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At least 343 records · Page 19Linked to original sources
PubMed1998

Organotypic culture of HPV-transformed keratinocytes: a model for testing lymphocyte infiltration of (pre)neoplastic lesions of the uterine cervix.

The aim of our study was to establish the relevance of an in vitro model for analysing the ability of human lymphocytes to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. To mimic these lesions, we have used the organotypic raft culture of HPV-transformed keratinocytes (SiHa). The SiHa organotypic raft culture was co-cultured with resting or prestimulated (IL-2 or IL-2+anti-CD3 mAb) allogeneic peripheral blood mononuclear cells (PBMC) for 24 and 72 h. The majority of infiltrating cells were T lymphocytes. Occasional NK cells were also identified. The stimulation with IL-2+anti-CD3 mAb induced the highest number of infiltrating cells, with the maximum lymphocyte infiltration observed after 24 h of co-culture. The lymphocyte infiltration was associated with an increased number of apoptotic cells in the organotypic cultures. The ability of PBMC and purified T cell and NK cell populations to lyse HPV-transformed keratinocytes was also investigated on monolayer cultures. As expected in an allogenic model, the highest cytotoxicity was mediated by NK cells activated by IL-2 or IL-2+anti-CD3 mAb. The cytotoxic activity of T cells was weak but, interestingly, increased in the presence of phytohaemagglutinin A (PHA), assuming that T cells were able to kill HPV-infected keratinocytes when a bridge between T cells and keratinocytes was provided. In conclusion, the organotypic culture of HPV-transformed keratinocytes may provide an effective in vitro model for investigating novel T cell-based immunotherapy protocols for the treatment of HPV-associated lesions.

Antibodies, Monoclonal↗
PubMed1983

An information-theory model of cellular survival, mutation and transformation and the relevance of this model to chemical carcinogenesis.

A model of cellular survival, mutation and transformation is presented in accordance with information theory. A cellular system is considered to be stable with respect to its environment when the vital information the cell expresses at least equals the information requirements of the environment. Environmental agents, such as mutagens, perturb the cell's expression of information such that an imbalance occurs between the cell's information requirement and the cell's ability to express vital information. This imbalance, which is interpreted as the intrinsic entropy of the cell, serves as a measure of biological cell death. If the cell compensates for the altered ability to express information by adapting to a less restricted set of information requirements, then one may view the cell as having undergone a "transformation" to a less restricted phenotype. This paper will elucidate the mathematical inter-relationships of cellular survival, mutation and transformation and will relate these mathematical concepts to chemical carcinogenesis.

Animals↗
PubMed1999

Development of new adherent mutant from human myeloma-derived cell line: in vitro model of anaplastic transformation of myeloma.

Anaplastic myeloma is a rare but distinct, biologically aggressive variant of myeloma which usually results from dedifferentiation or anaplastic transformation of the myeloma cells. The molecular mechanisms that determine the biologic behavior of anaplastic myeloma and effective treatment modalities have not been well known due to lack of in vitro models. In the present study, we have developed an anaplastically transformed mutant from a human myeloma-derived cell line. In the process of long-term culture of the myeloma-derived IM-9 cell line in low serum and nutrient conditions, an adherent mutant line was developed and named IM-9/AD. This mutant cell line displayed several characteristics resembling anaplastic myeloma such as: 1, large cells with large vesicular nucleus and prominent nucleolus, multinuclearity and high mitotic figures; 2, loss of leukocyte-associated antigens; and 3, higher tumorigenecity in scid mice than its parental cell line. This newly developed mutant cell line may serve as a readily available in vitro model to investigate the biology of anaplastic myeloma.

Animals↗
PubMed1988

Models of sensorimotor transformations and vestibular reflexes.

The vestibulo-ocular and vestibulo-collic reflexes are well-studied sensorimotor systems with dynamic properties that have been successfully modeled. Recently proposed matrix and tensorial models attempt to describe the spatial organization of these reflexes in three dimensions. Here we describe experiments that test these models. We show that a matrix model of the vestibulo-ocular reflex provides a satisfactory description of its spatial properties. The vestibulo-collic reflex is more complex, but a tensorial model makes close predictions of neck muscle excitation by the vestibulo-collic reflex. In addition, our preliminary data show that the cervico-collic or neck stretch reflex produces essentially the same spatial pattern of neck muscle excitation as the vestibulo-collic reflex, a finding predicted by the tensorial model. We conclude by showing electromyographic and single neuron responses that can be modeled only by combining models of dynamics with models of spatial organization. We believe that the development of such models is the next major challenge in the application of quantitative methods to analysis of reflex behavior.

Animals↗
PubMed2005

Bridging the strategic leadership gap: a model program for transformational change.

The University of Pittsburgh Medical Center (UPMC) recognized the impending crisis--a vast nurse leader shortage, especially at the strategic level. UPMC's new development model establishes a dependable leadership pipeline. The model identifies high-potential individuals, verifies required competencies, assesses participants' strengths, and provides a didactic and experiential learning curriculum. Within 2 years, the program produced a 450% return on investment and evolved into the Health Care Leadership Academy, an open enrollment program for emerging, operational, and strategic leaders nationwide.

Curriculum↗
PubMed2002

Vacuolation in T-tubules as a model for tubular-vesicular transformations in biomembrane systems.

This review outlines the basic properties of T-tubules in skeletal muscle cells, and the factors that govern reversible vacuolation in T-tubules under experimental conditions. Comparable membranous transformations, involving the plasma membrane or occurring intracellularly, in non-muscle cells are then considered. Finally, the mechanisms of similar transformations in various model membrane systems are discussed. In view of the similarities between reversible vacuolation in the T-system and membrane transformations occurring in a variety of non-muscle cells, it is suggested that reversible vacuolation in T-tubules may be regarded as a general model for tubular-vesicular transformations in biomembranes.

Animals↗
PubMed2000

Cell proliferation in normal and malignant transformed cells: thermodynamic model of signal transduction.

We present a new thermodynamic model for the mechanism of activation and regulation of cell proliferation in the G1 stage. In this model, the interactions between growth factors and transmembrane proteins play a crucial role in cell growth control for a normal tissue-culture system. We calculate a phase diagram of normal and malignant transformed states of a cell signal transduction system. We propose thermodynamic reasons why cancer cells can continually grow without activation by the growth factors.

Biophysical Phenomena↗
PubMedDate not supplied

[Determination of the parameters for producing a biobinder from wood: a mathematical modeling of the transformation of lignocellulose substrate by the fungus Panus tigrinus].

A biochemical scheme for the transformation of wood lignocellulose during enzymatic hydrolysis of polysaccharides and lignin destruction in reactions involving free radicals was developed, and a corresponding mathematical model was constructed. Processing (fermentation) of wood particles by the fungus Panus tigrinus in a submerged culture for producing a biobinder of wood composites--woodchip boards and fiber-boards--is considered. The mathematical model was used to study the technological parameters that influence the production of enzymes and fungal biomass and the level of free radical accumulation in the substrate, i.e., the factors determining the production of the biobinder. The optimal values of these parameters were determined, namely: the specific surface of wood particles, amounting to 2000 cm2/g; processing time of 56 h; and an initial concentration of 3.0 g/l of fungal biomass in the submerged culture.

Cellulose↗
PubMed1995

Fast freeze-fixation/freeze-substitution reveals the secretory membranes of the gastric parietal cell as a network of helically coiled tubule. A new model for parietal cell transformation.

The parietal cell of the gastric mucosa undergoes rapid morphological transformation when it is stimulated to produce hydrochloric acid. In chemically fixed cells, this process is seen as a reduction in number of cytoplasmic 'tubulovesicles' as the apical surface of the cell progressively invaginates to increase the secretory surface area. It is widely believed that the tubulovesicles represent stored secretory membrane in the cytoplasm of the unstimulated cell, which is incorporated into the apical membrane upon stimulation, because they share H+,K+-ATPase activity with the apical membrane. However, fusion of tubulovesicles with the apical membrane concomitant with parietal cell activation has never been convincingly demonstrated. We have used fast freeze-fixation and freeze-substitution to study stages of morphological transformation in these cells. Tubulovesicles were not seen in the cytoplasm of any of our cryoprepared cells. Instead, the cytoplasm of the unstimulated cell contained numerous and densely packed helical coils of tubule, each having an axial core of cytoplasm. The helical coils were linked together by connecting tubules, lengths of relatively straight tubule. Lengths of straight connecting tubule also extended from coils lying adjacent to the apical and canalicular surfaces and ended at the apical and canaliculus membranes. Immunogold labelling with alpha- and beta-subunit-specific antibodies showed that the gastric H+,K+-ATPase was localized to the membranes of this tubular system, which therefore represented the configuration of the secretory membrane in the cytoplasm of the unstimulated parietal cell. Stimulation of the cells with histamine and isobutylmethylxanthine lead to modification of the tubular membrane system, correlated with progressive invagination of the apical membrane. The volume of the tubule lumen increased and, as this occurred, the tight spiral twist of the helical coils was lost, indicating that tubule distension was accounted for by partial unwinding. This exposed the cores of cytoplasm in the axes of the coils as rod-shaped elements of a three-dimensional reticulum, resembling a series of microvilli in random thin sections. Conversely, treatment with the H2 antagonist cimetidine caused severe contraction of the tubular membrane system and intracellular canaliculi. Our results indicate that tubulovesicles are an artifact of chemical fixation; consequently, they cannot have a role in parietal cell transformation. From our findings we propose an alternative model for morphological transformation in the parietal cell. This model predicts cytoskeleton-mediated control over expansion and contraction of the tubular membrane network revealed by cryopreparation. The model is compatible with the localization of cytoskeletal components in these cells.

Animals↗
PubMed1988

Temperature-sensitive v-sea transformed erythroblasts: a model system to study gene expression during erythroid differentiation.

The isolation and characterization of a temperature-sensitive mutant (ts1 S13) of the avian erythroblastosis virus, S13, is described. The temperature-sensitive lesion in ts1 S13 was identified as affecting the tyrosine kinase activity but not the plasma membrane localization of the ts1 S13 v-sea gene product. Erythroblasts transformed by ts1 S13 can be induced to synchronously differentiate into erythrocytes in an erythropoietin (EPO)-dependent fashion. Analysis of erythrocyte-specific gene expression in ts1 S13 erythroblasts reveals that the transformed, self-renewing erythroblasts obtained at permissive temperature already express all erythrocyte genes tested for, although at a low level. Upon differentiation induction, expression of erythrocyte-specific genes is not coordinately regulated but rather involves complex regulatory mechanisms that appear to be specific for the individual genes.

Alpharetrovirus↗
PubMed2002

Use of diffusion weighted MRI to predict the occurrence and severity of hemorrhagic transformation in a rabbit model of embolic stroke.

Severe hemorrhagic transformation (HT) is an important complication of thrombolytic therapy. A method to identify stroke victims destined to severe HT could improve the patient selection and thus the safety of such treatment. In this study, we investigated whether very early serial diffusion weighted magnetic resonance imaging (DWI) could predict the occurrence of HT in an embolic model of experimental stroke. We tested the hypothesis that the ischemic brains with very low initial apparent diffusion coefficients (ADC) are destined to severe early (<or=5.5 h) HT. We retrospectively analyzed DWI scans of 45 New Zealand white rabbits subjected to thromboembolic stroke and treated with thrombolysis. DWI was obtained 0.5, 2, 3 and 5 h after embolization. Various thrombolytics were administered 1 h post embolization. The percentage of pixels within the ischemic hemisphere with ADC values below 550 x 10(-6) mm(2)/s was calculated and then compared to the severity of HT observed on gross brain sections at 5.5 h. As early as 30 min after embolization, ischemic brains destined to severe HT exhibited a significantly greater percentage of pixels below the cut-off value compared to those without HT: severe HT: 25%, 18.75-37.25% vs. no HT: 12%, 5.00-16.00% (median, 25th-75th %, P<0.001). Petechial HT when percentages were in the intermediate range. Quantitative analysis of initial ADC value might identify individual stroke patients at risk of severe HT.

Animals↗
PubMed2001

Learning Hough transform: a neural network model.

A single-layered Hough transform network is proposed that accepts image coordinates of each object pixel as input and produces a set of outputs that indicate the belongingness of the pixel to a particular structure (e.g., a straight line). The network is able to learn adaptively the parametric forms of the linear segments present in the image. It is designed for learning and identification not only of linear segments in two-dimensional images but also the planes and hyperplanes in the higher-dimensional spaces. It provides an efficient representation of visual information embedded in the connection weights. The network not only reduces the large space requirement, as in the case of classical Hough transform, but also represents the parameters with high precision.

Algorithms↗
PubMed1971

DNA-induced transformation in Drosophila: genetic analysis of transformed stocks.

The exosome model of transformation in Drosophila melanogaster proposes that DNA fragments enter the cells of treated individuals and become firmly associated with their homologous chromosome segments, but are never integrated into the linear structure of the chromosome. This paper reports results that validate two central predictions of the model: (a) the introduced genetic information usually maps precisely at the site of the target locus, and (b) the original chromosomal information is still present at that site.

Animals↗
PubMed2003

Task-specific internal models for kinematic transformations.

Numerous studies of motor learning have focused on how people adapt their reaching movements to novel dynamic and visuomotor perturbations that alter the actual or visually perceived motion of the hand. An important finding from this work is that learning of novel dynamics generalizes across different movement tasks. Thus adaptation to an unusual force field generalizes from center-out reaching movements to circular movements (Conditt et al. 1997). This suggests that subjects acquired an internal model of the dynamic environment that could be used to determine the motor commands needed for untrained movements. Using a task interference paradigm, we investigated whether transfer across tasks is also observed when learning visuomotor transformations. On day 1, all subjects adapted to a +30 degrees rotation while making center-out-and-back reaching movements. After a delay of 5 min, different groups of subjects then adapted to a -30 degrees rotation while performing either a continuous tracking task, a figure-eight drawing task, or the center-out-and-back reaching task. All subjects were then retested the next day on the +30 degrees rotation in the reaching task. As expected, subjects who experienced the opposing rotations while performing the same reaching tasks showed no retention of learning for the first rotation when tested on day 2 (Krakauer et al. 1999). In contrast, such retrograde interference was not observed in the two groups of subjects who experienced the opposing rotations while performing different tasks. In fact, their performance on day 2 was similar to that of control subjects who never experienced the opposite rotation. This lack of interference suggests that memory resources for visuomotor rotations are task specific.

Adult↗