3,241 research outputs found
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Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen.
Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor-bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors
Polymeric Nanoparticles for the Delivery of miRNA to Treat Chronic Obstructive Pulmonary Disease (COPD).
RNA interference (RNAi) based therapeutics are considered an endogenous mechanism for modulating gene expression. In addition, microRNAs (miRNAs) may be tractable targets for the treatment of Chronic Obstructive Pulmonary Disease (COPD). In this study miR146a was adsorbed onto poly (glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, nanoparticles (NPs) to reduce target gene IRAK1 expression. NPs were prepared using an oil-in-water single emulsion solvent evaporation method incorporating cationic lipid dioleoyltrimethylammoniumpropane (DOTAP). This resulted in NPs of 244.80±4.40 nm at 15 % DOTAP concentration, zeta potential (ZP) of +14.8±0.26 mV and miR-146a (40 µg/ml) maximum adsorption onto 15 % DOTAP NPs was 36.25±0.35 µg per 10 mg NP following 24 h incubation. Using the MTT assay, it was observed that over 75 % at 0.312 mg/ml of A549 cells remained viable after 18 h exposure to cationic NPs at a concentration of 1.25 mg/ml. Furthermore, the in vitro release profile of miR-146a from loaded NPs showed a continuous release up to 77 % after 24 h. Internalization of miR-146a loaded cationic NPs was observed in A549 cell lines using fluorescence and confocal microscopy. The miR146a delivered as miR-146a-NPs had a dose dependent effect of highest NPs concentrations 0.321 and 0.625 mg/ml and reduced target gene IRAK1 expression to 40 %. In addition, IL-8 promoter reporter output (GFP) was dampened by miR-146a-NPs. In conclusion, miR-146a was successfully adsorbed onto PGA-co-PDL-DOTAP NPs and the miR-146a retained biological activity. Therefore, these results demonstrate the potential of PGA-co-PDL NPs as a delivery system for miR-146a to treat COPD
How many sentinel nodes should be harvested in oral squamous cell carcinoma?
The number of harvested lymph nodes when performing sentinel lymph node (SLN) biopsy remains controversial. The aim of this study was to examine the maximum number of nodes to be harvested for histopathological analysis. We also wanted to determine if the level of radioactivity within a SLN or its size were indicators for the likelihood of nodal metastases. The SLNs from 34 neck dissection specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were included. Altogether 76 SLNs were measured for radioactivity and lymph node dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes), and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16 cases, metastases were in the hottest node. Two patients had more than one positive SLN: the first and fourth hottest in one and the second and fourth hottest nodes in another contained tumour. However, all patients would have been staged accurately if only the hottest three sentinel nodes had been retrieved. Lymph nodes that contained tumour had a greater maximum diameter than non-metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes required sampling
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INVESTIGATION OF THE TOTAL ORGANIC HALOGEN ANALYTICAL METHOD AT THE WASTE SAMPLING CHARACTERIZATION FACILITY (WSCF)
Total organic halogen (TOX) is used as a parameter to screen groundwater samples at the Hanford Site. Trending is done for each groundwater well, and changes in TOX and other screening parameters can lead to costly changes in the monitoring protocol. The Waste Sampling and Characterization Facility (WSCF) analyzes groundwater samples for TOX using the United States Environmental Protection Agency (EPA) SW-846 method 9020B (EPA 1996a). Samples from the Soil and Groundwater Remediation Project (S&GRP) are submitted to the WSCF for analysis without information regarding the source of the sample; each sample is in essence a 'blind' sample to the laboratory. Feedback from the S&GRP indicated that some of the WSCF-generated TOX data from groundwater wells had a number of outlier values based on the historical trends (Anastos 2008a). Additionally, analysts at WSCF observed inconsistent TOX results among field sample replicates. Therefore, the WSCF lab performed an investigation of the TOX analysis to determine the cause of the outlier data points. Two causes were found that contributed to generating out-of-trend TOX data: (1) The presence of inorganic chloride in the groundwater samples: at inorganic chloride concentrations greater than about 10 parts per million (ppm), apparent TOX values increase with increasing chloride concentration. A parallel observation is the increase in apparent breakthrough of TOX from the first to the second activated-carbon adsorption tubes with increasing inorganic chloride concentration. (2) During the sample preparation step, excessive purging of the adsorption tubes with oxygen pressurization gas after sample loading may cause channeling in the activated-carbon bed. This channeling leads to poor removal of inorganic chloride during the subsequent wash step with aqueous potassium nitrate. The presence of this residual inorganic chloride then produces erroneously high TOX values. Changes in sample preparation were studied to more effectively remove inorganic chloride from the activated carbon adsorption tubes. With the TOX sample preparation equipment and TOX analyzers at WSCF, the nitrate wash recommended by EPA SW-846 method 9020B was found to be inadequate to remove inorganic chloride interference. Increasing the nitrate wash concentration from 10 grams per liter (g/L) to 100 g/L potassium nitrate and increasing the nitrate wash volume from 3 milliliters (mL) to 10 mL effectively removed the inorganic chloride up to at least 100 ppm chloride in the sample matrix. Excessive purging of the adsorption tubes during sample preparation was eliminated. These changes in sample preparation have been incorporated in the analytical procedure. The results using the revised sample preparation procedure show better agreement of TOX values both for replicate analyses of single samples and for the analysis of replicate samples acquired from the same groundwater well. Furthermore, less apparent column breakthrough now occurs with the revised procedure. One additional modification made to sample preparation was to discontinue the treatment of groundwater samples with sodium bisulfite. Sodium bisulfite is used to remove inorganic chlorine from the sample; inorganic chlorine is not expected to be a constituent in these groundwater samples. Several other factors were also investigated as possible sources of anomalous TOX results: (1) Instrument instability: examination of the history of results for TOX laboratory control samples and initial calibration verification standards indicate good long-term precision for the method and instrument. Determination of a method detection limit of 2.3 ppb in a deionized water matrix indicates the method and instrumentation have good stability and repeatability. (2) Non-linear instrument response: the instrument is shown to have good linear response from zero to 200 parts per billion (ppb) TOX. This concentration range encompasses the majority of samples received at WSCF for TOX analysis. (3) Improper sample preservation: ion-chromatographic analysis of several samples with anomalous TOX results revealed that the samples were properly preserved with sulfuric acid and not hydrochloric acid
Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens
Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various “Ross-Macdonald” mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955–1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention
Sri Lankan tsunami refugees: a cross sectional study of the relationships between housing conditions and self-reported health
BACKGROUND: On the 26th December 2004 the Asian tsunami devastated the Sri Lankan coastline. More than two years later, over 14,500 families were still living in transitional shelters. This study compares the health of the internally displaced people (IDP), living in transitional camps with those in permanent housing projects provided by government and non-government organisations in Sri Lanka. METHODS: This study was conducted in seven transitional camps and five permanent housing projects in the south west of Sri Lanka. Using an interviewer-led questionnaire, data on the IDPs' self-reported health and housing conditions were collected from 154 participants from transitional camps and 147 participants from permanent housing projects. Simple tabulation with non-parametric tests and logistic regression were used to identify and analyse relationships between housing conditions and the reported prevalence of specific symptoms. RESULTS: Analysis showed that living conditions were significantly worse in transitional camps than in permanent housing projects for all factors investigated, except 'having a leaking roof'. Transitional camp participants scored significantly lower on self-perceived overall health scores than those living in housing projects. After controlling for gender, age and marital status, living in a transitional camp compared to a housing project was found to be a significant risk factor for the following symptoms; coughs OR: 3.53 (CI: 2.11-5.89), stomach ache 4.82 (2.19-10.82), headache 5.20 (3.09-8.76), general aches and pains 6.44 (3.67-11.33) and feeling generally unwell 2.28 (2.51-7.29). Within transitional camp data, the only condition shown to be a significant risk factor for any symptom was household population density, which increased the risk of stomach aches 1.40 (1.09-1.79) and headaches 1.33 (1.01-1.77). CONCLUSION: Internally displaced people living in transitional camps are a vulnerable population and specific interventions need to be targeted at this population to address the health inequalities that they report to be experiencing. Further studies need to be conducted to establish which aspects of their housing environment predispose them to poorer health
Cytomegalovirus Infection of the Cervix Detected By Cytology and Histology: A Report of Five Cases
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72846/1/j.1365-2303.1993.tb00094.x.pd
Using the MitoB method to assess levels of reactive oxygen species in ecological studies of oxidative stress
In recent years evolutionary ecologists have become increasingly interested in the effects of reactive
oxygen species (ROS) on the life-histories of animals. ROS levels have mostly been inferred indirectly
due to the limitations of estimating ROS from in vitro methods. However, measuring ROS (hydrogen
peroxide, H2O2) content in vivo is now possible using the MitoB probe. Here, we extend and refine
the MitoB method to make it suitable for ecological studies of oxidative stress using the brown trout
Salmo trutta as model. The MitoB method allows an evaluation of H2O2 levels in living organisms over
a timescale from hours to days. The method is flexible with regard to the duration of exposure and
initial concentration of the MitoB probe, and there is no transfer of the MitoB probe between fish. H2O2
levels were consistent across subsamples of the same liver but differed between muscle subsamples
and between tissues of the same animal. The MitoB method provides a convenient method for
measuring ROS levels in living animals over a significant period of time. Given its wide range of possible
applications, it opens the opportunity to study the role of ROS in mediating life history trade-offs in
ecological settings
The association between iliocostal distance and the number of vertebral and non-vertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO)
BACKGROUND: The identification of new methods of evaluating patients with osteoporotic fracture should focus on their usefulness in clinical situations such that they are easily measured and applicable to all patients. Thus, the purpose of this study was to examine the association between iliocostal distance and vertebral and non-vertebral fractures in patients seen in a clinical setting. METHODS: Patient data were obtained from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). A total of 549 patients including 508 women and 41 men participated in this cross-sectional study. There were 142 women and 18 men with prevalent vertebral fractures, and 185 women and 21 men with prevalent non-vertebral fractures. RESULTS: In women multivariable regression analysis showed that iliocostal distance was negatively associated with the number of vertebral fractures (-0.18, CI: -0.27, -0.09; adjusted for bone mineral density at the Ward's triangle, epilepsy, cerebrovascular disease, inflammatory bowel disease, etidronate use, and calcium supplement use) and for the number of non-vertebral fractures (-0.09, CI: -0.15, -0.03; adjusted for bone mineral density at the trochanter, cerebrovascular disease, inflammatory bowel disease, and etidronate use). However, in men, multivariable regression analysis did not demonstrate a significant association between iliocostal distance and the number of vertebral and non-vertebral fractures. CONCLUSIONS: The examination of iliocostal distance may be a useful clinical tool for assessment of the possibility of vertebral fractures. The identification of high-risk patients is important to effectively use the growing number of available osteoporosis therapies
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