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At least 505 records · Page 28Linked to original sources
PubMed1983

A model for the study of the long duration pathogenesis of cancer and its relevance to therapy.

The problem of comparing human cancer, a disease of long evolution, with experimental models in short life span animals is discussed. It is suggested that malignant tumors are more common in long life span animals because of the requirement of long periods of time for tumor progression. Increased malignancy may result from the ability of tumor cells to change, coupled with the long exposure of the neoplastic cells to the selective forces of the organism and the environment. It is proposed that the dynamic nature of tumors and the time required for changes to be expressed, should be taken into account in the study of the changing biological behavior of tumor cells and their changing responses to therapy. The use of transplantable tumors which increase in malignancy during successive transfers, artificially prolongs the existence of the neoplastic cells in isogeneic hosts, permitting thereby tumor progression. Tumor progression, occurs during a period which is accessible to the therapist. This dynamic process should be of primary interest to cancer researchers and therapists.

Animals↗
PubMed2004

[Drug eluting stents: lessons from registries and literature].

Discussion about drug eluting stents (DES) was a highlight of the High Tech 2004 congress. This new kind of coronary stent represents a new revolution in the field of coronary angioplasty. After the excellent results with the bare metal stent compared with balloon angioplasty, concerning clinical events and restenosis in the 90s, DES have showed a spectacular decrease in restenosis rate. If it does not mean the end of restenosis, its decrease opens new therapeutic perspectives in percutaneous coronary intervention. A lot of registries and trials are now available and allow to assess the current use of DES, assess the incidence of (acute) stent thrombosis, assess the new therapeutic indications (intra-stent restenosis, left main coronary artery, chronic total occlusion, acute myocardial infarction...) and experimentations concerning evolution of the device are in process.

Combined Modality Therapy↗
PubMed2006

A real-time RT-PCR assay for quantifying the fitness of tobacco etch virus in competition experiments.

Relative fitness determination has become a standard tool in experimental virus evolution studies. In this type of studies, the tested strain is mixed with a reference strain, which differs in an easy-to-score and genetically stable marker, and allowed to compete for a limited common pool of resources during a given number of generations. In this report, a TaqMan real-time PCR methodology is proposed for quantifying the relative fitness of tobacco etch potyvirus strains (TEV) in in planta mixed infections with a reference TEV strain. Two different forward primers along with a common reverse one are used into separated reactions mixes from the same RNA preparation. The reference strain, named TEV-PC1, was genetically engineered to carry a neutral marker in a highly conserved region of the RNA polymerase NIb gene. This marker allows tracking the frequency of both competitors during competition experiments by real-time quantitative PCR using specific primers. Both the reproducibility and sensitivity of the method have been explored. Reproducibility was assessed by running multiple competition experiments for the same genotype. Sensitivity was assessed by comparing the results of competition experiments against TEV-PC1 of 24 single-nucleotide substitutions mutants.

Gene Amplification↗
PubMed2002

Modeling coagulation kinetics incorporating fractal theories: comparison with observed data.

There are currently four possible approaches in modeling coagulation kinetics: the traditional Euclidean rectilinear; the Euclidean curvilinear; the fractal rectilinear; and the fractal curvilinear. The fractal model includes the Euclidean case as a subset. The primary purpose of this research is to investigate which of the rectilinear models among these best predicts the evolution of experimental observed particle size distribution (PSD). Using a fractal rectilinear model previously developed by the authors, model predictions were compared with a series of observed PSD data obtained from estuarine sediment particles in a 2m settling column, where the average velocity gradient (G) was 20 or 40s(-1). Nonlinear parameter estimation was performed to estimate two free parameters for the fractal model (the fractal dimension, DF, and the collision efficiency factor, a), and one free parameter (the collision efficiency factor, alpha) for the Euclidean model. Compared with the observed PSD, the simulation showed that the fractal rectilinear model was best, and that this model fit better for the larger size particles. The estimated DF was between 2.6 and 3.0. The research demonstrated that the alpha's have multiple values for the same observed data, depending on the coagulation model used. This finding is significant because a is currently used as a single value based on the conventional Euclidean rectilinear model.

Geologic Sediments↗
PubMed2001

Tolerance to lipopolysaccharide (LPS) regulates the endotoxin effects on Shiga toxin-2 lethality.

It has been suggested that Shiga toxin (Stx) is necessary but not sufficient for hemolytic uremic syndrome (HUS) development, and pro-inflammatory stimuli such as lipopolysaccharide (LPS) from Gram negative bacteria are needed. Taking into account that LPS is present in the natural infection during HUS development, detoxification or regulation of LPS activity could be crucial to define the course of the disease. The objective of the present study was to investigate whether tolerance to LPS and/or antibodies to LPS, are able to modify the LPS-induced modulation of Stx type-2 (Stx2) lethality in a mouse model. Our results demonstrate that the high levels of IgG anti-LPS antibodies in immunized mice did not modify the dual effects of LPS (enhancement or protection) on Stx2 action. This could be attributed to the fact that antibodies do not recognize the active portion of LPS molecule (lipid A). However, the enhancement of Stx2 toxicity exerted by LPS was inhibited in tolerant mice. This effect could be ascribed to the inhibition of LPS-induced TNF-alpha and IL-1beta secretion in tolerant animals, two cytokines known to be involved in the overexpression of Stx receptors. The phenomenon of LPS-induced protection on Stx2 toxicity was also inhibited in tolerant animals, although the mechanism involved in this effect is not clear. This is the first description which shows the influence of endotoxin tolerance on the evolution of experimental HUS. However, like in Gram negative infections, further knowledge on tolerance mechanism is necessary in order to achieve a comprehensive view of this phenomenon.

Animals↗
PubMed1997

Synergism between sirolimus and 1,25-dihydroxyvitamin D3 in vitro and in vivo.

The active form of vitamin D, 1 alpha, 25-(OH)2D3, displays immunomodulatory effects in vitro and in vivo at pharmacological levels. We evaluated the dose-effect relationship of 1,25(OH)2D3 and sirolimus (rapamycin, RAP) in vitro, on the inhibition of PHA-stimulated PBMC proliferation, by using the median effect analysis. Pharmacological concentrations of 1,25(OH)2D3 (between 10(-9) and 3 x 10(-6) M) interacted synergistically with RAP (combination index value of 0.01 for 50% suppression of PBMC proliferation). In vivo, the effect of 1,25(OH)2D3 and RAP combinations on the evolution of experimental allergic encephalomyelitis in SJL mice was analyzed. 1,25(OH)2D3, given i.p., in monotherapy, at a dose of 2 micrograms/kg every two days, from day -3 until day +19 after disease induction, or RAP, injected daily at a dose of 0.3 mg/kg for the same period, decreased EAE incidence (paralysis in 70 and 55% of the animals, respectively, versus 98% in the placebo treated group, p < 0.001). The combination treatment using the two drugs in these subtherapeutical doses provided near-total clinical (8% paralysis, p < 0.001 compared to monotherapy with 1,25(OH)2D3 or RAP) and histological protection, comparable to that obtained with RAP in monotherapy at a threefold higher dose (1 mg/kg/d). When the two drugs were given using an alternate day administration schedule (RAP at 0.6 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to 19), near total protection was again obtained (13% paralysis, p < 0.001 versus control). These in vitro and in vivo data support the existence of synergistic interactions between 1,25(OH)2D3 and RAP. Considering the narrow therapeutic windows of both RAP and vitamin D-related compounds in autoimmune disease models, combinations of these drugs could find clinical application in reducing their individual therapeutically efficient doses to non-toxic levels.

Animals↗
PubMed2001

Nitrate-cancrinite precipitation on quartz sand in simulated Hanford tank solutions.

Caustic NaNO3 solutions containing dissolved Al were reacted with quartz sand at 89 degrees C to simulate possible reactions between leaked nuclear waste and primary subsurface minerals at the U.S. Department of Energy's Hanford site in Washington. Nitrate-cancrinite began to precipitate onto the quartz after 2-10 days, cementing the grains together. Estimates of the equilibrium constant for the precipitation reaction differ for solutions with 0.1 or 1.0 m OH- (log Keq = 30.4 +/- 0.8 and 36.2 +/- 0.6, respectively). The difference in solubility may be attributable to more perfect crystallinity (i.e., fewer stacking faults) in the higher-pH cancrinite structure. This is supported by electron micrographs of crystal morphology and measured rates of Na volatilization under an electron beam. Precipitate crystallinity may affect radionuclide mobility, because stacking faults in the cancrinite structure can diminish its zeolitic cation exchange properties. The precipitation rate near the onset of nucleation depends on the total Al and Si concentrations in solution. The evolution of experimental Si concentrations was modeled by considering the dependence of quartz dissolution rate on AI(OH)4- activity, cancrinite precipitation, and the reduction of reactive surface area of quartz due to coverage by cancrinite.

Aluminum↗
PubMed1989

Effect of larval crowding on adult mating behaviour in Drosophila melanogaster.

The effect of larval density on male mating success has been investigated with two strains of Drosophila melanogaster, a wild strain and a mutant strain, under low and high larval competition, and four different genotypic frequencies. The results show a strong sexual selection against mutant males when flies have been raised under low larval competition. Under high larval competition, there is a reduction in mating disadvantage of mutant males. In both instances, a frequency-dependent sexual selection exists. These results explain adequately the evolution of experimental populations where egg to adult viability and male mating success are the most important components of fitness.

Alleles↗