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SMA
Terms modified by SMA Selected AbstractsCell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinomaCYTOPATHOLOGY, Issue 4 2010W. D. Delgallo W. D. Delgallo, J. R. P. Rodrigues, S. P. Bueno, R. M. Viero and C. T. Soares Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma Objective:, Gene expression studies have revealed several molecular subtypes of breast carcinoma with distinct clinical and biological behaviours. DNA microarray studies correlated with immunohistochemical profiling of breast carcinomas using cytokeratin (CK) markers, Her2/neu, oestrogen receptor (ER), and basal myoepithelial cell markers have identified five breast tumour subtypes: (i) luminal A (ER+; Her2/neu,), (ii) luminal B (ER+; Her2/neu+), (iii) Her2 overexpression (ER,; Her2/neu+), (iv) basal-like (ER,; Her2/neu,, CK5/6 and 14+), and (v) negative for all markers. Luminal carcinomas express cytokeratins in a luminal pattern (CK8/18), and the basal-like type expresses CK5/6 and CK14 or basal epithelial cell markers. CK5/6, CK8/18, and smooth muscle actin (SMA) expression were assessed in cell blocks and compared with expression in surgical specimens. Methods:, Sixty-two cases of breast carcinoma diagnosed by fine needle aspiration cytology with cell blocks and available surgical specimens were included. Cell blocks containing at least 10 high-power fields each with at least 10 tumour cells and surgical specimens were immunostained for CK5/6, CK8/18 and SMA. Results:, Percentage sensitivity, specificity, positive predictive value, negative predictive value and accuracy were, respectively, 77, 100, 100, 92 and 94 for CK5/6; 98, 66, 96, 80 and 95 for CK8/18; and 92, 96, 85, 98 and 95 for SMA. Conclusion:, The identification of CK5/6, CK8/18 and SMA by immunohistochemistry in cell blocks can be a reliable method that yields results close to those obtained in surgical specimens, and can contribute to the classification of breast carcinomas with luminal and basal expression patterns, providing helpful information in the choice of treatment and in the evaluation of prognostic and predictive factors. [source] Alpha-smooth muscle actin expression enhances cell traction forceCYTOSKELETON, Issue 4 2007Jianxin Chen Abstract Using an established corneal stromal cell differentiation model, we manipulated ,-smooth muscle actin (,-SMA) protein expression levels in fibroblasts by treating them with TGF-,1, bFGF, TGF-, type I receptor inhibitor (SB-431542), and siRNA against ,-SMA. The corresponding cell traction forces (CTFs) were determined by cell traction force microscopy. With all these treatments, we found that ,-SMA is not required for CTF induction, but its expression upregulates CTF. This upregulation involves the modification of stress fibers but does not appear to relate to non-muscle myosin II expression or ,-actin expression. Moreover, there exists a linear relationship between ,-SMA protein expression level and CTF magnitude. Finally, CTFs were found to vary among a population of myofibroblasts, suggesting that ,-SMA protein expression levels of individual cells also vary. Cell Motil. Cytoskeleton 2007. © 2006 Wiley-Liss, Inc. [source] Transient production of ,-smooth muscle actin by skeletal myoblasts during differentiation in culture and following intramuscular implantationCYTOSKELETON, Issue 4 2002Matthew L. Springer Abstract ,-smooth muscle actin (SMA) is typically not present in post-embryonic skeletal muscle myoblasts or skeletal muscle fibers. However, both primary myoblasts isolated from neonatal mouse muscle tissue, and C2C12, an established myoblast cell line, produced SMA in culture within hours of exposure to differentiation medium. The SMA appeared during the cells' initial elongation, persisted through differentiation and fusion into myotubes, remained abundant in early myotubes, and was occasionally observed in a striated pattern. SMA continued to be present during the initial appearance of sarcomeric actin, but disappeared shortly thereafter leaving only sarcomeric actin in contractile myotubes derived from primary myoblasts. Within one day after implantation of primary myoblasts into mouse skeletal muscle, SMA was observed in the myoblasts; but by 9 days post-implantation, no SMA was detectable in myoblasts or muscle fibers. Thus, both neonatal primary myoblasts and an established myoblast cell line appear to similarly reprise an embryonic developmental program during differentiation in culture as well as differentiation within adult mouse muscles. Cell Motil. Cytoskeleton 51:177,186, 2002. © 2002 Wiley-Liss, Inc. [source] Induction of initial heart ,-actin, smooth muscle ,-actin, in chick pregastrula epiblast: The role of hypoblast and fibroblast growth factor-8DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2008Hiroko Matsui During heart development at the gastrula stage, inhibition of bone morphogenetic protein (BMP) activity affects the heart specification but does not impair the expression of smooth muscle , -actin (SMA), which is first expressed in the heart mesoderm and recruited into initial heart myofibrils. Interaction of tissues between posterior epiblast and hypoblast at the early blastula stage is necessary to induce the expression of SMA, in which Nodal and Chordin are thought to be involved. Here we investigated the role of fibroblast growth factor-8 (FGF8) in the expression of SMA. In situ hybridization and reverse transcription,polymerase chain reaction showed that Fgf8b is expressed predominantly in the nascent hypoblast. Anti-FGF8b antibody inhibited the expression of SMA, cTNT, and Tbx5, which are BMP-independent heart mesoderm/early cardiomyocyte genes, but not Brachyury in cultured posterior blastoderm, and combined FGF8b and Nodal, but neither factor alone induced the expression of SMA in association with heart specific markers in cultured epiblast. Although FGF8b did not induce the upregulation of phospho-Smad2, anti-FGF8b properties suppressed phospho-Smad2 in cultured blastoderm. FGF8b was able to reverse the BMP-induced inhibition of cardiomyogenesis. The results suggest that FGF8b acts on the epiblast synergistically with Nodal at the pregastrula stage and may play a role in the expression of SMA during early cardiogenesis. [source] Shaking table tests on reinforced concrete frames without and with passive control systemsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 14 2005Mauro Dolce Abstract An extensive experimental program of shaking table tests on reduced-scale structural models was carried out within the activities of the MANSIDE project, for the development of new seismic isolation and energy dissipation devices based on shape memory alloys (SMAs). The aim of the experimental program was to compare the behaviour of structures endowed with innovative SMA-based devices to the behaviour of conventional structures and of structures endowed with currently used passive control systems. This paper presents a comprehensive overview of the main results of the shaking table tests carried out on the models with and without special braces. Two different types of energy dissipating and re-centring braces have been considered to enhance the seismic performances of the tested model. They are based on the hysteretic properties of steel elements and on the superelastic properties of SMAs, respectively. The addition of passive control braces in the reinforced concrete frame resulted in significant benefits on the overall seismic behaviour. The seismic intensity producing structural collapse was considerably raised, interstorey drifts and shear forces in columns were drastically reduced. Copyright © 2005 John Wiley & Sons, Ltd. [source] Comparative response analysis of conventional and innovative seismic protection strategiesEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 5 2002S. Bruno Abstract The paper presents a numerical investigation aimed at evaluating the improvements achievable through devices for passive seismic protection of buildings based on the use of shape memory alloys (SMA) in place of conventional steel or rubber devices. To get some generality in the results, different resisting reinforced concrete plane frames were analysed, either protected or not. ,New' and ,existing' buildings were considered depending on whether seismic provisions are adopted in the building design or not. Base isolation and energy dissipation were equally addressed for both conventional and innovative SMA-based devices. Fragility analyses were performed using specific damage measures to account for comparisons among different damage types; the results were then used to estimate quantitatively the effectiveness of the various protection systems. More specifically, the assessment involved a direct comparison of the damage reduction provided by each protection system with respect to the severe degradation experienced by the corresponding non-protected frame. Structural damage, non-structural damage and damage to contents were used on purpose and included in a subsequent phase of cost analysis to evaluate the expected gains also in terms of economic benefits and life loss prevention. The results indicate that base isolation, when applicable, provides higher degrees of safety than energy dissipation does; moreover, the use of SMA-based devices generally brings about better performances, also in consideration of the reduced functional and maintenance requirements. Copyright © 2002 John Wiley & Sons, Ltd. [source] Stress-Induced Wall Motion Abnormalities with Low-Dose Dobutamine Infusion Indicate the Presence of Severe Disease and Vulnerable MyocardiumECHOCARDIOGRAPHY, Issue 7 2007Stephen G. Sawada M.D. Background: Patients with left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) may develop stress-induced wall motion abnormalities (SWMA) with low-dose (10 ,g/kg/min) dobutamine infusion. The clinical significance of low-dose SWMA is unknown. Objective: We investigated the clinical, hemodynamic and angiographic correlates of low-dose SWMA in patients with chronic ischemic LV systolic dysfunction. Methods: Seventy patients with chronic ischemic LV systolic dysfunction who had dobutamine stress echocardiography were studied. Clinical, hemodynamic, and angiographic parameters at rest and low-dose were compared between 38 patients (mean ejection fraction (EF) of 30 ± 8%) with low-dose SWMA and 32 patients (EF 30 ± 11%) without low-dose SWMA. Results: Multivariate analysis showed that the number of coronary territories with severe disease (stenosis ,70%)(P = 0.001, RR = 6.3) was an independent predictor of low-dose SWMA. An increasing number of collateral vessels protected patients from low-dose SWMA (P = 0.011, RR = 0.25). A higher resting heart rate was a negative predictor of low-dose SWMA (P = 0.015, RR = 0.92) but no other hemodynamic variables were predictors. In the patients with low-dose SMA, regions with low-dose SWMA were more likely to be supplied by vessels with severe disease than regions without low-dose SWMA (92% vs 58%, P < 0.001). Conclusion: In patients with ischemic LV systolic dysfunction, the extent of severe disease and a lower numbers of collaterals predict the occurrence of low-dose SWMA. Low-dose SWMA is a highly specific marker for severe disease. [source] Universal multiplex PCR and CE for quantification of SMN1/SMN2 genes in spinal muscular atrophyELECTROPHORESIS, Issue 7 2009Chun-Chi Wang Abstract We established a universal multiplex PCR and CE to calculate the copy number of survival motor neuron (SMN1 and SMN2) genes for clinical screening of spinal muscular atrophy (SMA). In this study, one universal fluorescent primer was designed and applied for multiplex PCR of SMN1, SMN2 and two internal standards (CYBB and KRIT1). These amplicons were separated by conformation sensitive CE. Mixture of hydroxyethyl cellulose and hydroxypropyl cellulose were used in this CE system. Our method provided the potential to separate two 390-bp PCR products that differ in a single nucleotide. Differentiation and quantification of SMN1 and SMN2 are essential for clinical screening of SMA patients and carriers. The DNA samples included 22 SMA patients, 45 parents of SMA patients (obligatory carriers) and 217 controls. For evaluating accuracy, those 284 samples were blind-analyzed by this method and denaturing high pressure liquid chromatography (DHPLC). Eight of the total samples showed different results. Among them, two samples were diagnosed as having only SMN2 gene by DHPLC, however, they contained both SMN1 and SMN2 by our method. They were further confirmed by DNA sequencing. Our method showed good agreement with the DNA sequencing. The multiplex ligation-dependent probe amplification (MLPA) was used for confirming the other five samples, and showed the same results with our CE method. For only one sample, our CE showed different results with MLPA and DNA sequencing. One out of 284 samples (0.35%) belonged to mismatching. Our method provided a better accurate method and convenient method for clinical genotyping of SMA disease. [source] Quantification of SMN1 and SMN2 genes by capillary electrophoresis for diagnosis of spinal muscular atrophyELECTROPHORESIS, Issue 13 2008Chun-Chi Wang Abstract We present the first CE method for the separation and quantification of SMN1 and SMN2 genes. Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder deleted or mutated in SMN1 gene and retained at least one copy of SMN2 gene. However, these two genes are highly homologous, differentiation and quantification of SMN1 and SMN2 are therefore required in diagnosis to identify SMA patients and carriers. We developed a fluorescence-labeled conformation-sensitive CE method to quantitatively analyze PCR products covering the variable position in the SMN1/SMN2 genes using a copolymer solution composed of hydroxyethylcellulose and hydroxypropylcellulose. The DNA samples included 24 SMA patients, 52 parents of SMA patients (obligatory carriers), and 255 controls. Those 331 samples were blind analyzed to evaluate the method, and the results compared with those obtained using denaturing HPLC (DHPLC). Validation of accuracy was performed by comparing the results with those of DHPLC. Nine of total samples showed different results. Diagnosis of one fetus DNA among them was related to abortion or not, which was further confirmed by gel electrophoresis and DNA sequencing. Our method showed good coincidence with them, and proved the misdiagnosis of DHPLC. This simple and reliable CE method is a powerful tool for clinical genotyping of large populations to detect carriers and SMA patients. [source] Palilalia, echolalia, and echopraxia,palipraxia as ictal manifestations in a patient with left frontal lobe epilepsyEPILEPSIA, Issue 6 2009Yang-Je Cho Summary Palilalia is a relatively rare pathologic speech behavior and has been reported in various neurologic and psychiatric disorders. We encountered a case of palilalia, echolalia, and echopraxia,palipraxia as ictal phenomena of left frontal lobe epilepsy. A 55-year-old, right-handed man was admitted because of frequent episodes of rapid reiteration of syllables. Video-electroencephalography monitoring revealed stereotypical episodes of palilalia accompanied by rhythmic head nodding and right-arm posturing with ictal discharges over the left frontocentral area. He also displayed echolalia or echopraxia,palipraxia, partially responding to an examiner's stimulus. Magnetic resonance imaging revealed encephalomalacia on the left superior frontal gyrus and ictal single photon emission computed tomography showed hyperperfusion just above the lesion, corresponding to the left supplementary motor area (SMA), and subcortical nuclei. This result suggests that the neuroanatomic substrate involved in the generation of these behaviors as ictal phenomena might exist in the SMA of the left frontal lobe. [source] A case series investigating acceptance and commitment therapy as a treatment for previously treated, unremitted patients with anorexia nervosaEUROPEAN EATING DISORDERS REVIEW, Issue 6 2009M. I. Berman Abstract The aim of the present study was to evaluate the effectiveness of Acceptance and Commitment Therapy (ACT) for treatment of anorexia nervosa (AN) using a case series methodology among participants with a history of prior treatment for AN. Three participants enrolled; all completed the study. All participants had a history of 1,20 years of intensive eating disorder treatment prior to enrollment. Participants were seen for 17,19 twice-weekly sessions of manualized ACT. Symptoms were assessed at baseline, post-treatment and 1-year follow-up. All participants experienced clinically significant improvement on at least some measures; no participants worsened or lost weight even at 1-year follow-up. Simulation modelling analysis (SMA) revealed for some participants an increase in weight gain and a decrease in eating disorder symptoms during the treatment phase as compared to a baseline assessment phase. These data, although preliminary, suggest that ACT could be a promising treatment for subthreshold or clinical cases of AN, even with chronic participants or those with medical complications. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Carrier frequency of SMA by quantitative analysis of the SMN1 deletion in the Iranian populationEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2010M. Hasanzad Background and purpose:, Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Carrier frequency studies of SMA have been reported for various populations. Although no large-scale population-based studies of SMA have been performed in Iran, previous estimates have indicated that the incidence of autosomal recessive disorder partly because of the high prevalence of consanguineous marriage is much higher in the Iranian population than in other populations. Methods:, In this study, we used a reliable and highly sensitive quantitative real-time PCR assay with SYBR green I dye to detect the copy number of the SMN1 gene to determine the carrier frequency of SMA in 200 healthy unrelated, non-consanguineous couples from different part of Iran. Results:, To validate the method in our samples, we determined the relative quantification (RQ) of patients with homozygous deletion (0.00) and hemyzygous carriers (0.29,0.55). The RQ in 10 of 200 normal individuals were within the carrier range of 0.31,0.57, estimating a carrier frequency of 5% in the Iranian population. Conclusions:, Our data show that the SMA carrier frequency in Iran is higher than in the European population and that further programs of population carrier detection and prenatal testing should be implemented. [source] Nanoindentation of a Pseudoelastic NiTiFe Shape Memory Alloy,ADVANCED ENGINEERING MATERIALS, Issue 1-2 2010Janine Pfetzing-Micklich Nanoindentation is a suitable tool for characterizing the local mechanical properties of shape memory alloys (SMA) and to study their pseudoelastic behavior. There is a special interest in indenting with different indenter tips (as not all tips are associated with strain states that predominantly induce the martensitic transformation) and in indenting at different temperatures, where different phases are present. In this study, we perform nanoindentation on a ternary NiTiFe SMA with different indenter tips and at various testing temperatures. For nanoindentation with spherical tips, load,displacement hystereses clearly indicate pseudoelastic behavior, whereas indentation with Berkovich tips results in more pronounced plastic deformation. Testing at different temperatures is associated with different volume fractions of austenite, martensite, and R-phase. The corresponding nanoindentation responses differ considerably in terms of pseudoelastic behavior. Best pseudoelastic recovery is found at testing temperatures close to the R-phase start temperature, even though this temperature is below the austenite finish temperature, which is a well-known lower temperature bound for full recovery in macroscopic tests. Our results are discussed considering micromechanical aspects and the interaction between stress-induced phase transformation and dislocation plasticity. [source] mTOR as a potential therapeutic target for treatment of keloids and excessive scarsEXPERIMENTAL DERMATOLOGY, Issue 5 2007C. T. Ong Abstract:, Keloid is a dermal fibroproliferative disorder characterized by excessive deposition of extracellular matrix (ECM) components such as collagen, glycoproteins and fibronectin. The mammalian target of rapamycin (mTOR) is a serine/theronine kinase which plays an important role in the regulation of metabolic processes and translation rates. Published reports have shown mTOR as regulator of collagen expression and its inhibition induces a decrease in ECM deposition. Our aim was to investigate the role of mTOR in keloid pathogenesis and investigate the effect of rapamycin on proliferating cell nuclear antigen (PCNA), cyclin D1, collagen, fibronectin and alpha-smooth muscle actin (, -SMA) expression in normal fibroblasts (NF) and keloid fibroblasts (KF). Tissue extracts obtained from keloid scar demonstrated elevated expression of mTOR, p70KDa S6 kinase (p70S6K) and their activated forms, suggesting an activated state in keloid scars. Serum stimulation highlighted the heightened responsiveness of KF to mitogens and the importance of mTOR and p70S6K during early phase of wound healing. Application of rapamycin to monoculture NF and KF, dose- and time-dependently downregulates the expression of cytoplasmic PCNA, cyclin D1, fibronectin, collagen and , -SMA, demonstrating the anti-proliferative effect and therapeutic potential of rapamycin in the treatment of keloid scars. The inhibitory effect of rapamycin was found to be reversible following recovery in the expression of proteins following the removal of rapamycin from the culture media. These results demonstrate the important role of mTOR in the regulation of cell cycle and the expression of ECM proteins: fibronectin, collagen and , -SMA. [source] Porous TiNi Biomaterial by Self-Propagating High-Temperature Synthesis,ADVANCED ENGINEERING MATERIALS, Issue 6 2004J.S. Kim Abstract Porous TiNi shape-memory alloy (TiNi SMA) bodies with controlled pore structure were produced from the (Ti+Ni) powder mixture by self-propagating high-temperature synthesis (SHS) method. The effect of processing variables such as the kind of starting powders, ignition temperature and preheating schedule on the behavior of combustion wave propagation, the formation of phases and pore structure was investigated. The relationship between pore structure and mechanical properties was also investigated. An in vivo test was performed to evaluate bone tissue response and histocompatibility of porous TiNi SMA using 15 New Zealand white rabbits. No apparent adverse reactions such as inflammation and foreign body reaction were noted on or around all implanted porous TiNi SMA blocks. Bone ingrowth was found in the pore space of all implanted blocks. [source] Embedded Shape-Memory Alloy Wires for Improved Performance of Self-Healing Polymers,ADVANCED FUNCTIONAL MATERIALS, Issue 15 2008Eva L. Kirkby Abstract We report the first measurements of self-healing polymers with embedded shape-memory alloy (SMA) wires. The addition of SMA wires shows improvements of healed peak fracture loads by up to a factor of 1.6, approaching the performance of the virgin material. Moreover, the repairs can be achieved with reduced amounts of healing agent. The improvements in performance are due to two main effects: (i) crack closure, which reduces the total crack volume and increases the crack fill factor for a given amount of healing agent and (ii) heating of the healing agent during polymerization, which increases the degree of cure of the polymerized healing agent. [source] A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populationsHEPATOLOGY, Issue 5 2004Scott T. Magness Activation of hepatic stellate cells (HSCs) and other resident mesenchymal cells into myofibroblasts expressing alpha smooth muscle actin (,SMA) and collagen I is a key event in liver fibrogenesis. However, the temporal expression profiles of ,SMA and collagen I genes in these cells is unknown. To address this question, we studied ,SMA and collagen ,1(I) transcriptional patterns in primary cultures of HSCs, and additionally, in an in vivo model of secondary biliary fibrosis using transgenic mice that express the Discomsoma sp. red fluorescent protein (RFP) and the enhanced green fluorescent protein (EGFP) reporter genes under direction of the mouse ,SMA and collagen ,1(I) promoter/enhancers, respectively. The ,SMA-RFP mice were crossed with collagen-EGFP mice to generate double transgenic mice. Reporter gene expression in cultured HSCs demonstrated that both transgenes were induced at day 3 with continued expression through day 14. Interestingly, ,SMA and collagen ,1(I) transgenes were not coexpressed in all cells. Flow cytometry analysis showed three different patterns of gene expression: ,SMA-RFP positive cells, collagen-EGFP positive cells, and cells expressing both transgenes. ,SMA-only and ,SMA/collagen expressing cells showed higher expression levels of synaptophysin, reelin, MMP13, TIMP1, and ICAM-1 compared to collagen-only expressing cells, as assessed by real-time PCR. Following bile duct ligation, ,SMA and collagen ,1(I) transgenes were differentially expressed by peribiliary, parenchymal and vascular fibrogenic cells. Peribiliary cells preferentially expressed collagen ,1(I), while parenchymal myofibroblasts expressed both ,SMA and collagen ,1(I). In conclusion, these data demonstrate heterogeneity of gene expression in myofibroblastic cells during active fibrogenesis. These reporter mice provide a useful tool to further characterize fibrogenic cell types and to evaluate antifibrotic drugs. (HEPATOLOGY 2004.) [source] Tissue inhibitor of metalloproteinases-1 attenuates spontaneous liver fibrosis resolution in the transgenic mouseHEPATOLOGY, Issue 4 2002Hitoshi Yoshiji It has been suggested that the tissue inhibitor of metalloproteinases-1 (TIMP-1) is involved in spontaneous resolution of liver fibrosis. The aim of this study was to investigate whether TIMP-1 altered spontaneous resolution of liver fibrosis in conjunction with matrix metalloproteinases (MMP) inhibition and hepatic stellate cell (HSC) activation. The livers of liver-targeted TIMP-1 transgenic (TIMP-Tg) and control hybrid (Cont) mice were harvested at 0, 3, 7, and 28 days following spontaneous recovery from CCl4 -induced liver fibrosis. The extent of fibrosis resolution, MMP expression, ,-smooth-muscle actin (,-SMA) positive cells, and procollagen-(I) messenger RNA (mRNA) in the liver were assessed at the respective periods in both groups. We also examined the effect of TIMP-1 on HSC apoptosis. The TIMP-Tg mice showed significantly attenuated resolution of spontaneous liver fibrosis compared with the Cont mice. The hydroxyproline content, number of ,-SMA positive cells, and procollagen-(I) mRNA rapidly decreased with time in the Cont mice, whereas these markers were little changed in TIMP-Tg mice. The level of the active form of metalloproteinases-2 (MMP-2) in the TIMP-Tg mice was less than that in the Cont mice. TIMP-1 markedly decreased the nonparenchyma apoptotic cells in the liver fibrosis resolution model, and it also inhibited HSC apoptosis associated with suppression of caspase-3 activity in vitro. In conclusion, TIMP-1 significantly attenuated spontaneous resolution of liver fibrosis by the combination of a net reduction of the MMP activity and suppression of apoptosis in HSC. [source] Tissue inhibitor of metalloproteinases-1 promotes liver fibrosis development in a transgenic mouse modelHEPATOLOGY, Issue 6 2000Hitoshi Yoshiji Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to be increased in liver fibrosis development both in murine experimental models and human samples. However, the direct role of TIMP-1 during liver fibrosis development has not been defined. To address this issue, we developed transgenic mice overexpressing human TIMP-1 (hTIMP-1) in the liver under control of the albumin promoter/enhancer. A model of CCl4 -induced hepatic fibrosis was used to assess the extent of fibrosis development in TIMP-1 transgenic (TIMP-Tg) mice and control hybrid (Cont) mice. Without any treatment, overexpression of TIMP-1 itself did not induce liver fibrosis. There were no significant differences of pro-(,1)-collagen-I, (,2)-collagen-IV, and ,-smooth muscle actin (,-SMA) mRNA expression in the liver between TIMP-Tg and Cont-mice, suggesting that overexpression of TIMP-1 itself did not cause hepatic stellate cell (HSC) activation. After 4-week treatment with CCl4, however, densitometric analysis revealed that TIMP-Tg-mice had a seven-fold increase in liver fibrosis compared with the Cont-mice. The hepatic hydroxyproline content and serum hyaluronic acid were also significantly increased in TIMP-Tg-mice, whereas CCl4 -induced liver dysfunction was not altered. An active form of matrix metalloproteinases-2 (MMP-2) level in the liver of TIMP-Tg-mice was decreased relative to that in Cont-mice because of the transgenic TIMP-1. Immunohistochemical analysis revealed that collagen-I and collagen-IV accumulation was markedly increased in the liver of CCl4 -treated TIMP-Tg-mice with a pattern similar to that of ,-SMA positive cells. These results suggest that TIMP-1 does not by itself result in liver fibrosis, but strongly promotes liver fibrosis development. [source] Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in ratsHEPATOLOGY, Issue 5 2000Yan Qing Wang Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl4)- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl4 -induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or ,-smooth muscle actin (,SMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., ,SMA and PDGF receptor ,, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect. [source] Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in ratsHEPATOLOGY RESEARCH, Issue 7 2008Kazunori Maeda Aim:, The aim of this study was to examine the preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation (BDL) in rats. Methods:, ME3738 (20 mg/day) was administered orally for 21 days immediately after BDL. Fibrosis was assessed by measuring hepatic hydroxyproline (Hyp) content. Activated hepatic stellate cells (HSCs) were assessed by ,-smooth muscle actin (,-SMA) immunostaining. Hepatic thiobarbituric acid-reactive substance (TBARS), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) immunostaining were used to analyze oxidative stress. The gene expressions of collagen-I, transforming growth factor-,1 (TGF-,1), tissue inhibitor of metalloproteinases-1 (TIMP-1), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the liver were examined by real-time reverse transcriptase polymerase chain reaction (RT,PCR). Results:, Hepatic Hyp content and the area of hepatic fibrosis in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non-treated BDL rats (hepatic Hyp, 9.40 ± 2.85 vs. 12.39 ± 3.91 mg/liver; P = 0.036; area of hepatic fibrosis, 13.1 ± 3.8 vs. 21.5 ± 10.9; P = 0.045). Furthermore, ,-SMA-positive cells were significantly reduced by 40% (22.3 ± 14.8 vs. 37.6 ± 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 ± 2.2 vs. 38.3 ± 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 ± 1.22 vs. 9.73 ± 1.80; P = 0.018) and hepatic HO-1 content by 26% (2.13 ± 0.80 vs. 2.87 ± 0.19; P = 0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG and mRNA levels of TGF-,1, TIMP-1 and IL-6 in the liver were unchanged by ME3738 treatment. Conclusion:, Oral ME3738 administration may prevent the progression of hepatic fibrosis in BDL rats through suppression of the activation and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has potential as a therapeutic drug for cholestatic liver fibrosis. [source] Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approachHISTOPATHOLOGY, Issue 7 2010Uta Flucke Flucke U, Flucke M T, Hoy L, Breuer E, Goebbels R, Rhiem K, Schmutzler R, Winzenried H, Braun M, Steiner S, Buettner R & Gevensleben H (2010) Histopathology,56, 852,859 Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach Aims:, Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. Methods and results:, Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2,, AP-2,). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2, and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2,: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). Conclusions:, Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2, overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs. [source] fMRI changes in relapsing-remitting multiple sclerosis patients complaining of fatigue after IFN,-1a injectionHUMAN BRAIN MAPPING, Issue 5 2007Maria A. Rocca Abstract If fatigue in multiple sclerosis (MS) is related to an abnormal activation of the sensorimotor brain network, the activity of such a network should vary with varying fatigue. We studied 22 patients treated with interferon beta 1a (IFN,-1a; Avonex, Biogen, Cambridge, MA) with no fatigue (10) and with reversible fatigue (12). fMRI examinations were performed: 1) the same day of IFN,-1a injection (no fatigue; entry), 2) the day after IFN,-1a injection (fatigue; time 1), and 3) 4 days after IFN,-1a injection (no fatigue; time 2). Patients performed a simple motor task with the right, clinically unaffected hand. At time 1, compared with entry and time 2, MS patients with reversible fatigue showed an increased activation of the thalamus bilaterally. In MS patients without fatigue thalamus was more activated at entry than at time 1. In both groups at entry the primary SMC and the SMA were more activated than at times 1 and 2. At entry and time 1, when compared to patients with reversible fatigue, those without showed increased activations of the SII. Conversely, patients with reversible fatigue had increased activations of the thalamus and of several regions of the frontal lobes. An abnormal recruitment of the fronto-thalamic circuitry is associated with IFN,-1a-induced fatigue in MS patients. Hum Brain Mapp, 2007. © 2006 Wiley-Liss, Inc. [source] Temporal dynamics of ipsilateral and contralateral motor activity during voluntary finger movementHUMAN BRAIN MAPPING, Issue 1 2004Ming-Xiong Huang Abstract The role of motor activity ipsilateral to movement remains a matter of debate, due in part to discrepancies among studies in the localization of this activity, when observed, and uncertainty about its time course. The present study used magnetoencephalography (MEG) to investigate the spatial localization and temporal dynamics of contralateral and ipsilateral motor activity during the preparation of unilateral finger movements. Eight right-handed normal subjects carried out self-paced finger-lifting movements with either their dominant or nondominant hand during MEG recordings. The Multi-Start Spatial Temporal multi-dipole method was used to analyze MEG responses recorded during the movement preparation and early execution stage (,800 msec to +30 msec) of movement. Three sources were localized consistently, including a source in the contralateral primary motor area (M1) and in the supplementary motor area (SMA). A third source ipsilateral to movement was located significantly anterior, inferior, and lateral to M1, in the premotor area (PMA) (Brodmann area [BA] 6). Peak latency of the SMA and the ipsilateral PMA sources significantly preceded the peak latency of the contralateral M1 source by 60 msec and 52 msec, respectively. Peak dipole strengths of both the SMA and ipsilateral PMA sources were significantly weaker than was the contralateral M1 source, but did not differ from each other. Altogether, the results indicated that the ipsilateral motor activity was associated with premotor function, rather than activity in M1. The time courses of activation in SMA and ipsilateral PMA were consistent with their purported roles in planning movements. Hum. Brain Mapp. 23:26,39, 2004. © 2004 Wiley-Liss, Inc. [source] Alcohol intoxication effects on visual perception: An fMRI studyHUMAN BRAIN MAPPING, Issue 1 2004Vince D. Calhoun Abstract We examined the effects of two doses of alcohol (EtOH) on functional magnetic resonance imaging (fMRI) activation during a visual perception task. The Motor-Free Visual Perception Test,Revised (MVPT-R) provides measures of overall visual perceptual processing ability. It incorporates different cognitive elements including visual discrimination, spatial relationships, and mental rotation. We used the MVPT-R to study brain activation patterns in healthy controls (1) sober, and (2) at two doses of alcohol intoxication with event-related fMRI. The fMRI data were analyzed using a general linear model approach based upon a model of the time course and a hemodynamic response estimate. Additionally, a correlation analysis was performed to examine dose-dependent amplitude changes. With regard to alcohol-free task-related brain activation, we replicate our previous finding in which SPM group analysis revealed robust activation in visual and visual association areas, frontal eye field (FEF)/dorsolateral prefrontal cortex (DLPFC), and the supplemental motor area (SMA). Consistent with a previous study of EtOH and visual stimulation, EtOH resulted in a dose-dependent decrease in activation amplitude over much of the visual perception network and in a decrease in the maximum contrast-to-noise ratio (in the lingual gyrus). Despite only modest behavior changes (in the expected direction), significant dose-dependent activation increases were observed in insula, DLPFC, and precentral regions, whereas dose-dependent activation decreases were observed in anterior and posterior cingulate, precuneus, and middle frontal areas. Some areas (FEF/DLPFC/SMA) became more diffusely activated (i.e., increased in spatial extent) at the higher dose. Alcohol, thus, appears to have both global and local effects upon the neural correlates of the MVPT-R task, some of which are dose dependent. Hum. Brain Mapping 21:15,26, 2004. © 2003 Wiley-Liss, Inc. [source] Evaluation of ferromagnetic shape-memory alloys by the extended Hückel methodIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 3 2007Kei Ehara Student Member Abstract Ferromagnetic shape-memory alloy (SMA) are powerful candidates as actuators, pressure sensors, magnetic sensors, etc. Magnetic-field-induced strain has been observed in many ferromagnetic SMA. The magnetic-field-induced strain is a reversible transformation in the martensite phase with the magnetic field. We have investigated the property of the ferromagnetic shape-memory materials by the extended Hückel method, and estimated the ferromagnetic shape-memory of Fe,Pt and Fe,Pd alloys at high temperatures. We used two physical quantities, i.e. cohesive energy and energy fluctuation, to measure the stability of the materials. On the basis of the cohesive energy and energy fluctuation, we discuss the characteristics of ferromagnetic SMA, in which the energy fluctuation is a measure of thermal stability of the metals and/or alloys. The martensite structure is unstable, which means that the energy fluctuation has to be controlled to a small value to keep the martensite phase. Furthermore, it is estimated that the energy fluctuation is associated with the Curie temperature. The Curie temperature is an essential parameter for ferromagnetic materials. From the discussion presented above, we can propose the following: (i) Alloys possessing a low cohesive energy are associated with a high mobility of atoms and are suitable for ferromagnetic shape-memory materials; (ii) Alloys showing a low energy fluctuation show ferromagnetic shape-memory and are favored for use as memory devices. We found that I (iodine) is the best dopant for Fe,Pt ferromagnetic SMA, and Tc (technetium) is the best dopant for Fe,Pd ferromagnetic SMA. Copyright © 2007 Institute of Electrical Engineers of Japan© 2007 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] A three-dimensional model describing stress-temperature induced solid phase transformations: solution algorithm and boundary value problemsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 6 2004Ferdinando Auricchio Abstract An always increasing knowledge on material properties as well as a progressively more sophisticated production technology make shape memory alloys (SMA) extremely interesting for the industrial world. At the same time, SMA devices are typically characterized by complex multi-axial stress states as well as non-homogeneous and non-isothermal conditions both in space and time. This aspect suggests the finite element method as a useful tool to help and improve application design and realization. With this aim, we focus on a three-dimensional macroscopic thermo-mechanical model able to reproduce the most significant SMA features (Int. J. Numer. Methods Eng. 2002; 55: 1255,1264), proposing a simple modification of such a model. However, the suggested modification allows the development of a time-discrete solution algorithm, which is more effective and robust than the one previously discussed in the literature. We verify the computational tool ability to simulate realistic mechanical boundary value problems with prescribed temperature dependence, studying three SMA applications: a spring actuator, a self-expanding stent, a coupling device for vacuum tightness. The effectiveness of the model to solve thermo-mechanical coupled problems will be discussed in a forthcoming work. Copyright © 2004 John Wiley & Sons, Ltd. [source] Improvements and algorithmical considerations on a recent three-dimensional model describing stress-induced solid phase transformationsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 11 2002Ferdinando Auricchio Abstract During mechanical loading,unloading cycles shape-memory alloys (SMA) are able to undergo large deformations without showing residual strains (pseudoelasticity) or recovering them through thermal cycles (shape memory effect). Motivated by stress-induced solid phase transformations, these unique behaviours induce the SMA exploitation in innovative and commercially valuable applications, stimulating, consequently, the interest in the development of constitutive models. Also if many models are now available in the literature, effective three-dimensional proposals are still few and limited in several aspects. In this paper, a three-dimensional thermomechanical model recently proposed by Souza et al. (European Journal of Mechanics,A/Solids, 1998; 17: 789,806.) is taken into consideration; such a model is of particular interest for its effectiveness and flexibility, but it also shows some limitations and missing links in the algorithmical counterparts. This work discusses some improvements to the original model as well as the development and the implementation of a robust integration algorithm to be adopted in a numerical scheme, such as a finite-element framework. Copyright © 2002 John Wiley & Sons, Ltd. [source] Mycotic aneurysm of the superior mesenteric artery in a young womanINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2005P-H Chu Summary Aneurysm of the superior mesenteric artery (SMA) is rare. We, in this study, present the case of a 21-year-old woman with a history of heroin abuse who was admitted to our hospital for infective endocarditis complicated by floating vegetation at the posterior mitral valve. After receiving 2-week antibiotic treatment, the patient had acute abdominal pain. Computed tomography demonstrated an aneurysm at the SMA. The mycotic aneurysm was resected and the mitral valve was repaired successfully. This report reviews the pathophysiology of mycotic aneurysms of the SMA and role of computed tomography in the differential diagnosis of this condition from acute mesenteric ischaemia. [source] The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis modelINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2010Marilena Vered Summary The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; ,-smooth muscle actin (,SMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior ,thirds'. The histopathological changes per ,third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma- in-situ, and superficial and invasive carcinoma. The PCNA and ,SMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells. [source] | ||||||||||||||||||||||||||||||||||||||||||||||