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PubMed2002

Effects of transforming growth factor-beta deficiency on bone development: a Fourier transform-infrared imaging analysis.

Transforming growth factor-beta 1 (TGF-beta1) is a cytokine member of the TGF-beta superfamily involved in the control of proliferation and differentiation of various cell types. TGF-beta1 plays an important role in bone formation and resorption. To determine the effect of TGF-beta1 deficiency on bone mineral and matrix, tibias from mice in which TGF-beta1 expression had been ablated (TGF-beta1 null) were analyzed and compared with background- and age-matched wild-type (WT) control animals by Fourier transform-infrared imaging (FTIRI) and histochemistry. FTIRI allows the characterization of nondemineralized thin tissue sections at the ultrastructural level with a spatial resolution of approximately 7 microm. The spectroscopic parameters calculated were: mineral-to-matrix ratio (previously shown to correspond to ash weight); mineral crystallinity (related to the crystallographically determined crystallite size and perfection in the apatite c-axis direction); and collagen maturity (related to the ratio of pyridinoline:deH-DHLNL collagen cross-links). Several fields were selected to represent different stages of bone development within the same specimen from the secondary ossification center to the distal diaphysis. Anatomically equivalent areas were compared as a function of age and genotype. The spectroscopic results were expressed both as color-coded images and as pixel population distributions for each of the three parameters monitored. Based on comparisons of histochemistry and FTIRI, there were distinctive age and genotype variations. At all ages examined, in the TGF-beta1 null mice growth plates, alkaline phosphatase (ALP) activity and collagen maturity were reduced, but no effect on mineral content or crystallinity was noted. In the TGF-beta1 null mice metaphyses, there was a persistence of trabeculae, but no significant alterations in mineral content or crystallinity. In contrast, mineral content, mineral crystallinity, and collagen maturity were reduced in the secondary ossification center and cortical bone of the TGF-beta1 null mice. These results, consistent with a mechanism of impaired bone maturation in the TGF-beta1 null mice, may be directly related to TGF-beta1 deficiency and indirectly to increased expression of inflammatory cytokines in the TGFbeta1 null mice.

Animals↗

PubMed1997

Decreased Stability of Transforming Growth Factor beta Type II Receptor mRNA in RER+ Human Colon Carcinoma Cells

Transforming growth factor beta (TGF-beta) is a potent inhibitor of cell growth and tumor progression. Previous work has shown that loss of functional TGF-beta type II receptor (RII) due to a frameshift mutation in the 5' half of the RII gene leads to TGF-beta resistance in a highly progressed, RER+ human colon carcinoma cell line designated HCT116. Expression of this mutated RII gene was highly repressed in RER+ cell lines such as HCT116 and RKO, as analyzed by RNase protection assays. Nuclear run-on and RII promoter-reporter (CAT) assays showed that the transcriptional levels of the RII gene in these RER+ cells were not reduced, compared to RII-expressing cells. However, the half-lives of the RII mRNA, as analyzed by RNase protection assays following actinomycin D treatment, were significantly decreased. This suggested that the decreased expression of the RII gene mutant was due to decreased mRNA stability. Furthermore, RII mRNA from HCT116 transfected with wild-type RII had a longer half-life than the endogenous mutated RII mRNA. A dominant negative RII mutant, which encodes a similarly truncated RII protein as HCT116 but lacks the extensive 3' untranslated region of RII mRNA, gave the same half-life as endogenous wild-type RII mRNA. We conclude that the frameshift mutation which results in a premature stop codon in the 5' half of the mRNA transcript accounts for the reduced RII mRNA levels in RER+ cells.

Journal Article↗

PubMed2006

Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation.

The transforming growth factor-beta (TGF-beta) signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colon cancer. TGF-beta is a secreted ligand that mediates its effects through a transmembrane heteromeric receptor complex, which consists of type I (TGFBR1) and type II subunits (TGFBR2). Approximately 30% of colon cancers carry TGFBR2 mutations, demonstrating that it is a common target for mutational inactivation in this cancer. To assess the functional role of TGFBR2 inactivation in the multistep progression sequence of colon cancer, we generated a mouse model that recapitulates two common genetic events observed in human colon cancer by mating Apc(1638N/wt) mice with mice that are null for Tgfbr2 in the intestinal epithelium, Villin-Cre;Tgfbr2(E2flx/E2flx) mice. In this model, we observed a dramatic increase in the number of intestinal adenocarcinomas in the Apc(1638N/wt);Villin-Cre;Tgfbr2(E2flx/E2flx) mice (called Apc(1638N/wt);Tgfbr2(IEKO)) compared with those mice with intact Tgfbr2 (Apc(1638N/wt);Tgfbr2(E2flx/E2flx)). Additionally, in vitro analyses of epithelial tumor cells derived from the Apc(1638N/wt);Tgfbr2(IEKO) mice showed enhanced expression and activity of matrix metalloproteinase MMP-2 and MMP-9, as well as increased TGF-beta1 secretion in the conditioned medium. Similarly, primary tumor tissues from the Apc(1638N/wt);Tgfbr2(IEKO) mice also showed elevated amounts of TGF-beta1 as well as higher MMP-2 activity in comparison with Apc(1638N/wt);Tgfbr2(E2flx/E2flx)-derived tumors. Thus, loss of TGFBR2 in intestinal epithelial cells promotes the invasion and malignant transformation of tumors initiated by Apc mutation, providing evidence that Wnt signaling deregulation and TGF-beta signaling inactivation cooperate to drive the initiation and progression, respectively, of intestinal cancers in vivo.

Animals↗

PubMed1991

Production of a transforming growth factor-beta-like growth factor by RSV-transformed rat cerebral microvascular endothelial cells.

This study describes the preliminary characterization of a Rous sarcoma virus (RSV)-transformed rat cerebral microvascular endothelial cell (RCE-T1)-derived growth factor with biological properties similar to transforming growth factor-beta (TGF-beta). A significant portion of this RCE-T1-derived TGF-beta-like growth factor was secreted in an active form and its secretion was elevated 2- to 3-fold in late passage cultures comprised of rapidly growing, less differentiated cells exhibiting reduced sensitivity to the growth-inhibitory effects of exogenous TGF-beta 1. These data suggest that the RCE-T1 cell line may be a useful system in which to study the role of autocrine TGF-beta production in normal and aberrant endothelial cell growth.

Animals↗

PubMed2005

Visualisation of transforming growth factor-beta 1, tissue kallikrein, and kinin and transforming growth factor-beta receptors on human clear-cell renal carcinoma cells.

Transforming growth factor-beta1 (TGF-beta1) has a biphasic effect on the growth of renal epithelial cells. In transformed cells, TGF-beta1 appears to accelerate the proliferation of malignant cells. The diverse cellular functions of TGF-beta1 are regulated by three high-affinity serine/threonine kinase receptors, namely TbetaRI, TbetaRII and TbetaRIII. The renal serine protease tissue kallikrein acts on its endogenous protein substrate kininogen to form kinin peptides. The cellular actions of kinins are mediated through B1 and B2 G protein-coupled rhodopsin receptors. Both kinin peptides and TGF-beta1 are mitogenic, and therefore may play an important role in carcinogenesis. Experiments were designed to immunolabel tissue kallikrein, TGF-beta1, TbetaRII, TbetaRIII and kinin receptors using specific antibodies on serial sections of normal kidney and clear-cell renal carcinoma (CCRC) tissue, which included both the tumour and the adjacent renal parenchyma. The essential result was the localisation of tissue kallikrein, kinin B 1 and B 2 receptors and TGF-beta1 primarily on the cell membranes of CCRC cells. In the distal and proximal tubules of the renal parenchyma adjacent to the carcinoma (RPTAC), immunolabelling for tissue kallikrein was reduced, but the expression of kinin B1 and B2 receptors was enhanced. Immunolabelling for TbetaRII and TbetaRIII was more pronounced in the proximal tubules of the tissue adjacent to the carcinoma when compared to the normal kidney. The expression of tissue kallikrein, kinin receptors, and TbetaRII and TbetaRIII may be relevant to the parenchymal invasion and metastasis of clear-cell renal carcinoma.

Adenocarcinoma, Clear Cell↗

PubMed2005

[Expression of Smad4 and transforming growth factor-beta1, transforming growth factor-beta receptor II in cholangiocarcinoma tissue and its biological significance].

OBJECTIVE: To study the expression of Smad4 and transforming growth factor-beta(1) (TGFbeta(1)), transforming growth factor-beta receptor II (TGFbetaRII) in cholangiocarcinoma tissue and its relationship with the biological behaviour and prognosis of the disease. METHODS: The expressions of Smad4, TGFbeta(1) and TGFbetaRII were detected by immunohistochemical technique in 47 specimens of cholangiocarcinoma and the normal bile duct tissue adjacent to the tumor. The expressions of Smad4, TGFbeta(1) and TGFbetaRII were compared with the clinical stages and pathological grades of the patients. RESULTS: The expression of TGFbeta(1) was positive in 36 cholangiocarcinomas (76.6%), which was higher than that in the normal tissue adjacent to the lesion. The positive expressions of Smad4 and TGFbetaRII were 14 (29.8%) and 28 (59.6%) in the carcinoma tissues, respectively (P < 0.05). The expression of TGFbeta(1) was related to the clinical stage, metastasis of lymph node and liver of the tumor (P < 0.05), but not with the histological grade (P > 0.05). There was positive correlation between TGFbetaRII expression and the clinical stage (P < 0.05), but no correlation between the TGFbetaRII expression and histological grade or metastasis of lymph node and liver (P > 0.05). The expression of Smad4 was associated with the histological grade, clinical stage and metastasis of lymph node and liver (P < 0.05). CONCLUSIONS: The expressions of Smad4, TGFbeta(1) and TGFbetaRII correlate with the histological grading, clinical staging and metastasis of the lymph node and liver in cholangiocarcinoma. Combined detection of Smad4, TGFbeta(1) and TGFbetaRII may be helpful in the determination of the malignant degree and the prognosis of this disease.

Adult↗

PubMed1989

Microbial transformations of steroids--III. Transformation of progesterone by Sepedonium ampullosporum.

The 16 alpha-steroid hydroxylating fungus Sepedonium ampullosporum (CMI strain 203 033) transformed progesterone into 16 alpha-hydroxyprogesterone and four other major metabolites which have not been reported previously for this organism, 6 beta-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, 16 alpha-hydroxyandrostenedione and 16-oxotestosterone (16-ketotestosterone). Among the minor metabolites we have been able to identify 15 alpha-hydroxyprogesterone. This compound has not been reported for S. ampullosporum. The conditions used for transformation had comparatively little effect on the relative proportions of products formed, 16 alpha-hydroxyprogesterone always being the predominant metabolite, but had a major effect on the total yields of metabolites isolatable. These findings suggest that one or more constitutive enzyme systems were responsible for the transformations.

Biotransformation↗

PubMed2005

Comparison of the fast Fourier transform and continuous wavelet transform for examining mechanomyographic frequency versus eccentric torque relationships.

The purpose of this study was to compare the eccentric torque-related patterns for mechanomyographic (MMG) center frequencies (mean power frequency (MPF), median frequency (MDF), and average instantaneous mean power frequency (AIMPF)) determined by the fast Fourier transform (FFT) and continuous wavelet transform (CWT). Eight adults (mean+/-S.D. age=22.5+/-2.4 years) performed submaximal to maximal, eccentric isokinetic muscle actions of the biceps brachii on a Cybex 6,000 dynamometer. The mean MMG MPF, MDF, and AIMPF values for both the absolute and normalized data from 10 to 100% eccentric peak torque (PT) were highly intercorrelated at r=0.908-0.985. Linear models provided the best fit for the absolute MMG MPF (r=0.873), MDF (r=0.831), and AIMPF (r=0.924), as well as normalized MMG MPF (r=0.869), MDF (r=0.816), and AIMPF (r=0.920) versus percentage eccentric PT relationships. There were no significant differences (p>0.05) among the linear slope coefficients for the MMG MPF, MDF, and AIMPF versus percentage eccentric PT relationships for either the absolute or normalized data. These results suggested that Fourier or wavelet transform procedures can be used to examine the patterns of MMG responses during eccentric muscle actions of the biceps brachii.

Adult↗

PubMed2005

Hilbert transform assisted complex wavelet transform for neuroelectric signal analysis.

In this work, we present a new approach for shift invariant complex wavelet analysis of neuroelectric signals. A key idea is to preprocess the signal with the Hilbert transformer to yield an analytic signal, which is then wavelet transformed using the linear phase complex scaling and wavelet filters. In different scales, the total energy of the wavelet transform coefficients is shift invariant. The decimated analytic wavelet coefficients suffer no aliasing effects, which are predominant in conventional wavelet analysis. We show the usefulness of the present method in multi-scale analysis of the neuroelectric signal waveforms.

Action Potentials↗

PubMed2002

Studies on the accumulation and transformation of arsenic in freshwater organisms II. Accumulation and transformation of arsenic compounds by Tilapia mossambica.

Bioaccumulation and biotransformation of arsenic (As) compounds in freshwater Tilapia mossambica was investigated. The direct accumulation of As by T mossambica was proportional to the concentration of arsenicals in water. Small amounts of accumulated As were transformed to methylated As, including trimethylarsenic (TMA) species. Accumulation and transformation of As(III) by T. mossambica via freshwater food chain results in the transformation of As(III) to As(V) with little biomethylation of accumulated As. Approximately 90% of accumulated As was depurated to water.

Animals↗

PubMed2000

Transformation of Antirrhinum majus L. by a rol-type multi-auto-transformation (MAT) vector system.

A total of 11 independent beta-glucuronidase (GUS) positive hairy roots were induced following co-cultivation of leaf explants of Antirrhinum majus L. with Agrobacterium tumefaciens strain GV2260 containing rol-type multi-auto-transformation (MAT) vector pNPI702. A total of 326 adventitious shoots were regenerated from the hairy root lines on 1/2 MS medium without plant growth regulators at 25 degrees C under a 16 h/day photoperiod condition 4 months after infection of the A. tumefaciens GV2260. The absence of the rol genes in five plants was verified by polymerase chain reaction (PCR) and Southern blot analysis. Acclimatized transformants exhibited normal phenotypes in height and in the morphology of leaves and flowers. Furthermore, the GUS gene was strongly expressed in the leaves, inflorescence of the transformed plant, and the progeny. This result demonstrates that the rol-type MAT vector can be used to study gene functions controlling the morphogenesis of Antirrhinum majus plants.

Journal Article↗

PubMed1976

Transformation of cercariae to schistosomula: a quantitative comparison of transformation techniques and of infectivity by different injection routes of the organisms produced.

Six transformation techniques ((1) incubation of cercariae in isotonic medium; (ii) penetration of isolated skin; (iii) stimulation with crude egg lecithin; (iv) mechanical disruption by passage through a syringe and 21 gauge needle; (v) by whorling of cercariae with a vortex mixer; (vi) syringe transformation followed by incubation) were evaluated. The organism produced were assessed for infectivity for mice by 6 different routes of infection (percutaneous, intradermal, subcutaneous, intra-peritoneal, intravenous and intra-muscular). At perfusion the largest numbers of adult worms were recovered from mice injected intramuscularly with organisms produced by the syringe technique and control mice given cercariae percutaneously. The peak for migration of schistosomula (following syringe transformation and intramuscular injection) through the lungs and the appearance of adult worms in the mesenteries was shown to be similar to cercarie administered percutaneously.

Animals↗

PubMed1990

Hadamard transform measurement of tandem Fourier-transform mass spectra.

The simultaneous collection of multiple spectra using tandem (MS/MS) and multidimensional (MS/MS/MS) mass spectrometry from multiple precursors is demonstrated to yield correspondingly enhanced sensitivity. This approach utilizes Hadamard transform deconvolution and takes advantage of the multichannel dissociation capability of Fourier-transform mass spectrometry. By application of this to an 11-component mixture, the 11 spectra of the products of dissociating 11 different combinations of six of the component molecular ions are measured; Hadamard transformation yields individual spectra of the precursor ions exhibiting a signal-to-noise improvement of 1.8x over spectra measured separately, as predicted by theory. Precursor ion selection with high specificity and product formation with high abundance reproducibility are critical; spurious peaks resulting from imperfect reproducibility can be minimized by using simultaneous equation coefficients reflecting the degree of precursor dissociation. Extension of this technique to MSn spectra is demonstrated with simultaneous MS/MS/MS monitoring of three precursors and three daughters yielding nine spectra representing the nine possible dissociation pathways. For MSn spectra, coding the product relationships for each additional step (e.g., precursor----daughter, daughter----granddaughter) requires elimination of half of the remaining ions. No ions are lost for coding in an improved Hadamard approach in which the combined daughter spectrum of the selected half of the precursors is subtracted from that of the other half.

Fourier Analysis↗

PubMed2005

Accelerated transformation and deactivation of erythromycin in superheated water. 1. Temperature effects, transformation rates, and the impacts of dissolved organic matter.

The presence of antibiotics and other pharmaceuticals in the environment is of increasing concern. The stringent treatment of point discharges of antibiotic wastes holds promise as an approach for curtailing growing trends of microbial resistance. The work described in this two-part series explores the use of superheated water as a medium forthe accelerated transformation and deactivation of a specific target antibiotic, erythromycin. Part 1 of the series focuses on parent compound conversion, and Part 2 examines transformation mechanisms and reaction products. This paper, Part 1, highlights the results of reactor studies performed in both batch and flow-through modes. The data presented confirm that accelerated conversion of erythromycin, based on parent compound disappearance as measured by high-pressure liquid chromatography, occurs in water under superheated conditions. Given an initial erythromycin concentration of 50 mg/L, greaterthan 85% apparent conversion was achieved within 30 min in the batch system at all temperatures investigated in the range from 125 to 200 degrees C. The presence of dissolved organic matter extracted from two natural soil materials, at concentrations of 2.5-20 mg/L, was shown to have little effect on the overall extent of transformation of erythromycin in the batch system. The rates of decomposition observed were found to be best described by a psuedo-first-order expression, one in which the rate coefficient increased linearly with increasing initial concentration of the antibiotic. First-order rate behavior was verified in subsequent flow reactor experiments. The temperature dependence of rate was also examined, and an activation energy of 68.8 kJ/mol was determined.

Anti-Bacterial Agents↗

PubMed2006

Strain-induced disorder, phase transformations, and transformation-induced plasticity in hexagonal boron nitride under compression and shear in a rotational diamond anvil cell: in situ x-ray diffraction study and modeling.

Plastic shear significantly reduces the phase transformation (PT) pressure when compared to hydrostatic conditions. Here, a paradoxical result was obtained: PT of graphitelike hexagonal boron nitride (hBN) to superhard wurtzitic boron nitride under pressure and shear started at about the same pressure ( approximately 10 GPa) as under hydrostatic conditions. In situ x-ray diffraction measurement and modeling of the turbostratic stacking fault concentration (degree of disorder) and PT in hBN were performed. Under hydrostatic pressure, changes in the disorder were negligible. Under a complex compression and shear loading program, a strain-induced disorder was observed and quantitatively characterized. It is found that the strain-induced disorder suppresses PT which compensates the promotion effect of plastic shear. The existence of transformation-induced plasticity (TRIP) was also proved during strain-induced PT. The degree of disorder is proposed to be used as a physical measure of plastic straining. This allows us to quantitatively separate the conventional plasticity and transformation-induced plasticity. Surprisingly, it is found that TRIP exceeds the conventional plasticity by a factor of 20. The cascade structural changes were revealed, defined as the reoccurrence of interacting processes including PTs, disordering, conventional plasticity, and TRIP. In comparison with hydrostatic loading, for the same degree of disorder, plastic shear indeed reduces the PT pressure (by a factor of 3-4) while causing a complete irreversible PT. The analytical results based on coupled strain-controlled kinetic equations for disorder and PT confirm our conclusions.

Journal Article↗

PubMed2006

Exact site percolation thresholds using a site-to-bond transformation and the star-triangle transformation.

I construct a two-dimensional lattice on which the inhomogeneous site percolation threshold is exactly calculable and use this result to find two more lattices on which the site thresholds can be determined. The primary lattice studied here, the "martini lattice," is a hexagonal lattice with every second site transformed into a triangle. The site threshold of this lattice is found to be 0.764826..., i.e., the solution to p4 - 3p3 + 1 = 0, while the others have (square root 5 - 1)/2 (the inverse of the golden ratio) and 1/square root 2. This last solution suggests a possible approach to establishing the bound for the hexagonal site threshold, pc < 1/square root 2. To derive these results, I solve a correlated bond problem on the hexagonal lattice by use of the star-triangle transformation and then, by a particular choice of correlations derived from a site-to-bond transformation, solve the site problem on the martini lattice.

Journal Article↗

PubMed1994

Lie transformation groups, integral transforms, and invariant pattern recognition.

This paper considers image representations based on integral transforms which are invariant under certain transformations, while preserving the uniqueness of the encoding. Necessary and sufficient conditions are determined for the existence of such representations and a method to determine the kernels of the related integral transforms is presented. Finally, the possible relevance of such considerations for the understanding of invariant recognition systems in biological vision is also explored.

Humans↗

PubMed2001

Transformation works for non-normality? On one-sample transformation trimmed t methods.

If the assumption of normality is not satisfied, there is no simple solution to this problem for the one-sample t test. The present study proposes Hall's or Johnson's transformation in conjunction with the trimmed mean to deal with the problem. Computer simulation is carried out to evaluate the small-sample behaviour of the proposed methods in terms of Type I error rate and statistical power. The proposed methods are compared with the conventional Student t, Yuen's trimmed t, Johnson's transformation untrimmed t, and Hall's transformation untrimmed t statistics for one-sided and two-sided tests. The simulation results indicate that the proposed methods can control Type I error well in very extreme conditions and are more powerful than the conventional methods.

Bias↗