic renal disease. A strong demand exists for better technologies to provide accurate diabetic nephropathy risk estimates before renal functional or structural disturbances already become established. Here, we present the application of a novel proteomics technology identifying urinary polypeptides and proteins. In this pilot study, we investigated 44 Type 1 diabetic patients with more than 5 years of diabetes duration compared with an age-matched control group. Random spot urine samples were examined utilizing high-resolution capillary electrophoresis (CE), coupled to mass spectrometry (MS). More than 1000 different polypeptides, characterized by their separation time and mass, were found between 800 Da and 66.5 kDa. Mathematical analysis revealed specific clusters of 54 polypeptides only found in Type 1 diabetic patients and an additional 88 polypeptides present or absent in patients with beginning nephropathy defined by the albumin-to-creatinine ratio (ACR; >35 mg/mmol). We observed polypeptide patterns characteristic for healthy controls and diabetic patients and subdivision of patients according to the excretion of polypeptides typical for diabetic nephropathy. Our study revealed that the urinary proteome contains a much greater variety of polypeptides than previously recognized and demonstrated the successful application of a novel high-throughput technology towards the human urinary proteome. Future prospective studies with the application of this technique may enable the earlier and more accurate detection of individuals at high risk to develop diabetic nephropathy.  相似文献   
60.
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