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PubMed2002

Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation.

Transcription factor oncogenes such as GLI and c-MYC are central to the pathogenesis of human tumors. GLI encodes a zinc finger protein that is activated by Sonic Hedgehog signaling. Mutations in this pathway induce GLI expression in basal cell carcinoma, and expression of GLI in mice is sufficient to induce these skin tumors. We used microarrays to identify transcripts regulated by GLI or c-MYC after retroviral transduction and short-term culture of epithelial RK3E cells. Although each of these oncogenes induces malignant transformation of RK3E, two distinct sets of genes were identified. Of approximately 17,500 transcripts represented on the microarrays, GLI up-regulated the expression of 158 and repressed the expression of 52. In contrast, transcripts regulated by c-MYC were mainly repressed (424 of 682 regulated transcripts). Transcripts induced by the GLI transgene are likewise expressed in association with endogenous GLI in Ptch-deficient murine fibroblasts or in human skin tumors, but are not up-regulated in RK3E cells transformed by c-MYC, KLF4, or HRAS1. Unlike these other oncogenes, GLI induced the expression of mesenchymal cell markers including Snail, a zinc finger protein implicated in epithelial-mesenchymal transition in development and during tumor progression. A novel GLI-estrogen receptor fusion protein rapidly induced Snail mRNA expression in a manner like Ptch, a known direct transcriptional target gene. Induction of Snail expression and epithelial-mesenchymal transition by GLI may account for certain histopathological features of basal cell carcinoma, such as the absence of a well-defined, intraepithelial precursor lesion. In addition, consistent expression of the newly identified GLI-induced transcripts within GLI-expressing tumors in vivo indicates that oncogene-specific transcriptional profiles may be useful diagnostic tools for analysis of human tumors.

Animals↗
PubMed2006

[Arterial hypertension in schizophrenia as a model of benign transformation of somatic pathology].

AIM: To detect characteristics of arterial hypertension in schizophrenia. MATERIAL AND METHODS: The course of arterial hypertension and structural-functional alterations of the left ventricle were studied in the group of hypertensive schizophrenics and hypertensive patients without schizophrenia. RESULTS: Arterial hypertension in schizophrenics occurs less frequently, is not so high, is associated with insignificant structural-functional rearrangement of the left ventricle. This is true for cases when arterial hypertension onset precedes onset of psychosis when somatic disease does not combine with atherosclerosis. Incidence rate of hypertension diagnosis, mean levels of pressure and structural-functional indices of the left ventricle (for the first degree of arterial hypertension) for patients given and not given vasoactive psychotropic drugs do not differ significantly. CONCLUSION: Arterial hypertension in schizophrenia is characterized by benign transformation as seen from less prevalence and severity of the disease in mild structural-functional alterations of the left ventricle than in population of somatic patients.

Adult↗
PubMed1991

Reversible transformation by v-sis: a model cell line for analysis of transformation by antisense methods.

Cellular homologs of v-sis are implicated in numerous human tumor types (Eva et al., 1982; Betsholtz et al., 1984; Johnson et al., 1985; Bronzert et al., 1987; Igarashi et al., 1987; Nister et al., 1988a,b; Versnel et al., 1988; Matsui et al., 1989), but whether tumor growth is maintained by sis expression alone or requires additional changes is unknown. To distinguish these possibilities, we studied reversible transformation of NIH-3T3 cells bearing an inducible v-sis construction. Cells subcultured from 10 of 18 tumors, all less than 0.1 gram and less than or equal to 21 days in age, reverted to a normal phenotype by four criteria, but again exhibited transformation upon induction. Thus, activation of the v-sis autocrine loop alone is sufficient for initiation of tumors. Cells from the remaining and larger, 0.5 +/- 0.7 gram, tumors did not revert by any criteria. This suggests that subsequent tumor growth is maintained by acquisition of irreversible change(s) that occurs at high frequency in vivo.

3T3 Cells↗
PubMed1996

Müllerian inhibiting substance as a model for the transforming growth factor-beta family: development of new treatment strategies.

The study of ligand receptor interactions and receptor function often requires multifaceted experimental approaches. In the course of studying the function and mechanism of action of müllerian inhibiting substance (MIS), we have used a wide range of molecular and cellular techniques. These have led to the identification, cloning, and characterization of the MIS receptors and of other receptors for the transforming growth factor-beta (TGF beta) family. This article describes the use of polymerase chain reaction (PCR) cloning to isolate candidate receptor genes, transfection and flow cytometry to study ligand binding, nonhomologous recombination targeted gene disruption (knockout) to analyze receptor function, and yeast genetics to identify other proteins that interact with the receptor complex. Together these techniques have led to the development of therapeutics and therapeutic strategies that are ready for clinical application.

Anti-Mullerian Hormone↗
PubMed1979

A biochemical and ultrastructural comparison of Triton X-100 models of normal and transformed cells.

We have compared the two-dimensional gel profiles of Triton models of normal rat kidney (NRK) cells and their Kirsten viral transformant, 442. Several protein differences were detected. The models of the transformed line lacked five acidic polypeptides and possessed a much higher intermediate filament to actin ratio. Scanning microscopy reveals significant ultrastructural differences in these models, with the NRK line exhibiting a much more filamentous structure. In addition, nuclease treatment of NRK models causes a dramatic change in their scanning image while the 442 models are unaffected. Nuclease treated models lack microfilaments and appear to contain only intermediate filaments, although actin is still a prominent protein constituent.

Actins↗
PubMed2006

Methods for regeneration and transformation in Eschscholzia californica: A model plant to investigate alkaloid biosynthesis.

Eschscholzia californica Cham. (California poppy) is a plant species that accumulates pharmacologically active alkaloids biosynthetically related to the morphinan alkaloids of Papaver somniferum. This, in combination with the relative ease with which it is propagated in vitro, makes it a key model for benzylisoquinoline biosynthesis. Transformation techniques are an important tool for these studies and for metabolic engineering attempts. Agrobacterium mediated transformation techniques for this model species have been developed in our lab and used for modulation of transcript levels relevant to the biosynthesis of these alkaloids. Here we describe the techniques used in our lab for production of transgenic callus, hairy root cultures, and whole plants.

Alkaloids↗
PubMedDate not supplied

Metamorphosis of 3D polyhedral models using progressive connectivity transformations.

Three-dimensional metamorphosis is a powerful technique to produce a 3D shape transformation between two or more existing models. In this paper, we propose a novel 3D morphing technique that avoids creating a merged embedding that contains the faces, edges, and vertices of two given embeddings. This novel 3D morphing technique dynamically adds or removes vertices to gradually transform the connectivity of 3D polyhedrons from a source model into a target model and simultaneously creates the intermediate shapes. In addition, a priority control function provides the animators with control of arising or dissolving of input models' features in a morphing sequence. This is a useful tool to control a morphing sequence more easily and flexibly. Several examples of aesthetically pleasing morphs are demonstrated using the proposed method.

Algorithms↗
PubMed2001

Predicting percentage of intramuscular fat using two types of real-time ultrasound equipment.

In the present study, 500 steers were used to develop models for predicting the percentage of intramuscular fat (PIMF) in live beef cattle. Before slaughter, steers were scanned across the 11th and 13th ribs using Aloka 500V (AL-500) and Classic Scanner 200 (CS-200) machines. Four to five images were collected per individual steer using each machine. After slaughter, a cross-sectional slice of the longissimus muscle from the 12th rib facing was used for chemical extraction to determine actual carcass percentage of intramuscular fat (CPIMF). Texture analysis software was used by two interpreters to select a region for determination of image parameters, which included Fourier, gradient, histogram, and co-occurrence parameters. Four prediction models were developed separately for each of AL-500 and CS-200 based on images captured by the respective machines. These included models developed without transformation of CPIMF (Model I), models based on logarithmic transformation of CPIMF (Model II), ridge regression procedure (Model III), and principal component regression procedure (Model IV). Model R2 and root mean square error of AL-500 Models I, II, III, and IV were 0.72, 0.84%; 0.72, 0.85%; 0.69, 0.91%; and 0.71, 0.86%; respectively. The corresponding R2 and root mean square error values of CS-200 Models I, II, III, and IV were 0.68, 0.87%; 0.70, 0.85%; 0.64, 0.94%; and 0.65, 0.91%; respectively. Initially, AL-500 and CS-200 prediction models were validated separately on an independent data set from 71 feedlot steers. The overall mean bias, standard error of prediction, and rank correlation coefficient across the four AL-500 models were 0.42%, 0.84%, and 0.88, respectively. For the four CS-200 models, the corresponding overall mean values were 0.67%, 0.81%, and 0.91, respectively. In a second validation test, only Model II of AL-500 and CS-200 was evaluated separately based on data from 24 feedlot steers. The overall mean bias, absolute difference, and standard error of prediction of AL-500 Model II were 0.71, 0.92, and 0.98%. For CS-200 Model II, the corresponding values were 0.59, 0.97, and 1.03%. Both AL-500 and CS-200 equipment can be used to accurately predict PIMF in live cattle. Further improvement in the accuracy of prediction equations could be achieved through increasing the development data set and the variation in PIMF of cattle used.

Adipose Tissue↗
PubMed2000

Five-factor model of personality and transformational leadership.

This study linked traits from the 5-factor model of personality (the Big 5) to transformational leadership behavior. Neuroticism, Extraversion, Openness to Experience, and Agreeableness were hypothesized to predict transformational leadership. Results based on 14 samples of leaders from over 200 organizations revealed that Extraversion and Agreeableness positively predicted transformational leadership; Openness to Experience was positively correlated with transformational leadership, but its effect disappeared once the influence of the other traits was controlled. Neuroticism and Conscientiousness were unrelated to transformational leadership. Results further indicated that specific facets of the Big 5 traits predicted transformational leadership less well than the general constructs. Finally, transformational leadership behavior predicted a number of outcomes reflecting leader effectiveness, controlling for the effect of transactional leadership.

Adult↗
PubMed1988

Capture and characterization of 5-aza-2'-deoxycytidine-treated C3H/10T1/2 cells prior to transformation.

A model system was developed to capture phenotypically normal cells committed to transformation to address two fundamental questions in cancer biology: (i) what are the earliest events in transformation; and (ii) what is the role of DNA methylation in carcinogenesis? Individual C3H/10T1/2 cells were treated with 5-aza-2'-deoxycytidine, which causes hypomethylation of DNA. Cells were grown to subconfluence, and individual microcolonies were trypsinized into two fractions. One fraction was cryopreserved, and the other was replated and maintained in culture. Ten percent of these replated colonies became morphologically transformed after 4-6 weeks. The cryopreserved ancestral cells of both transformed and nontransformed microcolonies were then cultured and compared to each other and to the transformants for phenotypic properties of cellular transformation. Pretransformed and nonpretransformed ancestral cells were initially morphologically indistinguishable, their early growth curves did not differ significantly, and they did not form colonies in soft agar. On continued growth in culture, however, the pretransformants displayed all of the phenotypic characteristics of transformation. Furthermore, transformation occurred in a given pretransformant in most or all of the cells of that clone. Thus, cells committed to transformation could be isolated in this way prior to phenotypic transformation. Studies of these pretransformed cells will permit examination of the earliest events in carcinogenesis and the role of DNA methylation in transformation.

Animals↗