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At least 559 records · Page 31Linked to original sources
PubMed2006

In vivo attenuation of myointimal hyperplasia using transforming growth factor-beta3 in an interposition graft model.

PURPOSE: To examine if transforming growth factor-beta3 (TGFbeta3) can attenuate the development of para-anastomotic myointimal hyperplasia in an animal model of small-diameter vascular graft failure. METHODS: Under general anesthesia, 10 adult goats underwent bilateral polyurethane interposition graft insertion in the carotid position. Following completion of the anastomoses, each artery received adventitial infiltration of 50 ng of TGFbeta3 around the anastomoses; a placebo was administered to the other side. Postoperatively, each animal received 150 mg of aspirin daily. The arteries were explanted, half at 6 weeks and the remaining 5 at 3 months, for histological examination. RESULTS: Vessel wall thickness surrounding the anastomosis was reduced by 37% in TGFbeta3-treated arteries compared to placebo at 6 weeks and 3 months, principally due to reduced smooth muscle cell proliferation. There was decreased overall luminal loss on angiography. Total collagen content was not significantly different between TGFbeta3 and placebo sides. Further analysis for the subendothelial matrix component collagen type VIII showed decreased levels on the treated side. Total elastin content was reduced on the TGFbeta3-treated side. CONCLUSION: Direct single-dose subadventitial infiltration of TGFbeta3 following insertion of an interposition graft reduces SMC proliferation and elastin content. It would appear that TGFbeta3 holds promise as a prophylaxis against the development of myointimal hyperplasia, the predominant cause of graft failure in peripheral bypass surgery.

Actins↗
PubMed2004

Modeling and monitoring of polymorphic transformations during the drying phase of wet granulation.

PURPOSE: The purpose of this work was to monitor polymorphic transformations of glycine during the drying phase of a wet granulation and model the polymorphic conversions using a time-based reconciliation model. METHODS: Near-infrared spectroscopy (NIR) was used for quantitation of polymorphs, and X-ray powder diffraction (XRPD) was used for qualitative analysis of polymorphs. RESULTS: The data show that the faster the granulation was dried, the more kinetic trapping of the metastable alpha-glycine polymorph, as predicted by reconciliation of the time scales of both the drying rate and the rate of the solution-mediated conversion. CONCLUSIONS: By knowing basic properties of the drug substance (solubility of the polymorphic forms and the rate of the solution-mediated conversion), processing conditions, such as the drying rate, can be adjusted to anticipate and prevent potential polymorphic transformations.

Calibration↗
PubMed2003

Fate and transport of 17beta-estradiol in soil-water systems.

Over the past several years, there has been an increase in concern regarding reproductive hormones in the environment To date, there exists limited research on the fate and transport of these chemicals in the environment. In this study, a series of laboratory batch sorption and miscible-displacement experiments were done using radiolabeled [14C]17beta-estradiol. The 17beta-estradiol concentrations that were used were similar to those found in manures that are applied to field soils. Equilibrium batch experiments indicated high sorption affinity with correlations to mineral particle size and organic matter content. The sorption affinity appeared to be associated with the surface area and/or the cation-exchange capacity of the soil. The miscible-displacement breakthrough curves indicated chemical nonequilibrium transport, and a single highly polar metabolite was present in the column effluent along with sporadic and trace detections of estriol. Sorbed to the soil within the column were found 17beta-estradiol, estrone, and trace and sporadic detections of estriol. Two chemical nonequilibrium, miscible-displacement models were used to describe the column breakthrough curves; one without transformations and the other with transformations. Both models resulted in excellent descriptions of the data, which indicated nonunique solutions and less confidence in the parameter estimates. Nonetheless, the modeling and experimental results implied that degradation/transformation occurred in the sorbed phase and was rapid. Also, both models indicated that sorption was fully kinetic.

Adsorption↗
PubMed2006

The Developmental Leadership Questionnaire (DLQ): some psychometric properties.

The development leadership model (Larsson et al., 2003), designed to introduce refinements to the transformational leadership model, has been adopted for use in the Swedish Armed Forces. The Developmental Leadership Questionnaire (DLQ) was constructed to measure important parts of the model. The main aim of the study was to evaluate some psychometric properties of the DLQ. Most analyses are based on two subsets of individuals from a sample mostly consisting of male Swedish, military officers, each of whom has rated a given leader (n = 450 and 449 respectively). A second sample consisted of Swedish military cadets (n = 141). The dimensionality was assessed with a confirmatory factor analysis. Most DLQ scales were reasonably well reproduced and showed high or acceptable internal consistency. When related to perceived results of leadership (self-rated by leaders and rated by subordinates), results from multiple regression analyses supported what could be predicted by the theoretical model. It was concluded that the DLQ has acceptable psychometric properties and that the theoretical refinements introduced to the developmental leadership model were empirically supported.

Adult↗
PubMed1985

Regression models for prognostic prediction: advantages, problems, and suggested solutions.

Multiple regression models have wide applicability in predicting the outcome of patients with a variety of diseases. However, many researchers are using such models without validating the necessary assumptions. All too frequently, researchers also "overfit" the data by developing models using too many predictor variables and insufficient sample sizes. Models developed in this way are unlikely to stand the test of validation on a separate patient sample. Without attempting such a validation, the researcher remains unaware that overfitting has occurred. When the ratio of the number of patients suffering endpoints to the number of potential predictors is small (say less than 10), data reduction methods are available that can greatly improve the performance of regression models. Regression models can make more accurate predictions than other methods such as stratification and recursive partitioning, when model assumptions are thoroughly examined; steps are taken (ie, choosing another model or transforming the data) when assumptions are violated; and the method of model formulation does not result in overfitting the data.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

The blast cells of acute myeloblastic leukaemia.

Cell culture methods are available that permit colony formation by the normal progenitors of myelopoiesis and lymphopoiesis. The blast cells of acute myeloblastic leukaemia may also form colonies under selective conditions in culture. It is feasible, therefore, to determine some of the properties of blast progenitors. These were found to be uniformly in active cell cycle. However, great patient-to-patient variation was seen in the sensitivity of blast progenitors to chemotherapeutic agents and in their capacity to undergo self-renewal. The latter attribute, but not the former, was correlated with clinical outcome. These culture findings were used to propose a model of AML that includes an increase in diversity with malignant transformation. The model finds further support from studies of the phenotypes of blast cells freshly obtained from AML patients.

Cell Differentiation↗
PubMed2005

Segmentation in echocardiographic sequences using shape-based snake model combined with generalized Hough transformation.

A novel method for segmentation of cardiac structures in temporal echocardiographic sequences based on the snake model is presented. The method is motivated by the observation that the structures of neighboring frames have consistent locations and shapes that aid in segmentation. To cooperate with the constraining information provided by the neighboring frames, we combine the template matching with the conventional snake model. It means that the model not only is driven by conventional internal and external forces, but also combines an additional constraint, the matching degree to measure the similarity between the neighboring prior shape and the derived contour. Furthermore, in order to auto or semi-automatically segment the sequent images without manually drawing the initial contours in each image, generalized Hough transformation (GHT) is used to roughly estimate the initial contour by transforming the neighboring prior shape. The method is particularly useful in case of the large frame-to-frame displacement of structure such as mitral valve. As a result, the active contour can easily detect the desirable boundaries in ultrasound images and has a high penetrability through the interference of various undesirables, such as the speckle, the tissue-related textures and the artifacts.

Algorithms↗
PubMed2001

Worm plot: a simple diagnostic device for modelling growth reference curves.

The worm plot visualizes differences between two distributions, conditional on the values of a covariate. Though the worm plot is a general diagnostic tool for the analysis of residuals, this paper focuses on an application in constructing growth reference curves, where the covariate of interest is age. The LMS model of Cole and Green is used to construct reference curves in the Fourth Dutch Growth Study 1997. If the model fits, the measurements in the reference sample follow a standard normal distribution on all ages after a suitably chosen Box-Cox transformation. The coefficients of this transformation are modelled as smooth age-dependent parameter curves for the median, variation and skewness, respectively. The major modelling task is to choose the appropriate amount of smoothness of each parameter curve. The worm plot assesses the age-conditional normality of the transformed data under a variety of LMS models. The fit of each parameter curve is closely related to particular features in the worm plot, namely its offset, slope and curvature. Application of the worm plot to the Dutch growth data resulted in satisfactory reference curves for a variety of anthropometric measures. It was found that the LMS method generally models the age-conditional mean and skewness better than the age-related deviation and kurtosis.

Adolescent↗
PubMed2002

Alterations in matrix metalloproteinase-9 levels and tissue inhibitor of matrix metalloproteinases-1 expression in a transforming growth factor-beta transgenic model of hydrocephalus.

The development of spontaneous hydrocephalus in mouse models resulting from the overexpression of transforming growth factor-beta (TGFbeta-1) has been previously described, although the mechanism by which this occurs remains obscure. It has been previously demonstrated that increased expression of TGFbeta has consequences for the levels of matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitors of MMPs, or TIMPs). These remodeling proteins play an important role in extracellular matrix (ECM) maintenance through degradation and deposition of ECM components. The present study investigated the relationship between elevated levels of TGFbeta-1, the ECM modulators TIMP-1 and MMP-9, and development of hydrocephalus in the neonatal mouse. In newborn pups, TIMP-1 mRNA levels were equal between animals expressing the TGFbeta-1 transgene and littermates without the transgene. However, immunohistochemistry of littermate pups shows that the distribution of TIMP-1 was changed from homogeneous with large punctate concentrations of signal to uniform, dense staining in hydrocephalic animals carrying the TGFbeta-1 transgene. The mRNA levels of MMP-9 were decreased in the transgenic animals, as were the activity levels MMP-9. These results suggest that the remodeling protein MMP-9 and its specific inhibitor, TIMP-1, may contribute to the spontaneous development of hydrocephalus in this transgenic model by altering the ECM environment.

Actins↗
PubMed2002

Validation using sensitivity and target transform factor analyses of neural network models for classifying bacteria from mass spectra.

Temperature constrained cascade correlation networks (TCCCNs) are computational neural networks that configure their own architecture, train rapidly, and give reproducible prediction results. TCCCN classification models were built using the Latin-partition method for five classes of pathogenic bacteria. Neural networks are problematic in that the relationships among the inputs (i.e., mass spectra) and the outputs (i.e., the bacterial identities) are not apparent. In this study, neural network models were constructed that successfully classified the targeted bacteria and the classification model was validated using sensitivity and target transformation factor analysis (TTFA). Without validation of the classification model, it is impossible to ascertain whether the bacteria are classified by peaks in the mass spectrum that have no causal relationships with the bacteria, but instead randomly correlate with the bacterial classes. Multiple single output network models did not offer any benefits when compared to single network models that had multiple outputs. A multiple output TCCCN model achieved classification accuracies of 96 +/- 2% and exhibited improved performance over multiple single output TCCCN models. Chemical ionization mass spectra were obtained from in situ thermal hydrolysis methylation of freeze-dried bacteria. Mass spectral peaks that pertain to the neural network classification model of the pathogenic bacterial classes were obtained by sensitivity analysis. A significant number of mass spectral peaks that had high sensitivity corresponded to known biomarkers, which is the first time that the significant peaks used by a neural network model to classify mass spectra have been divulged. Furthermore, TTFA furnishes a useful visual target as to which peaks in the mass spectrum correlate with the bacterial identities.

Bacteria↗
PubMed2000

Computational approaches to sensorimotor transformations.

Behaviors such as sensing an object and then moving your eyes or your hand toward it require that sensory information be used to help generate a motor command, a process known as a sensorimotor transformation. Here we review models of sensorimotor transformations that use a flexible intermediate representation that relies on basis functions. The use of basis functions as an intermediate is borrowed from the theory of nonlinear function approximation. We show that this approach provides a unifying insight into the neural basis of three crucial aspects of sensorimotor transformations, namely, computation, learning and short-term memory. This mathematical formalism is consistent with the responses of cortical neurons and provides a fresh perspective on the issue of frames of reference in spatial representations.

Animals↗
PubMed2006

Use of wavelet and fast Fourier transforms in pharmacodynamics.

Progress has been made in the development and application of mechanism-based pharmacodynamic models for describing the drug-specific and physiological factors influencing the time course of responses to the diverse actions of drugs. However, the biological variability in biosignals and the complexity of pharmacological systems often complicate or preclude the direct application of traditional structural and nonstructural models. Mathematical transforms may be used to provide measures of drug effects, identify structural and temporal patterns, and visualize multidimensional data from analyses of biomedical signals and images. Fast Fourier transform (FFT) and wavelet analyses are two methodologies that have proven to be useful in this context. FFT converts a signal from the time domain to the frequency domain, whereas wavelet transforms colocalize in both domains and may be utilized effectively for nonstationary signals. Nonstationary drug effects are common but have not been well analyzed and characterized by other methods. In this review, we discuss specific applications of these transforms in pharmacodynamics and their potential role in ascertaining the dynamics of spatiotemporal properties of complex pharmacological systems.

Animals↗
PubMed2006

[Continuously modeling research on the transfer and transform processes of phosphorus in Heihe River watershed].

Taking supply water source of Xi'an city as an example, by the help of Matlab software, using fill and yield model, the Inverse-Gauss flow concentration model, runoff-sediment relation model and Viney model, the transfer and transform processes of phosphorus from 1981 to 1990 were modeled continuously. Phosphorus pollution loads of Heihe River were also estimated. The result shows that the continuous modeling result accorded with the generic law of phosphorus loss. The relative error between modeling result and monitor interpolation result was not more than +/-30%. So the modeling method proposed in this paper could be used to model continuously the transfer and transform processes of phosphorus in Heihe river watershed. This study was only primary attempt to non-point source pollution continous model, therefore, the modeling method needed to be improved and perfected further.

China↗
PubMed2004

In vivo videomicroscopy reveals differential effects of the vascular-targeting agent ZD6126 and the anti-angiogenic agent ZD6474 on vascular function in a liver metastasis model.

Metastases require a functional blood supply for progressive growth. Thus, therapies that target metastatic vasculature have potential clinical utility. The effects of the vascular-targeting agent (VTA), ZD6126, and the anti-angiogenic agent, ZD6474, on vascular development and function within metastases were compared in an experimental liver metastasis model. Ras-transformed PAP2 fibroblasts were injected into the mesenteric veins of SCID mice to produce a control liver metastasis burden of approximately 40% at 14 days. Mice given a single dose of ZD6126 (200 mg/kg, i.p.) on day 13 were examined 24 h later. Histology revealed a significant reduction in metastatic burden, associated with extensive tumor necrosis, increased tumor cell apoptosis and a reduction in tumor-associated vasculature. In vivo videomicroscopy (IVVM) revealed disrupted, non-functional vascular channels within metastases, with no blood flow. Mice given ZD6474 on days 4 to 10 (50 mg/kg daily, oral gavage) were examined on day 11. Histology revealed a lower metastatic burden, significant reductions in metastasis size and vasculature, and a significant increase in tumor cell apoptosis. IVVM revealed extensive reductions in vascularity and blood flow within metastases. Neither ZD6126 nor ZD6474 treatment affected surrounding normal liver tissue. This study shows that both agents can reduce experimental liver metastasis with no apparent effect on normal vasculature. However, these reductions were attained through distinct effects on the metastatic vasculature. Understanding differences in the modes of action of VTAs and anti-angiogenic agents will be important in optimizing their clinical application and in developing appropriate combination strategies.

Angiogenesis Inhibitors↗
PubMed1986

Interaction, functional relations and evolution of large and small subunits in Rubisco from prokaryota and eukaryota.

In early biological evolution anoxygenic photosynthetic bacteria may have been established through the acquisition of ribulose bisphosphate carboxylase-oxygenase (Rubisco). The establishment of cyanobacteria may have followed and led to the production of atmospheric oxygen. It has been postulated that a unicellular cyanobacterium evolved to cyanelles which were evolutionary precursors of chloroplasts of both green and non-green algae. The latter probably diverged from ancestors of green algae as evidenced by the occurrence of large (L) and small (S) subunit genes for Rubisco in the chloroplast genome of the chromophytic algae Olisthodiscus luteus. In contrast, the gene for the S subunit was integrated into the nucleus in the evolution of green algae and higher plants. The evolutionary advantages of this integration are uncertain because the function of S subunits is unknown. Recently, two forms of Rubisco (L8 and L8S8) of almost equivalent carboxylase and oxygenase activity have been isolated from the photosynthetic bacterium Chromatium vinosum. This observation perpetuates the enigma of S subunit function. Current breakthroughs are imminent, however, in our understanding of the function of catalytic L subunits because of the application of deoxyoligonucleotide-directed mutagenesis. Especially interesting mutated Rubisco molecules may have either enhanced carboxylase activity or higher carboxylase:oxygenase ratios. Tests of expression, however, must await the insertion of modified genes into the nucleus and chloroplasts. Methodology to accomplish chloroplast transformation is as yet unavailable. Recently, we have obtained the first transformation of cyanobacteria by a colE1 plasmid. We regard this transformation as an appropriate model for chloroplast transformation.

Bacteria↗
PubMed1999

Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.

BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.

Adult↗
PubMed2006

Melanocyte transformation associated with substrate adhesion impediment.

Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for beta1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyltransferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.

Animals↗