Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transformers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed1996

Similar architectures of native and transformed human alpha2-macroglobulin suggest the transformation mechanism.

The refined three-dimensional structure of native human alpha2-macroglobulin (alpha2M) has been determined by cryoelectron microscopy and three-dimensional reconstruction. New features corresponding to "sigmoid arches," "basal bodies," and "apical connections" were observed in the molecule. Since similar elements are found in the architecture of transformed alpha2M, the 2 volumes were aligned in three dimensions. In their common orientations, they show many similarities except near the openings of the central chamber. In the native conformation, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structure, they are partially closed. These structures suggest that alpha2M conformational change involves a strong lateral compression and a vertical stretching of the native particle seen in its four-petaled flower view to produce the H view of the transformed form. A model of structural transformation, in which all the parts of the alpha2M molecule seem involved in the entrapment of the proteinases is proposed.

Cryopreservation↗
PubMed1988

Growth support and toxicity of homocysteine and its effects on methionine metabolism in non-transformed and chemically transformed C3H/10T1/2 cells.

The effects of homocysteine (Hcy) on one non-transformed (Cl 8) and two malignant clones (Cl 16 and Cl T422) of the C3H/10T1/2 mouse embryo fibroblasts, were examined with regard to toxicity, ability to support growth and effects on methionine (Met) metabolism and glutathione level. Homocysteine in its reduced form (Hcy-SH) was toxic to all cell lines, and the LD90 was estimated to be 1.0 X 10(-4) M for Cl 8 and Cl 16 cells measured by plating efficiency, 0.8 X 10(-4) M for Cl 8 and 0.3 X 10(-4) M for Cl 16 when measured by total cell growth. At toxic concentrations, Hcy-SH showed a drastic effect on cell morphology both in the presence and absence of Met. The same effect was demonstrated with L-cysteine. No toxic effect was seen with homocystine (Hcy-SS-Hcy) or homocysteine thiolactone (Hcy-tl) at similar concentrations. Hcy-tl supported growth of both the non-transformed and malignant cells in Met-deficient medium but with decreasing efficiency in the order Cl 8, Cl 16 and Cl T422. The growth rate constant compared to that of Met-supplemented medium was 0.62 for Cl 8, 0.44 for Cl 16 and 0.38 for Cl T422 cells. The intracellular level of S-adenosylhomocysteine (AdoHcy) increased in all three cell lines in Hcy-tl-supplemented medium. The S-adenosylmethionine (AdoMet) content increased in Cl 8 cells, was constant in Cl 16 cells and decreased in Cl T422 cells under the same conditions. This resulted in a constant ratio of AdoMet/AdoHcy in the non-transformed cells (Cl 8) whereas this ratio decreased by 40% in Cl 16 and by 72% in Cl T422 cells when Hcy-tl replaced Met in the medium. The ability of Hcy-tl to support growth thus seemed to correlate well with alteration in Met metabolism in this cell culture system. The intracellular level of glutathione (GSH) was measured during exponential growth, but showed small variations between non-transformed cells and Cl 16 cells. However, Cl T422 cells showed a distinct lower level of GSH in Met-supplemented medium, and this increased 3- to 4-fold when Met was replaced with Hcy-tl.

Animals↗
PubMed2006

Interplay between diffusive and displacive phase transformations: time-temperature-transformation diagrams and microstructures.

Materials which can undergo extremely fast displacive transformations as well as very slow diffusive transformations are studied using a Ginzburg-Landau framework. This simple model captures the essential physics behind microstructure formation and time-temperature-transformation diagrams in alloys such as steels. It also predicts the formation of mixed microstructures by an interplay between diffusive and displacive mechanisms. The intrinsic volume changes associated with the transformations stabilize mixed microstructures such as martensite-retained austenite (responsible for the existence of a martensite finish temperature) and martensite-pearlite.

Journal Article↗
PubMed2003

Application of a nonuniform spectral resampling transform in Fourier-transform spectrometry.

We describe a nonuniform spectral resampling transform (NUSRT) that resamples a frequency-scaled spectrum that has been measured by a Fourier-transform spectrometer (FTS). Frequency scaling of a spectrum can arise from measurements made with off-axis detectors and Doppler shift induced by motion of a spaceborne FTS relative to an input radiation source. In addition, a spectrum may need to be rescaled in frequency to match spectral lines for applications such as the retrieval of atmospheric state parameters. The NUSRT is cast as a linear algebraic expression that relates a nonuniformly sampled interferogram to an input spectrum. A polynomial approximation is applied to this expression that reduces the inverse of the NUSRT to a series of Fourier transforms that can be implemented as fast Fourier transforms (FFTs). We show that this NUSRT algorithm requires on the order of 6N log N flops, which reduces the computational cost of rescaling by more than 1 order of magnitude compared with conventional FFT-based Shannon interpolation techniques while comparable accuracy is maintained.

Journal Article↗
PubMed2003

Fractional Hankel transform studied by charge-amplitude state representations and complex fractional Fourier transformation.

Starting from a complex fractional Fourier transformation [Opt. Lett. 28, 680 (2003)], it is shown that the integral kernel of a fractional Hankel transformation is equivalent to the matrix element of an appropriate operator in the charge-amplitude state representations; i.e., the fractional Hankel transformation is endowed with a definite physical meaning (definite quantum-mechanical representation transform).

Journal Article↗
PubMed2006

Transformation of time-resolved spectra to lifetime-resolved spectra by maximum entropy inversion of the laplace transform.

We present a method for the analysis of time-resolved spectroscopic data following first-order kinetics. The time traces at all the available spectroscopic channels (e.g., wavelength or wavenumber) are inverse Laplace transformed. The transformation is stabilized by the maximum entropy method generalized for solutions without sign-restriction. In this way, time-resolved spectra can be converted to lifetime-resolved spectra, where bands appear at coordinates corresponding to their spectroscopic maxima and time constant of appearance (negative amplitude) or disappearance (positive amplitude). From the lifetime-resolved spectra, the number of exponentially decaying components, their time constants, and their decay-associated spectra are readily available. Moreover, since bands are spread in two dimensions extra band-resolution is possible. We named this method of transforming time-resolved spectra into lifetime-resolved spectra multi-spectroscopic channel maximum entropy inversion of the Laplace transform (M-MaxEnt-iLT). The basis of M-MaxEnt-iLT is presented in detail and its properties and limitations are thoroughly discussed. We also show how the combination of M-MaxEnt-iLT with spectral smoothing or deconvolution can improve the appearance and/or band resolution of the obtained lifetime-resolved spectra.

Journal Article↗
PubMed1984

Evidence for a transforming growth factor(s) in the serum-free conditioned medium of SV40-transformed 3T3 fibroblasts.

Unlike untransformed 3T3 fibroblasts, Simian Virus 40-transformed 3T3 cells (SV3T3) do not require the presence of exogenous polypeptide mitogens in order to become competent for the initiation of DNA synthesis. As an explanation for this state of perpetual competence, growth activity for 3T3 cells was found in the serum-free conditioned medium of SV3T3 cells. This activity, which is abolished by incubation with pepsin, but withstands to a fair degree denaturants (8 M urea and 4 M guanidinium HCl) and a reducing agent (65 mM dithioerythritol), enhances the growth of Swiss and BALB/c 3T3 cells in 1% (v/v) calf serum medium and ensures the complete survival of Swiss 3T3 cells for several days in the total absence of serum. The growth activity appears to be derived from the SV3T3 cells, since it is not found in the non-conditioned medium (and the insulin and transferrin components of this serum-free medium have only weak growth activity alone) and the chances of it being due to residual serum growth factors are slight because of the method of growing the cells and the collection of the conditioned medium. Moreover, in a separate experiment to test the possible involvement of cell attachment factors, rat fibronectin was found not to affect 3T3 growth in the standard growth assay. The conditioned medium growth activity apparently has the biological capabilities of transforming growth factors. After concentration by ammonium sulfate precipitation, it can stimulate DNA synthesis in confluent, quiescent Swiss 3T3 cells, in both the absence and presence of 10% depleted calf serum. It also permits the growth of large colonies of Swiss 3T3 cells in soft agar. As part of a preliminary characterization of the conditioned medium growth activity, gel filtration in 0.15 M NaCl, 0.001 M HCl resolves the activity into high (mol. wt. greater than or equal to 100,000) and low (mol. wt. 5,000-6,000) molecular weight factors. Since re-chromatography of the high molecular weight factor, which may still be in an aggregated form, does not generate the smaller, the latter is not a dissociation product of the former. The precise relationship of these SV3T3-conditioned medium growth factors to other growth factors, including known transforming growth factors, has not yet been determined.

Animals↗
PubMed1992

Regulation of surface-differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene.

Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2'-deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class-I molecules, human milk-fat-globule-I antigen, and EGF receptor was reduced in ras-transfected cells, although other differentiation markers were unchanged. Exogenous EGF down-regulated the expression of functional EGF-R, selectively in transformed cells. TGF-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.

Antigens, Differentiation↗
PubMed1993

Infection with a transforming growth factor alpha anti-sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line.

Transforming growth factor alpha (TGF alpha) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGF alpha. GEO cells, from a human colon carcinoma cell line that expresses TGF alpha and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein I promoter. Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGF alpha AS cells). A 50 to 70% inhibition in the production of secreted and cell-associated TGF alpha protein was observed in GEO TGF alpha AS cells that had been maintained in CdCl2-supplemented medium. Moreover, a growth inhibition of 70% and 50% was observed in CdCl2-treated GEO TGF alpha AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively. In contrast, CdCl2 treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGF alpha may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor.

Animals↗
PubMed1984

Immunoglobulin synthesis and gene rearrangements in lymphoid cells transformed by replication-competent Rauscher murine leukemia virus: transformation of B cells at various stages of differentiation.

Lymphoid cells transformed by Rauscher murine leukemia virus (R-MuLV) belonged to the B cell lineages. One group of cells exhibited Fc receptors but completely lacked immunoglobulin mu heavy and kappa light chains. The majority of the cells resemble pre-B type. They displayed mu chains but kappa chains were completely absent. Very rarely certain cells synthesized both mu and kappa chains. Based on the presence of Fc receptors and IgM synthesis the cells transformed by R-MuLV belonged to three B cell developmental stages. These cells were tested for immunoglobulin gene rearrangements using JH and CK probes. DNA from cell lines without any detectable levels of IgM mu exhibited embryonic as well as rearranged JH genes, whereas cells expressing IgM possess, in addition, productive and non-productive light chain gene rearrangements. The most terminally differentiated cell possesses JH and CK rearrangement associated with the synthesis of mu and kappa chains. Presumably the cells with rearranged JH and CK genes without immunoglobulin synthesis represent a developmental transition. We conclude that cells transformed by R-MuLV belonged to five step-wise compartments of B cell development. Our findings implicate definite sequential events of immunoglobulin gene rearrangement and expression during B cell development.

Animals↗
PubMed1988

Potassium inhibition of transforming protein P85gag-mos and reversal of the transformed phenotype in 6m2 cells.

K+ at high concentrations (52-72 mM hypertonic KCl) has been reported to induce reverse transformation in the 6m2 cell, which is a clone of normal rat kidney cells (NRK) infected with a temperature-sensitive transformation virus. When exposed to high K+, 6m2 cells grown at the permissive temperature (33 degrees C) exhibit normal morphology and reduced soft agar growth, characteristics of cells grown at nonpermissive temperature (39 degrees C). In the current study, flattening of cells and rearrangement of surface microvilli were demonstrated by scanning electron microscopy to occur within 6 hr of exposure to high K+, similar to the effect of temperature shift to 39 degrees C. Exposure to K+ resulted in a 90% inhibition of P85gag-mos-associated serine kinase activity within 5 min, with a subsequent reduction of up to 75% of the synthesis of this protein. These alterations in the putative transforming protein were similar to those induced by temperature shift and were considered to be the basis for retrotransformation. The cell microtubular system and F-actin cables were affected more slowly by K+ than by a temperature shift to 39 degrees C. The former did not achieve the fine reticulum network seen in NRK cells until 72 hr later, but the latter remained aberrant. The effect on the enzyme might be mediated by alteration in phosphorylation, but the mechanism by which kinase inactivation induces retrotransformation is not yet known.

Actins↗
PubMed1992

Additive effects of c-erbB-2, c-Ha-ras, and transforming growth factor-alpha genes on in vitro transformation of human mammary epithelial cells.

MCF-10A cells are a spontaneously immortalized untransformed human mammary epithelial cell line. We have previously shown that overexpression of a human point-mutated c-Ha-ras proto-oncogene, the rat c-neu (c-erbB-2) proto-oncogene, or the human transforming growth factor-alpha (TGF-alpha) gene in MCF-10A cells leads to in vitro transformation of such cells. To ascertain whether the introduction of two of these genes into MCF-10A human mammary epithelial cells induces a completely tumorigenic phenotype, we infected MCF-10A Ha-ras and MCF-10A TGF-alpha cells with a recombinant retroviral vector containing the human c-erbB-2 proto-oncogene and the hygromycin-resistance gene. Ten MCF-10A TGF-alpha/c-erbB-2 (MCF-10A TE) and 10 MCF-10A Ha-ras/c-erbB-2 (MCF-10A HE) hygromycin-resistant clones were randomly selected and expanded into cell lines. MCF-10A TE and MCF-10A HE clones expressed a 10-fold to 40-fold increase in p185 erbB-2 protein levels compared with parental uninfected cells. These cells exhibited a fourfold increase in their growth rate in serum-free medium and showed a strongly reduced mitogenic response to exogenous epidermal growth factor or TGF-alpha compared with MCF-10A cells. Moreover, both MCF-10A TE and MCF-10A HE clones exhibited a fivefold to 20-fold higher cloning efficiency in soft agar than MCF-10A Ha-ras, MCF-10A c-erbB-2, or MCF-10A TGF-alpha clones. However, neither MCF-10A TE nor MCF-10A HE cells were able to grow as tumors in vivo when they were injected into nude mice. These results suggest that c-Ha-ras, c-erbB-2, and TGF-alpha genes have an additive effect on the in vitro transformation of an immortalized human mammary epithelial cell line, but that additional genetic changes such as activation of other proto-oncogenes or inactivation of a tumor suppressor gene may be necessary to elicit a fully tumorigenic phenotype.

Animals↗
PubMed1992

Regulation of growth and gene expression in human papillomavirus-transformed keratinocytes by transforming growth factor-beta: implications for the control of papillomavirus infection.

Cervical carcinogenesis is a multistep process that appears to be initiated by infection of squamous epithelial cells in the cervix with one of a limited number of human papillomavirus (HPV) types. However, the mechanisms involved in the evolution of benign, HPV-induced lesions to malignancy have not yet been fully elucidated. Transforming growth factor-beta (TGF-beta), a multifunctional growth factor produced by cells in the skin, inhibits the proliferation of foreskin and cervical keratinocytes in vitro. We examined the effects of TGF-beta on growth and virus early-gene expression in cell lines immortalized by two HPV types associated with cervical carcinogenesis as well as the expression of TGF-beta 1 mRNA transcripts in normal and HPV-positive cells in vivo and in vitro. We found that normal and HPV-positive cells expressed similar levels of TGF-beta 1 mRNAs and exhibited similar patterns of responsiveness to three isoforms of TGF-beta in both monolayer and modified organotypic cultures. Of particular interest is our finding that the expression of the E6 and E7 early viral transforming regions of both HPV16 and HPV18 was reversibly and rapidly inhibited by TGF-beta. In one HPV16-positive cell line examined in detail, inhibition of HPV expression required protein synthesis and occurred at the level of transcription. HPV-immortalized cells selected for resistance to in vitro differentiation signals remained sensitive to TGF-beta-mediated growth inhibition. These results, showing that both growth and virus gene expression in HPV-transformed cells were responsive to TGF-beta, suggest that endogenous growth factors produced by different cell types in squamous epithelium may play a role in the progression of cervical neoplasia.

Blotting, Northern↗
PubMed2001

Transforming growth factor beta may act as an autocrine-survival-promoting factor for transformed trophoblasts.

Using five trophoblast cell lines of different differentiation status, we have shown that trophoblasts could constitutively release the transforming growth factor beta-1 (TGFbeta1), but not TGFbeta2. Treatment of the human tumorigenic, TL, and BeWo cells with a differentiating agent and a potent protein kinase C activator--the tumor-promoting agent--or the JEG-3 cells with cholera toxin--a potent cyclic adenosine 3':5'monophosphate (cAMP) inducer--or its analogue 8-bromo-cAMP, potentiates TGFbeta production, but the two signaling pathways appear to be mutually exclusive. Surprisingly, the JAR tell line failed to respond to either type of TGFbeta activator. Based on reverse transcriptase (RT)-polymerase chain reaction (PCR), it was found that only the JAR cell line expressed messenger ribonucleic acid for decorin, a natural inhibitor of TGFbeta, and none of the cell lines had detectable protein expression as determined by immunocytochemical studies. The tell number in cultures with decorin was invariably lesser than in those without decorin under serum-free conditions for all the cell lines tested. These results suggest that TGFbeta may act as an autocrine-survival factor for transformed trophoblasts by allowing the cells to survive longer under a microenvironment which is not favorable for growth. Lastly, our results indicate that decorin, acting in a paracrine manner, may also play an important negative regulatory role in the development of transformed trophoblasts by sequestering TGFbeta, thereby preventing its action.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Comparison of the effects of transforming growth factor beta, N,N-dimethylformamide, and retinoic acid on transformed and nontransformed fibroblasts.

In order to compare the effects of transforming growth factor (TGF beta) with those of the differentiation promoters N,N-dimethylformamide (DMF) and retinoic acid (RA), the antiproliferative and fibronectin-inducing activities of the three agents were examined. AKR-2B mouse embryo fibroblasts and their chemically transformed counterpart AKR-MCA cells were used as the model system. Growth in monolayer culture of both cell lines was inhibited by TGF beta (EC50 approximately 1 ng/ml), DMF (EC50 approximately 0.5%), and RA (EC50 approximately 1 microM) in a concentration-dependent manner. Time-dependent elevation in fibronectin expression was also observed with all three agents. The EC50 for growth inhibition of both cell lines by TGF beta agreed well with that obtained for stimulation of fibronectin synthesis. A 3-h exposure to TGF beta is sufficient to obtain the maximal fibronectin level observed at 48 h in AKR-2 B cells but not in AKR-MCA cells. Our results indicate that in this system the effects of TGF beta are similar to those of the chemical differentiation inducers DMF and RA. Furthermore, our data also suggest that the TGF beta signal may be processed differently by nontransformed and transformed fibroblasts.

Animals↗
PubMed1984

Decreased adenylate cyclase responsiveness of transformed cells correlates with the presence of a viral transforming protein.

The adenylate cyclase responsiveness of transformed fibroblastic and epithelial cell lines to forskolin, fluoride, guanine nucleotides and cholera toxin was reduced compared to their parental counterparts. This phenomenon was observed in lines transformed by either RNA or DNA tumor viruses, and in the case of polyoma virus, coincided with the expression of middle T antigen. The data suggest that decreased responsiveness of adenylate cyclase to non-hormone activators is a general consequence of viral transformation and may be related to viral regulation of protein kinase activity.

Adenylyl Cyclases↗
PubMed1986

Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation.

Acquisition of the ability to produce and respond to a growth factor may result in increased cellular proliferation and could lead to malignant transformation. The fact that a large variety of tumor cells secrete transforming growth factor-alpha (TGF-alpha) suggests involvement of TGF-alpha in cellular transformation and provides supporting evidence for the autocrine stimulation model. In order to determine directly the role of TGF-alpha in tumorigenicity, we introduced a human TGF-alpha cDNA expression vector into established nontransformed Fischer rat fibroblast (Rat-1) cells. Synthesis and secretion of human TGF-alpha by these cells results in the loss of anchorage-dependent growth and induces tumor formation in nude mice. Anti-human TGF-alpha monoclonal antibodies prevent TGF-alpha expressing Rat-1 cells from forming colonies in soft agar.

Animals↗
PubMed1991

Correlated abnormalities of transforming growth factor-beta 1 response and p53 expression in thyroid epithelial cell transformation.

Using the thyroid follicular cell as a model for multi-stage carcinogenesis, we have investigated the role of two potential negative growth regulators ('anti-oncogenes') in epithelial tumour progression--transforming growth factor-beta 1 (TGF beta 1) and p53. Normal follicular cells, as expected, showed marked growth inhibition in response to TGF beta 1. Adenoma cells were equally inhibited. In contrast, spontaneously and SV40-immortalised follicular cell lines showing features of malignant transformation (notably loss of growth factor dependence) had lost all responsiveness to TGF beta 1, accompanied by a partial loss of its receptors. p53 protein was below detectable limits in normal and in adenoma cells but in contrast very high levels were observed in all three transformed lines. In the SV40-immortalised cells, this was expected in view of the known stabilising effect of the viral large T protein. In the spontaneous line we found strong evidence for point mutation of p53, which is known to have the same effect. Both mechanisms result in loss of p53 tumour suppressor function despite increased protein content. We conclude that loss of inhibition by TGF beta and inactivation of p53 are important steps in in vitro immortalisation and/or in vivo tumour progression in human thyroid follicular cells, and speculate that p53 may mediate or be required for the inhibitory signal normally induced by TGF beta 1.

Adenoma↗