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Sample records for cells pathologic mechanism

  1. Mechanical behavior of pathological and normal red blood cells in microvascular flow based on modified level-set method

    Science.gov (United States)

    Zhang, XiWen; Ma, FangChao; Hao, PengFei; Yao, ZhaoHui

    2016-01-01

    The research of the motion and deformation of the RBCs is important to reveal the mechanism of blood diseases. A numerical method has been developed with level set formulation for elastic membrane immersed in incompressible fluid. The numerical model satisfies mass and energy conservation without the leaking problems in classical Immersed Boundary Method (IBM), at the same time, computing grid we used can be much smaller than the general literatures. The motion and deformation of a red blood cell (including pathological & normal status) in microvascular flow are simulated. It is found that the Reynolds number and membrane's stiffness play an important role in the transmutation and oscillation of the elastic membrane. The normal biconcave shape of the RBC is propitious to create high deformation than other pathological shapes. With reduced viscosity of the interior fluid both the velocity of the blood and the deformability of the cell reduced. With increased viscosity of the plasma both the velocity of the blood and the deformability of the cell reduced. The tank treading of the RBC membrane is observed at low enough viscosity contrast in shear flow. The tank tread fixed inclination angle of the cell depends on the shear ratio and viscosity contrast, which can be compared with the experimental observation well.

  2. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  3. Power loss mechanisms in pathological tracheas.

    Science.gov (United States)

    Bates, A J; Comerford, A; Cetto, R; Schroter, R C; Tolley, N S; Doorly, D J

    2016-07-26

    The effort required to inhale a breath of air is a critically important measure in assessing airway function. Although the contribution of the trachea to the total flow resistance of the airways is generally modest, pathological alterations in tracheal geometry can have a significant negative effect. This study investigates the mechanisms of flow energy loss in a healthy trachea and in four geometries affected by retrosternal goitre which can cause significant distortions of tracheal geometry including constriction and deviation with abnormal curvature. By separating out the component of energy loss related to the wall shear (frictional loss), striking differences are found between the patterns of energy dissipation in the normal and pathological tracheas. Furthermore the ratio of frictional to total loss is dramatically reduced in the pathological geometries. PMID:26686396

  4. CELL THERAPY OF HEART PATHOLOGIES

    OpenAIRE

    Lukash, L.

    2008-01-01

    The review article is devoted to cellular cardiomyoplasty as a novel technology of treatment of cardiac insufficiency. The experiments on animals and the first clinical trials have shown the possibility to improve the contractile function of diseased heart after transplantation of different types of donor cells: cardiomyocytes, bone marrow enriched by hematopoietic stem cells and mesenchymal stem cells. The problems of cellular cardiomyoplasty are discussed.

  5. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

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    Daniela Fanni

    2014-06-01

    Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease occurring in preterm infants, typically before 28 weeks of gestational age, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation. The normal stages of lung development and their relation to the timing of preterm birth is strategic in order to understand the pathogenesis of BPD. In embryonic and pseudoglandular stages the lungs arise from the anterior foregut as a bud where the branching morphogenesis generate a tree-like network of airways. The canalicular stage is characterized by increasing proliferation of distal lung epithelial cells and rapid expansion of the intra-acinar capillaries. The complexity of the airways increases, secondary crests begin to form and full maturation of the alveolus occurs during the saccular and the alveolar stages. Mesechyme components, expecially elastin and myofibroblast, display a major role in normal lung development. BPD is thought to result after an acute insult to the neonatal lung following therapy with oxygen supplementation and mechanical ventilation. Chorioamnionitis, infections and genetic susceptibly are hypothesized to contribute to the injury that affect the normal human lung development. Abnormalities in the mesenchyme were consistently seen in association with inhibition of alveolarization. The pathological features that characterize BPD are complex and differ according with the disease progression. Alveolar simplification, interstitial fibrosis, septal thickness, large airways, smooth muscle hypertrophy, fetal artery persistance and decrease in the arterial number can be histologically observed. In conclusion, in order to reach a complete clinical-pathological diagnosis, the correlation of the pathological features with the fundamental steps of lung morphogenesis and a strict dialogue between the neonatologist and the perinatal pathologist are required. Given these conditions, in our experience, a

  6. Pilocytic astrocytoma: pathology, molecular mechanisms and markers.

    Science.gov (United States)

    Collins, V Peter; Jones, David T W; Giannini, Caterina

    2015-06-01

    Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90%. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. While most show classical morphology, they may present a spectrum of morphological patterns, and there are difficult cases that show similarities to other gliomas, some of which are malignant and require aggressive treatment. Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a ≈2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. Additional infrequent fusion partners have been identified, along with other abnormalities of the MAP-K pathway, affecting tyrosine kinase growth factor receptors at the cell surface (e.g., FGFR1) as well as BRAF V600E, KRAS, and NF1 mutations among others. However, while the KIAA1549-BRAF fusion occurs in all areas, the incidence of the various other mutations identified differs in PAs that develop in different regions of the brain. Unfortunately, from a diagnostic standpoint, almost all mutations found have been reported in other brain tumor types, although some retain considerable utility. These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed. PMID:25792358

  7. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    OpenAIRE

    Sara Calafate; Arjan Buist; Katarzyna Miskiewicz; Vinoy Vijayan; Guy Daneels; Bart de Strooper; Joris de Wit; Patrik Verstreken; Diederik Moechars

    2015-01-01

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close dista...

  8. Obesity Associated Pathology: Frequency, Character and Some Mechanisms of Formation

    OpenAIRE

    2013-01-01

    There have been considered modern views on the problem of obesity as a widespread disease, which manifests itself as multi-syndrome pathology involving all organs and systems, mostly cardiovascular system. There has been emphasized an unfavorable role of abdomino-visceral (android) obesity as a strong risk factor of cardiovascular pathology and type 2 diabetes mellitus — the diseases that currently are the main causes of lethal outcomes in economically developed countries. Some mechanisms...

  9. The mechanism of pathological changes of intraventricular hemorrhage in dogs

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    Dai Jiong

    2009-12-01

    Full Text Available Background : Intraventricular hemorrhage (IVH is an independent risk factor for both morbidity and mortality in patients with intracerebral hemorrhage and subarchnoid hemorrhage. The pathophysiological mechanisms by which blood within the ventricles causes brain damage are still poorly understood. Settings and Design : We developed a canine (dog model with long-term survival. Aims : To study the mechanisms of pathological changes associated with IVH. Materials and Methods : The neurological status, cranial computed tomographic findings, and the pathological changes were studied in the dogs with IVH and also in the control dogs, intraventiricular saline injection. Results : In all the dogs in the control group there were no abnormalities in all the three parameters studied. The dogs in the IVH group developed neurological deficits after the blood injection. There was linear relationship between the ventricular volume and blood clot volume in the first week. After the first week, there was progressive enlargement of the ventricular volume, while the clots continued to shrink. There was complete lysis of the clots within 4 weeks. Pathological studies showed distruction of the ependymal lining of the ventricular system, subependymal gliosis and ischemia of the neurons in the subependymal areas, prominently around the aqueduct. Conclusion : Ventricular dilation was the prominent feature following intraventricular injection of the blood. The other pathological features included disruption of ependymal lining, subependymal gliosis, and ischemic necrosis of neurons in the periventricular tissue of the third ventricle, aqueduct, and the fourth ventricle. These pathological may have some role in the ventricular dilatation following IVH.

  10. The mechanism of pathological changes of intraventricular hemorrhage in dogs

    OpenAIRE

    Dai Jiong; Li Shanquan; Li Xiaoxiong; Xiong Wenhao; Qiu Yongming

    2009-01-01

    Background : Intraventricular hemorrhage (IVH) is an independent risk factor for both morbidity and mortality in patients with intracerebral hemorrhage and subarchnoid hemorrhage. The pathophysiological mechanisms by which blood within the ventricles causes brain damage are still poorly understood. Settings and Design : We developed a canine (dog) model with long-term survival. Aims : To study the mechanisms of pathological changes associated with IVH. Materials and Methods : The neurologi...

  11. Cell Biology and Pathology of Podocytes

    Science.gov (United States)

    Greka, Anna; Mundel, Peter

    2013-01-01

    As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman’s capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist’s view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. PMID:22054238

  12. Small renal cell carcinoma: CT and pathologic correlation

    International Nuclear Information System (INIS)

    Objective: To analyze the correlation of CT and pathological manifestation of small renal cell carcinoma (SRCC). Methods: Thirty-six SRCC were all diagnosed by surgical pathology. On CT, attenuation value and the amount of enhancement were observed; on pathology, tumor cell characteristics, cell arrangement, the stage and grade of the tumor et al were observed. Results: 31 tumors were iso- or hypo-attenuation on CT and clear cell tumors were dominant in 28 cases; 5 cases were hyper-attenuation and 2 of them were granular cell carcinoma. After the contrast enhancement, 31 tumors were enhanced more than 40 HU. 27 of them were solid which had abundant sinusoid vessels; Enhancement in 29 cases was heterogeneous, and on pathology, hemorrhage and necrosis were found in 27 of them. Conclusion: The CT findings of SRCC were correlated with tumor cell characteristic and architecture

  13. Stem cell applications for pathologies of the urinary bladder

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    New stem cell based therapies are undergoing intenseresearch and are widely investigated in clinical fieldsincluding the urinary system. The urinary bladderperforms critical complex functions that rely on its highlycoordinated anatomical composition and multiplex ofregulatory mechanisms. Bladder pathologies resulting insevere dysfunction are common clinical encounter andoften cause significant impairment of patient's quality oflife. Current surgical and medical interventions to correcturinary dysfunction or to replace an absent or defectivebladder are sub-optimal and are associated with notablecomplications. As a result, stem cell based therapiesfor the urinary bladder are hoped to offer new venuesthat could make up for limitations of existing therapies.In this article, we review research efforts that describethe use of different types of stem cells in bladderreconstruction, urinary incontinence and retentiondisorders. In particular, stress urinary incontinence hasbeen a popular target for stem cell based therapiesin reported clinical trials. Furthermore, we discuss therelevance of the cancer stem cell hypothesis to thedevelopment of bladder cancer. A key subject thatshould not be overlooked is the safety and quality ofstem cell based therapies introduced to human subjectseither in a research or a clinical context.

  14. Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

    OpenAIRE

    Berres, Marie-Luise; Allen, Carl E.; Merad, Miriam

    2013-01-01

    Histiocytic disorders represent a group of complex pathologies characterized by the accumulation of histiocytes, an old term for tissue-resident macrophages and dendritic cells. Langerhans cell histiocytosis is the most frequent of histiocytosis in humans and has been thought to arise from the abnormal accumulation of epidermal dendritic cells called Langerhans cells. In this chapter, we discuss the origin and differentiation of Langerhans cells and dendritic cells and present accumulated evi...

  15. Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia Virus Type 1- (HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP

    Directory of Open Access Journals (Sweden)

    Mineki Saito

    2010-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

  16. Pathological modifications of plant stem cell destiny

    Science.gov (United States)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  17. [Molecular pathology of plasma cell neoplasms].

    Science.gov (United States)

    Fend, F

    2010-10-01

    Plasma cell myeloma (PCM) and related immunosecretory disorders are a group of B-cell proliferations with a wide clinical and prognostic spectrum, characterized by the production of monoclonal immunoglobulin by immortalized plasma cells. Recent years have seen an explosion in knowledge on the genetic basis and biology of these diseases, followed by improved clinical risk stratification and the introduction of novel therapeutic concepts, such as treatment with proteasome inhibitors or immunomodulatory substances. PCM is a common malignancy, accounting for approximately 10% of all hematological neoplasms. There is good evidence to support a multistep transformation process in plasma cell neoplasms, which corresponds to clinically discernible disease stages. Monoclonal gammopathy of unknown significance is a common asymptomatic precursor lesion for PCM which carries an approximately 1% annual risk for progression. Terminal disease stages are characterized by increasing genetic complexity and independence from bone marrow stromal cells and show a rapidly increasing tumour load with severe clinical symptoms. Modern diagnostics of plasma cell neoplasms require inclusion of clinical, morphological, immunophenotypical and cytogenetic features to allow for individual risk assessment and therapy planning. PMID:20852863

  18. Sphingolipid mediators in cardiovascular cell biology and pathology.

    Science.gov (United States)

    Levade, T; Augé, N; Veldman, R J; Cuvillier, O; Nègre-Salvayre, A; Salvayre, R

    2001-11-23

    Sphingolipids have emerged as a new class of lipid mediators. In response to various extracellular stimuli, sphingolipid turnover can be stimulated in vascular cells and cardiac myocytes. Subsequent generation of sphingolipid molecules such as ceramide, sphingosine, and sphingosine-1-phosphate, is followed by regulation of ion fluxes and activation of various signaling pathways leading to smooth muscle cell proliferation, endothelial cell differentiation or apoptotic cell death, cell contraction, retraction, or migration. The importance of sphingolipids in cardiovascular signaling is illustrated by recent observations implicating them in physiological processes such as vasculogenesis as well as in frequent pathological conditions, including atherosclerosis and its complications. PMID:11717151

  19. Nonredundant Functions of αβ and γδ T Cells in Acrolein-Induced Pulmonary Pathology

    OpenAIRE

    Borchers, Michael T.; Wesselkamper, Scott C.; Eppert, Bryan L.; Motz, Gregory T.; Sartor, Maureen A; Tomlinson, Craig R.; Medvedovic, Mario; Tichelaar, Jay W.

    2008-01-01

    Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we ...

  20. T1 relaxation in renal cell carcinoma with pathologic correlation

    International Nuclear Information System (INIS)

    Renal cell carcinoma, unlike most tumors, can have a shorter T1 on MR imaging than its host tissue. The author compared the signal intensity of renal tumor and normal renal tissue on T1 images obtained using contrast agents. A short T1 signal was seen in 16 of 23 cases of clear cells and/or hemorrhage. In six of eight cases with a long T1 signal, necrosis was found on gross pathologic examination. In four of five cases of isointense signal an unusual pathology was found; one of the five patients was in end-stage renal failure. Fat-containing clear cells and hemorrhage produce a short T1 signal, whereas necrosis produces a long T1 signal

  1. Genes and pathology of non-small cell lung carcinoma.

    Science.gov (United States)

    Sakashita, Shingo; Sakashita, Mai; Sound Tsao, Ming

    2014-02-01

    While histopathology has traditionally been the cornerstone of treatment decisions in the management of lung cancer patients, the complexity and heterogeneity of histological classification has had a limited impact in the routine practice of oncology. This has changed dramatically in the last few years, owing to discoveries of genomic aberrations and results of clinical trials of novel and targeted therapies. These discoveries have resulted in a new way of classifying non-small cell lung cancer (NSCLC), based on the occurrence of putative or proven driver and targetable genomic changes. The rapidity by which the landscape of mutation and genomic changes is being identified also has led to a new paradigm and approaches to pathological diagnosis of NSCLC. In this context, international consortia have proposed new classifications of lung adenocarcinoma and guidelines for molecular testing in lung cancer and have provided concrete recommendations on new ways to practice lung cancer pathology. PMID:24565579

  2. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    International Nuclear Information System (INIS)

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra. (letter)

  3. Synaptic pathology: A shared mechanism in neurological disease.

    Science.gov (United States)

    Henstridge, Christopher M; Pickett, Eleanor; Spires-Jones, Tara L

    2016-07-01

    Synaptic proteomes have evolved a rich and complex diversity to allow the exquisite control of neuronal communication and information transfer. It is therefore not surprising that many neurological disorders are associated with alterations in synaptic function. As technology has advanced, our ability to study the anatomical and physiological function of synapses in greater detail has revealed a critical role for both central and peripheral synapses in neurodegenerative disease. Synapse loss has a devastating effect on cellular communication, leading to wide ranging effects such as network disruption within central neural systems and muscle wastage in the periphery. These devastating effects link synaptic pathology to a diverse range of neurological disorders, spanning Alzheimer's disease to multiple sclerosis. This review will highlight some of the current literature on synaptic integrity in animal models of disease and human post-mortem studies. Synaptic changes in normal brain ageing will also be discussed and finally the current and prospective treatments for neurodegenerative disorders will be summarised. PMID:27108053

  4. The Pathology of T Cells in Systemic Lupus Erythematosus

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    Anselm Mak

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the production of a wide array of autoantibodies. Thus, the condition was traditionally classified as a “B-cell disease”. Compelling evidence has however shown that without the assistance of the helper T lymphocytes, it is indeed difficult for the “helpless” B cells to become functional enough to trigger SLE-related inflammation. T cells have been recognized to be crucial in the pathogenicity of SLE through their capabilities to communicate with and offer enormous help to B cells for driving autoantibody production. Recently, a number of phenotypic and functional alterations which increase the propensity to trigger lupus-related inflammation have been identified in lupus T cells. Here, potential mechanisms involving alterations in T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and oxidative stress which favour activation of lupus T cells will be discussed. Additionally, how regulatory CD4+, CD8+, and γδ T cells tune down lupus-related inflammation will be highlighted. Lastly, while currently available outcomes of clinical trials evaluating therapeutic agents which manipulate the T cells such as calcineurin inhibitors indicate that they are at least as efficacious and safe as conventional immunosuppressants in treating lupus glomerulonephritis, larger clinical trials are undoubtedly required to validate these as-yet favourable findings.

  5. Mechanical shielded hot cell

    International Nuclear Information System (INIS)

    A plan to erect a mechanical shielded hot cell in the process hall of the Radiochemical Laboratory at Inchas is described. The hot cell is designed for safe handling of spent fuel bundles, from the Inchas reactor, and for dismantling and cutting the fuel rods in preparation for subsequent treatment. The biological shielding allows for the safe handling of a total radioactivity level up to 10,000 MeV-Ci. The hot cell consists of an α-tight stainless-steel box, connected to a γ-shielded SAS, through an air-lock containing a movable carriage. The α-box is tightly connected with six dry-storage cavities for adequate storage of the spent fuel bundles. Both the α-box, with the dry-storage cavities, and the SAS are surrounded by 200-mm thick biological lead shielding. The α-box is equipped with two master-slave manipulators, a lead-glass window, a monorail crane and Padirac and Minirag systems. The SAS is equipped with a lead-glass window, tong manipulator, a shielded pit and a mechanism for the entry of the spent fuel bundle. The hot cell is served by adequate ventilation and monitoring systems. (author)

  6. Design of CMOS Based Image Sensor with Cantilever Mechanism for Smart Pathological Detection with Opto-Mechanical System

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    Rajeshlaik

    2012-06-01

    Full Text Available patient immobilized on slide under the microscope is extracted with imaging device. Similar kind of setup is designed to detect object with analog transducer circuit system which the mines worker use torchlight over the helmet underground with 4.5 volt of light, with 1 watt bulb is sufficient our Eye can recognize the object, but with CFL it is more brighter in dark condition to detect the object. Here the biomechanical action of the miners Eye & brain coordination inside the mining region where it is very dark to focus the object, the inverter like headlight operates in this condition and helps him to work smoothly for his neural coordination works in balanced. Focal length inversely proportional to the magnification is required to clearly visualize any object, Physically when we see any object we move nearer or far-away and maintain the distance from the object, if any person cannot clearly identify they wear glass of varying power as per their disorder, Electronic CMOS Biosensor with signal conditioning OPAMP gives the strong power to the eye to visualize the image under the microscope converting the charge of APS into the voltage amplified in a nano-second time response. The inverting action of the Eye with 01,which is simulated for Photo-sensor circuit, with equivalent silicon-on-chip based CMOS combination. Thus the detection of cancer cells is very cheap and efficient way in pathological laboratory with CMOS microscope. Comparative studies makes the efficient detection of morphological features of gross tissue section of tumor Cells clearly detected when magnified under 40 x,with CMOS biosensor phototransistor. Patient requires to check his or her body weight, prior to pathological check up, therefore the weighing machine is the very important piezo convertor of mechanical energy of the body into weight and when the smart nano-mechanical cantilever sensor chip integrates with this machine the signal will be more fast .The PH paper as a

  7. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

    International Nuclear Information System (INIS)

    Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a 137Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone

  8. Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes

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    Salvatore Andrea Mastrolia

    2014-11-01

    Full Text Available Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental, therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal–fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

  9. Multi-slice spiral CT and pathological correlation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze relationship between characteristics on multi-slice spiral CT (MSCT) and pathology of renal cell carcinoma. Methods: Multi-slice spiral CT and surgical pathological results on 32 cases of renal cell carcinoma were retrospectively analyzed. Results: Of the 32 cases, 28 were pathologically diagnosed as clear cell carcinoma, with tumor contrast enhancement similar to the normal cortex in the renal cortical phase (146-175HU), slight contrast washout in the renal parenchyma phase and significant contrast washout from the tumor in the pyelographic phase. Granular cell carcinoma in 4 patients showed no or mild contrast enhancement (38- 55HU) in all three phase. The overall diagnostic accordance rate was 100%, with preoperative staging accordance rate of 96.42%. Conclusion: The triple-phase contrast-enhanced MSCT is useful in predicting the tumor cell type and staging of renal cell carcinoma. (authors)

  10. Cell mechanics as a marker for diseases: Biomedical applications of AFM

    Science.gov (United States)

    Rianna, Carmela; Radmacher, Manfred

    2016-08-01

    Many diseases are related to changes in cell mechanics. Atomic Force Microscopy (AFM) is one of the most suitable techniques allowing the investigation of both topography and mechanical properties of adherent cells with high spatial resolution under physiological conditions. Over the years the use of this technique in medical and clinical applications has largely increased, resulting in the notion of cell mechanics as a biomarker to discriminate between different physiological and pathological states of cells. Cell mechanics has proven to be a biophysical fingerprint able discerning between cell phenotypes, unraveling processes in aging or diseases, or even detecting and diagnosing cellular pathologies. We will review in this report some of the works on cell mechanics investigated by AFM with clinical and medical relevance in order to clarify the state of research in this field and to highlight the role of cell mechanics in the study of pathologies, focusing on cancer, blood and cardiovascular diseases.

  11. Mechanically facilitated cell-cell electrofusion.

    OpenAIRE

    Jaroszeski, M. J.; Gilbert, R.; Fallon, P.G.; Heller, R

    1994-01-01

    Apparatus and methods were developed to enable mechanically facilitated cell-cell electrofusion to be performed. The apparatus and methods mechanically place cells in contact before fusion. The key component of this fusion system was a newly developed fusion chamber. The chamber was composed of two functionally identical electrodes that were housed in a multi-layer structure. The layers functioned as support for the electrodes. They also allowed adjustment of the distance between opposing ele...

  12. Immune regulation of epithelial cell function: Implications for GI pathologies

    Science.gov (United States)

    The mammalian immune system is a complex and dynamic network that recognizes, responds, and adapts to numerous foreign and self molecules. CD4+ T cells orchestrate adaptive immune responses, and upon stimulation by antigen, naive CD4+ T cells proliferate and differentiate into various T cell subsets...

  13. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    International Nuclear Information System (INIS)

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  14. Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics

    OpenAIRE

    Pavone, Lucio A; Albert, Scott; Carney, David; Gatto, Louis A; Halter, Jeffrey M; Nieman, Gary F.

    2007-01-01

    Introduction Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we ...

  15. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology

    OpenAIRE

    Buonocore, Sofia; Ahern, Philip P.; Uhlig, Holm H; Ivanov, Ivaylo I.; Dan R. Littman; Maloy, Kevin J.; Powrie, Fiona

    2010-01-01

    The key role of IL-23 in the pathogenesis of autoimmune and chronic inflammatory disorders is supported by the identification of IL-23R susceptibility alleles associated with IBD, psoriasis and ankylosing spondylitis. IL-23 driven inflammation has primarily been linked to the actions of Th17 cells 1 . Somewhat overlooked, IL-23 also has inflammatory effects on innate immune cells 2 and can drive T cell- independent colitis. However the downstream cellular and molecular pathways involved in th...

  16. Complete pathological resolution of pulmonary Langerhans cell histiocytosis

    OpenAIRE

    Ninaber, Maarten; Dik, Hans; Peters, Elke

    2014-01-01

    Cigarette smoking is a major risk factor for pulmonary Langerhans cell histiocytosis (pLCH) and lung cancer. Resolution of pLCH may occur spontaneously, after smoking cessation or other interventions. However, despite clinicoradiological resolution, residual pulmonary Langerhans cells may be present and may lead to recurrent disease. We report the first case of pLCH with a complete histological resolution.

  17. An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology.

    Science.gov (United States)

    Klika, Václav; Gaffney, Eamonn A; Chen, Ying-Chun; Brown, Cameron P

    2016-09-01

    There is a long history of mathematical and computational modelling with the objective of understanding the mechanisms governing cartilage׳s remarkable mechanical performance. Nonetheless, despite sophisticated modelling development, simulations of cartilage have consistently lagged behind structural knowledge and thus the relationship between structure and function in cartilage is not fully understood. However, in the most recent generation of studies, there is an emerging confluence between our structural knowledge and the structure represented in cartilage modelling. This raises the prospect of further refinement in our understanding of cartilage function and also the initiation of an engineering-level understanding for how structural degradation and ageing relates to cartilage dysfunction and pathology, as well as informing the potential design of prospective interventions. Aimed at researchers entering the field of cartilage modelling, we thus review the basic principles of cartilage models, discussing the underlying physics and assumptions in relatively simple settings, whilst presenting the derivation of relatively parsimonious multiphase cartilage models consistent with our discussions. We proceed to consider modern developments that start aligning the structure captured in the models with observed complexities. This emphasises the challenges associated with constitutive relations, boundary conditions, parameter estimation and validation in cartilage modelling programmes. Consequently, we further detail how both experimental interrogations and modelling developments can be utilised to investigate and reduce such difficulties before summarising how cartilage modelling initiatives may improve our understanding of cartilage ageing, pathology and intervention. PMID:27195911

  18. A review of novel optical imaging strategies of the stroke pathology and stem cell therapy in stroke

    Directory of Open Access Journals (Sweden)

    Markus eAswendt

    2014-08-01

    Full Text Available Transplanted stem cells can induce and enhance functional recovery in experimental stroke. Invasive analysis has been extensively used to provide detailed cellular and molecular characterization of the stroke pathology and engrafted stem cells. But post mortem analysis is not appropriate to reveal the time scale of the dynamic interplay between the cell graft, the ischemic lesion and the endogenous repair mechanisms. This review describes non-invasive imaging techniques which have been developed to provide complementary in vivo information. Recent advances were made in analyzing simultaneously different aspects of the cell graft (e.g. number of cells, viability state and cell fate, the ischemic lesion (e.g. blood brain barrier consistency, hypoxic and necrotic areas and the neuronal and vascular network. We focus on optical methods, which permit simple animal preparation, repetitive experimental conditions, relatively medium-cost instrumentation and are performed under mild anesthesia, thus nearly under physiological conditions. A selection of recent examples of optical intrinsic imaging, fluorescence imaging (FLI and bioluminescence imaging (BLI to characterize the stroke pathology and engrafted stem cells are discussed. Special attention is paid to novel optimal reporter genes/probes for genetic labeling and tracking of stem cells and appropriate transgenic animal models. Requirements, advantages and limitations of these imaging platforms are critically discussed and placed into the context of other non-invasive techniques, e.g. magnetic resonance imaging (MRI and positron emission tomography (PET, which can be joined with optical imaging in multimodal approaches.

  19. Comparison of prefrontal cell pathology between depression and alcohol dependence

    OpenAIRE

    Miguel-Hidalgo, José J.; Rajkowska, Grazyna

    2003-01-01

    Chronic alcohol abuse is often co-morbid with depression symptoms and in many cases it appears to induce major depressive disorder. Structural and functional neuroimaging has provided evidence supporting some degree of neuropathological convergence of alcoholism and mood disorders. In order to understand the cellular neuropathology of alcohol dependence and mood disorders, postmortem morphometric studies have tested the possibility of alterations in the number and size of cells in the prefron...

  20. An overview of renal cell cancer: Pathology and genetics

    OpenAIRE

    Moch, Holger

    2012-01-01

    Renal cell carcinoma is a group of malignancies arising from the epithelium of the renal tubules. The pattern of somatic mutations in kidney tumors has been extensively investigated. In the current 2004 WHO classification, the molecular background of a renal tumor has become, in addition to histopathology, a major criterion for tumor classification. The goal of this review is to discuss morphology and genetics of adult renal epithelial cancer included in the 2004 WHO classification and to men...

  1. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Jian-Zhao Niu; Ji-Feng Wang; Yu Li; Xiao-Hua Tao

    2005-01-01

    AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension.METHODS: Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type Ⅳ collagen (CoⅣ) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-μm thick sectiors were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated,total protein was extracted and separated by SDS-PAGE.MMP-2 and TIMP-1 protein expression was estimated by Western blotting.RESULTS: The diameter (2.207 ± 0.096 vs 1.528 ± 0.054 mm, P<0.01) and pressure (11.014±0.395 vs 8.533±0.274 mmHg, P<0.01) of portal vein were significantly higher in model group than those in the control group. Plasma HA (129.97±16.10 vs 73.09±2.38 ng/mL, P<0.01), ColⅣ (210.49±4.36 vs 89.65±4.42 ng/mL, P<0.01) and LN (105.00±7.29 vs 55.70±4.32 ng/mL, P<0.01) were upregulated in model group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ.Immunohistochemical staining showed that ColⅣ protein level (0.130±0.007 vs 0.032±0.004, P<0.01) and LN protein level (0.152±0.005 vs 0.029±0.005, P<0.01)were up-regulated remarkably in model group. MMP-2 protein expression (2.306±1.089 vs 0.612±0.081,P<0.01) and TIMP-1 protein expression (3.015±1.364 vs 0.446±0.009, P<0

  2. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    International Nuclear Information System (INIS)

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  3. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  4. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    International Nuclear Information System (INIS)

    Highlights: ► A HK-2 cells model of inflammation-induced acute kidney injury. ► Two oximetry methods: high resolution respirometry and ESR spectroscopy. ► Oxygen consumption rates of renal cells decrease when treated with LPS. ► Cells do not recover normal respiration when the LPS treatment is removed. ► This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  5. Connectivity of pathology: The olfactory system as a model for network-driven mechanisms of Alzheimer’s disease pathogenesis

    OpenAIRE

    Vickers, James C.

    2015-01-01

    The pathogenesis of Alzheimer’s disease has been postulated to preferentially impact specific neural networks in the brain. The olfactory system is a well-defined network that has been implicated in early stages of the disease, marked by impairment in olfaction as well as the presence of pathological hallmarks of the disease, even before clinical presentation. Discovering the cellular mechanisms involved in the connectivity of pathology will provide insight into potential targets for treatmen...

  6. Characterization of T cell clones from chagasic patients: predominance of CD8 surface phenotype in clones from patients with pathology

    Directory of Open Access Journals (Sweden)

    Washington R. Cuna

    1995-08-01

    Full Text Available Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated with pathological processes whose mechanisms are not known. To address this question, T cell lines were developed from chronic chagasic patients peripheral blood mononuclear cells (PBMC and cloned. These T cell clones (TCC were analyzed phenotypically with monoclonal antibodies by the use of a fluorescence microscope. The surface phenotype of the TCC from the asymptomatic patient were predominantly CD4 positive (86%. On the contrary, the surface phenotype CD8 was predominant in the TCC from the patients suffering from cardiomegaly with right bundle branch block (83%, bradycardia with megacolon (75 % and bradycardia (75%. Future studies will be developed in order to identify the antigens eliciting these T cell subpopulations.

  7. T cell mediated pathogenesis in EAE: Molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Florian C Kurschus

    2015-06-01

    Full Text Available T cells are major initiators and mediators of disease in multiple sclerosis (MS and in its animal model experimental autoimmune encephalomyelitis (EAE. EAE is an antigen-driven autoimmune model in which immunization against myelin autoantigens elicits strong T cell responses which initiate its pathology with CNS myelin destruction. T cells cause pathogenic events by several mechanisms; some work in a direct fashion in the CNS, such as direct cytokine-induced damage, granzyme-mediated killing, or glutamate-induced neurotoxicity, whereas most are indirect mechanisms, such as activation of other cell types like macrophages, B cells, or neutrophils. This review aims to describe and discuss the molecular effector mechanism by which T cells harm the CNS during EAE.

  8. Review: Animal Models of Diabetes Mellitus: Pathology and Mechanism of Some Diabetogenics

    Directory of Open Access Journals (Sweden)

    AGUNG ENDRO NUGROHO

    2006-10-01

    Full Text Available Animal models of diabetes mellitus were made and used in laboratorium according to the pathology of diabetic patient and its complications. Animal models of diabetes mellitus were designed by two methods: induced method such as pancreatectomy, chemicals (diabetogenic, viruses, and spontaneous method such BB (bio breeding rats and NOD (non-obese diabetic mice.The techniques of animal models of diabetes mellitus frequently used in the research were usage of diabetogenic such as alloxan and streptozotocin. Alloxan and its reduction metabolite (dialuric acid establish a redox cycle and form superoxide radicals, and they undergo dismutation to hydrogen peroxide. By Fenton reaction, the formation of reactive hydroxyl radicals was stimulated. These radicals with high concentration of cytosolic calcium cause rapid destruction of β cells. Besides, streptozotocin enters the β cell through a glucose transporter (GLUT2, and stimulates superoxide radicals, hydrogen peroxide and hydroxyl radicals which in turn causes rapid destruction of β cells. Streptozotocin also releases toxic amounts of nitric oxide that inhibits aconitase activity and contributes in DNA damage.

  9. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    OpenAIRE

    Dierssen, Jan Willem Frederik

    2010-01-01

    This thesis describes molecular methods to distinguish separate colon tumour entities. Furthermore, it shows that distinct immune escape mechanisms, in particular distinct mechanisms of corrupting the HLA system, are operational in subsets of colon tumours. The apparent necessity of some colon tumours to circumvent the immune system might underscore the potential of immune based therapy approaches. Alternatively, it may suggest that such therapies will only lead to selection of tumour cells w...

  10. On tensegrity in cell mechanics.

    Science.gov (United States)

    Volokh, K Y

    2011-09-01

    All models are wrong, but some are useful. This famous saying mirrors the situation in cell mechanics as well. It looks like no particular model of the cell deformability can be unconditionally preferred over others and different models reveal different aspects of the mechanical behavior of living cells. The purpose of the present work is to discuss the so-called tensegrity models of the cell cytoskeleton. It seems that the role of the cytoskeleton in the overall mechanical response of the cell was not appreciated until Donald Ingber put a strong emphasis on it. It was fortunate that Ingber linked the cytoskeletal structure to the fascinating art of tensegrity architecture. This link sparked interest and argument among biologists, physicists, mathematicians, and engineers. At some point the enthusiasm regarding tensegrity perhaps became overwhelming and as a reaction to that some skepticism built up. To demystify Ingber's ideas the present work aims at pinpointing the meaning of tensegrity and its role in our understanding of the importance of the cytoskeleton for the cell deformability and motility. It should be noted also that this paper emphasizes basic ideas rather than carefully follows the chronology of the development of tensegrity models. The latter can be found in the comprehensive review by Dimitrije Stamenovic (2006) to which the present work is complementary. PMID:21977516

  11. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  12. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype

    Institute of Scientific and Technical Information of China (English)

    Jing Ye; Yun-Lin Wu; Shu Zhang; Zi Chen; Li-Xia Guo; Ruo-Yu Zhou; Hong Xie

    2005-01-01

    AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901)and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism,and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells.METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay.RESULTS: Telomerase activity was detected in well,moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively).Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 μmol/L, and was entirely inhibited at 10 μmol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901gastric cancer cell lines (the inhibition ratio was 40.89%and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0

  13. Mice Engrafted With Human Fetal Thymic Tissue And Hematopoietic Stem Cells Develop Pathology Resembling Chronic GVHD

    OpenAIRE

    Lockridge, Jennifer L.; Ying ZHOU; Becker, Yusof A.; Ma, Shidong; Kenney, Shannon C.; Hematti, Peiman; Capitini, Christian M.; Burlingham, William J.; Gendron-Fitzpatrick, Annette; Gumperz, Jenny E.

    2013-01-01

    Chronic Graft versus Host Disease (cGVHD) is a significant roadblock to long-term hematopoeitic stem cell (HSC) transplantation success. Effective treatments for cGVHD have been difficult to develop, in part because of a paucity of animal models that recapitulate the multi-organ pathologies observed in clinical cGVHD. Here we present an analysis of the pathology that occurs in immunodeficient mice engrafted with human fetal HSCs and implanted with fragments of human fetal thymus and liver. St...

  14. A diagnostic dilemma in breast pathology – benign fibroadenoma with multinucleated stromal giant cells

    Directory of Open Access Journals (Sweden)

    Tobbia Igdam

    2008-08-01

    Full Text Available Abstract Fibroadenomas are common benign breast tumours that display a characteristic pathological morphology, although several epithelial and stromal variations exist. A very rare histological finding is the presence of multinucleated giant cells throughout the stroma of a benign fibroadenoma. Cells of this type, which are more commonly found incidentally within the interlobular stroma of breast tissue, are benign and should not be mistaken for malignant cells on microscopic examination. Unfortunately a lack of awareness of this pathological entity can lead to diagnostic confusion amongst pathologists resulting in the multinucleate giant cells being mistaken for highly mitotic cells and consequently the fibroadenoma being mistaken for a malignant lesion. This may have serious implications for the subsequent management of the patient. The presence of this unusual cell type in the stroma does not alter the prognosis of otherwise benign lesion. We encountered two such cases at our institution in a six month period recently. We present their histories along with relevant radiological, microscopic and immunohistochemical features, followed by a discussion of this unusual pathological entity.

  15. Cell Interactomics and Carcinogenetic Mechanisms

    CERN Document Server

    Baianu, IC; Report to the Institute of Genomics

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  16. Physiological and pathological role of local and immigrating colonic stem cells

    Institute of Scientific and Technical Information of China (English)

    Ferenc Sipos; Gábor Valcz; Béla Molnár

    2012-01-01

    The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstances where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stem cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

  17. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle; Gormsen, Magdalena; Pedersen, Karen Damgaard; Buchvald, Frederik; Heilmann, Carsten; Nielsen, Kim Gjerum; Mortensen, Jann; Moser, Claus; Sengeløv, Henrik; Müller, Klaus Gottlob

    2015-03-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases. PMID:25498923

  18. Plasmacytoid Transitional Cell Carcinoma of Bladder: A Clinico-pathological Study and Review of Literatures

    Institute of Scientific and Technical Information of China (English)

    FENG Xiaoli; ZHANG Hongtu; SUN Yuntian; LIU Xiuyun

    2006-01-01

    Objective: To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods: Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results: A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion: The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

  19. α-Synuclein vaccination modulates regulatory T cell activation and microglia in the absence of brain pathology

    DEFF Research Database (Denmark)

    Christiansen, Josefine R; Olesen, Mads N; Otzen, Daniel E; Romero-Ramos, Marina; Sanchez-Guajardo, Vanesa

    2016-01-01

    have studied the changes induced by vaccination with α-synuclein in the CD4 T cell pool and its impact on brain microglia to understand the immune mechanisms behind successful vaccination strategies in Parkinson's disease animal models. METHODS: Mice were immunized with WT or nitrated α-synuclein at a......BACKGROUND: Passive and active immunization with α-synuclein has been shown to be neuroprotective in animal models of Parkinson's disease. We have previously shown that vaccination with α-synuclein, long before α-synuclein-induced brain pathology, prevents striatal degeneration by inducing...... regulatory T cell infiltration in parenchyma and antibody deposition on α-synuclein overexpressing neurons. However, the effect of peripheral α-synuclein on the immune system is unknown, as are the mechanistic changes induced in the CD4 T cell population during successful neuroprotective animal studies. We...

  20. Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms

    OpenAIRE

    Carroll, Steven L.

    2011-01-01

    Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types have distinct pathologies and clinical behaviors; a growing body of evidence indicates that they also arise via distinct pathogenic mechanisms. Identification of the genes that are mutated in genetic diseases characterized by the development of either neurofibromas and MPNSTs [neurofibromatosis type 1 (NF1)] or schwannomas [ne...

  1. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    International Nuclear Information System (INIS)

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients

  2. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

    2015-11-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

  3. [Indications and mechanisms of action of the intravenous immunoglobulines in the systemic autoimmune and inflammatory pathologies].

    Science.gov (United States)

    Mouthon, L; Bussone, G; Kaveri, S

    2009-12-01

    Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG obtained from pools of more than 1000 healthy blood donors. Initially used for the treatment of immunodeficiencies, IVIg have increasingly been used as immunomodulatory agent in autoimmune and inflammatory disorders. Several mechanisms of action have been described during the last 25 years, including : (i) modulation of Fcgamma receptors expression on leukocytes and endothelial cells ; (ii) interaction with complement proteins ; (iii) modulation of cytokines and chemiokines synthesis and release ; (iv) modulation of cell proliferation and apoptosis ; (v) remyelinisation ; (vi) neutralisation of circulating antibodies ; (vii) selection of immune repertoires and (viii) interaction with other cell-surface molecules on lymphocytes and monocytes. We here discuss the recent advances in the understanding of immunoregulatory effects of IVIg, and we point out the need of new strategies to overcome the predicted increasing worldwide shortage of IVIg. PMID:19995651

  4. Development and function of protective and pathologic memory CD4 T cells

    Directory of Open Access Journals (Sweden)

    Megan KL Macleod

    2015-09-01

    Full Text Available IImmunological memory is one of the defining features of the adaptive immune system. As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses. Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation. These responses can either benefit the host by hastening the control of pathogens or cause damaging immunopathology. Here, we will discuss the diversity of the memory CD4 T cell pool, the signals that influence the transition of activated T cells into that pool, and highlight how activation requirements differ between naïve and memory CD4 T cells. A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

  5. A46, a Benzothiophene Derived Compound, Suppresses Jak2-Mediated Pathologic Cell Growth

    OpenAIRE

    Majumder, Anurima; Magis, Andrew T.; Park, Sung O.; Figueroa, Nicholas C.; Baskin, Rebekah; Kirabo, Annet; Robert W Allan; Zhao, Zhizhuang Joe; Bisht, Kirpal S.; Keserű, György M.; Sayeski, Peter P.

    2011-01-01

    Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several hematological disorders including the myeloproliferative neoplasms (MPNs). Effective Jak2 inhibitors can thus have significant therapeutic potential. Here, using structure based virtual screening, we identified a benzothiophene derived Jak2 inhibitor named A46. We hypothesized that this compound would inhibit Jak2-V617F mediated pathologic cell growth. To test this, A46 was analyzed for its ability to i) inhibit recomb...

  6. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    OpenAIRE

    John Martin Barrett; Patrick Degenaar

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was ...

  7. Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

  8. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer

    OpenAIRE

    Youn, Je-in; Kumar, Vinit; Collazo, Michelle; Nefedova, Yulia; Condamine, Thomas; Cheng, Pingyan; Villagra, Alejandro; Antonia, Scott; McCaffrey, Judith C.; Fishman, Mayer; Sarnaik, Amod; Horna, Pedro; Sotomayor, Eduardo; Gabrilovich, Dmitry I.

    2013-01-01

    Two major populations of myeloid-derived suppressor cells (MDSC), monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC) regulate immune responses in cancer and other pathologic conditions. Under physiologic conditions, Ly6ChiLy6G− inflammatory monocytes, which are the normal counterpart of M-MDSC, differentiate into macrophages and dendritic cells (DCs). PMN-MDSC is the predominant group of MDSC that accumulates in cancer. Here we show that a large proportion of M-MDSC in tumor-bearin...

  9. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

    Science.gov (United States)

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Muller, Werner; Cretney, Erika; Nutt, Stephen L.; Smyth, Mark J.; Haque, Ashraful; Hill, Geoffrey R.; Sundar, Shyam; Kallies, Axel; Engwerda, Christian R.

    2016-01-01

    Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. PMID:26765224

  10. Choroidal mast cells in retinal pathology: a potential target for intervention.

    Science.gov (United States)

    Bousquet, Elodie; Zhao, Min; Thillaye-Goldenberg, Brigitte; Lorena, Viera; Castaneda, Beatriz; Naud, Marie Christine; Bergin, Ciara; Besson-Lescure, Bernadette; Behar-Cohen, Francine; de Kozak, Yvonne

    2015-08-01

    Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention. PMID:26166807

  11. Cell mechanics of alveolar epithelial cells (AECs) and macrophages (AMs).

    OpenAIRE

    Féréol, Sophie; Fodil, Redouane; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2008-01-01

    Cell mechanics provides an integrated view of many biological phenomena which are intimately related to cell structure and function. Because breathing constitutes a sustained motion synonymous with life, pulmonary cells are normally designed to support permanent cyclic stretch without breaking, while receiving mechanical cues from their environment. The authors study the mechanical responses of alveolar cells, namely epithelial cells and macrophages, exposed to well-controlled mechanical stre...

  12. Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Gabriella Schiera

    2015-01-01

    Full Text Available Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies.

  13. Clinical and surgical-pathological staging in early non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Koukis

    2013-12-01

    Full Text Available Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC, a tumor, node, and metastases (TNM staging system is currently used for NSCLC. Clinical staging (c-TNM is achieved via non-invasive modalities such as examination of case history, clinical assessment and radiological tests. Pathological staging (p-TNM is based on histological examination of tissue specimens obtained with the aid of invasive techniques, either non-surgical or during the intervention. This review is a critical evaluation of the roles of current pre-operative staging modalities, both invasive and non-invasive. In particular, it focuses on new techniques and their role in providing accurate confirmation of patient TNM status. It also evaluates the surgical-pathological staging modalities used to obtain the true-pathological staging for NSCLC.

  14. Regulatory T cells delay disease progression in Alzheimer-like pathology.

    Science.gov (United States)

    Dansokho, Cira; Ait Ahmed, Dylla; Aid, Saba; Toly-Ndour, Cécile; Chaigneau, Thomas; Calle, Vanessa; Cagnard, Nicolas; Holzenberger, Martin; Piaggio, Eliane; Aucouturier, Pierre; Dorothée, Guillaume

    2016-04-01

    Recent studies highlight the implication of innate and adaptive immunity in the pathophysiology of Alzheimer's disease, and foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results in mouse models, but severe side effects attributed to T cell responses in the first clinical trial AN1792 underlined the need for better understanding adaptive immunity in Alzheimer's disease. We previously showed that regulatory T cells critically control amyloid-β-specific CD4(+)T cell responses in both physiological and pathological settings. Here, we analysed the impact of regulatory T cells on spontaneous disease progression in a murine model of Alzheimer's disease. Early transient depletion of regulatory T cells accelerated the onset of cognitive deficits in APPPS1 mice, without altering amyloid-β deposition. Earlier cognitive impairment correlated with reduced recruitment of microglia towards amyloid deposits and altered disease-related gene expression profile. Conversely, amplification of regulatory T cells through peripheral low-dose IL-2 treatment increased numbers of plaque-associated microglia, and restored cognitive functions in APPPS1 mice. These data suggest that regulatory T cells play a beneficial role in the pathophysiology of Alzheimer's disease, by slowing disease progression and modulating microglial response to amyloid-β deposition. Our study highlights the therapeutic potential of repurposed IL-2 for innovative immunotherapy based on modulation of regulatory T cells in Alzheimer's disease. PMID:26912648

  15. Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia.

    Science.gov (United States)

    Collet, Guillaume; Szade, Krzysztof; Nowak, Witold; Klimkiewicz, Krzysztof; El Hafny-Rahbi, Bouchra; Szczepanek, Karol; Sugiyama, Daisuke; Weglarczyk, Kazimierz; Foucault-Collet, Alexandra; Guichard, Alan; Mazan, Andrzej; Nadim, Mahdi; Fasani, Fabienne; Lamerant-Fayel, Nathalie; Grillon, Catherine; Petoud, Stéphane; Beloeil, Jean-Claude; Jozkowicz, Alicja; Dulak, Jozef; Kieda, Claudine

    2016-01-28

    Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta-gonad-mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded Matrigel(TM)-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation. PMID:26577811

  16. Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series.

    Science.gov (United States)

    Brinkerhoff, Brian T; Houghton, Donald C; Troxell, Megan L

    2016-06-01

    Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury. PMID:27015134

  17. Acinar Cell Cyst adenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

    Energy Technology Data Exchange (ETDEWEB)

    Gumus, Mehmet; Algin, Oktay; Gundogdu, Haldun [Ataturk Training and Research Hospital, Ankara (Turkmenistan); Ugras, Serdar [Selcuk University, Selcuklu Medical Faculty, Konya (Turkmenistan)

    2011-02-15

    Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC

  18. Bioluminescence imaging of β cells and intrahepatic insulin gene activity under normal and pathological conditions.

    Directory of Open Access Journals (Sweden)

    Tokio Katsumata

    Full Text Available In diabetes research, bioluminescence imaging (BLI has been applied in studies of β-cell impairment, development, and islet transplantation. To develop a mouse model that enables noninvasive imaging of β cells, we generated a bacterial artificial chromosome (BAC transgenic mouse in which a mouse 200-kbp genomic fragment comprising the insulin I gene drives luciferase expression (Ins1-luc BAC transgenic mouse. BLI of mice was performed using the IVIS Spectrum system after intraperitoneal injection of luciferin, and the bioluminescence signal from the pancreatic region analyzed. When compared with MIP-Luc-VU mice [FVB/N-Tg(Ins1-lucVUPwrs/J] expressing luciferase under the control of the 9.2-kbp mouse insulin I promoter (MIP, the bioluminescence emission from Ins1-luc BAC transgenic mice was enhanced approximately 4-fold. Streptozotocin-treated Ins1-luc BAC transgenic mice developed severe diabetes concomitant with a sharp decline in the BLI signal intensity in the pancreas. Conversely, mice fed a high-fat diet for 8 weeks showed an increase in the signal, reflecting a decrease or increase in the β-cell mass. Although the bioluminescence intensity of the islets correlated well with the number of isolated islets in vitro, the intensity obtained from a living mouse in vivo did not necessarily reflect an absolute quantification of the β-cell mass under pathological conditions. On the other hand, adenovirus-mediated gene transduction of β-cell-related transcription factors in Ins1-luc BAC transgenic mice generated luminescence from the hepatic region for more than 1 week. These results demonstrate that BLI in Ins1-luc BAC transgenic mice provides a noninvasive method of imaging islet β cells and extrapancreatic activity of the insulin gene in the liver under normal and pathological conditions.

  19. Evidence from human and animal studies: Pathological roles of CD8+ T cells in autoimmune peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Mu eYang

    2015-10-01

    Full Text Available Autoimmune peripheral neuropathies such as Guillain Barre Syndrome (GBS and chronic inflammatory demyelinating polyneuropathy (CIDP affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN. As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicate that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathy. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice in which the T cell co-stimulator molecule B7.2 (CD86 is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies.

  20. Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

    Science.gov (United States)

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

  1. Alzheimer's Disease: Mechanism and Approach to Cell Therapy.

    Science.gov (United States)

    Amemori, Takashi; Jendelova, Pavla; Ruzicka, Jiri; Urdzikova, Lucia Machova; Sykova, Eva

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells. PMID:26556341

  2. Alzheimer’s Disease: Mechanism and Approach to Cell Therapy

    Directory of Open Access Journals (Sweden)

    Takashi Amemori

    2015-11-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells.

  3. LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

    Directory of Open Access Journals (Sweden)

    Zvi Ioav Cabantchik

    2014-03-01

    Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

  4. Ouabain at pathological concentrations might induce damage in human vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Yan-ping REN; Ruo-wen HUANG; Zhuo-ren L(U)

    2006-01-01

    Aim: To examine the time- and dose-dependent effects of ouabain on human umbilical vein endothelial cells (HUVEC) in vivo, and the changes in aortic endothelium and the different expression levels of Kv4.2 in vitro. Methods: The proliferation of HUVEC and cell death were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the incorporation of [3H]TdR,trypan blue staining, and lactate dehydrogenase (LDH) release. The response of endothelial cells to ouabain was explored with a complementary DNA microarray and a candidate gene was found. "Ouabain-sensitive" hypertensive rats were established by chronic administration of ouabain. Changes in the aortic endothelium were observed by electron microscopy, and the expression level of Ky4.2 in different animals was studied by using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Ouabain stimulated the proliferation of HUVEC at physiological concentrations (0.3-0.9 nmol/L). Ouabain at pathological concentrations (0.9-1.8 nmol/L) inhibited proliferation and induced cell death, mRNA profile analysis indicated that 340 genes were differentially expressed after ouabain treatment: 145 were upregulated, of which 6 were upregulated significantly, including KCND2 (encoding the potassium voltagegated channel shal-related subfamily member 2). The upregulated genes were mainly related to cell metabolism and transcription. In ouabain-sensitive hypertensive rats, the aortic endothelium was damaged and Kv4.2 (coded by KCND2)was over-expressed. Conclusion: The physiological role of ouabain in HUVEC might involve the control of growth and metabolism. Ouabain at pathological concentrations might affect the structure and function of the vascular endothelium by modification of expression of the KCND2 gene, and participate vascular remodeling in hypertension.

  5. F-18-FDG positron emission tomography findings correlate pathological proliferative activity of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    It is still controversial whether fluorodeoxyglucose (FDG) uptake is correlated with cellular proliferation and prognosis of oral squamous cell carcinoma (OSC). In this study, we performed positron emission tomography (PET) study and immunohistochemical analysis to elucidate the relationship between FDG uptake and expression of cellular proliferative markers and pathological prognostic markers in patients with OSC. FDG PET and immunohistochemical staining have been carried out in sixteen patients with OSC. Tumor uptake of FDG was expressed with standardized uptake value (SUV). The expression of Ki-67, Topoisomerase IIα (Topo IIα), p53, and p63 in cancer cells was quantitatively assessed with positivity of the immunohistochemical staining. SUV was compared with the results of immunohistochemical analysis. FDG PET study revealed that SUV ranged from 3.6 to 22.1 with average of 10.4. Average positive rate of Ki-67, Topo IIα, p53, and p63 was 68.9%, 58.9%, 72.0%, and 65.2%, respectively. Pearson product-moment correlation coefficient analysis revealed that SUV was significantly correlated with Ki-67 (r=0.616, p=0.01), Topo IIα (r=0.677, p=0.004), p53 (r=0.613, p=0.01), and p63 (r=0.710, p=0.002), respectively. The present preliminary study indicated that FDG uptake was closely correlated with pathological cellular proliferative and prognostic markers in patients with OSC. (author)

  6. Correlation between apparent diffusion coefficient value and pathological grading in pT1b clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the correlation of ADC values on 3.0 T MR with the pathological grades in pT1b clear cell renal cell carcinoma (CCRCC). Methods: Conventional MR images, ADC values and Fuhrman pathological grading of pT1b CCRCC were performed in 30 patients. Grade Ⅰ and Ⅱ were defined as low-grade group; grade Ⅲ and Ⅳ were defined as high-grade group. The differences of ADC values among four different pathologic grades were compared with a one-way analysis of variance. The comparison of ADC values of two different grade groups was performed with t test, and the ROC curve was performed to evaluate the diagnostic efficacy of ADC value. Correlation between pathological grading and ADC values was assessed with Spearman rank correlation analysis. Results: (1) The mean ADC value of grading Ⅰ (10 patients), Ⅱ (8 patients), Ⅲ (7 patients), Ⅳ (5 patients) was (0.94 ± 0.11) ×10-3 mm2/s, (0.82 ±0.13) × 10-3 mm2/s,(0.68 ±0.09) × 10-3 mm2/s, (0.59 ±0.03) × 10-3 mm2/s, respectively. Significant differences of ADC values among the four grades were present (F=16.422, P=0.000). (2) The mean ADC value of the low-grade group was significantly higher than that of the high-grade group (t=5.738, P=0.000). Sensitivity and specificity of diagnosing the low-grade group was 88.9% and 83.3% respectively. There was a negative correlation between pathological grading and ADC value (r=-0.807, P<0.05). Conclusions: The ADC values of pT1b CCRCC have close correlation with pathological grading. They can be used to predict the degree of tumor malignancy preoperatively and guide surgical planning. (authors)

  7. Mechanical communication in cardiac cell synchronized beating

    Science.gov (United States)

    Nitsan, Ido; Drori, Stavit; Lewis, Yair E.; Cohen, Shlomi; Tzlil, Shelly

    2016-05-01

    Cell-cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours. The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical field stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modifications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.

  8. Molecular Mechanisms of Cell-cell Recognition

    Institute of Scientific and Technical Information of China (English)

    WANG Jia-Huai

    2004-01-01

    Cell-cell recognition is the key for multicellular organisms to survive. This recognition critically depends on protein-protein interactions from opposing cell surfaces. Recent structural investigations reveal unique features of these cell surface receptors and how they interact. These interactions are specific, but usually relatively weak, with more hydrophilic forces involved in binding. The receptors appear to have specialized ways to present their key interacting elements for ligand-binding from the cell surface. Cell-cell contacts are multivalent. A large group of cell surface molecules are engaged in interactions. Characteristic weak interactions make possible for each individual molecule pair within the group to constantly associate-dissociate-reassociate, such that the cell-cell recognition becomes a dynamic process. The immunological synapse is a good example for immune receptors to be orchestrated in performing immunological function in a collective fashion.

  9. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    Directory of Open Access Journals (Sweden)

    Cassali Geovanni D

    2010-02-01

    Full Text Available Abstract Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER, progesterone receptor (PgR, high molecular weight cytokeratin (34βE-12, E-cadherin, Ki-67, HER-2 and P53 was perfomed. Results Columnar cell lesions were identified in 67 (53.1% of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2% were without and 26 (38.8% with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%. Sixty (89.5% of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors. The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

  10. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    International Nuclear Information System (INIS)

    It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34βE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions

  11. The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

    International Nuclear Information System (INIS)

    Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

  12. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    International Nuclear Information System (INIS)

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  13. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  14. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    Science.gov (United States)

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  15. Ultrasonographic Pattern of Testicular Metastasis of Clear Cell Renal Cell Carcinoma with Pathological Correlation

    OpenAIRE

    Libert, Florent; Cabri-Wiltzer, Mathieu; Dardenne, Emmanuel; Draguet, Anne-Philippe; Puttemans, Thierry

    2016-01-01

    Two cases of testicular metastases of a clear cell renal cell carcinoma sharing a very similar ultrasonographic pattern are reported. The observed pattern – masses containing multiple tiny cyst-like areas – is very similar to that of a previously described ovarian metastasis of clear cell renal parenchymal tumor and can be explained by histopathologic features. Despite the small number of cases, this ultrasonographic pattern of testicular mass may be specific for metastasis of clear cell rena...

  16. Key Physical Mechanisms in Nanostructured Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dr Stephan Bremner

    2010-07-21

    The objective of the project was to study both theoretically and experimentally the excitation, recombination and transport properties required for nanostructured solar cells to deliver energy conversion efficiencies well in excess of conventional limits. These objectives were met by concentrating on three key areas, namely, investigation of physical mechanisms present in nanostructured solar cells, characterization of loss mechanisms in nanostructured solar cells and determining the properties required of nanostructured solar cells in order to achieve high efficiency and the design implications.

  17. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.

    Science.gov (United States)

    Veronese, F; Rotman, S; Smith, R N; Pelle, T D; Farrell, M L; Kawai, T; Benedict Cosimi, A; Colvin, R B

    2007-04-01

    The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. PMID:17286616

  18. Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission

    Directory of Open Access Journals (Sweden)

    Christine Gross

    2016-03-01

    Full Text Available The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1, a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1 polarized budding of HTLV-1 into synaptic clefts; and (2 cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation.

  19. [A pathologic study of adenohypophyseal growth hormone cells in the rabbit after severe burn].

    Science.gov (United States)

    Wu, J

    1989-06-01

    The growth hormone(GH), produced by the growth hormone cell in pars distalis of the adenohypophysis, acts on the sugar, protein and fat metabolism in various degrees. After trauma, the GH has relations with the energy supply, the maintenance of nitrogen balance, the tissue repair and the body resistance. However, pathological study on the GH cell after burn injury is rare in the literature so far. The purpose of the present investigation is to take a dynamic observation on the ultrastructural changes of the rabbit GH cell after napalm burn within one week. 46 male rabbits were used and divided into two groups, napalm burn group (N = 36) and control group (N = 10). The former is inflicted with 3rd degree burn covering 30% TBSA. The animals of former group were sacrificed at 3, 6, 12, 24, 48, 72, 96, 120, 168 hours postburn respectively. Using the light and electron microscopy and stereological method, the results revealed that: (1) the synthesis activity in GH cell was enhanced, the process of secretion was rapid, and the rate of granule maturation was increased; (2) the nude GH granules were found both in the sinusoids and the endothelial cells; (3) the newly formed mitochondria may be originated from the Golgi complex, and the newly formed Golgi complex from the reutilization of the plasma membrane components; (4) some endothelial cells manifested degeneration, and the others showed in active condition; (5) under the light microscopy, the distribution of the lower tint-phil GH cells had its regional-characteristics. PMID:2509038

  20. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle;

    2015-01-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National...... Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies...... vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients...

  1. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis; Isaacs, Adrian M; Nielsen, Jørgen E

    2012-01-01

    BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT...... and that the knockdown causes reversal of the abnormal endosomal phenotype observed in patient fibroblasts. CONCLUSIONS: This is the first description of a treatment that reverses the cellular pathology caused by mutant CHMP2B and suggests that RNA interference might be a feasible therapeutic strategy....... Furthermore, it provides the first proof of a direct link between the disease-causing mutation and the cellular phenotype in cells originating from CHMP2B mutation patients. Copyright © 2012 John Wiley & Sons, Ltd....

  2. TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

    Directory of Open Access Journals (Sweden)

    Elena Horna-Terrón

    2014-12-01

    Full Text Available Thioredoxin domain-containing 5 (TXNDC5 is a member of the protein disulfide isomerase family, acting as a chaperone of endoplasmic reticulum under not fully characterized conditions As a result, TXNDC5 interacts with many cell proteins, contributing to their proper folding and correct formation of disulfide bonds through its thioredoxin domains. Moreover, it can also work as an electron transfer reaction, recovering the functional isoform of other protein disulfide isomerases, replacing reduced glutathione in its role. Finally, it also acts as a cellular adapter, interacting with the N-terminal domain of adiponectin receptor. As can be inferred from all these functions, TXNDC5 plays an important role in cell physiology; therefore, dysregulation of its expression is associated with oxidative stress, cell ageing and a large range of pathologies such as arthritis, cancer, diabetes, neurodegenerative diseases, vitiligo and virus infections. Its implication in all these important diseases has made TXNDC5 a susceptible biomarker or even a potential pharmacological target.

  3. Molecular biological mechanism II. Molecular mechanisms of cell cycle regulation

    International Nuclear Information System (INIS)

    The cell cycle in eukaryotes is regulated by central cell cycle controlling protein kinase complexes. These protein kinase complexes consist of a catalytic subunit from the cyclin-dependent protein kinase family (CDK), and a regulatory subunit from the cyclin family. Cyclins are characterised by their periodic cell cycle related synthesis and destruction. Each cell cycle phase is characterised by a specific set of CDKs and cyclins. The activity of CDK/cyclin complexes is mainly regulated on four levels. It is controlled by specific phosphorylation steps, the synthesis and destruction of cyclins, the binding of specific inhibitor proteins, and by active control of their intracellular localisation. At several critical points within the cell cycle, named checkpoints, the integrity of the cellular genome is monitored. If damage to the genome or an unfinished prior cell cycle phase is detected, the cell cycle progression is stopped. These cell cycle blocks are of great importance to secure survival of cells. Their primary importance is to prevent the manifestation and heritable passage of a mutated genome to daughter cells. Damage sensing, DNA repair, cell cycle control and apoptosis are closely linked cellular defence mechanisms to secure genome integrity. Disregulation in one of these defence mechanisms are potentially correlated with an increased cancer risk and therefore in at least some cases with an increased radiation sensitivity. (orig.)

  4. Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. Materials and Methods: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. Results: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (pp = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). Conclusion: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less

  5. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro

    OpenAIRE

    Takakuni Maki; Yoko Takahashi; Nobukazu Miyamoto; Liang, Anna C.; Masafumi Ihara; Eng H Lo; Ken Arai

    2015-01-01

    Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs). However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM) promotes the in vitro differentiation of OPCs under pathological cond...

  6. Electrodeformation for single cell mechanical characterization

    Science.gov (United States)

    Chen, Jian; Abdelgawad, Mohamed; Yu, Liming; Shakiba, Nika; Chien, Wei-Yin; Lu, Zhe; Geddie, William R.; Jewett, Michael A. S.; Sun, Yu

    2011-05-01

    This paper presents the use of electrodeformation as a method for single cell mechanical characterization in which mechanical properties of SiHa and ME180 cells (two cervical cancer cell lines) were quantified. Cells were directly placed between two microelectrodes with a rectangular ac electric field applied, and cell deformation was recorded under certain experimental conditions. Numerical simulations were performed to model cell electrodeformation based on the Maxwell stress tensor formulation. In these simulations, effects of cell electrical property variations on their electrodeformed behavior were investigated. By comparing the measured morphological changes with those obtained from numerical simulations, we were able to quantify Young's modulus of SiHa cells (601 ± 183 Pa) and ME180 cells (1463 ± 649 Pa). These values were consistent with Young's modulus values (SiHa: 400 ± 290 Pa and ME180: 1070 ± 580 Pa) obtained from conventional micropipette aspiration.

  7. Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment.

    Science.gov (United States)

    Warram, Jason M; de Boer, Esther; van Dam, Gooitzen M; Moore, Lindsay S; Bevans, Stephanie L; Walsh, Erika M; Young, Erik S; Carroll, William R; Stevens, Todd M; Rosenthal, Eben L

    2016-04-01

    Accurately identifying close or positive margins in real-time permits re-excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence-guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease-specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence-guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab-IRDye800CW. In a preclinical model of luciferase-positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed-field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human-derived tumour tissues, as little as 0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2). When the sensitivity/specificity of fluorescence-guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence-guided surgery, the technique was highly accurate with a sensitivity of 91

  8. Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

    Directory of Open Access Journals (Sweden)

    Yanlin Wang

    Full Text Available Alzheimer's disease (AD is the most common type of senile dementia affecting elderly people. The processing of amyloid precursor protein (APP leading to the generation of β-amyloid (Aβ peptide contributes to neurodegeneration and development of AD pathology. The endocytic trafficking pathway, which comprises of the endosomes and lysosomes, acts as an important site for Aβ generation, and endocytic dysfunction has been linked to increased Aβ production and loss of neurons in AD brains. Since insulin-like growth factor-II (IGF-II receptor plays a critical role in the transport of lysosomal enzymes from the trans-Golgi network to endosomes, it is likely that the receptor may have a role in regulating Aβ metabolism in AD pathology. However, very little is known on how altered levels of the IGF-II receptor can influence the expression/function of various molecules involved in AD pathology. To address this issue, we evaluated the expression profiles of 87 selected genes related to AD pathology in mouse fibroblast MS cells that are deficient in murine IGF-II receptor and corresponding MS9II cells overexpressing ∼ 500 times the human IGF-II receptors. Our results reveal that an elevation in IGF-II receptor levels alters the expression profiles of a number of genes including APP as well as enzymes regulating Aβ production, degradation and clearance mechanisms. Additionally, it influences the expression of various lysosomal enzymes and protein kinases that are involved in Aβ toxicity. IGF-II receptor overexpression also alters expression of several genes involved in intracellular signalling as well as cholesterol metabolism, which play a critical role in AD pathology. The altered gene profiles observed in this study closely match with the corresponding protein levels, with a few exceptions. These results, taken together, suggest that an elevation in IGF-II receptor levels can influence the expression profiles of transcripts as well as proteins

  9. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    Directory of Open Access Journals (Sweden)

    John Martin Barrett

    2015-08-01

    Full Text Available Retinitis pigmentosa (RP is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity.We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2 in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-ß-glycyrrhetinic acid (18BGA, another gap junction blocker or flupirtine (Flu, a Kv7 potassium channel opener. All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses.Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic

  10. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice.

    Science.gov (United States)

    Barrett, John M; Degenaar, Patrick; Sernagor, Evelyne

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-β-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses

  11. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology.

    Science.gov (United States)

    Sagaert, Xavier; Tousseyn, Thomas; Yantiss, Rhonda K

    2012-12-15

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms. PMID:23443141

  12. Nondrowning Asphyxia in Veterinary Forensic Pathology: Suffocation, Strangulation, and Mechanical Asphyxia.

    Science.gov (United States)

    McEwen, B J

    2016-09-01

    Asphyxia in a forensic context refers to death by rapid cerebral anoxia or hypoxia due to accidental or nonaccidental injury. Death due to nondrowning asphyxia can occur with strangulation, suffocation, and mechanical asphyxia, each of which is categorized based on the mechanism of injury. Individuals dying due to various types of asphyxia may or may not have lesions, and even those lesions that are present may be due to other causes. The interpretation or opinion that death was due to asphyxia requires definitive and compelling evidence from the postmortem examination, death scene, and/or history. Beyond the postmortem examination, pathologists may be faced with questions of forensic importance that revolve around the behavioral and physiological responses in animals subjected to strangulation, suffocation, or mechanical asphyxia to determine if the animal suffered. While there is no prescriptive answer to these questions, it is apparent that, because of physiological and anatomical differences between humans and animals, for some mechanisms of asphyxia, consciousness is maintained for longer periods and the onset of death is later in animals than that described for people. Veterinary pathologists must be cognizant that direct extrapolation from the medical forensic literature to animals may be incorrect. This article reviews the terminology, classification, mechanisms, and lesions associated with asphyxial deaths in companion animals and highlights significant comparative differences of the response to various types of asphyxia in animals and people. PMID:27084399

  13. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    Science.gov (United States)

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  14. Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Purpose: To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer. Materials and methods: Twenty-three patients with squamous cell carcinoma of the oral tongue had PET–CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET–CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques. Results: Multiple MTV’s were associated with pathologic tumor volume; however the correlation was poor (R2 range 0.29–0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p = 0.0005) and tumor grade (p = 0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R2 = 0.63). Conclusions: Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET–CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

  15. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    Science.gov (United States)

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  16. BASEBALL THROWING MECHANICS AS THEY RELATE TO PATHOLOGY AND PERFORMANCE - A REVIEW

    Directory of Open Access Journals (Sweden)

    Rod Whiteley

    2007-03-01

    Full Text Available It is a commonly held perception amongst biomechanists, sports medicine practitioners, baseball coaches and players, that an individual baseball player's style of throwing or pitching influences their performance and susceptibility to injury. With the results of a series of focus groups with baseball managers and pitching coaches in mind, the available scientific literature was reviewed regarding the contribution of individual aspects of pitching and throwing mechanics to potential for injury and performance. After a discussion of the limitations of kinematic and kinetic analyses, the individual aspects of pitching mechanics are discussed under arbitrary headings: Foot position at stride foot contact; Elbow flexion; Arm rotation; Arm horizontal abduction; Arm abduction; Lead knee position; Pelvic orientation; Deceleration-phase related issues; Curveballs; and Teaching throwing mechanics. In general, popular opinion of baseball coaching staff was found to be largely in concordance with the scientific investigations of biomechanists with several notable exceptions. Some difficulties are identified with the practical implementation of analyzing throwing mechanics in the field by pitching coaches, and with some unquantified aspects of scientific analyses

  17. T cell migration, search strategies and mechanisms.

    Science.gov (United States)

    Krummel, Matthew F; Bartumeus, Frederic; Gérard, Audrey

    2016-03-01

    T cell migration is essential for T cell responses; it allows for the detection of cognate antigen at the surface of antigen-presenting cells and for interactions with other cells involved in the immune response. Although appearing random, growing evidence suggests that T cell motility patterns are strategic and governed by mechanisms that are optimized for both the activation stage of the cell and for environment-specific cues. In this Opinion article, we discuss how the combined effects of T cell-intrinsic and -extrinsic forces influence T cell motility patterns in the context of highly complex tissues that are filled with other cells involved in parallel motility. In particular, we examine how insights from 'search theory' can be used to describe T cell movement across an 'exploitation-exploration trade-off' in the context of activation versus effector function and lymph nodes versus peripheral tissues. PMID:26852928

  18. Early Biomarkers in 1H Nuclear Magnetic Resonance Spectroscopy of Striatal Pathological Mechanisms after Acute Carbon Monoxide Poisoning in Rats

    Institute of Scientific and Technical Information of China (English)

    GUAN Li; LI Zong Yang; ZHANG Yan Lin; CONG Cui Cui; ZHAO Jin Yuan

    2015-01-01

    Objective In vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain. Methods We conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning. Results Compared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning. Conclusion The present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.

  19. Parkinson's disease: Studies on the pathology of the disease and the mechanism of action of the neurotoxin MPTP

    International Nuclear Information System (INIS)

    In humans and animals, exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) causes certain clinical, pathological, and neurochemical features of Parkinson's disease (PD). MPTP is metabolized in the brain by monoamine oxidase (MAOb) to 1-methyl-4-phenylpyridine (MPP+), which is selectively accumulated and concentrated by high affinity uptake mechanisms into catecholamine neurons. We have demonstrated high affinity binding of MPP+ to neuromelanin which may result in a toxic intraneuronal sequestration of MPP+. The involvement of neuromelanin is further supported by the demonstration that monkeys pretreated with chloroquine prior to the administration of MPTP are protected from MPTP induced neurotoxicity. Decreases in serotonin levels have been reported in the brains and spinal fluid of patients with both Parkinson's and Alzheimer's disease. In an effort to investigate the pathology of serotonin neurons in postmortem brain tissue from Parkinson's and Alzheimer's patients, [3H]citalopram was characterized as a means of labeling serotonin uptake sites present on serotonin terminals

  20. Pathologic characteristics of resected squamous cell carcinoma of the trachea: prognostic factors based on an analysis of 59 cases.

    NARCIS (Netherlands)

    Honings, J.; Gaissert, H.A.; Ruangchira-Urai, R.; Wain, J.C.; Wright, C.D.; Mathisen, D.J.; Mark, E.J.

    2009-01-01

    While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including

  1. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology

    OpenAIRE

    2012-01-01

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 d...

  2. Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission.

    Science.gov (United States)

    Gross, Christine; Thoma-Kress, Andrea K

    2016-01-01

    The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4⁺ T-cells, and to a lesser extent, CD8⁺ T-cells, dendritic cells, and monocytes. Efficient infection of CD4⁺ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4⁺ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID:27005656

  3. Identification of the cellular mechanisms undelying the contribution of stress and glucocorticoids to Alzheimer's disease pathology

    OpenAIRE

    Sotiropoulos, Ioannis

    2006-01-01

    Clinical evidence suggests the involvement of stress and glucocorticoids (GC) in the etiopathogenesis of Alzheimer’s disease (AD), a disease marked by severe memory impairments as well as alterations in mood and emotional state. The experiments described in this dissertation represent an attempt to establish the cellular mechanisms through which stress and GC may impact on the development of AD. These studies focused on the hippocampus and prefrontal cortex (PFC), brain areas that are severel...

  4. BASEBALL THROWING MECHANICS AS THEY RELATE TO PATHOLOGY AND PERFORMANCE - A REVIEW

    OpenAIRE

    Rod Whiteley

    2007-01-01

    It is a commonly held perception amongst biomechanists, sports medicine practitioners, baseball coaches and players, that an individual baseball player's style of throwing or pitching influences their performance and susceptibility to injury. With the results of a series of focus groups with baseball managers and pitching coaches in mind, the available scientific literature was reviewed regarding the contribution of individual aspects of pitching and throwing mechanics to potential for injury...

  5. Molecular mechanisms of fibroblast growth factor signaling in physiology and pathology.

    Science.gov (United States)

    Belov, Artur A; Mohammadi, Moosa

    2013-06-01

    Fibroblast growth factors (FGFs) signal in a paracrine or endocrine fashion to mediate a myriad of biological activities, ranging from issuing developmental cues, maintaining tissue homeostasis, and regulating metabolic processes. FGFs carry out their diverse functions by binding and dimerizing FGF receptors (FGFRs) in a heparan sulfate (HS) cofactor- or Klotho coreceptor-assisted manner. The accumulated wealth of structural and biophysical data in the past decade has transformed our understanding of the mechanism of FGF signaling in human health and development, and has provided novel concepts in receptor tyrosine kinase (RTK) signaling. Among these contributions are the elucidation of HS-assisted receptor dimerization, delineation of the molecular determinants of ligand-receptor specificity, tyrosine kinase regulation, receptor cis-autoinhibition, and tyrosine trans-autophosphorylation. These structural studies have also revealed how disease-associated mutations highjack the physiological mechanisms of FGFR regulation to contribute to human diseases. In this paper, we will discuss the structurally and biophysically derived mechanisms of FGF signaling, and how the insights gained may guide the development of therapies for treatment of a diverse array of human diseases. PMID:23732477

  6. Two-domain mechanics of a spherical, single chamber heart with applications to specific cardiac pathologies

    OpenAIRE

    Puwal, Steffan

    2013-01-01

    Continuum approximations of tissue consider responses averaged over many cells in a region. This simplified approach allows consideration of macroscopic effects, such as deformation or action potential propagation. A bidomain (sometimes known as biphasic) approach retains the macroscopic character of a continuum approximation while allowing one to consider microscopic effects; novel behavior arising from interactions between the intracellular and extracellular spaces can also be noted. I cons...

  7. Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

    OpenAIRE

    Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

    2011-01-01

    The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MD...

  8. Mechanisms of DNA uptake by cells

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1977-01-01

    Three categories of cellular uptake of DNA can be distinguished. First, in the highly transformable bacteria, such as Diplococcus pneumoniae, Haemophilus influenzae and Bacillus subtilis, elaborate mechanisms of DNA transport have evolved, presumably for the purpose of genetic exchange. These mechanisms can introduce substantial amounts of DNA into the cell. Second, methods have been devised for the forced introduction of DNA by manipulation of bacterial cells under nonphysiological conditions. By such means small but significant amounts of DNA have been introduced into various bacteria, including Escherichia coli. Third, mammalian cells are able to take up biologically active DNA. This has been most clearly demonstrated with viral DNA, although the mechanism of uptake is not well understood. The intention, here, is to survey current understanding of the various mechanisms of DNA uptake. A review of experience with the bacterial systems may throw some light on the mammalian system and lead to suggestions for enhancing DNA uptake by mammalian cells.

  9. Oxyphil Cell Parathyroid Adenomas Causing Primary Hyperparathyroidism: a Clinico-Pathological Correlation.

    Science.gov (United States)

    Howson, Pamela; Kruijff, Schelto; Aniss, Ahmad; Pennington, Thomas; Gill, Anthony J; Dodds, Tristan; Delbridge, Leigh W; Sidhu, Stan B; Sywak, Mark S

    2015-09-01

    Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically silent. It has been our clinical impression that these adenomas present more often than previously thought and may manifest a more severe form of primary hyperparathyroidism than classical adenoma. The aim of this study was to describe the incidence and clinical presentation of OPA. An observational case-control study was undertaken. The study group comprised patients undergoing parathyroidectomy for PHPT where the final pathology confirmed OPA. The controls were made up of an age- and sex-matched group of patients having parathyroidectomy in the same time period where the final pathology confirmed a classical or non-oxyphil adenoma. OPA were defined as parathyroid tumours containing >75% oxyphilic cells. The OPA cases were obtained by reviewing all histopathology slides over an 11-year period (2002-12) where the reports contained the words 'oxyphil' or 'oxyphilic' parathyroid adenomas. These were then reviewed by two independent pathologists to confirm a diagnosis of OPA. The primary outcome measures were preoperative serum calcium and parathyroid hormone (PTH) levels. Secondary outcome measures were symptoms at presentation, accuracy of preoperative localization studies, parathyroid gland weight following surgery, and type of surgery undertaken. In the period 2002-2012, 2739 patients underwent surgery for PHPT. Following pathological review, 91 cases were confirmed as being OPA and formed the study group. A control group (n = 91) from the same period was selected following matching on the basis of age at presentation and sex. OPA were associated with higher preoperative serum calcium (10.84 versus 10.48 mg/dL, p < 0.001) and parathyroid hormone (139 versus 64 ng/L, p < 0.001). At presentation, a lower proportion of OPA cases had asymptomatic disease (15 versus 29%, p = 0.03). There was

  10. Pathological evaluation of ganglion cells in biopsies from upper side of the dentate line in patients with perianal problems

    Directory of Open Access Journals (Sweden)

    Marjan Joudi

    2014-07-01

    Full Text Available Introduction: Constipation is one of the most common complaints of individuals, which may present with complication like hemorrhoid and fissure. Hirschsprung is a disease presenting with chronic constipation and its diagnosis may be delayed until adulthood. It is diagnosed by biopsies from anorectal transitional zone. This study aimed to evaluate the association between Hirschsprung and anorectal problems. Method: Sixty three patients with anorectal problems who underwent surgery enrolled in this study. Some consecutive biopsies were obtained from anal canal at 2, 4 and 6 cm above the dentate line. Biopsies were assessed for ganglion cells changes. Patients' data and biopsies results were analyzed with SPSS version18. Results: Out of 63 patients 29 (46 % patients were female and 34 (54 % were male with the mean of 32.65 ± 13.73 years. Fifty six (73 % patients complained from constipation with the mean time of 57.65 ± 45.21 months. Aganglionic zone were reported in six patients with the mean length of 43.33 mm. There was not any relation between anal ganglion cells pathology and constipation (p=0.363, but there was a significant relation between duration of constipation and pathologic changes (p=0.001. The ratio of constipation duration to age was related to anal ganglion cell pathology (p=0.001. Hemorrhoid degree was also affected anal ganglion cells pathology (p=0.037. Conclusion: The relation between Hirschsprung's disease and anorectal problems in adults were significant. The pathologic findings were more presented in younger patients, and those with longer history of constipation and lower degree hemorrhoids. Key words: Anal ganglion cells, Hemorrhoids, Constipation  

  11. Nanodiamond internalization in cells and the cell uptake mechanism

    International Nuclear Information System (INIS)

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed

  12. Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

    Directory of Open Access Journals (Sweden)

    Aruna K.R. Gupta

    2016-01-01

    Full Text Available Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK, 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK, 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05, while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV, i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained.

  13. Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

    Science.gov (United States)

    Gupta, Aruna K.R.; Gupta, Roopam K.R.

    2016-01-01

    Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK) and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK), 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK), 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK) cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05), while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV), i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained. PMID:27121519

  14. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

    2014-09-01

    The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

  15. Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages.

    Science.gov (United States)

    Michel, Jean-Baptiste; Martin-Ventura, José Luis; Nicoletti, Antonino; Ho-Tin-Noé, Benoit

    2014-06-01

    Atherothrombotic diseases are still major causes of inability and mortality and fighting atherothrombosis remains a public health priority. The involvement of repeated intraplaque haemorrhages (IPH) in the evolution of atherothrombotic lesions towards complications was proposed as early as 1936. This important topic has been recently revisited and reviewed. Histological observations have been corroborated by magnetic resonance imaging (MRI) of human carotid atheroma, identifying IPH as the main determinant of plaque evolution towards rupture. Beside the intimal integration of asymptomatic luminal coagulum, inward sprouting of neovessels from the adventitia towards the plaque, is one source of IPH in human atheroma. We recently described that directed neo-angiogenesis from the adventitia towards the plaque, across the media, is initiated by lipid mediators generated by the plaque on the luminal side, outwardly convected to the medial VSMCs. Subsequent stimulation of VSMC PPAR-γ receptors induces VEGF expression which causes centripetal sprouting of adventitial vessels. However, this neovascularization is considered to be immature and highly susceptible to leakage. The main cellular components of IPH are Red Blood Cells (RBCs), which with their haemoglobin content and their cell membrane components, particularly enriched in unesterified cholesterol, participate in both the oxidative process and cholesterol accumulation. The presence of iron, glycophorin A and ceroids provides evidence of RBCs. IPH also convey blood leukocytes and platelets and are sites prone to weak pathogen contamination. Therefore prevention and treatment of the biological consequences of IPH pave the way to innovative preventive strategies and improved therapeutic options in human atherothrombotic diseases. PMID:24726899

  16. The mechanics of activated semitendinosus are not representative of the pathological knee joint condition of children with cerebral palsy.

    Science.gov (United States)

    Ateş, Filiz; Temelli, Yener; Yucesoy, Can A

    2016-06-01

    Characteristic cerebral palsy effects in the knee include a restricted joint range of motion and forcefully kept joint in a flexed position. To show whether the mechanics of activated spastic semitendinosus muscle are contributing to these effects, we tested the hypothesis that the muscle's joint range of force exertion is narrow and force production capacity in flexed positions is high. The isometric semitendinosus forces of children with cerebral palsy (n=7, mean (SD)=7years (8months), GMFCS levels III-IV, 12 limbs tested) were measured intra-operatively as a function of knee angle, from flexion (120°) to full extension (0°). Peak force measured in the most flexed position was considered as the benchmark. However, peak force (mean (SD)=112.4N (54.3N)) was measured either at intermediate or even full knee extension (three limbs) indicating no narrow joint range of force exertion. Lack of high force production capacity in flexed knee positions (e.g., at 120° negligible or below 22% of the peak force) was shown except for one limb. Therefore, our hypothesis was rejected for a vast majority of the limbs. These findings and those reported for spastic gracilis agree, indicating that the patients' pathological joint condition must rely on a more complex mechanism than the mechanics of individual spastic muscles. PMID:27128957

  17. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y. [Department of Radiology, Mayo Clinic, 200 First Street SW, MN 55905, Rochester (United States)

    2003-12-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  18. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    International Nuclear Information System (INIS)

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  19. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    Science.gov (United States)

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  20. The Mechanics of Mitotic Cell Rounding

    OpenAIRE

    Stewart, Martin

    2012-01-01

    During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round, in a process known as mitotic cell rounding (MCR). The aim of this thesis was to critically examine the physical and biological basis of MCR. The experimental part of this thesis employed a combined optical microscope-atomic force microscope (AFM) setup in conjunction with flat tipless cantilevers to analyze cell mechanics, shape and volume. To this end, two AFM assays were developed: the ...

  1. Renal cell carcinoma of clear type: correlation of CT features with tumor size, architectural patterns, and pathologic staging

    International Nuclear Information System (INIS)

    The purpose of this study was to report the CT findings of renal cell carcinoma of clear type (RCCCT) and to determine if there are characteristic morphologic features in RCCCT with respect to tumor size, architectural patterns, and pathologic stage. The CT scans of 35 patients with RCCCT were reviewed retrospectively. The CT findings (tumor size, attenuation patterns, presence of calcifications, encapsulation, margins of neoplasms, venous involvement by neoplasms) were correlated with tumor size, architectural patterns, and pathologic staging. Of the 35 neoplasms, 28 (80 %) were solid, 4 (11 %) were papillary, and 3 (9 %) were cystic. Complete encapsulation was more frequent in lower pathologic stages (40 % in stages 1 and 2 vs 0 % in stages 3 and 4; p < 0.05). Venous involvement was less frequent with completely encapsulated neoplasms (0 of 10, 0 %) than with incompletely or nonencapsulated neoplasms (8 of 25, 32 %; p < 0.05). Encapsulated RCCCT are more likely to have lower pathologic stage. Nonencapsulated neoplasms are more likely to have a higher pathologic stage. (orig.). With 4 figs., 3 tabs

  2. Investigating cell mechanics with atomic force microscopy.

    Science.gov (United States)

    Haase, Kristina; Pelling, Andrew E

    2015-03-01

    Transmission of mechanical force is crucial for normal cell development and functioning. However, the process of mechanotransduction cannot be studied in isolation from cell mechanics. Thus, in order to understand how cells 'feel', we must first understand how they deform and recover from physical perturbations. Owing to its versatility, atomic force microscopy (AFM) has become a popular tool to study intrinsic cellular mechanical properties. Used to directly manipulate and examine whole and subcellular reactions, AFM allows for top-down and reconstitutive approaches to mechanical characterization. These studies show that the responses of cells and their components are complex, and largely depend on the magnitude and time scale of loading. In this review, we generally describe the mechanotransductive process through discussion of well-known mechanosensors. We then focus on discussion of recent examples where AFM is used to specifically probe the elastic and inelastic responses of single cells undergoing deformation. We present a brief overview of classical and current models often used to characterize observed cellular phenomena in response to force. Both simple mechanistic models and complex nonlinear models have been used to describe the observed cellular behaviours, however a unifying description of cell mechanics has not yet been resolved. PMID:25589563

  3. Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

    Directory of Open Access Journals (Sweden)

    Maryam Mohammadian

    2016-01-01

    Full Text Available Objective(s:Bone marrow-derived mesenchymal stem cells (BMSCs have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized, asthma group (animals were sensitized by ovalbumin, asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs. BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU. After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC count in bronchoalveolar lavage (BAL fluid were evaluated. Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.

  4. The role of biofluid mechanics in the assessment of clinical and pathological observations: sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008 Pasadena, California

    NARCIS (Netherlands)

    M. Siebes; Y. Ventikos

    2010-01-01

    Biofluid mechanics is increasingly applied in support of diagnosis and decision-making for treatment of clinical pathologies. Exploring the relationship between blood flow phenomena and pathophysiological observations is enhanced by continuing advances in the imaging modalities, measurement techniqu

  5. Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available OBJECTIVES: To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA first pass and delayed enhancement patterns with histopathological changes. MATERIALS AND METHODS: Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9 and II (n = 9 then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg and gadolinium-based macromolecular agent (P792, 15 µmol/kg, respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF staining were performed for infarct characterization. RESULTS: Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium. CONCLUSIONS: Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd

  6. Mast Cell-Mediated Mechanisms of Nociception

    Science.gov (United States)

    Aich, Anupam; Afrin, Lawrence B.; Gupta, Kalpna

    2015-01-01

    Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner. PMID:26690128

  7. Mast Cell-Mediated Mechanisms of Nociception

    Directory of Open Access Journals (Sweden)

    Anupam Aich

    2015-12-01

    Full Text Available Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner.

  8. Cell mechanics measured with Atomic force microscopy

    International Nuclear Information System (INIS)

    Full text: In this contribution, I would like to present recent results about cell mechanics obtained with atomic force microscopy and its relation with basic soft matter science. We will present a novel way to obtain viscoelastic properties (Young modulus, relaxation time and viscosity) of breast cancer cells based on stress relaxation and creep measurements. Additionally we will show the influence of applied stress on red blood cell shape. The importance of such type of measurements on soft matter physics, cell biology, and biomedical science. (author)

  9. Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies

    Directory of Open Access Journals (Sweden)

    S. Salvioli

    2007-01-01

    Full Text Available Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

  10. Defense mechanisms of normal and tumor cells

    International Nuclear Information System (INIS)

    This paper reviews the protective systems of normal and tumor cells against chemical and radiation injury. The glutathione redox cycle is an important cell defense system that can be compromised by various chemical modifiers. Acute cell injury can involve the glutathione pools of both the cytosol and the mitochondria. Intracellular calcium may have a role in cell death following acute cell injury but extracellular calcium does not seem to initiate the events leading to cell death. Changes in the glutathione redox status affects the distribution of intracellular calcium and the protein thiol-disulfide redox status. Formation of glutathione protein-mixed disulfides is discussed in terms of a possible protective mechanism against oxidative injury. 46 references

  11. Mammalian cell transformation: Mechanisms of carcinogenesis and assays for carcinogens

    International Nuclear Information System (INIS)

    This book contains nine sections, each consisting of several papers. The section titles are: Molecular Changes in Cell Transformation; Differentiation, Growth Control, and Cell Transformation; Mutagenesis and Cell Transformation; Tumor Promotion and Cell Transformation; Mechanisms of Transformation of Human Fibroblasts; Mechanisms of Transformation of Epithelial Cells; Mechanisms of C3H 10T12 Cell Transformation; Mechanisms of Radiation-Induced Cell Transformation; and Use of Cell Transformation Assays for Carcinogen Testing

  12. NKG2D Mediates NK Cell Hyperresponsiveness and Influenza-Induced Pathologies in a Mouse Model of COPD

    OpenAIRE

    Wortham, Brian W.; Eppert, Bryan L.; Motz, Greg T.; Flury, Jennifer L.; Orozco-Levi, Mauricio; Hoebe, Kasper; Panos, Ralph J.; Maxfield, Melissa; Glasser, Stephan W.; Senft, Albert P; Raulet, David H.; Borchers, Michael T.

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or toll-like receptor ligands....

  13. Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng-De; Wang; Xin-Rong; Wang; Chao-Yang; Wang; Yi-Jun; Tang; Ming-Wen; Hao

    2015-01-01

    Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

  14. Cell Mechanosensitivity: Mechanical Properties and Interaction with Gravitational Field

    Directory of Open Access Journals (Sweden)

    I. V. Ogneva

    2013-01-01

    Full Text Available This paper addressed the possible mechanisms of primary reception of a mechanical stimulus by different cells. Data concerning the stiffness of muscle and nonmuscle cells as measured by atomic force microscopy are provided. The changes in the mechanical properties of cells that occur under changed external mechanical tension are presented, and the initial stages of mechanical signal transduction are considered. The possible mechanism of perception of different external mechanical signals by cells is suggested.

  15. Mechanically activated artificial cell by using microfluidics

    Science.gov (United States)

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-01-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology. PMID:27610921

  16. Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

  17. Pathological Role of Tonsillar B Cells in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Yusuke Suzuki

    2011-01-01

    Full Text Available Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.

  18. An historical perspective on cell mechanics.

    Science.gov (United States)

    Pelling, Andrew E; Horton, Michael A

    2008-04-01

    The physical properties of the protoplasm have long been of interest, and today, several intricate methods, including atomic force microscopy, have been employed in studies of cellular mechanics. However, many current concepts and experimental approaches actually have their beginnings over 300 years ago. Unfortunately, these pioneering studies have been all but forgotten. In this paper, we have reviewed some of the early literature on cellular mechanics to place modern work within an historical framework. It is clear that with current nanoscience approaches, modern experiments employing cell indentation, manipulation, particle rheology and micro- or nano-needle poking are now quantifying mechanical properties which were only qualitatively described 100 years ago. Aside from the variety of approaches our predecessors have employed to understand cellular mechanics, we feel an understanding of the past will help to propel nanoscience into the future. As nanophysiology and nanomedicine are developing, we as a community should take time to consider the early roots of these fields. PMID:18064487

  19. Ultrastructural changes in aster yellows phytoplasma affected Limonium sinuatum Mill. plants II. Pathology of cortex parenchyma cells

    Directory of Open Access Journals (Sweden)

    Anna Rudzińska-Langwald

    2014-02-01

    Full Text Available In Limonium sinuatum Mill, plants with severe symptoms of aster yellows infection phytoplasmas were present not only in the phloem but also in some cortex parenchymas cells. These parenchyma cells were situated at some distance from the conducting bundles. The phytoplasmas were observed directly in parenchyma cells cytoplasm. The number of phytoplasmas present in each selected cell varies. The cells with a small number of phytoplasmas show little pathological changes compared with the unaffected cells of the same zone of the stem as well with the cells of healthy plants. The cells filled with a number of phytoplasmas had their protoplast very much changed. The vacuole was reduced and in the cytoplasm a reduction of the number of ribosomes was noted and regions of homogenous structure appeared. Mitochondria were moved in the direction of the tonoplast and plasma membrane. Compared to the cells unaffected by phytoplasma, the mitochondria were smaller and had an enlarged cristae internal space. The chloroplasts from affected cells had a very significant reduction in size and the tylacoids system had disappeared. The role of these changes for creating phytoplasma friendly enviroment is discused.

  20. Pathological Mobilization and Activities of Dendritic Cells in Tumor-Bearing Hosts: Challenges and Opportunities for Immunotherapy of Cancer

    Science.gov (United States)

    Tesone, Amelia J.; Svoronos, Nikolaos; Allegrezza, Michael J.; Conejo-Garcia, Jose R.

    2013-01-01

    A common characteristic of solid tumors is the pathological recruitment of immunosuppressive myeloid cells, which in certain tumors includes dendritic cells (DCs). DCs are of particular interest in the field of cancer immunotherapy because they induce potent and highly specific anti-tumor immune responses, particularly in the early phase of tumorigenesis. However, as tumors progress, these cells can be transformed into regulatory cells that contribute to an immunosuppressive microenvironment favoring tumor growth. Therefore, controlling DC phenotype has the potential to elicit effective anti-tumor responses while simultaneously weakening the tumor’s ability to protect itself from immune attack. This review focuses on the dual nature of DCs in the tumor microenvironment, the regulation of DC phenotype, and the prospect of modifying DCs in situ as a novel immunotherapeutic approach. PMID:24339824

  1. Mechanics and polarity in cell motility

    Science.gov (United States)

    Ambrosi, D.; Zanzottera, A.

    2016-09-01

    The motility of a fish keratocyte on a flat substrate exhibits two distinct regimes: the non-migrating and the migrating one. In both configurations the shape is fixed in time and, when the cell is moving, the velocity is constant in magnitude and direction. Transition from a stable configuration to the other one can be produced by a mechanical or chemotactic perturbation. In order to point out the mechanical nature of such a bistable behaviour, we focus on the actin dynamics inside the cell using a minimal mathematical model. While the protein diffusion, recruitment and segregation govern the polarization process, we show that the free actin mass balance, driven by diffusion, and the polymerized actin retrograde flow, regulated by the active stress, are sufficient ingredients to account for the motile bistability. The length and velocity of the cell are predicted on the basis of the parameters of the substrate and of the cell itself. The key physical ingredient of the theory is the exchange among actin phases at the edges of the cell, that plays a central role both in kinematics and in dynamics.

  2. Mechanical injury and repair of cells

    Science.gov (United States)

    Miyake, Katsuya; McNeil, Paul L.

    2003-01-01

    OBJECTIVE: To concisely review the field of cell plasma membrane disruption (torn cell surface) and repair. MAIN POINTS: Plasma membrane disruption is a common form of cell injury under physiologic conditions, after trauma, in certain muscular dystrophies, and during certain forms of clinical intervention. Rapid repair of a disruption is essential to cell survival and involves a complex and active cell response that includes membrane fusion and cytoskeletal activation. Tissues, such as cardiac and skeletal muscle, adapt to a disruption injury by hypertrophying. Cells adapt by increasing the efficiency of their resealing response. CONCLUSION: Plasma membrane disruption is an important cellular event in both health and disease. The disruption repair mechanism is now well understood at the cellular level, but much remains to be learned at the molecular level. Cell and tissue level adaptational responses to the disruption either prevent its further occurrence or facilitate future repairs. Therapeutically useful drugs might result if, using this accumulating knowledge, chemical agents can be developed that can enhance repair or adaptive responses.

  3. Mechanisms of DNA Repair in Mammalian Cells

    International Nuclear Information System (INIS)

    The authors examined DNA synthesis in cultured mammalian cells after irradiation with X-rays or ultraviolet light, using equilibrium density gradient and autoradiographic techniques. Unscheduled DNA synthesis (the synthesis of DNA by cells not in S phase of the cell cycle) occurs at doses of u.v. where survival is greater than 90% and at doses of X-rays where survival is of the order of 50%. At higher doses it was established that repair replication (insertion of precursors into parental strands of DNA ) occurs in these cells, and it is presumed that these two phenomena (unscheduled DNA synthesis and repair replication) are manifestations of the same repair process. During the time that these phenomena occur, very little degradation of DNA takes place, as measured by appearance of prelabelled components of DNA in the medium or in the acid soluble portion of the cell. This is in direct contrast to the situation in bacteria, in which extensive degradation of DNA occurs after irradiation, presumably as a result of enzymatic processes that remove many undamaged bases in addition to the ones injured by the irradiation. A small amount of radioactivity does appear in the acid soluble portion and in the media from prelabelled cells from both irradiated and control mammalian cell cultures. The amount in the medium from irradiated cultures is slightly, but significantly, greater than that from controls; thus there does appear to be a very low level of degradation of DNA in irradiated mammalian cells. These data indicate that the repair of DNA in mammalian cells does not involve the same steps as those that occur in bacteria. The results suggest instead that mammalian cells have a much more specific system for repair, which involves excision of only the damaged portion of the DNA. Possible mechanisms of repair of mammalian DNA are considered. (author)

  4. An Important Method in the Investigation of Vascular Pathologies: Endothelial Cell Culture

    Directory of Open Access Journals (Sweden)

    Yusufhan Yazır

    2012-12-01

    Full Text Available Endothelial cells line the interior surface of blood vessels and form an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells are involved in many aspects of vascular biology, including barrier function, vasoconstriction, coagulation and inflamation. The endothelial cells in different organs have different functions and surface phenotype. These cells express prostoglandin-I2, platelet activating factor, collagen, endothelin-1, laminin, fibronectin and growth factors including platelet derived growth factor, fibroblast growth factor. İn the cell culture, cells can be isolated, maintened and proliferate in the laboratory conditions. The techniques of the cell culture have allowed scientists to use the cells in vitro for experimental studies, such as the production of vaccine, antibody and enzime, drug research, cell-cell interactions. Human umbilical vein endothelial cell is a good source for endothelial cell, because it is cheaper, easy to find and has the basic features of the normal endothelial cells.

  5. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Directory of Open Access Journals (Sweden)

    Hymie Anisman

    2014-10-01

    Full Text Available Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs, and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF. Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool and BDNF (as a protective factor influenced neuronal outcomes Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide and chronic stressor challenges upon subventricular zone adult neurogenesis and the iPSC-derived neural progenitor cells alone blunted the stressor induced corticosterone response. Moreover, our findings also indicate that mature dopamine producing neurons can also be generated using iPSC procedures and these cells appeared to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology.

  6. Cell Mechanosensitivity: Mechanical Properties and Interaction with Gravitational Field

    OpenAIRE

    I. V. Ogneva

    2013-01-01

    This paper addressed the possible mechanisms of primary reception of a mechanical stimulus by different cells. Data concerning the stiffness of muscle and nonmuscle cells as measured by atomic force microscopy are provided. The changes in the mechanical properties of cells that occur under changed external mechanical tension are presented, and the initial stages of mechanical signal transduction are considered. The possible mechanism of perception of different external mechanical signals by c...

  7. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

    International Nuclear Information System (INIS)

    To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC). This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUVmax) and mean SUV of the liver and spleen (liver and spleen SUVmean) were measured by two independent observers. Tumour SUVmax, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades. Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77 %, respectively, for observer 1, and 79, 88, 85, and 83 %, respectively, for observer 2. The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC. (orig.)

  8. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Yoshifumi; Goshima, Satoshi; Kondo, Hiroshi; Watanabe, Haruo; Kawada, Hiroshi; Kawai, Nobuyuki; Tanahashi, Yukichi [Gifu University Hospital, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University Hospital, Department of Radiology, Gifu (Japan); Gifu University Hospital, Department of Radiology Services, Gifu (Japan); Suzui, Natsuko [Gifu University Hospital, Department of Pathology, Gifu (Japan); Hirose, Yoshinobu [Osaka Medical College, Department of Pathology, Osaka (Japan); Matsunaga, Kengo [Kizawa Memorial Hospital, Department of Pathology, Minokamo (Japan); Nishibori, Hironori [Kizawa Memorial Hospital, Department of Radiology, Minokamo (Japan); Bae, Kyongtae T. [University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States)

    2015-10-15

    To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC). This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUV{sub max}) and mean SUV of the liver and spleen (liver and spleen SUV{sub mean}) were measured by two independent observers. Tumour SUV{sub max}, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades. Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77 %, respectively, for observer 1, and 79, 88, 85, and 83 %, respectively, for observer 2. The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC. (orig.)

  9. Mechanical properties of hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Gang Zhang; Mian Long; Zhe-Zhi Wu; Wei-Qun Yu

    2002-01-01

    of hepatocytes generallyincreased or tended to increase while those of HCC cellsdecreased. HTC cells with 72.1% ofG1 phase and 98. 9 % ofS phase were achieved and high K1, k2 value and low μvalue were the general characlteristics of HTC cells. G1phase cells had higher K1 value and lower tμ value than Sphase cells had, and G1 phase HTC cells had strongeradhesive forces [(275.9±232.8) x 10-10N] than S phase cells[(161.2± 120.4) x l0-10N, P<0.001).CONCLUSION: The difference in both the pattern and themagnitude of the effect of cytoskeletal perturbing agent onthe viscoelastic properties between HCC cells andhepatocytes may reflect differencss in the state of thecytusieleton structure and function and in the sensitivity toperturbing agent treatment between trinse two types of cells.Change in the viscoelastic properties of cancer cells mayaffect significantly tumor cell invasion and metastasis as wellas interactions between tumor cells and their micro-mechanical environments.

  10. Bacterial cell curvature through mechanical control of cell growth

    DEFF Research Database (Denmark)

    Cabeen, M.; Charbon, Godefroid; Vollmer, W.;

    2009-01-01

    The cytoskeleton is a key regulator of cell morphogenesis. Crescentin, a bacterial intermediate filament-like protein, is required for the curved shape of Caulobacter crescentus and localizes to the inner cell curvature. Here, we show that crescentin forms a single filamentous structure that coll...... cell wall insertion to produce curved growth. Our study suggests that bacteria may use the cytoskeleton for mechanical control of growth to alter morphology......The cytoskeleton is a key regulator of cell morphogenesis. Crescentin, a bacterial intermediate filament-like protein, is required for the curved shape of Caulobacter crescentus and localizes to the inner cell curvature. Here, we show that crescentin forms a single filamentous structure that...

  11. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Science.gov (United States)

    Liu, Gele; Rustom, Nazneen; Litteljohn, Darcy; Bobyn, Jessica; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

    2014-01-01

    Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes. Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide) and chronic stressor challenges upon subventricular zone adult neurogenesis, and the iPSC-derived neural progenitor cells alone blunted the stressor-induced corticosterone response. Moreover, our findings indicate that mature dopamine producing neurons can be generated using iPSC procedures and appear to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology. PMID:25352778

  12. Quantitation and renewal of alveolar and bronchiolar cell populations of rat lungs. Changes during some pathological processes

    International Nuclear Information System (INIS)

    The various cells of alveolar and bronchiolar tissues of rat lungs were studied qualitatively and quantitatively. In physiological conditions, the renewal rate of the cell populations is low and the frequency of the various cell types is constant. This stability, especially at the level of the alveolar tissue, was also found during the latency period and the development of radiation-induced lung cancers. A particular cellular population was demonstrated: marginated leukocyte pool at the level of the pulmonary circulation. This pool was different both qualitatively and quantitatively from the leukocytes of the systemic circulation and, in physiological conditions, behaved as a cellular reservoir of monocytes chiefly re-distributed according to the body needs. In pathological conditions, its fast migration contributed to the defence of the alveolar medium. A quantitative study of the renewal of alveolar macrophages showed that under 1 p. cent of the marginated leukocyte pool is used daily to keep up this population. This fraction undergoes a maturation stage by cellular division within the endoalveolar medium. In some pathological conditions, this division can be completely inhibited

  13. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro

    Directory of Open Access Journals (Sweden)

    Takakuni Maki

    2015-07-01

    Full Text Available Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs. However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM promotes the in vitro differentiation of OPCs under pathological conditions. Primary OPCs were prepared from neonatal rat brains, and differentiated into myelin-basic-protein expressing oligodendrocytes over time. This in vitro OPC differentiation was inhibited by prolonged chemical hypoxic stress induced by non-lethal CoCl2 treatment. However, AM promoted the OPC differentiation under the hypoxic stress conditions, and the AM receptor antagonist AM22–52 canceled the AM-induced OPC differentiation. In addition, AM treatment increased the phosphorylation level of Akt in OPC cultures, and correspondingly, the PI3K/Akt inhibitor LY294002 blocked the AM-induced OPC differentiation. Taken together, AM treatment rescued OPC maturation under pathological conditions via an AM-receptor-PI3K/Akt pathway. Oligodendrocytes play critical roles in white matter by forming myelin sheath. Therefore, AM signaling may be a promising therapeutic target to boost oligodendrocyte regeneration in CNS disorders.

  14. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro.

    Science.gov (United States)

    Maki, Takakuni; Takahashi, Yoko; Miyamoto, Nobukazu; Liang, Anna C; Ihara, Masafumi; Lo, Eng H; Arai, Ken

    2015-07-01

    Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs). However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM) promotes the in vitro differentiation of OPCs under pathological conditions. Primary OPCs were prepared from neonatal rat brains, and differentiated into myelin-basic-protein expressing oligodendrocytes over time. This in vitro OPC differentiation was inhibited by prolonged chemical hypoxic stress induced by non-lethal CoCl(2) treatment. However, AM promoted the OPC differentiation under the hypoxic stress conditions, and the AM receptor antagonist AM(22-52) canceled the AM-induced OPC differentiation. In addition, AM treatment increased the phosphorylation level of Akt in OPC cultures, and correspondingly, the PI3K/Akt inhibitor LY294002 blocked the AM-induced OPC differentiation. Taken together, AM treatment rescued OPC maturation under pathological conditions via an AM-receptor-PI3K/Akt pathway. Oligodendrocytes play critical roles in white matter by forming myelin sheath. Therefore, AM signaling may be a promising therapeutic target to boost oligodendrocyte regeneration in CNS disorders. PMID:26002630

  15. Molecular Pathways Regulating Macrovascular Pathology and Vascular Smooth Muscle Cells Phenotype in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Sara Casella

    2015-10-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a disease reaching a pandemic proportion in developed countries and a major risk factor for almost all cardiovascular diseases and their adverse clinical manifestations. T2DM leads to several macrovascular and microvascular alterations that influence the progression of cardiovascular diseases. Vascular smooth muscle cells (VSMCs are fundamental players in macrovascular alterations of T2DM patients. VSMCs display phenotypic and functional alterations that reflect an altered intracellular biomolecular scenario of great vessels of T2DM patients. Hyperglycemia itself and through intraparietal accumulation of advanced glycation-end products (AGEs activate different pathways, in particular nuclear factor-κB and MAPKs, while insulin and insulin growth-factor receptors (IGFR are implicated in the activation of Akt and extracellular-signal-regulated kinases (ERK 1/2. Nuclear factor-κB is also responsible of increased susceptibility of VSMCs to pro-apoptotic stimuli. Down-regulation of insulin growth-factor 1 receptors (IGFR-1R activity in diabetic vessels also influences negatively miR-133a levels, so increasing apoptotic susceptibility of VSMCs. Alterations of those bimolecular pathways and related genes associate to the prevalence of a synthetic phenotype of VSMCs induces extracellular matrix alterations of great vessels. A better knowledge of those biomolecular pathways and related genes in VSMCs will help to understand the mechanisms leading to macrovascular alterations in T2DM patients and to suggest new targeted therapies.

  16. Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells

    Science.gov (United States)

    Jung, Wonhyuek; Seong, Young Jin; Park, Eunkyung; Bramos, Athanasios; Kim, Kyu Eui; Lee, Sunju; Daghlian, George; Seo, Jung In; Choi, Inho; Choi, In-Seon; Koh, Chester J.; Kobielak, Agnieszka; Ying, Qi-Long; Johnson, Maxwell; Gardner, Daniel; Wong, Alex K.; Choi, Dongwon; Hong, Young-Kwon

    2016-01-01

    Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research. PMID:27280889

  17. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    DEFF Research Database (Denmark)

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.;

    2008-01-01

    In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... stem cells or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells...

  18. CT features on increased cerebral vascular density and its pathological mechanism in patients with cyanotic congenital disease

    International Nuclear Information System (INIS)

    Objective: To investigate CT features on increased cerebral vascular density and its pathological mechanism in patients with cyanotic congenital heart disease (CCHD). Methods: Preoperative brain CT scan and clinical data in 82 patients suffering from CCHD were analyzed. According to the increased levels of vascular density, patients were divided into 4 groups: normal, mild, moderate and severe. Relationships between the increased levels of vascular density and Hb, RBC, HCT, as well as the degree of cyanosis,were studied. AVONA was carried out to test blood CT value of cerebral sinuses, Hb, RBC and HCT in different groups. Descriptive analysis and linear regression were adopted to study the correlation between blood CT value and Hb concentration. The relationship of increased vascular density to degrees of cyanosis was analysed by Spearman. Results: Among 82 patients, 12 patients (14.6%) were found in the group of normal vascular density and 70 patients (85.4%) in the increased vascular density group. Among 70 patients with increased vascular density, 22 patients (26.8% ) with (55.4 ± 2.6) HU, (169 ±6)g/L of Hb, (5.8 ±0.3) × 1012/L of RBC and 0.51 ±0.03 of HCT, 29 patients (35.4%) with (61.3 ± 2.9) HU, (209 ± 15 ) g/L, (7.1 ± 0.4) × 1012/L, 0.66 ± 0.06 and 19 patients (23.2%) with (68.8 ± 4.2) HU, (242 ± 23) g/L, (8.3 ± 0.9) × 1012/L, 0.78 ± 0.08 were observed in the mild,moderate and severe group,respectively. There were significant differences in distribution of blood CT value (HU), Hb, RBC and HCT in different groups (F=163.263, 134.703, 120.974, 136.541; P<0.01). Blood CT value was positively correlated with Hb concentration (r=0.98, P<0.01). Vascular density was also positively correlated with the degree of cyanosis (r=0.86, P<0.01). Conclusions: Cerebral vascular density of patients suffering from CCHD presented different levels of increases based on CT scan results due to rise of RBC stimulated by anoxia. The increased level of vascular density

  19. Analysis of Alterations in Morphologic Characteristics of Mesenchymal Stem Cells by Mechanical Stimulation during Differentiation into Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Shokrgozar

    2010-01-01

    Full Text Available Objective: Mesenchymal stem cells (MSCs can be expanded and differentiated intomany mature cell types including smooth muscle cells (SMCs. In addition to growth factor,cyclic stretch contributes to differentiation of stem cells. Mechanical stimuli are criticalto morphological changes, development, regeneration, differentiation and pathology ofmesenchymal tissues. The aim of this study is to investigate effects of cyclic stretch withdiffering amplitudes on morphology and differentiation of mesenchymal stem cells.Materials and Methods: Mesenchymal stem cells are extracted from human bone marrow.Cells are cultured on silicone membrane and exposed to cyclic stretch by a custommade device. Cellular images are captured before and after tests. Effects of 5% and 15%uniaxial strain with 1Hz frequency and 1-8 hour durations on morphology of human mesenchymalstem cells are investigated. It is assumed that environmental factors such asmechanical loading regulate MSCs differentiation to SMCs. Fractal analysis is used toquantify alterations in cellular morphology. An image processing method with a designedcode is used for evaluation of fractal dimension parameter.Results: Results demonstrate statistically significant change in cell morphology due tomechanical stretch. By elevation of strain amplitude and number of load cycles, fractaldimensions of cell images decrease. Such decrease is equivalent to alignment of cells bymechanical stimulus. Cells are differentiated to SMCs purely by cyclic stretch. The initiationand rate of differentiation depend on mechanical conditions.Conclusion: To produce functional SMCs for engineered tissues, MSCs can be exposed to uniaxialcyclic stretch. The functionality of differentiated SMCs depends on loading conditions.

  20. Endoplasmic reticulum redox state is not perturbed by pharmacological or pathological endoplasmic reticulum stress in live pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Irmgard Schuiki

    Full Text Available Accumulation of unfolded, misfolded and aggregated proteins in the endoplasmic reticulum (ER causes ER stress. ER stress can result from physiological situations such as acute increases in secretory protein biosynthesis or pathological conditions that perturb ER homeostasis such as alterations in the ER redox state. Here we monitored ER redox together with transcriptional output of the Unfolded Protein Response (UPR in INS-1 insulinoma cells stably expressing eroGFP (ER-redox-sensor and mCherry protein driven by a GRP78 promoter (UPR-sensor. Live cell imaging, flow cytometry and biochemical characterization were used to examine these parameters in response to various conditions known to induce ER stress. As expected, treatment of the cells with the reducing agent dithiothreitol caused a decrease in the oxidation state of the ER accompanied by an increase in XBP-1 splicing. Unexpectedly however, other treatments including tunicamycin, thapsigargin, DL-homocysteine, elevated free fatty acids or high glucose had essentially no influence on the ER redox state, despite inducing ER stress. Comparable results were obtained with dispersed rat islet cells expressing eroGFP. Thus, unlike in yeast cells, ER stress in pancreatic β-cells is not associated with a more reducing ER environment.

  1. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology

    Directory of Open Access Journals (Sweden)

    Palve Devendra

    2008-01-01

    Full Text Available Oral squamous cell carcinoma accounts for 90% to 95% of all oral malignancies. Though its diagnosis seldom presents difficulty, it is the cancer staging and histopathological grading that are important to prognostication; and micronuclei are good prognostic indicators. Micronucleus frequencies in oral exfoliated cells stained with papanicolaou stain were counted and correlated with the histopathological grades and clinical stages of squamous cell carcinoma patients. They were also compared with healthy control subjects. Micronuclei (MN frequencies were found higher in squamous cell carcinoma patients than in control subjects. MN frequencies were also found to be raised with increasing histological grades of squamous cell carcinoma.

  2. Mechanism of hematopoietic stem cell homing

    International Nuclear Information System (INIS)

    The clinical transplantation of hematopoietic stem cell (HSC) originating from many sources such as bone marrow, peripheral blood and cord blood has been widely applied in recent years. At the same time, the development of the study on the mechanism of HSC homing which involves multi-procedures has been achieved. And a lot of molecular and cytokines on the surface or in the microenvironment of HSC are functioning in homing. The purpose of is to review those molecular and cytokines on which more studies have been focused in the past

  3. Pathological clavicular fracture as ifrst presentation of renal cell carcinoma:a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Yan Kong; Jin Wang; Huan Li; Peng Guo; Jian-Fa Xu; He-Lin Feng

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 3%of all cancer cases. RCCs usually metastasize to the lungs, bones, liver, or brain. Only<1%of patients with bone metastases manifested clavicular RCC metastases. hTus, clavicular metastasis as the initial presentation of RCC is extremely rare. We report a patient with RCC metastasis to the letf clavicle, which was ifrst presented with pain caused by a pathological fracture. Magnetic resonance image revealed a renal tumor, and technetium-99m–methylene diphosphonate bone scintigraphy showed multiple osseous metastases. The patient eventually underwent surgery to remove the lateral end of the letf clavicle and right kidney. Histopathology revealed renal tumor and clear cell carcinoma in the clavicle. Finally, we review 17 cases of clavicular metastases originating from different malignancies.

  4. 病理性赌博的发生机制研究综述%A Review on the Mechanism of Pathological Gambling

    Institute of Scientific and Technical Information of China (English)

    叶绿; 马红宇; 史文文; 李娜; 王斌

    2013-01-01

    Pathological gambling refers to a gambling behavior conducted by the individuals who can't control the impulse and then addict to gamble,which adversely affects individuals,families and society.On the basis of referring to relevant literatures,it was found that the mechanism of pathological gambling may be attributed to the interaction of three factors,including biologic,psychological and social facets.Future research should pay attention to the building of the causal model of pathological gambling,and strengthening the study of pathological gambling intervention and prevention.%病理性赌博是指个体难以控制赌博冲动,使其持久地沉溺于赌博中,以致个人、家庭和社会受到不良影响的赌博行为.本研究在参阅病理性赌博和其它行为成瘾相关文献的基础上,对病理性赌博的发生机制进行探讨,指出其是生物、心理和社会因素共同作用的结果.未来研究应注重构建病理性赌博的成因模型、加强病理性赌博的干预和预防研究.

  5. Solitary pulmonary metastases from renal cell carcinoma. Comparison of high-resolution CT with pathological findings

    International Nuclear Information System (INIS)

    The aim of this study was to examine the radiographic features of solitary pulmonary metastases from renal cell carcinoma by comparing high-resolution CT (HRCT) findings with histopathological observations. Three thoracic radiologists retrospectively reviewed HRCT findings from eight patients who underwent surgery on the basis of the diagnosis of solitary pulmonary metastatic renal cell carcinoma. The histopathological diagnoses for six of these eight lesions were metastases from clear cell carcinoma of the kidney, one case was a metastasis from papillary renal cell carcinoma, and the remaining case was a metastasis from a poorly differentiated carcinoma including predominantly spindle cells, papillary cells, and clear cells. The HRCT findings of all cases of clear cell carcinoma showed solid nodular lesions without ground-glass attenuation (GGA). The HRCT findings for one case of papillary renal cell carcinoma showed a lobulated nodule with a small amount of GGA in an area in the periphery and an air bronchogram. The HRCT findings of the remaining case of poorly differentiated carcinoma showed an ill-defined nodule with a GGA area and pleural indentations. In brief, solitary pulmonary metastases from renal cell carcinoma may present as a smoothly marginated nodule, lobulated nodule, or a nodule with peripheral GGA. (author)

  6. Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice

    Science.gov (United States)

    Sakai, Kenzo; Nakano, Keisuke; Matsuda, Saeka; Tsujigiwa, Hidetsugu; Ochiai, Takanaga; Shoumura, Masahito; Osuga, Naoto; Hasegawa, Hiromasa; Kawakami, Toshiyuki

    2016-01-01

    In this study, cholesterin was implanted in the subcutaneous tissue in mice to induce the formation of cholesterol granuloma. Histological examination was carried out to determine the type and source of cells. The tissue surrounding the embedded cholesterin was examined histologically within the period of 6 months. Cell differentiation in cholesterol granulomas was investigated using ddY mice and GFP bone marrow transplanted mice. Cholesterin was embedded in mice subcutaneously and histopathological examination was carried out in a period of 6 months. Results showed that at 2 weeks, cholesterin was replaced partly by granulation tissues. The majority of cells in the granulation tissues were macrophages and foreign body giant cells and the center consists of small amount of fibroblasts, collagen fibers and capillaries. At 3 months, more granulation tissue was observed compared to 2 weeks. Similar cells were observed, however, there were more fibroblasts, collagen bundles and capillaries present compared to 2 weeks. At 6 months, the cholesterin was mostly substituted by fibrous tissues consisting mainly of fibroblasts and collagen fibers with some macrophages and foreign body giant cells. Specifically, the outer part of the tissue consists of fibroblasts, collagen bundles and capillaries and the inner portion is filled with collagen bundles. Immunohistochemistry revealed that macrophages and foreign body giant cells were positive to GFP and CD68 although the fibroblasts and capillaries in the outer portion of cholesterol granulomas were GFP negative. Some spindle shape fibroblasts were also GFP positive. Immunofluorescent double staining revealed that cells lining the blood vessels were both positive to GFP and CD31 indicating that those were endothelial cells and were actually derived from the transplanted bone marrow cells. The results suggest that macrophages, foreign body giant cells as well as fibroblasts and capillary endothelial cells are bone marrow derived

  7. Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.

    Science.gov (United States)

    Douville, Nicholas J; Zamankhan, Parsa; Tung, Yi-Chung; Li, Ran; Vaughan, Benjamin L; Tai, Cheng-Feng; White, Joshua; Christensen, Paul J; Grotberg, James B; Takayama, Shuichi

    2011-02-21

    Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings. PMID:21152526

  8. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology

    OpenAIRE

    Palve Devendra; Tupkari Jagdish

    2008-01-01

    Oral squamous cell carcinoma accounts for 90% to 95% of all oral malignancies. Though its diagnosis seldom presents difficulty, it is the cancer staging and histopathological grading that are important to prognostication; and micronuclei are good prognostic indicators. Micronucleus frequencies in oral exfoliated cells stained with papanicolaou stain were counted and correlated with the histopathological grades and clinical stages of squamous cell carcinoma patients. They were al...

  9. Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes.

    OpenAIRE

    Embury, S H; Clark, M R; Monroy, G; Mohandas, N

    1984-01-01

    The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very den...

  10. Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition

    Directory of Open Access Journals (Sweden)

    Kinoshita Ayako

    2005-05-01

    Full Text Available Abstract Background Cell simulation, which aims to predict the complex and dynamic behavior of living cells, is becoming a valuable tool. In silico models of human red blood cell (RBC metabolism have been developed by several laboratories. An RBC model using the E-Cell simulation system has been developed. This prototype model consists of three major metabolic pathways, namely, the glycolytic pathway, the pentose phosphate pathway and the nucleotide metabolic pathway. Like the previous model by Joshi and Palsson, it also models physical effects such as osmotic balance. This model was used here to reconstruct the pathology arising from hereditary glucose-6-phosphate dehydrogenase (G6PD deficiency, which is the most common deficiency in human RBC. Results Since the prototype model could not reproduce the state of G6PD deficiency, the model was modified to include a pathway for de novo glutathione synthesis and a glutathione disulfide (GSSG export system. The de novo glutathione (GSH synthesis pathway was found to compensate partially for the lowered GSH concentrations resulting from G6PD deficiency, with the result that GSSG could be maintained at a very low concentration due to the active export system. Conclusion The results of the simulation were consistent with the estimated situation of real G6PD-deficient cells. These results suggest that the de novo glutathione synthesis pathway and the GSSG export system play an important role in alleviating the consequences of G6PD deficiency.

  11. Mechanical behavior of open cell aluminum foams

    Science.gov (United States)

    Zhou, Jikou

    Open cell metallic foams are relatively new materials with increasingly applications due to their attractive combinations of physical, chemical, mechanical and optical properties. Since plastic deformation in the struts involves dislocation motion, dislocation slip bands are used to track the initiation/propagation and locations of plastic deformation in individual struts. We find that the onset of plastic deformation in struts is far beyond the observable strut/cell shape changes, and both plastic bending and buckling are strut deformation modes. To measure the strut mechanical properties, an existing micro-scale tensile tester was updated to test the individual struts extracted from foams using electro-discharged machining. The micro-tensile testing results show that the foam struts are typically more ductile and one time stronger than the corresponding fully dense alloy. To integrate the measured strut and foam properties, a four-strut structure unit is identified as a structural representative of the open cell foam structure. Based on the observed strut deformation modes, mechanics analysis is performed on the structure unit to predict the foam stiffness and strength. The predictions are in good agreement with the measured data, suggesting the significance of the studies on the foam strut properties and deformation. This model also predicts the bounds of the foam strengths. Under cyclic compression, foams fail due to damage accumulation in individual struts, in which surface cracks initiate and grow. At low stress levels, surface cracks are formed in multiple struts that are distributed across the foam block. This results in an abrupt strain jump due to the crush of foam block, upon foam failure. To meet applications requirements, open cell aluminum foams are usually annealed or strengthened. The studies are carried out in the foams in the as-fabricated (F), annealed (O) and T6-strengthed (T6) conditions. We find that annealing and T6 strengthening

  12. Video-Assisted Thoracic Surgery (VATS) Lobectomy for Pathologic Stage I Non-Small Cell Lung Cancer: A Comparative Study with Thoracotomy Lobectomy

    OpenAIRE

    Park, Joon Suk; Kim, Kwhanmien; Choi, Min Suk; Chang, Sung Wook; Han, Woo-sik

    2011-01-01

    Background Surgical treatment of stage I non-small cell lung cancer (NSCLC) can be performed either by thoracotomy or by employing video-assisted thoracic surgery (VATS). The aim of this study was to evaluate the feasibility of VATS lobectomy for pathologic stage I NSCLC. Material and Methods Between December 2003 and December 2007, 529 patients with pathologic stage I NSCLC underwent lobectomies (373 thoracotomy, 156 VATS). Patients in both groups were selected after being matched by age, ge...

  13. Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling;

    2015-01-01

    Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system...... (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with...... three populations of myeloid cells: CD11c(+) microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished...

  14. Pathological study of breast cancer by method postneaadyuvancia RCB (residual tumor burden) associated with cell proliferation index report preliminary data

    International Nuclear Information System (INIS)

    Full text: Introduction: The evaluation of residual disease increases prognostic information postneaadyuvancia and obtained by the study of pathological response. Using method index residual tumor burden (RCB)developed at M D Anderson where from morphological parameters (Size of the tumor bed, residual percentage of invasive carcinoma, carcinoma in situ percentage residual metastatic nodes number and size of largest metastasis)the index is calculated. Proliferation index represents an independent predictor of response to particular drugs. A high rate of cell proliferation after chemotherapy is linked with a poor survival We compared the results of both indices Material and Methods: We applied method residual tumor burden index (RCB)in 30 patients operated breast carcinoma after neoadjuvant therapy. Documentation was performed digital macroscopic bed residual tumor, printing and bulk sampling mapping performed on serially reading sheets histological double-blind by two pathologists using graphical illustrations of the percentage of cellularity neoplastic. The application of the formula classified as: RCB 0, complete pathological response (Rpc), RCB I, minimal residual disease, moderate residual disease RCB II, III RBC extensive disease residual. We immunohistochemical proliferation index (PI)with K i 67 in 14 cases (RCB II and III) with double-blinded histological evaluation by performing a percentage of stained nuclei in the greater staining sector thereof and with a cutoff of 14% of stained nuclei. Results: The size of the residual tumor bed was between 4x3mm and 110x60mm. Percentages cellularity invasive component between 0 and 86%, carcinoma in situ between 0 and 30 %. RCB case 0, RCB I a case, RCB RCB II and III seventeen cases eleven cases. Proliferation index was between 1% to 90 %, greater than 14 % in 29% of III and 21% RCB RCB II. Less than 14% was seen in 29% of RCB II and 7% RCB III In six cases there was variation in the rate of pre and post neoadjuvant

  15. Mechanism regulating reactive oxygen species in tumor induced myeloid-derived suppressor cells1: MDSC and ROS in cancer

    OpenAIRE

    Corzo, Cesar A.; Cotter, Matthew J.; Cheng, Pingyan; Cheng, Fendong; Kusmartsev, Sergei; Sotomayor, Eduardo; Padhya, Tapan; McCaffrey, Thomas V.; McCaffrey, Judith C.; Gabrilovich, Dmitry I.

    2009-01-01

    Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head ...

  16. Alteration of chaperonin60 and pancreatic enzyme in pancreatic acinar cell under pathological condition

    OpenAIRE

    Li, Yong-Yu; Bendayan, Moise

    2005-01-01

    AIM: To investigate the changes of chaperonin60 (Cpn60) and pancreatic enzymes in pancreatic acinar cells, and to explore their roles in the development of experimental diabetes and acute pancreatitis (AP).

  17. Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

    OpenAIRE

    Gredmark-Russ, Sara; Söderberg-Nauclér, Cecilia

    2012-01-01

    Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognitio...

  18. Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings.

    Science.gov (United States)

    Bagnasco, Giorgio; Properzi, Roberto; Porto, Roberto; Nardini, Vincenzo; Poli, Alessandro; Abramo, Francesca

    2003-04-01

    A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour. PMID:12662269

  19. Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

    OpenAIRE

    Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

    2011-01-01

    Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulati...

  20. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism.

    Science.gov (United States)

    Kim, Hun Sik; Kwon, Hyung-Joon; Kim, Gye Eun; Cho, Mi-Hyang; Yoon, Seung-Yong; Davies, Alexander J; Oh, Seog Bae; Lee, Heuiran; Cho, Young Keol; Joo, Chul Hyun; Kwon, Seog Woon; Kim, Sun Chang; Kim, Yoo Kyum

    2014-07-01

    The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance. PMID:24743513

  1. Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management.

    Science.gov (United States)

    Daniele, Luca; Nikolarakos, Dimitrios; Keenan, Jonathon; Schaefer, Nathan; Lam, Alfred King-Yin

    2016-06-01

    Clear cell carcinoma, not otherwise specified (NOS)/hyalinising clear cell carcinoma (HCCC) is a rare entity in salivary gland tumour. The aim of the research is to review the current concepts and characteristics of this carcinoma. The clinical and pathological data of the disease obtained from literature and two original cases were analysed. Overall, 152 cases were reviewed up to the year 2014. The carcinomas were noted often in woman, in the seventh decade of life, located in oral cavity and as early-stages cancers. On pathological examination, they were characterized by tumour cells having clear cell morphology with hyalinised stroma. Immunohistochemical studies revealed that the carcinoma is positive for cytokeratin and negative for myoepithelial differentiation. EWSR1-ATF1 fusion is specific for the carcinoma. Also, 9% of the reported cases had local nodal metastasis, with 6 cases demonstrating distant metastases at presentation. On follow-up, 22% of patients had recurrent or with persistent diseases after surgery. The time for the first recurrence could be as long as 24 years. Risk factors for recurrence include advanced stage at diagnosis and metastases at presentation. To conclude, HCCC is a low grade malignancy but have the potential for local metastases, recurrence, distant metastases and cancer-related death. PMID:27150676

  2. Pathological gambling

    Science.gov (United States)

    ... to a gambling habit. Stressful situations can worsen gambling problems. ... to avoid letting other people know about their problem. The American Psychiatric Association defines pathological gambling as having five or more of the following ...

  3. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

    2015-07-15

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  4. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

    International Nuclear Information System (INIS)

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  5. Matter, metaphors, and mechanisms: rethinking cell theories.

    Science.gov (United States)

    Müller-Strahl, Gerhard

    2014-12-01

    This study analyzes the logical structure of classical cell theory (CCT) by pointing out that CCT conceives the properties of organic cellular matter as supervenient to successively emerging states of quasi-crystalline atoms. This concept supports the design of a metaphorical space the intelligible components of which display an explanatory structure in accordance with the contemporary complex-systems approach of mechanisms. These findings support the thesis of an explanatory turn within the life-sciences due to a conflict between anti-classificatory (Buffon), analogous (Wolff, Reil, Weber), and causal-mechanical (Kepler) strategies of explanation. The continuous process underlying these diverse discontinuities is taken to be the immanent process of objectifying scientific concepts for the need of explanation. This process repeatedly provides concepts which are identified as nomadic concepts. The meta-analysis of their interactions reveals that concepts of matter are obtained by idealizations which entertain one process with three dimensions: atomization originating from empirical classificatory regularities (classification) and aiming at an explanation of changing phenomena (dynamization). These dimensions are successfully incorporated into the explanatory scheme of CCT. The migrations of a second group of nomadic concepts beyond this historical point of transition are made responsible for blurring the explanatory turn. PMID:25156862

  6. Micro and Nano-scale Technologies for Cell Mechanics

    OpenAIRE

    Mustafa Unal; Yunus Alapan; Hao Jia; Adrienn G. Varga; Keith Angelino; Mahmut Aslan; Ismail Sayin; Chanjuan Han; Yanxia Jiang; Zhehao Zhang; Gurkan, Umut A.

    2014-01-01

    Cell mechanics is a multidisciplinary field that bridges cell biology, fundamental mechanics, and micro and nanotechnology, which synergize to help us better understand the intricacies and the complex nature of cells in their native environment. With recent advances in nanotechnology, microfabrication methods and micro-electro-mechanical-systems (MEMS), we are now well situated to tap into the complex micro world of cells. The field that brings biology and MEMS togethe...

  7. Single cell mechanics: stress stiffening and kinematic hardening

    CERN Document Server

    Fernández, Pablo

    2007-01-01

    Cell mechanical properties are fundamental to the organism but remain poorly understood. We report a comprehensive phenomenological framework for the nonlinear rheology of single fibroblast cells: a superposition of elastic stiffening and viscoplastic kinematic hardening. Our results show, that in spite of cell complexity its mechanical properties can be cast into simple, well-defined rules, which provide mechanical cell strength and robustness via control of crosslink slippage.

  8. Single cell mechanics: stress stiffening and kinematic hardening.

    Science.gov (United States)

    Fernández, Pablo; Ott, Albrecht

    2008-06-13

    Cell mechanical properties are fundamental to the organism but remain poorly understood. We report a comprehensive phenomenological framework for the complex rheology of single fibroblast cells: a superposition of elastic stiffening and viscoplastic kinematic hardening. Despite the complexity of the living cell, its mechanical properties can be cast into simple, well-defined rules. Our results reveal the key role of crosslink slippage in determining mechanical cell strength and robustness. PMID:18643547

  9. MicroRNAs in the pathology of B-Cell Chronic Lymphocytic Leukemia

    International Nuclear Information System (INIS)

    In chronic lymphocytic leukemia (B-CLL), aberrations along the p53 axis lead to decreased overall survival and therapy resistance. Recent studies identified miR-34a as a major downstream target of p53. We monitored the expression of miR-34a during disease development in a murine B-CLL model. miR-34a was upregulated >20-fold during the leukemic but not during the preleukemic phase. In the human system, B-CLL cells also had 4.6-fold higher miR-34a expression as compared to B-cells of healthy controls. In B-CLL cells of patients with p53 aberrations miR-34a expression was consistently low. The broad distribution of miR-34a levels in p53 wild-type individuals prompted us to study the correlation between SNP309 in the intronic promoter of MDM2 and miR-34a expression. B-CLL cells of patients with the SNP309 GG genotype had significantly lower miR-34a expression levels as compared to patients with the TT genotype (P =0.002). Low miR-34a levels were able to predict shorter time to treatment (P = 0.003) and were associated with an abbreviated lymphocyte doubling time. Further, overexpression of miR-34a in primary B-CLL cells induced apoptosis. These findings suggest miR-34a as a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in B-CLL. (author)

  10. Giant cells glioblastoma: case report and pathological analysis from this uncommon subtype of glioma

    Directory of Open Access Journals (Sweden)

    Telmo A.B. Belsuzarri

    2015-03-01

    Full Text Available Glioblastoma multiforme (GBM is the most common glial tumor of the brain system; nevertheless, the giant cell (GC subtype is uncommon. Recent reviews report for an incidence of 1% in adults and 3% in children. The GCs usually have a better prognosis than GBM and also an increasing long-term survival rate. It is known that the diagnosis of this tumor is due to its histological findings and patterns, such as the unusual increased number of giant cells. Unfortunately, due to its rarity, the immunohistochemical and cytogenetical analysis of this tumor is not well known. Some authors also suggest that there are few subtypes of GCs and their patterns of aggressiveness could be due to cytogenetical markers. It is recognized that maximum safe resection treatment and adjuvant radiotherapy can improve survival rate (5-13 months similar to GBM patients.

  11. Clinical-Pathological Parameters as Prognostic Indicators in Oral Squamous Cell

    Directory of Open Access Journals (Sweden)

    Raimundo Fernandes de ARAÚJO JÚNIOR

    2006-08-01

    Full Text Available Objective: To correlate the TNM classification and histological scores of malignancy, and these parameters with the prognosis in 38 cases of squamous cell carcinoma oral. Method: The cases were selected from the files of "Dr. Luiz Antônio" Cancer Hospital, Natal, RN, Brazil. After analysis of the patients' records, the data concerning TNM classification and prognosis (in a 5-year-follow-up were obtained. All cases were classified according to the histological malignancy grading system proposed by Bryne (1998. Results: There was correlation between histological scores of malignancy and prognosis and TNM classification with prognosis. Conclusion: It was concluded that TNM classification and histological malignancy grading are important prognostic indicators the squamous cell carcinoma oral.

  12. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death

    Science.gov (United States)

    Keatinge, Marcus; Bui, Hai; Menke, Aswin; Chen, Yu-Chia; Sokol, Anna M.; Bai, Qing; Ellett, Felix; Da Costa, Marc; Burke, Derek; Gegg, Matthew; Trollope, Lisa; Payne, Thomas; McTighe, Aimee; Mortiboys, Heather; de Jager, Sarah; Nuthall, Hugh; Kuo, Ming-Shang; Fleming, Angeleen; Schapira, Anthony H.V.; Renshaw, Stephen A.; Highley, J. Robin; Chacinska, Agnieszka; Panula, Pertti; Burton, Edward A.; O'Neill, Michael J.; Bandmann, Oliver

    2015-01-01

    Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 mutations (GBA1+/−) are the most common risk factor for Parkinson's disease (PD). Previous studies typically focused on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1+/− carriers and alpha-synuclein-mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to the increased risk of PD in GBA1+/− carriers. The zebrafish genome does not contain alpha-synuclein (SNCA), thus providing a unique opportunity to study pathogenic mechanisms unrelated to alpha-synuclein toxicity. Here we describe a mutant zebrafish line created by TALEN genome editing carrying a 23 bp deletion in gba1 (gba1c.1276_1298del), the zebrafish orthologue of human GBA1. Marked sphingolipid accumulation was already detected at 5 days post-fertilization with accompanying microglial activation and early, sustained up-regulation of miR-155, a master regulator of inflammation. gba1c.1276_1298del mutant zebrafish developed a rapidly worsening phenotype from 8 weeks onwards with striking reduction in motor activity by 12 weeks. Histopathologically, we observed marked Gaucher cell invasion of the brain and other organs. Dopaminergic neuronal cell count was normal through development but reduced by >30% at 12 weeks in the presence of ubiquitin-positive, intra-neuronal inclusions. This gba1c.1276_1298del zebrafish line is the first viable vertebrate model sharing key pathological features of GD in both neuronal and non-neuronal tissue. Our study also provides evidence for early microglial activation prior to alpha-synuclein-independent neuronal cell death in GBA1 deficiency and suggests upregulation of miR-155 as a common denominator across different neurodegenerative disorders. PMID:26376862

  13. Geometric characterization of red blood cells. Differentiation of normal and pathologic samples

    OpenAIRE

    Javier Rodríguez; Catalina Correa; Signed Prieto; Benjamín Ospino; Pedro Bernal; Liliana Ortiz; Ángela Munévar

    2008-01-01

    the irregularity of abstract and natural objectswith the fractal dimension. Fractal calculationshave been applied to the structures of the humanbody and to quantifications in physiology fromthe theory of dynamic systems.Material and Methods. The fractal dimensionswere calculated, the number of occupationspaces in the space border of box counting andthe area of two red blood cells groups, 7 normalones, group A, and 7 abnormal, group B, comingfrom patient and of bags for transfusion, werecalcul...

  14. Evaluation of Mast Cell Activation Syndromes: Impact of Pathology and Immunohistology

    OpenAIRE

    Horny, H.-P.; Sotlar, K; Valent, P

    2012-01-01

    Mast cell activation syndromes (MCAS) are clinically defined disease states with a largely unknown morphological background. Since mastocytosis may be associated with MCAS, it is crucial in every patient to document or exclude mastocytosis by appropriate histological, molecular, and serological investigations of tissues/organs that are commonly involved in mastocytosis like skin, mucosa of the gastrointestinal tract and bone marrow. Accordingly, histopathological investigation including immun...

  15. Clinical and surgical-pathological staging in early non-small cell lung cancer

    OpenAIRE

    Ioannis Koukis; Ioannis Gkiozos; Ioannis Ntanos; Elias Kainis; Konstantinos N. Syrigos

    2013-01-01

    Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC) because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for NSCLC. Clinical staging (c-...

  16. Systemic immunotherapy delays photoreceptor cell loss and prevents vascular pathology in Royal College of Surgeons rats

    OpenAIRE

    Adamus, Grazyna; Wang, Shaomei; Kyger, Madison; Worley, Aneta; Lu, Bin; Burrows, Gregory G.

    2012-01-01

    Purpose Degenerative retinopathies, including retinitis pigmentosa, age-related retinal degeneration, autoimmune retinopathy, and related diseases affect millions of people around the world. Currently, there is no effective treatment for most of those diseases. We investigated systemic recombinant T-cell receptor ligand (RTL) immunotherapy for preventing retinal degeneration and vascular damage in the Royal College of Surgeons (RCS) rat model of retinal degeneration. Methods RCS rats were tre...

  17. Sox17 regulates insulin secretion in the normal and pathologic mouse β cell.

    Directory of Open Access Journals (Sweden)

    Diva Jonatan

    Full Text Available SOX17 is a key transcriptional regulator that can act by regulating other transcription factors including HNF1β and FOXA2, which are known to regulate postnatal β cell function. Given this, we investigated the role of SOX17 in the developing and postnatal pancreas and found a novel role for SOX17 in regulating insulin secretion. Deletion of the Sox17 gene in the pancreas (Sox17-paLOF had no observable impact on pancreas development. However, Sox17-paLOF mice had higher islet proinsulin protein content, abnormal trafficking of proinsulin, and dilated secretory organelles suggesting that Sox17-paLOF adult mice are prediabetic. Consistant with this, Sox17-paLOF mice were more susceptible to aged-related and high fat diet-induced hyperglycemia and diabetes. Overexpression of Sox17 in mature β cells using Ins2-rtTA driver mice resulted in precocious secretion of proinsulin. Transcriptionally, SOX17 appears to broadly regulate secretory networks since a 24-hour pulse of SOX17 expression resulted in global transcriptional changes in factors that regulate hormone transport and secretion. Lastly, transient SOX17 overexpression was able to reverse the insulin secretory defects observed in MODY4 animals and restored euglycemia. Together, these data demonstrate a critical new role for SOX17 in regulating insulin trafficking and secretion and that modulation of Sox17-regulated pathways might be used therapeutically to improve cell function in the context of diabetes.

  18. Geometric characterization of red blood cells. Differentiation of normal and pathologic samples

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez

    2008-12-01

    Full Text Available the irregularity of abstract and natural objectswith the fractal dimension. Fractal calculationshave been applied to the structures of the humanbody and to quantifications in physiology fromthe theory of dynamic systems.Material and Methods. The fractal dimensionswere calculated, the number of occupationspaces in the space border of box counting andthe area of two red blood cells groups, 7 normalones, group A, and 7 abnormal, group B, comingfrom patient and of bags for transfusion, werecalculated using the method of box counting anda software developed for such effect. The obtainedmeasures were compared, looking for differencesbetween normal and abnormal red blood cells,with the purpose of differentiating samples.Results. The abnormality characterizes by anumber of squares of occupation of the fractalspace greater or equal to 180; values of areasbetween 25.117 and 33.548 correspond to normality.In case that the evaluation according tothe number of pictures is of normality, must beconfirmed with the value of the area applied toadjacent red blood cells within the sample, thatin case of having values by outside establishedand/or the greater or equal spaces to 180, theysuggest abnormality of the sample.Conclusions. The developed methodology iseffective to differentiate the red globules alterationsand probably useful in the analysis of bagsof transfusion for clinical use.

  19. Time to Relax: Mechanical Stress Release Guides Stem Cell Responses.

    Science.gov (United States)

    Sommerfeld, Sven D; Elisseeff, Jennifer H

    2016-02-01

    Stem cells integrate spatiotemporal cues, including the mechanical properties of their microenvironment, into their fate decisions. Chaudhuri et al. (2015) show that the ability of the extracellular matrix to dissipate cell-induced forces, referred to as stress-relaxation, is a key mechanical signal influencing stem cell fate and function. PMID:26849301

  20. Sox17 Regulates Insulin Secretion in the Normal and Pathologic Mouse β Cell

    OpenAIRE

    Jonatan, Diva; Spence, Jason R.; Method, Anna M.; Kofron, Matthew; Sinagoga, Katie; Haataja, Leena; Arvan, Peter; Deutsch, Gail H.; Wells, James M.

    2014-01-01

    SOX17 is a key transcriptional regulator that can act by regulating other transcription factors including HNF1β and FOXA2, which are known to regulate postnatal β cell function. Given this, we investigated the role of SOX17 in the developing and postnatal pancreas and found a novel role for SOX17 in regulating insulin secretion. Deletion of the Sox17 gene in the pancreas (Sox17-paLOF) had no observable impact on pancreas development. However, Sox17-paLOF mice had higher islet proinsulin prote...

  1. Whirler Mutant Hair Cells Have Less Severe Pathology than Shaker 2 or Double Mutants

    OpenAIRE

    Mustapha, Mirna; Lisa A. Beyer; Izumikawa, Masahiko; Swiderski, Donald L.; Dolan, David F.; Raphael, Yehoash; Camper, Sally A.

    2007-01-01

    MYOSIN XV is a motor protein that interacts with the PDZ domain-containing protein WHIRLIN and transports WHIRLIN to the tips of the stereocilia. Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior, probably because of abnormally short stereocilia. Whirler (wi) mice have a similar phenotype caused by a deletion in the third PDZ domain of WHIRLIN. We compared the morphology of Whrnwi/wi and Myo15sh2/sh2 sensory hair cells a...

  2. Acinar Cell Cystadenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

    OpenAIRE

    Gumus, Mehmet; Ugras, Serdar; Algin, Oktay; Gundogdu, Haldun

    2011-01-01

    Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT,...

  3. Pro-angiogenic Hematopoietic Progenitor Cells and Endothelial Colony Forming Cells in Pathological Angiogenesis of Bronchial and Pulmonary Circulation

    OpenAIRE

    Duong, Heng; Erzurum, Serpil; Asosingh, Kewal

    2011-01-01

    Dysregulation of angiogenesis is a common feature of many disease processes. Vascular remodeling is believed to depend on the participation of endothelial progenitor cells, but the identification of endothelial progenitors in postnatal neovascularization remains elusive. Current understanding posits a role for circulating pro-angiogenic hematopoietic cells, which interact with local endothelial cells to establish an environment that favors angiogenesis in physiologic and pathophysiologic resp...

  4. Neural Stem Cell Gene Therapy Ameliorates Pathology and Function in a Mouse Model of Globoid Cell Leukodystrophy

    OpenAIRE

    Neri, Margherita; Ricca, Alessandra; di Girolamo, Ilaria; Alcala'-Franco, Beatriz; Cavazzin, Chiara; Orlacchio, Aldo; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2011-01-01

    Murine neural stem cells (mNSCs), either naive or genetically modified to express supranormal levels of β-galactocerebrosidase (GALC), were transplanted into the brain of Twitcher mice, a murine model of globoid cell leukodystrophy, a severe sphingolipidosis. Cells engrafted long-term into the host cytoarchitecture, producing functional GALC. Levels of enzyme activity in brain and spinal cord tissues were enhanced when GALC-overexpressing NSC were used. Enzymatic correction correlated with re...

  5. Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

    Directory of Open Access Journals (Sweden)

    Fabio Ramoa Pires

    2013-09-01

    Full Text Available Epidemiological data from oral squamous cell carcinoma (OSCC is mostly derived from North American, European and East Asian populations. OBJECTIVE: The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. MATERIAL AND METHODS: All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. RESULTS: A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001. Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%, alveolar mucosa/gingiva (20% and floor of mouth/ventral tongue (19% were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091 and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5% were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004. CONCLUSIONS: The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients.

  6. Clinico-pathological study on non-squamous cell carcinomas of the oral cavity and oropharynx

    International Nuclear Information System (INIS)

    We reviewed 22 cases of non-squamous cell carcinoma (NSCC) of the oral cavity and oropharynx that were treated at the Kurume University Hospital between 1976 and 2005. Two percent of the oral carcinomas and 5% of the oropharyngeal carcinomas were NSCCs. The 5-year and 10-year survival rates of NSCC in the oropharynx were 90%. There was no statistically significant difference in survival rate between squamous cell carcinoma (SCC) and NSCC (p=0.06). The 5-year and 10-year survival rates of NSCC in the oral cavity were 75% and 37%, respectively. There was no statistically significant difference in the survival rate between SCC and NSCC. Survival results well correlated with clinical stages. A significant difference between Stage I, II and III versus Stage IV was found (p=0.04). In contrast, no significant relationship was found between survival and histologic type, or between survival and treatment. Patients with adenoid cystic carcinoma of Grade III, peri-neural invasion or vessel invasion, are recommended to receive adjuvant therapy. (author)

  7. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    Energy Technology Data Exchange (ETDEWEB)

    Azouz, E. Michel [University of Miami, Pediatric Radiology Section, Department of Radiology, Miami, FL (United States); Saigal, Gaurav [McGill University, Department of Medical Imaging, Quebec (Canada); Rodriguez, Maria M. [University of Miami, Department of Pathology, Miami, FL (United States); Podda, Antonello [University of Miami, Division of Pediatric Hematology/Oncology, Miami, FL (United States)

    2005-02-01

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  8. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  9. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    International Nuclear Information System (INIS)

    Brain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Fifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients

  10. Diffuse large B-Cell lymphoma: a clinico- pathologic and prognostic study on 1470 biopsy specimens

    Directory of Open Access Journals (Sweden)

    Sadighi S

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Diffuse large B Cell lymphoma (DLBCL is the most common subtype of non-Hogkin lymphoma (NHL. We performed a retrospective study of patients with de novo DLBCL treated in the Medical Oncology department of Cancer Institute of Iran, Tehran to assess the clinicopathologic and immunohistochemistry correlation and prognosis of the patients. "n"nMethods: World Health Organization (WHO classification was used to reexamine 1470 biopsy specimens related to the years 1985-2006. After excluding five cases of T Cell large cell lymphoma, 50 Patients diagnosed as DLBCL. "n"nResults: Median age of the patients was 45.5(20-85 years: 60% were male and 30% had primary extranodal disease. The most common extranodal sites were bone, gastrointestinal tract and Head and neck areas. The most common stages were stage II (32%, stage III (32%, stage IV (20% and stage I (16% retrospectively and 33% had B-symptoms. All of The Patients received chemotherapy (83% CHOP regimen and 46% treated by radiotherapy after chemotherapy. With a mean follow up time of 32 months, median survival time was 34 (95% CI 24-40 months. Prognostic factors for survival were tumor stage, B-symptoms and early relapse (less than 6 months."n"nConclusions: Our

  11. Digital pathology

    CERN Document Server

    Sucaet, Yves

    2014-01-01

    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  12. Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology

    Science.gov (United States)

    Loewendorf, Andrea I.; Matynia, Anna; Saribekyan, Hakob; Gross, Noah; Csete, Marie; Harrington, Mike

    2016-01-01

    Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood–brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients. PMID:27148260

  13. Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology.

    Science.gov (United States)

    Loewendorf, Andrea I; Matynia, Anna; Saribekyan, Hakob; Gross, Noah; Csete, Marie; Harrington, Mike

    2016-01-01

    Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood-brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients. PMID:27148260

  14. Mechanical tension drives cell membrane fusion

    OpenAIRE

    Kim, Ji Hoon; Ren, Yixin; Ng, Win Pin; Li, Shuo; Son, Sungmin; Kee, Yee-Seir; Zhang, Shiliang; Zhang, Guofeng; Fletcher, Daniel A.; Robinson, Douglas N.; Chen, Elizabeth H.

    2015-01-01

    Membrane fusion is an energy-consuming process that requires tight juxtaposition of two lipid bilayers. Little is known about how cells overcome energy barriers to bring their membranes together for fusion. Previously, we have shown that cell-cell fusion is an asymmetric process in which an “attacking” cell drills finger-like protrusions into the “receiving” cell to promote cell fusion. Here we show that the receiving cell mounts a Myosin II (MyoII)-mediated mechanosensory response to its inv...

  15. Mechanism for collective cell alignment in Myxococcus xanthus bacteria

    CERN Document Server

    Balagam, Rajesh

    2015-01-01

    M. xanthus cells self-organize into clusters, aligned cell groups, at various stages of its lifecycle. Formation of these clusters is crucial for complex dynamic multi-cellular behavior of these bacteria. However the mechanism underlying the cell alignment and clustering is not fully understood. Motivated by studies of clustering in self-propelled rods, we hypothesized that M. xanthus cells can align and form clusters through pure mechanical interactions among cells and between cells and substrate. We test this hypothesis using an agent-based simulation framework where each agent is based on biophysical model of individual M. xanthus cell. We show that model agents, under realistic cell flexibility values, can align and form cell clusters but only when periodic reversals of cell directions are suppressed. However, by extending our model to introduce observed ability of cells to lay and follow slime trails, we show that effective trail following leads to clusters in reversing cells. Furthermore, we conclude th...

  16. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  17. New mechanism for neural stem cell maintenance in early embryos

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Teamning up with co-workers from Japan, UK and US,CAS biochemists have revealed a novel mechanism for maintaining neural stem cells in early embryos. Their work was published on the 6 August issue of Cell Development.

  18. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    International Nuclear Information System (INIS)

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo

  19. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hun; Kim, Il Joong; Yang, Jae Han; Byun, Joo Nam; Lee, Bong Jae [Chosun University, College of Medicine, Gwangju (Korea, Republic of); Kim, Jeong Hun; Yu, Young Suk [Seoul National University, College of Medicine, Seoul (Korea, Republic of)

    2007-05-15

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo.

  20. Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    International Nuclear Information System (INIS)

    Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for ≥24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth ≥12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of ≥19.3 and tumor depth of ≥12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. Conclusion: The combination of the primary tumor SUVmax (≥19.3) and pathologic tumor depth (≥12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death

  1. Tapping out a mechanical code for T cell triggering.

    Science.gov (United States)

    Dustin, Michael L; Kam, Lance C

    2016-06-01

    Mechanical forces play increasingly recognized roles in T cell receptor (TCR) signal transduction. Hu and Butte (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511053) demonstrate that actin is required for T cells to generate forces at the TCR and that exogenous application of force can emulate these cytoskeletal forces and trigger T cell activation. PMID:27269063

  2. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  3. Impact of FDG-PET/CT on Radiotherapy Volume Delineation in Non-Small-Cell Lung Cancer and Correlation of Imaging Stage With Pathologic Findings

    International Nuclear Information System (INIS)

    Purpose: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. Methods and Materials: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. Results: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. Conclusion: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible

  4. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  5. The Interplay between Cell Wall Mechanical Properties and the Cell Cycle in Staphylococcus aureus

    OpenAIRE

    Bailey, Richard G.; Turner, Robert D.; Mullin, Nic; Clarke, Nigel,; Foster, Simon J.; Hobbs, Jamie K.

    2014-01-01

    The nanoscale mechanical properties of live Staphylococcus aureus cells during different phases of growth were studied by atomic force microscopy. Indentation to different depths provided access to both local cell wall mechanical properties and whole-cell properties, including a component related to cell turgor pressure. Local cell wall properties were found to change in a characteristic manner throughout the division cycle. Splitting of the cell into two daughter cells followed a local softe...

  6. Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

    DEFF Research Database (Denmark)

    Heinemeier, K M; Skovgaard, D; Bayer, M L;

    2012-01-01

    Overuse Achilles tendinopathy is a common and challenging problem in sports medicine. Little is known about the etiology of this disorder, and the development of a good animal model for overuse tendinopathy is essential for advancing insight into the disease mechanisms. Our aim was to test a...... tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading....

  7. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  8. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  9. Derivation of cochlear cells from pathological or isogenic human iPSCs for modeling hereditary hearing loss

    OpenAIRE

    Czajkowski, Amandine; Grobarczyk, Benjamin; Hanon, Kevin; Lefebvre, Philippe; Delacroix, Laurence; Malgrange, Brigitte

    2016-01-01

    Alström Syndrome (AS) is a human autosomal recessive genetic disorder characterized by numerous clinical symptoms including deafness. AS is caused by mutations in the ALMS1 gene encoding for ALMS1 protein expressed at the basal body and implicated in ciliogenesis, cell cycle and proliferation (Jagger et al., 2011; Zulato et al., 2011 & Shenje et al., 2014). We are interesting in understanding the unknown mechanisms involving this protein in the genetic deafness of AS patients. To develop a m...

  10. Abnormal Calcium Handling Properties Underlie Familial Hypertrophic Cardiomyopathy Pathology in Patient-Specific Induced Pluripotent Stem Cells

    OpenAIRE

    Lan, Feng; Lee, Andrew S.; Liang, Ping; Sanchez-Freire, Veronica; Nguyen, Patricia K; Wang, Li; Han, Leng; Yen, Michelle; Wang, Yongming; Sun, Ning; Abilez, Oscar J.; Hu, Shijun; Ebert, Antje D.; Navarrete, Enrique G.; Simmons, Chelsey S.

    2013-01-01

    Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs)...

  11. Early and late-onset acute GvHD following hematopoietic cell transplantation: CT features of gastrointestinal involvement with clinical and pathological correlation

    International Nuclear Information System (INIS)

    Objective: With the introduction of non-myeloablative hematopoietic cell transplantation, acute graft-versus-host-disease (GvHD) is frequently observed beyond the traditional 100 days cut-off. The aim of this study was to describe and compare CT features of gastrointestinal early and late-onset GvHD and to correlate findings with clinical and pathology grading. Subjects and methods: Abdominal CT scans were obtained in 20 patients with early and 15 with late-onset GvHD. Examinations were assessed for intestinal and extraintestinal abnormalities and findings compared between the two subgroups of GvHD. Distinct CT abnormalities as well as a CT-score integrating multiple pathologies were correlated with gut, clinical or pathology grading. Results: Frequent intestinal abnormalities included wall thickening, abnormal enhancement, and excessive fluid-filling (94%, 89%, and 94%). 86% of patients showed concomitant small and large bowel involvement. A discontinuous distribution was observed in 54%. Bile tract abnormality was the most common extra-intestinal finding (74%). The distribution of pathologies was equal between subgroups of early or late-onset disease. Wall thickening and mucosal attenuation in non-enhanced scans were significantly related to clinical and pathology scores (P ≤ 0.018). Number of abnormal segments, small bowel dilatation, engorgement of the vasa recta, mesenteric fat stranding and ascites were linked to clinical grading (P ≤ 0.019). A CT-score integrating multiple abnormalities was correlated to gut, overall clinical and pathology grading (r = 0.64, 0.57, 0.50). Conclusion: CT morphology of acute GvHD is independent of its time of onset and, thus, facilitates differential diagnosis of late-onset acute GvHD. Correlation of CT morphology with clinical and pathological grading is important in terms of prognosis and may help guiding the therapeutic approach.

  12. Mechanical properties of normal versus cancerous breast cells.

    Science.gov (United States)

    Smelser, Amanda M; Macosko, Jed C; O'Dell, Adam P; Smyre, Scott; Bonin, Keith; Holzwarth, George

    2015-11-01

    A cell's mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-D-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes-Einstein relation to estimate the interior viscoelastic modulus G* and its components, the elastic shear modulus G' and viscous shear modulus G", at angular frequencies between 0.126 and 628 rad/s. These moduli are the material coefficients that enter into stress-strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells. PMID:25929519

  13. Cellular pressure and volume regulation and implications for cell mechanics.

    Science.gov (United States)

    Jiang, Hongyuan; Sun, Sean X

    2013-08-01

    In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death, and migration. Volume and shape regulation also directly impacts the mechanics of cells and tissues. Here, we develop a mathematical model of cellular volume and pressure regulation, incorporating essential elements such as water permeation, mechanosensitive channels, active ion pumps, and active stresses in the cortex. The model can fully explain recent experimental data, and it predicts cellular volume and pressure for several models of cell cortical mechanics. Moreover, we show that when cells are subjected to an externally applied load, such as in an atomic force microscopy indentation experiment, active regulation of volume and pressure leads to a complex cellular response. Instead of the passive mechanics of the cortex, the observed cell stiffness depends on several factors working together. This provides a mathematical explanation of rate-dependent response of cells under force. PMID:23931309

  14. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Ch(a)vez-Gal(a)n L; Arenas-Del Angel MC; Zenteno E; Ch(a)vez R; Lascurain R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lyric molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

  15. Fluoride inhibits the response of bone cells to mechanical loading

    NARCIS (Netherlands)

    H.M.E. Willems; E.G.H.M. van den Heuvel; S. Castelein; J. Keverling Buisman; A.L.J.J. Bronckers; A.D. Bakker; J. Klein-Nulend

    2011-01-01

    The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-respon

  16. Parkinson's disease: Studies on the pathology of the disease and the mechanism of action of the neurotoxin MPTP

    Energy Technology Data Exchange (ETDEWEB)

    D' Amato, R.J.

    1988-01-01

    In humans and animals, exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) causes certain clinical, pathological, and neurochemical features of Parkinson's disease (PD). MPTP is metabolized in the brain by monoamine oxidase (MAOb) to 1-methyl-4-phenylpyridine (MPP{sup +}), which is selectively accumulated and concentrated by high affinity uptake mechanisms into catecholamine neurons. We have demonstrated high affinity binding of MPP{sup +} to neuromelanin which may result in a toxic intraneuronal sequestration of MPP{sup +}. The involvement of neuromelanin is further supported by the demonstration that monkeys pretreated with chloroquine prior to the administration of MPTP are protected from MPTP induced neurotoxicity. Decreases in serotonin levels have been reported in the brains and spinal fluid of patients with both Parkinson's and Alzheimer's disease. In an effort to investigate the pathology of serotonin neurons in postmortem brain tissue from Parkinson's and Alzheimer's patients, ({sup 3}H)citalopram was characterized as a means of labeling serotonin uptake sites present on serotonin terminals.

  17. Cell death signalling mechanisms in heart failure

    OpenAIRE

    Mughal, Wajihah; Kirshenbaum, Lorrie A.

    2011-01-01

    In 2003, cardiovascular disease was the most costly disease in Canada, and it is still on the rise. The loss of properly functioning cardiomyocytes leads to cardiac impairment, which is a consequence of heart failure. Therefore, understanding the pathways of cell death (necrosis and apoptosis) has potential implications for the development of therapeutic strategies. In addition, the role of B-cell lymphoma-2 family members is discussed and the importance of mitochondria in directing cell deat...

  18. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    Directory of Open Access Journals (Sweden)

    Philip G.R. Schmalz

    2011-02-01

    Full Text Available Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed.

  19. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    OpenAIRE

    Schmalz, Philip G.R.; Park, John K.; Shen, Michael J.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects o...

  20. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  1. Expression of Yes-associated protein in non-small cell lung cancer and its relationship with clinical pathological factors

    Institute of Scientific and Technical Information of China (English)

    SU Li-li; MA Wei-xia; YUAN Jian-feng; SHAO Yang; XIAO Wei; JIANG Shu-juan

    2012-01-01

    Background Yes-associated protein(YAP)plays an important role in signal transduction and gene transcription regulation in normal cells,with elevated and over-expressed YAP levels observed in various malignant tumors.The aim of this study was to investigate the expression of YAP in non-small cell lung cancer(NSCLC),and to study the possible relationship of YAP expression with the occurrence and development of NSCLC.Methods YAP expression was assessed in 40 cases of NSCLC tumor tissues by immunohistochemistry,and their protein and mRNA levels were evaluated through Western blotting and reverse transcription-polymerase chain reaction(PCR),respectively.Normal lung tissues obtained from the same patient were used as control.Statistical analysis was performed to correlate the YAP expression to clinical pathological factors,such as tumor type,stage and grade.Results YAP-positive expression was found in 28(70%)of the 40 cases of NSCLC,which included 10 cases of squamous cell carcinoma(25%),17 cases of adenocarcinoma(42.5%)and 1 case of squamous adenocarcinoma(2.5%).In the 28 YAP-positive cases,19 cases showed lymph node metastasis and were classified in TNM stage Ⅱ+Ⅲ(47.5%);the other nine cases showed no lymph node metastasis(22.5%)and were classified in the TNM stage Ⅰ.There was no relationship between YAP expression and patients'age,gender or tumor histological grades.However,YAP showed significant over expression in late period of T stage(P=0.012),TNM stage(P=0.039),and lymph node metastasis(P=0.013),respectively.Notably,YAP-positive expression was significantly higher in adenocarcinoma than that in squamous cell carcinoma(P=0.041).Conclusions Over-expression of YAP was associated with NSCLC,especially lung adenocarcinoma.The high YAP expression in late period of tumor stage and lymph node metastasis may indicate that YAP expression could be an early marker for NSCLC tumorigenesis.

  2. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy.

    Science.gov (United States)

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-06-15

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD. PMID:25749991

  3. Non-invasive in Situ Simultaneous Measurement of Multi-parameter Mechanical Properties of Red Blood Cell Membrane

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Yao-Xiong HUANG; Tao JI; Mei TU; Xuan MAO; Wen-Xin CHEN; Guang-Wei CHEN

    2005-01-01

    The purpose of this study was to develop a new dynamic image analyzing technique that will give us the ability to measure the viscoelastic parameters of individual living red blood cells non-invasively, in situ and in real time. With this technique, the bending modulus Kc, the shear elasticityμ and their ratio ε were measured under different temperatures, oxygen partial pressures and osmotic pressures. The results not only show the effects of external conditions on mechanical properties of cell membranes including deformability,flexibility, adhesive ability and plasticity, but also demonstrate that the technique can be used to measure cell membrane parameters continuously under several physiological and pathological conditions.

  4. Down-regulation of adipogenesis of mesenchymal stem cells by oscillating high-gradient magnetic fields and mechanical vibration

    Science.gov (United States)

    Zablotskii, V.; Lunov, O.; Novotná, B.; Churpita, O.; Trošan, P.; HoláÅ, V.; Syková, E.; Dejneka, A.; Kubinová, Š.

    2014-09-01

    Nowadays, the focus in medicine on molecular genetics has resulted in a disregard for the physical basis of treatment even though many diseases originate from changes in cellular mechanics. Perturbations of the cellular nanomechanics promote pathologies, including cardiovascular disease and cancer. Furthermore, whilst the biological and therapeutic effects of magnetic fields are a well-established fact, to date the underlying mechanisms remain obscure. Here, we show that oscillating high-gradient magnetic field (HGMF) and mechanical vibration affect adipogenic differentiation of mesenchymal stem cells by the transmission of mechanical stress to the cell cytoskeleton, resulting in F-actin remodelling and subsequent down-regulation of adipogenic genes adiponectin, PPARγ, and AP2. Our findings propose an insight into the regulation of cellular nanomechanics, and provide a basis for better controlled down-regulation of stem cell adipogenesis by HGMF, which may facilitate the development of challenging therapeutic strategies suitable for the remote control of biological systems.

  5. Complications of Pathologic Myopia.

    Science.gov (United States)

    Cho, Bum-Joo; Shin, Joo Young; Yu, Hyeong Gon

    2016-01-01

    Pathologic myopia (PM) is one of the leading causes of visual impairment worldwide. The pathophysiology of PM is not fully understood, but the axial elongation of the eye followed by chorioretinal thinning is suggested as a key mechanism. Pathologic myopia may lead to many complications such as chorioretinal atrophy, foveoschisis, choroidal neovascularization, rhegmatogenous retinal detachment, cataract, and glaucoma. Some complications affect visual acuity significantly, showing poor visual prognosis. This article aims to review the types, pathophysiology, treatment, and visual outcome of the complications of PM. PMID:26649982

  6. Mechanical behavior of alternative multicrystalline silicon for solar cells

    OpenAIRE

    Orellana Pérez, Teresa

    2013-01-01

    The usage of more inexpensive silicon feedstock for the crystallization of multicrystalline silicon blocks promises cost reduction for the photovoltaic industry. Less expensive substrates made out of metallurgical silicon (MG-Si) are used as a mechanical support for the epitaxial solar cell. Moreover, conventional inert solar cells can be produced from up-graded metallurgical silicon (UMG-Si). This feedstock has higher content of impurities which influences cell performance and mechanical str...

  7. Mechanism of regulation of stem cell differentiation by matrix stiffness

    OpenAIRE

    Lv, Hongwei; Li, Lisha; Sun, Meiyu; Zhang, Yin; Chen, Li; Rong, Yue; Li, Yulin

    2015-01-01

    Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by which stem cells respond to microenvironmental stiffness through the dynamics of the cytoskeletal network, leading to changes in gene expression via biophysical transduction sign...

  8. Mechanisms of dealing with DNA damage in terminally differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Fortini, P. [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, E., E-mail: eugenia.dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy)

    2010-03-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  9. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

    Cells are constantly exposed to changes in cell volume during cell metabolism, nutrient uptake, cell proliferation, cell migration and salt and water transport. In order to cope with these perturbations, potassium channels in line with chloride channels have been shown to be likely contributors to...... the process of cell volume adjustments. A great diversity of potassium channels being members of either the 6TM, 4 TM or 2 TM K+ channel gene family have been shown to be strictly regulated by small, fast changes in cell volume. However, the precise mechanism underlying the K+ channel sensitivity to...... cell volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have...

  10. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism

    OpenAIRE

    Coombes, Janine L.; Siddiqui, Karima R.R.; Arancibia-Cárcamo, Carolina V.; Hall, Jason; Sun, Cheng-Ming; Belkaid, Yasmine; Powrie, Fiona

    2007-01-01

    Foxp3+ regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3+ T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-β can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. H...

  11. [Researches on mechanism of cell toxicity caused by niclosamide].

    Science.gov (United States)

    Xu, Ying; Dai, Jian-rong

    2015-02-01

    Niclosamide is the most commonly used molluscicide. Along with a lot of application of niclosamide, more and more scientists studied its toxic effects to aquatic organisms as well as the related cell toxicity mechanism. This paper summarizes the toxicity on cell, organelle, enzyme, cell signaling pathway, and genetic material caused by niclosamide, and puts forward the future research direction. PMID:26094434

  12. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

    Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

  13. Pathological Propagation through Cell-to-Cell Transmission of Non-Prion Protein Aggregates in Neurodegenerative Disorders

    Science.gov (United States)

    Lee, Seung-Jae; Desplats, Paula; Sigurdson, Christina; Tsigelny, Igor; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, fronto-temporal dementia, Huntington's Disease and Creutzfeldt-Jakob Disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. While protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has been reserved to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence suggests that prion-like spreading may occur in other neurodegenerative disorders, taking place with secreted proteins, such as amyloid-β,) and cytosolic proteins, such as tau, huntingtin and α-synuclein. Underlying molecular mechanisms and therapeutic implications are discussed. PMID:21045796

  14. Mechanisms of daughter cell-size control during cell division.

    Science.gov (United States)

    Kiyomitsu, Tomomi

    2015-05-01

    Daughter cell size is tightly regulated during cell division. In animal cells, the position of the anaphase spindle specifies the cell cleavage site to dictate the relative size of the daughter cells. Although spindle orientation is regulated by dynein-dependent cortical pulling forces exerted on astral microtubules in many cell types, it was unclear how these forces are precisely regulated to center or displace the spindle. Recently, intrinsic signals derived from chromosomes or spindle poles have been demonstrated to regulate dynein-dependent pulling forces in symmetrically dividing cells. Unexpectedly, myosin-dependent contractile forces have also been shown to control spindle position by altering the cellular boundaries during anaphase. In this review, I discuss how dynein- and myosin-dependent forces are coordinately regulated to control daughter cell size. PMID:25548067

  15. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  16. The Mechanisms of Plant Cell Wall Deconstruction during Enzymatic Hydrolysis

    OpenAIRE

    Thygesen, Lisbeth G; Thybring, Emil E.; Johansen, Katja S.; Claus Felby

    2014-01-01

    Mechanical agitation during enzymatic hydrolysis of insoluble plant biomass at high dry matter contents is indispensable for the initial liquefaction step in biorefining. It is known that particle size reduction is an important part of liquefaction, but the mechanisms involved are poorly understood. Here we put forward a simple model based on mechanical principles capable of capturing the result of the interaction between mechanical forces and cell wall weakening via hydrolysis of glucosidic ...

  17. Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype: their possible involvement in pathological processes.

    Science.gov (United States)

    Ohnishi, Koji; Komohara, Yoshihiro; Sakashita, Naomi; Iyama, Ken-Ichi; Murayama, Toshihiko; Takeya, Motohiro

    2010-01-01

    Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3. PMID:20055949

  18. Cellular Pressure and Volume Regulation and Implications for Cell Mechanics

    OpenAIRE

    Jiang, Hongyuan; Sun, Sean X.

    2013-01-01

    In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death, and migration. Volume and shape regulation also directly impacts the mechanics of cells and tissues. Here, we develop a mathematical model of cellular volume and pressure regulation, incorporating essential elements such as water permeation, mechanosensitive channels, active ion pumps, and active stresses in the cortex. The model can fully explain recent experimental data, and it pr...

  19. Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases

    Science.gov (United States)

    Heidari, Moones; Gerami, Sam H.; Bassett, Brianna; Graham, Ross M.; Chua, Anita C.G.; Aryal, Ritambhara; House, Michael J.; Collingwood, Joanna F.; Bettencourt, Conceição; Houlden, Henry; Ryten, Mina; Olynyk, John K.; Trinder, Debbie; Johnstone, Daniel M.; Milward, Elizabeth A.

    2016-01-01

    ABSTRACT We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe−/−xTfr2mut mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family ‘neurodegeneration with brain iron accumulation’ (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading. Concordance between the mouse transcriptome changes and human myelin-related gene expression networks in normal and NBIA basal ganglia testifies to potential clinical relevance. These analyses implicate, among others, genes linked to various rare central hypomyelinating leukodystrophies and peripheral neuropathies including Pelizaeus-Merzbacher-like disease and Charcot-Marie-Tooth disease as well as genes linked to other rare neurological diseases such as Niemann-Pick disease. The findings may help understand interrelationships of iron and myelin in more common conditions such as hemochromatosis, multiple sclerosis and various psychiatric disorders. PMID:27500074

  20. Mechanism for Collective Cell Alignment in Myxococcus xanthus Bacteria.

    Directory of Open Access Journals (Sweden)

    Rajesh Balagam

    2015-08-01

    Full Text Available Myxococcus xanthus cells self-organize into aligned groups, clusters, at various stages of their lifecycle. Formation of these clusters is crucial for the complex dynamic multi-cellular behavior of these bacteria. However, the mechanism underlying the cell alignment and clustering is not fully understood. Motivated by studies of clustering in self-propelled rods, we hypothesized that M. xanthus cells can align and form clusters through pure mechanical interactions among cells and between cells and substrate. We test this hypothesis using an agent-based simulation framework in which each agent is based on the biophysical model of an individual M. xanthus cell. We show that model agents, under realistic cell flexibility values, can align and form cell clusters but only when periodic reversals of cell directions are suppressed. However, by extending our model to introduce the observed ability of cells to deposit and follow slime trails, we show that effective trail-following leads to clusters in reversing cells. Furthermore, we conclude that mechanical cell alignment combined with slime-trail-following is sufficient to explain the distinct clustering behaviors observed for wild-type and non-reversing M. xanthus mutants in recent experiments. Our results are robust to variation in model parameters, match the experimentally observed trends and can be applied to understand surface motility patterns of other bacterial species.

  1. Cytotoxinic Mechanism of Hydroxyapatite Nanoparticles on Human Hepatoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    CAO Xian-ying; QI Zhi-tao; DAI Hong-lian; YAN Yu-hua; LI Shi-pu

    2003-01-01

    Stable and single-dispersed HAP nanoparticles were synthesized with chemical method assisted by ultrasonic treatment.HAP nanoparticles were surveyed by AFM and Zataplus.The effect on the Bel-7402 human hepatoma cell lines treated with HAP nanoparticles was investigated by the MTT methods and observation of morphology,and the mechanism was studied in changes of cell cycle and ultrastructure.The result shows that inhibition of HAP nanoparticles on the Bel-7402 human hepatoma cell lines is obviously in vitro.HAP nanoparticles the entered cancer cytoplasm,and cell proliferation is stopped at G1 phase of cell cycle,thus,cancer cells die directly.

  2. Mechanisms of pancreatic beta-cell growth and regeneration

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1989-01-01

    Information about the mechanism of beta-cell growth and regeneration may be obtained by studies of insulinoma cells. In the present study the growth and function of the rat insulinoma cell lines RINm5F and 5AH were evaluated by addition of serum, hormones, and growth factors. It was found...... of insulin mRNA content showed that the insulinoma cells only contained about 2% of that of normal rat beta-cells. These results are discussed in relation to the role of growth factors, oncogenes, and differentiation in the growth and regeneration of beta-cells....

  3. Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network

    DEFF Research Database (Denmark)

    Klapper, W.; Hoster, E.; Determann, O.;

    2009-01-01

    Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very...... powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 x 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value.......37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 x 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given...

  4. Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy

    OpenAIRE

    Wang, Qifeng; Shufei YU; Xiao, Zefen; Liu, Xiao; Zhang, Wencheng; Zhang, Xun; He, Jie; Kelin SUN; Xu, Ting; Feng, Qinfu; Zhou, Zongmei; Wang, Lvhua; Yin, Weibo

    2015-01-01

    Objective To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Patients and methods Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of resi...

  5. Dynamic monitoring of cell mechanical properties using profile microindentation

    Science.gov (United States)

    Guillou, L.; Babataheri, A.; Puech, P.-H.; Barakat, A. I.; Husson, J.

    2016-02-01

    We have developed a simple and relatively inexpensive system to visualize adherent cells in profile while measuring their mechanical properties using microindentation. The setup allows simultaneous control of cell microenvironment by introducing a micropipette for the delivery of soluble factors or other cell types. We validate this technique against atomic force microscopy measurements and, as a proof of concept, measure the viscoelastic properties of vascular endothelial cells in terms of an apparent stiffness and a dimensionless parameter that describes stress relaxation. Furthermore, we use this technique to monitor the time evolution of these mechanical properties as the cells’ actin is depolymerized using cytochalasin-D.

  6. Mechanopathology of red blood cell diseases—Why mechanics matters

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures.These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and adhesion.As such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones.Here,we will present biomechanistic insights into red blood cell related diseases that manifest...

  7. Effects of estrogen on diverse stem cells and relevant intracellular mechanisms

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Sexual dimorphism definitely exists in the pathogenesis of a variety of cardiovascular,neurodegenerative and bone metabolism disorders.Estrogen affects the healing of ischemic myocardium partially through paracrine growth hormone production by bone marrow mesenchymal stem cells(MSCs) and facilitation on mobilization of endothelial progenitors cells(EPCs) to the ischemic myocardium.Estrogen can also inhibit the proliferation of the cardiac fibroblasts.Therefore,estrogen effectively enhances the neovascularization at the ischemic border zone and limits pathological myocardial remodeling.Moreover,estrogen increases proliferation of embryonic neural stem cells and accelerates differentiation of neurons during neurogenesis,suggesting a possible role of estrogen in transplantation of neural stem cells as a therapeutic approach for neurodegenerative diseases.Finally,estrogen can modulate osteogenic progenitors and osteoclasts,preventing the osteoporosis.In general,estrogen offers significant benefits on diverse stem/progenitor cell populations.A great understanding of estrogens on these cells and relevant intracellular mechanisms will allow modulation of the potent stem cells directly for the ultimate clinical applications.

  8. Establishing the Turing mechanism using synthetic cells

    Science.gov (United States)

    Girabawe, Camille; Tompkins, Nathan; Li, Ning; Bard Ermentrout, G.; Epstein, Irving R.; Fraden, Seth

    2013-03-01

    In 1952 Alan Turing published his seminal pape The Chemical Basis of Morphogenesiin which he described a basis for physical morphogenesis due solely to a reaction-diffusion system. His mechanism has been tested extensively but remains controversial and not fully demonstrated for cellular systems. Now 60 years after its debu, we describe an experimental system that demonstrates all six of his phenomenological predictions with additional support that these observations are due specifically to the Turing mechanism itsel. Further we demonstrate a nonlinear phenomena in the same system that was not predicted by Turing and which is not explained by a linear solution analysis of the governing system equations. Finally we also demonstrate that this system undergoes chemical and physical morphogenesis as Turing suggeste.

  9. Pathological gambling.

    Science.gov (United States)

    Hollander, E; Buchalter, A J; DeCaria, C M

    2000-09-01

    With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG. PMID:10986732

  10. Mechanical downstream processing of Single Cell Oils

    OpenAIRE

    De Coninck, Maarten; Van Hecke, Renaat; Deprez, Koen; De Baerdemaeker, Josse

    2011-01-01

    During the last years, the third generation of bio fuels has been arousing more and more interest. Under certain conditions some micro organisms: yeasts, algae, fungi and bacteria, can accumulate up to 50% oil (based on dry weight). These so-called ‘Single cell oils’ (SCO) are well known in this context. Nowadays, harvesting and recovery of interesting products from microalgae is one of the most problematic areas of algal biofuel production technology. The traditional downstream process,...

  11. Exosomes in liver pathology.

    Science.gov (United States)

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  12. Spectroscopic investigation of local mechanical impedance of living cells

    CERN Document Server

    Costa, Luca; Benseny-Cases, Núria; Mayeaux, Véronique; Chevrier, Joël; Comin, Fabio

    2013-01-01

    The mechanical properties of PC12 living cells have been studied at the nanoscale with a Force Feedback Microscope using two experimental approaches. Firstly, the local mechanical impedance of the cell membrane has been mapped simultaneously to the cell morphology at constant force. As the force of the interaction is gradually increased, we observed the appearance of the sub-membrane cytoskeleton. We shall compare the results obtained with this method with the measurement of other existing techniques. Secondly, a spectroscopic investigation has been performed varying the indentation of the tip in the cell membrane and consequently the force applied on it. In contrast with conventional dynamic atomic force microscopy techniques, here the small oscillation amplitude of the tip is not necessarily imposed at the cantilever first eigenmode. This allows the user to arbitrarily choose the excitation frequency in developing spectroscopic AFM techniques. The mechanical response of the PC12 cell membrane is found to be...

  13. Engineering Cell and Tissue Mechanical Microenvironments for Regenerative Medicine

    OpenAIRE

    Tsou, Danielle An-Chi

    2012-01-01

    One of the goals of tissue engineering is to create technologies that will improve or replace biological function of diseased or damaged cells and tissues. The purpose of my thesis work is to determine how the mechanical properties of the murine microenvironment, specifically matrix stiffness, can affect the function and behavior of cells and tissues. Previous research has shown that stiffness is a powerful mechanical property; it is associated with breast and liver cancer, and can also be ...

  14. The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis

    OpenAIRE

    Wang, Fei

    2009-01-01

    Chemotaxis—the directed movement of cells in a gradient of chemoattractant—is essential for neutrophils to crawl to sites of inflammation and infection and for Dictyostelium discoideum (D. discoideum) to aggregate during morphogenesis. Chemoattractant-induced activation of spatially localized cellular signals causes cells to polarize and move toward the highest concentration of the chemoattractant. Extensive studies have been devoted to achieving a better understanding of the mechanism(s) use...

  15. Atomic force microscopy and MD simulations reveal pore-like structures of all-D-enantiomer of Alzheimer's β-amyloid peptide: relevance to the ion channel mechanism of AD pathology.

    Science.gov (United States)

    Connelly, Laura; Jang, Hyunbum; Arce, Fernando Teran; Capone, Ricardo; Kotler, Samuel A; Ramachandran, Srinivasan; Kagan, Bruce L; Nussinov, Ruth; Lal, Ratnesh

    2012-02-01

    Alzheimer's disease (AD) is a protein misfolding disease characterized by a buildup of β-amyloid (Aβ) peptide as senile plaques, uncontrolled neurodegeneration, and memory loss. AD pathology is linked to the destabilization of cellular ionic homeostasis and involves Aβ peptide-plasma membrane interactions. In principle, there are two possible ways through which disturbance of the ionic homeostasis can take place: directly, where the Aβ peptide either inserts into the membrane and creates ion-conductive pores or destabilizes the membrane organization, or, indirectly, where the Aβ peptide interacts with existing cell membrane receptors. To distinguish between these two possible types of Aβ-membrane interactions, we took advantage of the biochemical tenet that ligand-receptor interactions are stereospecific; L-amino acid peptides, but not their D-counterparts, bind to cell membrane receptors. However, with respect to the ion channel-mediated mechanism, like L-amino acids, D-amino acid peptides will also form ion channel-like structures. Using atomic force microscopy (AFM), we imaged the structures of both D- and L-enantiomers of the full length Aβ(1-42) when reconstituted in lipid bilayers. AFM imaging shows that both L- and D-Aβ isomers form similar channel-like structures. Molecular dynamics (MD) simulations support the AFM imaged 3D structures. Previously, we have shown that D-Aβ(1-42) channels conduct ions similarly to their L- counterparts. Taken together, our results support the direct mechanism of Aβ ion channel-mediated destabilization of ionic homeostasis rather than the indirect mechanism through Aβ interaction with membrane receptors. PMID:22217000

  16. Mass transport mechanism in porous fuel cell electrodes

    Science.gov (United States)

    Jonsson, I.; Lindholm, I.

    1969-01-01

    Results of experiments on hydrogen-oxygen fuel cells show that higher current densities are obtained with cell anodes having a 100 micron thin active layer of porous nickel containing silver electrocatalyst. Increase in current density is attributed to a convective mass transport mechanism.

  17. Mechanism isolates load weighing cell during lifting of load

    Science.gov (United States)

    Haigler, J. S.

    1966-01-01

    Load weighing cell used in conjuction with a hoist is isolated during lifting and manipulation of the load. A simple mechanism, attached to a crane hook, provides a screw adjustment for engaging the load cell during weighing of the load and isolating it from lift forces during hoisting of the load.

  18. Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: Clinical, biochemical, and pathological improvements

    Directory of Open Access Journals (Sweden)

    Eriko Yasuda

    2015-03-01

    In conclusion, this long-term post-HSCT observation should shed light on a new aspect of therapeutic effect associated with skeletal pathology and GAG levels as a biomarker, indicating that HSCT is a primary choice at an early stage for not only CNS but also skeletal system in combination of appropriate surgical procedures.

  19. Microchimerism in Endocrine Pathology

    OpenAIRE

    Rust, Daniel W.; Bianchi, Diana W.

    2009-01-01

    Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated...

  20. T-cell Migration, Search Strategies and Mechanisms

    Science.gov (United States)

    Krummel, Matthew F; Bartumeus, Frederic; Gérard, Audrey

    2016-01-01

    T cell migration is essential for T cell responses, allowing for detection of cognate antigen at the surface of an Antigen-Presenting Cell (APC) and for interactions with other cells involved in the immune response. Although appearing random, growing evidence supports that T cell motility patterns are strategic and governed by mechanisms that are optimized for both activation-stage and environment-specific attributes. In this Opinion Article, we will discuss how to understand the combined effects of T cell- intrinsic and -extrinsic forces upon these motility patterns when viewed in highly complex tissues filled with other cells involved in parallel motility. In particular, we will examine how insights from ‘search theory’ describe T cell movement across exploitation-exploration gradients, in the context of activation versus effector function and in the context of lymph nodes versus peripheral tissues. PMID:26852928

  1. [NKT cells: their development, mechanisms and effects of action].

    Science.gov (United States)

    Bojarska-Junak, Agnieszka; Tabarkiewicz, Jacek; Roliński, Jacek

    2013-01-01

    NKT cells are a heterogeneous subset of T lymphocytes that share surface markers and functional characteristics with both conventional T lymphocytes and natural killer cells. Most NKT cells express a semi-invariant T cell receptor that reacts with glycolipid antigens presented by the CD1d molecule on the surface of antigen-presenting cells. NKT cells can modulate the immune response against infectious agents, autoantigens, tumors, tissue grafts and allergens. NKT cells mediate the activities through their ability to express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. The manuscript summarizes current views on development of NKT cells as well as mechanisms and effects of their action.  PMID:23475484

  2. Immunomodulatory functions of mesenchymal stem cells and possible mechanisms.

    Science.gov (United States)

    Wang, Qing; Ding, Gang; Xu, Xin

    2016-09-01

    In addition to their well-studied self-renewal capabilities and multipotent differentiation properties, mesenchymal stem cells (MSCs) have been reported to possess profound immunomodulatory functions both in vitro and in vivo. More and more studies have shown that MSCs are capable of interacting closely with almost all subsets of immune cells, such as T cells, B cells, dendritic cells, natural killer cells, macrophages, and neutrophils etc. The immunomodulatory property of MSCs may shed light on the treatment of a variety of autoimmune and inflammation-related diseases. In this article, we will review the studies on the immunomodulatory and anti-inflammatory functions of MSCs and the mechanisms responsible for the interaction between immune cells and MSCs, which could improve the development of promising approaches for cell-mediated immune therapies. PMID:26932157

  3. Application of ADC measurement in characterization of renal cell carcinomas with different pathological types and grades by 3.0 T diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Purpose: To test the feasibility of apparent diffusion coefficient (ADC) value obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of renal cell carcinomas (RCC) with different pathological subtypes and grades. Materials and methods: A total of 137 patients who were diagnosed with RCC and underwent DWI were included in this study. The diagnosis was confirmed by pathological examination of surgical specimens. Images of DWI were obtained with b values of 0 and 800 s/mm2. The ADC values in the solid area of tumors and in the corresponding regions of contralateral normal renal parenchyma were measured and analyzed statistically. Results: The mean ADC value was significantly lower in RCC (1.381 ± 0.444 × 10−3 mm2/s) than in normal renal parenchyma (2.232 ± 0.221 × 10−3 mm2/s) (P < 0.001). The ADC value was also statistically different between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of CCRCC except grade I vs II and grade III vs IV. Conclusion: ADC measurement on 3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of differentiation of RCC and normal renal parenchyma, and characterization of RCC with different pathological subtypes and grades.

  4. Application of ADC measurement in characterization of renal cell carcinomas with different pathological types and grades by 3.0 T diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiaoduo, E-mail: yxd98@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Lin, Meng, E-mail: linmeng77xp@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Ouyang, Han, E-mail: hbybj@sohu.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhou, Chunwu, E-mail: cjr.zhouchunwu@163.vip.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhang, Hongtu, E-mail: zhanghongtu1010@yahoo.com.cn [Department of Pathology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China)

    2012-11-15

    Purpose: To test the feasibility of apparent diffusion coefficient (ADC) value obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of renal cell carcinomas (RCC) with different pathological subtypes and grades. Materials and methods: A total of 137 patients who were diagnosed with RCC and underwent DWI were included in this study. The diagnosis was confirmed by pathological examination of surgical specimens. Images of DWI were obtained with b values of 0 and 800 s/mm{sup 2}. The ADC values in the solid area of tumors and in the corresponding regions of contralateral normal renal parenchyma were measured and analyzed statistically. Results: The mean ADC value was significantly lower in RCC (1.381 {+-} 0.444 Multiplication-Sign 10{sup -3} mm{sup 2}/s) than in normal renal parenchyma (2.232 {+-} 0.221 Multiplication-Sign 10{sup -3} mm{sup 2}/s) (P < 0.001). The ADC value was also statistically different between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of CCRCC except grade I vs II and grade III vs IV. Conclusion: ADC measurement on 3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of differentiation of RCC and normal renal parenchyma, and characterization of RCC with different pathological subtypes and grades.

  5. A Comprehensive Review of Optical Stretcher for Cell Mechanical Characterization at Single-Cell Level

    Directory of Open Access Journals (Sweden)

    Tie Yang

    2016-05-01

    Full Text Available This paper presents a comprehensive review of the development of the optical stretcher, a powerful optofluidic device for single cell mechanical study by using optical force induced cell stretching. The different techniques and the different materials for the fabrication of the optical stretcher are first summarized. A short description of the optical-stretching mechanism is then given, highlighting the optical force calculation and the cell optical deformability characterization. Subsequently, the implementations of the optical stretcher in various cell-mechanics studies are shown on different types of cells. Afterwards, two new advancements on optical stretcher applications are also introduced: the active cell sorting based on cell mechanical characterization and the temperature effect on cell stretching measurement from laser-induced heating. Two examples of new functionalities developed with the optical stretcher are also included. Finally, the current major limitation and the future development possibilities are discussed.

  6. Preclinical models for in vitro mechanical loading of bone-derived cells.

    Science.gov (United States)

    Michael Delaine-Smith, Robin; Javaheri, Behzad; Helen Edwards, Jennifer; Vazquez, Marisol; Rumney, Robin Mark Howard

    2015-01-01

    It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro. PMID:26331007

  7. T-cell regulatory mechanisms in specific immunotherapy.

    Science.gov (United States)

    Jutel, Marek; Akdis, Cezmi A

    2008-01-01

    Allergen-specific immunotherapy (SIT) is the only treatment which leads to a lifelong tolerance against previously disease-causing allergens due to restoration of normal immunity against allergens. The description of T-regulatory (Treg) cells being involved in prevention of sensitization to allergens has led to great interest whether they represent a major target for allergen-SIT and whether it would be possible to manipulate Treg cells to increase its efficacy. Activationinduced cell death, anergy and/or immune response modulation by Treg cells are essential mechanisms of peripheral T-cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to Treg cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen-SIT. The Treg cell response is characterized by abolished allergen- induced specific T-cell proliferation and suppressed Thelper (Th)1- and Th2-type cytokine secretion. In addition, mediators of allergic inflammation that trigger cAMP-associated G-protein-coupled receptors, such as histamine receptor-2, may contribute to peripheral tolerance mechanisms. The increased levels of interleukin-10 and transforming growth factor-Beta that are produced by Treg cells potently suppress IgE production, while simultaneously increasing production of non-inflammatory isotypes IgG4 and IgA, respectively. In addition, Treg cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response. By the application of the recent knowledge in Treg

  8. Mechanism of heavy ion radiation-induced cancer cell death

    International Nuclear Information System (INIS)

    We previously reported that the carbon beam triggers apoptosis in radio-resistant cancer cell lines via extracellular signal-regulated kinase (ERK)- and mitochondrial Bcl-2 family protein-dependant mechanism. Here, we further examined the further apoptosis-inducing mechanism of carbon beam in two glioma cell lines (T98G, U251). ERK1/2 knockdown experiments revealed that ERK regulates this apoptosis-inducing machinery upstream of mitochondria. Furthermore, we also found that both T98G cell and U251 cell stably expressing dominant-negative ERK2 suppress cell death induced by carbon beam irradiation. We also found proapoptotic PUMA and antiapoptotic Bcl-2 dynamically chang their expression levels corresponding to ERK activation after CB irradiation in U251 cell, and knockdown of PUMA decreased CB-induced U251 cell death. These data suggest that kinase action of ERK is essential for CB-induced glioma cell death, and proapoptotic PUMA and antiapoptotic Bcl-2 might be downstream targets of ERK in CB-induced glioma cell death mechanism. (author)

  9. Acetylation regulates DNA repair mechanisms in human cells.

    Science.gov (United States)

    Piekna-Przybylska, Dorota; Bambara, Robert A; Balakrishnan, Lata

    2016-06-01

    The p300-mediated acetylation of enzymes involved in DNA repair and replication has been previously shown to stimulate or inhibit their activities in reconstituted systems. To explore the role of acetylation on DNA repair in cells we constructed plasmid substrates carrying inactivating damages in the EGFP reporter gene, which should be repaired in cells through DNA mismatch repair (MMR) or base excision repair (BER) mechanisms. We analyzed efficiency of repair within these plasmid substrates in cells exposed to deacetylase and acetyltransferase inhibitors, and also in cells deficient in p300 acetyltransferase. Our results indicate that protein acetylation improves DNA mismatch repair in MMR-proficient HeLa cells and also in MMR-deficient HCT116 cells. Moreover, results suggest that stimulated repair of mismatches in MMR-deficient HCT116 cells is done though a strand-displacement synthesis mechanism described previously for Okazaki fragments maturation and also for the EXOI-independent pathway of MMR. Loss of p300 reduced repair of mismatches in MMR-deficient cells, but did not have evident effects on BER mechanisms, including the long patch BER pathway. Hypoacetylation of the cells in the presence of acetyltransferase inhibitor, garcinol generally reduced efficiency of BER of 8-oxoG damage, indicating that some steps in the pathway are stimulated by acetylation. PMID:27104361

  10. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  11. Pathology Reports

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer ... edge of the material removed Negative, not involved, clear, or free ... as carcinoma, melanoma, and lymphoma Help diagnose and classify leukemias ...

  12. Measurement of red blood cell mechanics during morphological changes

    Science.gov (United States)

    Popescu, Gabriel; Park, Yongkeun; Best, Catherine; Dasari, Ramachandra; Feld, Michael; Kuriabova, Tatiana; Henle, Mark; Levine, Alex

    2010-03-01

    The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell's morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a Noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane's shear and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery.

  13. Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization.

    Science.gov (United States)

    Durham, Paul L

    2016-08-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

  14. Tumor cell heterogeneity: impact on mechanisms of therapeutic drug resistance

    International Nuclear Information System (INIS)

    Purpose: The aim of these studies was to determine whether chemotherapy-resistant tumor cell sublines derived from a single starting cell population with identical treatment protocols, have the same mechanism of resistance. Methods and Materials: Twelve cyclophosphamide-resistant sublines were derived from KHT-iv murine sarcoma cells by repeated exposures to 2, 4, or 8 μg/ml doses of 4-hydroperoxycyclophosphamide (4-OOHCP). To investigate possible mechanisms of resistance, glutathione (GSH) levels, glutathione S-transferase (GST) activity, and aldehyde dehydrogenase (ALDH) activity were determined. In addition, studies with the GSH depletor buthionine sulfoximine (BSO) and the ALDH inhibitor diethylamino-benzaldehyde (DEAB) were undertaken. Results: Resistant factors to 4-OOHCP, assessed at 10% clonogenic cell survival, ranged from 1.5-7.0 for the various cell lines. Crossresistance to melphalan and adriamycin also were commonly observed. Increased GSH levels, GST activity and ALDH activity were detected in the sublines but not all exhibited the same pattern of biochemical alterations. The response to GSH and ALDH inhibitors also varied among the sublines; the resistance being reversible in some cell lines but not others. Conclusion: The present results indicate that when resistant sublines are derived simultaneously from the same starting cell population, the observed mechanisms of resistance may not be the same in each of the variants. These findings support the hypothesis that preexisting cellular heterogeneity may affect mechanisms of acquired resistance

  15. Investigation of the Biochemical Mechanism for Cell-Substrate Mechanical Sensing

    Science.gov (United States)

    Ricotta, Vincent Anthony

    Advancements in stem cell biology and materials science have enabled the development of new treatments for tissue repair. Dental pulp stem cells (DPSCs), which are highly proliferative and can be induced to differentiate along several mesenchymal cell lineages, offer the possibility for pulpal regeneration and treatment of injured dentition. Polybutadiene (PB) may be used as a substrate for these cells. This elastomer can be spun casted into films of different thicknesses with different moduli. DPSCs grown on PB films, which are relatively hard (less than 1500 A thick), biomineralize depositing crystalline calcium phosphate without a requirement for the typical induction factor, dexamethasone (Dex). The moduli of cells track with the moduli of the surface suggesting that mechanics controls mineralization. The purpose of this study was to determine whether the major effect of Dex on biomineralization is the result of its ability to alter cell mechanics or its ability to induce osteogenesis/odontogenesis. DPSCs sense substrate mechanics through the focal adhesions, whose function is in part regulated by the Ras homolog gene (Rho) and its downstream effectors Rho associated kinases (ROCKs). ROCKs control actin filament polymerization and interactions with myosin light chain. Because cells sense substrate mechanics through focal adhesion proteins whose function is regulated by ROCKs, the impact of a ROCK inhibitor, Y-27632, was monitored. Blocking this pathway with Y-27632 suppressed the ability of DPSCs to sense the PB substrate. The cell modulus, plasma membrane stiffness, and cytosol stiffness were all lowered and biomineralization was suppressed in all cultures independent of substrate modulus or the presence of Dex. In other words, the inability of DPSCs to sense mechanical cues suppressed their ability to promote mineralization. On the other hand the expression of osteogenic/odontogenic markers (alkaline phosphatase and osteocalcin) was enhanced, perhaps due to Y

  16. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    DEFF Research Database (Denmark)

    Lottrup, G; Nielsen, J E; Maroun, L L;

    2014-01-01

    STUDY QUESTION: What is the differentiation stage of human testicular interstitial cells, in particular Leydig cells (LC), within micronodules found in patients with infertility, testicular cancer and Klinefelter syndrome? SUMMARY ANSWER: The Leydig- and peritubular-cell populations in testes with......, are impaired in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of...... specimens and in 58 adult testis samples from patients with testicular germ cell tumours, including precursor carcinoma in situ (CIS), infertility or Klinefelter syndrome. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression patterns of DLK1, INSL3, chicken ovalbumin upstream promoter transcription...

  17. Mechanism of Suppression on Proliferation of QGY Cell by Oxaliplatin

    Institute of Scientific and Technical Information of China (English)

    HE Song; ZUO Guo-qing; ZHANG Yan; TANG Wei-xue; LIU Chang-an

    2007-01-01

    Objective: To observe the effects of oxaliplatin(L-OHP) on proliferation of human hepatoma cell line QGY in vitro and to investigate the mechanism. Methods: The inhibition of proliferation in QGY cell was assayed by MTT-test. Morphologic changes were observed under light microscope and electronic microscope. Distribution of cell cycle and apoptosis were analyzed using flow cytometry. The expressions of cell cycle proteins and apoptosis-associated proteins were detected with immuno-histochemical technique. Results: Oxaliplatin could inhibit the proliferation of QGY cells and the inhibition depended on the exposure time and dose. The cells showed morphologic changes of the early stage of apoptosis under the light microscope: the shrunk round cells, condensed cytoplasma and pycnosis of nucleus. Apoptotic cells and apoptotic body could be found under the transmission electronic microscope. The analysis of cell cycle indicated that oxaliplatin blocked cells at S and G2/M phases and the cells of G0/Gl phase reduced. When treated with oxaliplatin for 72h, the expressions of cyclin A and Bax were up-regulated, mutant type P53, Bcl-2 and Myc were down-regulated, and Fas was not changed. Conclusion: Oxaliplatin could inhibit the proliferation of the hepatoma cell lines. Cells were blocked at S and G2/M phases. The apoptosis was related to the up-regulation of Bax and down-regulation of mutant type P53, Bcl-2 and Myc. Oxaliplatin could not induce apoptosis through the Fas pathway.

  18. Stability and degradation mechanisms in organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Bernhard

    2012-04-26

    This thesis deals with stability improvements and the investigation of degradation mechanisms in organic solar cells. Organic solar cells have been in the focus of extensive academic research for over almost two decades and are currently entering the market in small scale applications. For successful large scale applications, next to the improvement of the power conversion efficiency, the stability of organic solar cells has to be increased. This thesis is dedicated to the investigation of novel materials and architectures to study stability-related issues and degradation mechanisms in order to contribute to the basic understanding of the working principles of organic solar cells. Here, impedance spectroscopy, a frequency domain technique, is used to gain information about stability and degradation mechanisms in organic solar cells. In combination with systematic variations in the preparation of solar cells, impedance spectroscopy gives the possibility to differentiate between interface and bulk dominated effects. Additionally, impedance spectroscopy gives access to the dielectric properties of the device, such as capacitance. This offers among other things the opportunity to probe the charge carrier concentration and the density of states. Another powerful way of evaluation is the combination of experimentally obtained impedance spectra with equivalent circuit modelling. The thesis presents results on novel materials and solar cell architectures for efficient hole and electron extraction. This indicates the importance of knowledge over interlayers and interfaces for improving both the efficiency and stability of organic solar cells.

  19. The Mechanisms of Plant Cell Wall Deconstruction during Enzymatic Hydrolysis

    DEFF Research Database (Denmark)

    Thygesen, Lisbeth Garbrecht; E. Thybring, Emil; Johansen, Katja Salomon;

    2014-01-01

    Mechanical agitation during enzymatic hydrolysis of insoluble plant biomass at high dry matter contents is indispensable for the initial liquefaction step in biorefining. It is known that particle size reduction is an important part of liquefaction, but the mechanisms involved are poorly understood....... Here we put forward a simple model based on mechanical principles capable of capturing the result of the interaction between mechanical forces and cell wall weakening via hydrolysis of glucosidic bonds. This study illustrates that basic material science insights are relevant also within biochemistry...

  20. Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis

    Science.gov (United States)

    Anuradha, Rajamanickam; George, Parakkal Jovvian; Hanna, Luke E.; Chandrasekaran, Vedachalam; Kumaran, Paul; Nutman, Thomas B.; Babu, Subash

    2013-01-01

    Th9 cells are a subset of CD4+ T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9+ Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9+Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9+Th2 cells, indicating that the Th9 cells are the predominant CD4+ T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4+ T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders. PMID:23913964

  1. Active Cellular Mechanics and Information Processing in the Living Cell

    Science.gov (United States)

    Rao, M.

    2014-07-01

    I will present our recent work on the organization of signaling molecules on the surface of living cells. Using novel experimental and theoretical approaches we have found that many cell surface receptors are organized as dynamic clusters driven by active currents and stresses generated by the cortical cytoskeleton adjoining the cell surface. We have shown that this organization is optimal for both information processing and computation. In connecting active mechanics in the cell with information processing and computation, we bring together two of the seminal works of Alan Turing.

  2. Matrix metalloproteinase activity and glycosaminoglycans in chronic venous disease: the linkage among cell biology, pathology and translational research

    OpenAIRE

    Mannello, Ferdinando; Raffetto, Joseph D.

    2010-01-01

    Primary chronic venous disease (CVD) is an inflammatory pathology involving an erratic structural remodeling in the venous well leading to vascular incompetence and the development of varicose vein, characterized by altered collagen and elastin content. In the early steps of varicose vein formation is crucial the role of MMP/TIMP balance, implicated in both ECM and vascular degradation during inflammation processes in early and late stages of venous diseases. Although several pharmacological ...

  3. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology.

    NARCIS (Netherlands)

    Winter, M.J.; Nagtegaal, I.D.; Krieken, J.H.J.M. van; Litvinov, S.V.

    2003-01-01

    Cell adhesion receptors (CAMs) are actively involved in regulating various cell processes, including growth, differentiation, and cell death. Therefore, CAMs represent a large group of morphoregulating molecules, mediating cross-talk between cells and of cells with their environment. From this persp

  4. Cell mechanics and immune system link up to fight infections

    Science.gov (United States)

    Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

    2015-03-01

    Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

  5. Mechanisms of mesenchymal stem/stromal cell function.

    Science.gov (United States)

    Spees, Jeffrey L; Lee, Ryang Hwa; Gregory, Carl A

    2016-01-01

    The past decade has seen an explosion of research directed toward better understanding of the mechanisms of mesenchymal stem/stromal cell (MSC) function during rescue and repair of injured organs and tissues. In addition to delineating cell-cell signaling and molecular controls for MSC differentiation, the field has made particular progress in defining several other mechanisms through which administered MSCs can promote tissue rescue/repair. These include: 1) paracrine activity that involves secretion of proteins/peptides and hormones; 2) transfer of mitochondria by way of tunneling nanotubes or microvesicles; and 3) transfer of exosomes or microvesicles containing RNA and other molecules. Improved understanding of MSC function holds great promise for the application of cell therapy and also for the development of powerful cell-derived therapeutics for regenerative medicine. Focusing on these three mechanisms, we discuss MSC-mediated effects on immune cell responses, cell survival, and fibrosis and review recent progress with MSC-based or MSC-derived therapeutics. PMID:27581859

  6. Mechanism of T cell regulation by microRNAs

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that can modulate target gene expression at post-transcriptional level and participate in cell proliferation, differentiation, and apoptosis. T cells have important functions in acquired immune response; miRNAs regulate this immune response by targeting the mRNAs of genes involved in T cell development, proliferation, differentiation, and function. For instance, miR-181 family members function in progression by targeting Bcl2 and CD69, among others. MiR-17 to miR-92 clusters function by binding to CREB1, PTEN, and Bim. Considering that the suppression of T cell-mediated immune responses against tumor cells is involved in cancer progression, we should investigate the mechanism by which miRNA regulates T cells to develop new approaches for cancer treatment

  7. Mechanism of vaso-occlusion in sickle cell anemia

    Science.gov (United States)

    Lei, Huan; Karniadakis, George

    2012-11-01

    Vaso-occlusion crisis is one of the key hallmark of sickle cell anemia. While early studies suggested that the crisis is caused by blockage of a single elongated cell, recent experimental investigations indicate that vaso-occlusion is a complex process triggered by adhesive interactions among different cell groups in multiple stages. Based on dissipative particle dynamics, a multi-scale model for the sickle red blood cells (SS-RBCs), accounting for diversity in both shapes and cell rigidities, is developed to investigate the mechanism of vaso-occlusion crisis. Using this model, the adhesive dynamics of single SS-RBC was investigated in arterioles. Simulation results indicate that the different cell groups (deformable SS2 RBCs, rigid SS4 RBCs, leukocytes, etc.) exhibit heterogeneous adhesive behavior due to the different cell morphologies and membrane rigidities. We further simulate the tube flow of SS-RBC suspensions with different cell fractions. The more adhesive SS2 cells interact with the vascular endothelium and further trap rigid SS4 cells, resulting in vaso-occlusion in vessels less than 15 μm . Under inflammation, adherent leukocytes may also trap SS4 cells, resulting in vaso-occlusion in even larger vessels. This work was supported by the NSF grant CBET-0852948 and the NIH grant R01HL094270.

  8. Transdifferentiation of pancreatic α-cells into insulinsecreting cells: From experimental models to underlying mechanisms

    Institute of Scientific and Technical Information of China (English)

    Jieli; Lu; Rami; Jaafer; Rémy; Bonnavion; Philippe; Bertolino; Chang-Xian; Zhang

    2014-01-01

    Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are cur-rently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.

  9. Cell volume homeostatic mechanisms: effectors and signalling pathways

    DEFF Research Database (Denmark)

    Hoffmann, E K; Pedersen, Stine Helene Falsig

    2011-01-01

    the historical context of studies of cell volume regulation, focusing on the lineage started by Krogh, Bodil Schmidt-Nielsen, Hans-Henrik Ussing, and their students. The early work was focused on understanding the functional behaviour, kinetics and thermodynamics of the volume-regulatory ion transport......Cell volume homeostasis and its fine-tuning to the specific physiological context at any given moment are processes fundamental to normal cell function. The understanding of cell volume regulation owes much to August Krogh, yet has advanced greatly over the last decades. In this review, we outline...... mechanisms. Later work addressed the mechanisms through which cellular signalling pathways regulate the volume regulatory effectors or flux pathways. These studies were facilitated by the molecular identification of most of the relevant channels and transporters, and more recently also by the increased...

  10. The molecular mechanism of embryonic stem cell pluripotency maintenance

    Institute of Scientific and Technical Information of China (English)

    WANG Qingzhong; LIU Yixun; HAN Chunsheng

    2005-01-01

    In vitro cultured embryonic stem (ES) cells are derived from the inner cell mass (ICM) of pre-implantation embryos, and are capable of giving rise to all cell and tissue types of the three germ layers upon being injected back into blastocysts. These cells are therefore said to possess pluripotency that can be maintained infinitely in culture under optimal conditions. Such pluripotency maintenance is believed to be due to the symmetrical cleavage of the cells in an undifferentiated state. The pluripotency of ES cells is the basis for their various practical and potential applications. ES cells can be used as donor cells to generate knockout or transgenic animals, as in vitro models of mammalian development, and as cell resources for cell therapy in regenerative medicine. The further success in these applications, particularly in the last two, is dependent on the establishment of a culture system with components in the medium clearly defined and the subsequent procedures for controlled differentiation of the cells into specific lineages. In turn, elucidating the molecular mechanism for pluripotency maintenance of ES cells is the prerequisite. This paper summarizes the recent progresses in this area, focusing mainly on the LIF/STAT3, BMPs/Smads, canonical Wnt, TGFβ/activin/nodal, PI3K and FGF signaling pathways and the genes such as oct4, nanog that are crucial in ES cell pluripotency maintenance. The regulatory systems of pluripotency maintenance in both mouse and human ES cells are also discussed. We believe that the cross-talkings between these signaling pathways, as well as the regulatory system underlying pluripotency maintenance will be the main focus in the area of ES cell researches in the future.

  11. Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of de-veloping TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

  12. Mechanism Suggests How HIV Protein Disrupts Immune Cell Migration

    OpenAIRE

    Janardhan Ajit; Swigut Tomek; Hill Brian; Myers Michael P; Skowronski Jacek

    2004-01-01

    The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, yet the mechanisms underlying these effects have remained elusive. Since Nef likely functions as an adaptor protein, we exploited a proteomic approach to directly identify molecules that Nef targets to subvert the signaling machinery in T cells. We purified to near homo...

  13. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

    OpenAIRE

    Martin, Lee J.

    2010-01-01

    Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and ani...

  14. Curriculum Guidelines for Pathology and Oral Pathology.

    Science.gov (United States)

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  15. Fuel starvation. Irreversible degradation mechanisms in PEM fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, Carmen M.; Silva, R.A.; Travassos, M.A.; Paiva, T.I.; Fernandes, V.R. [LNEG, National Laboratory for Energy and Geology, Lisboa (Portugal). UPCH Fuel Cells and Hydrogen Unit

    2010-07-01

    PEM fuel cell operates under very aggressive conditions in both anode and cathode. Failure modes and mechanism in PEM fuel cells include those related to thermal, chemical or mechanical issues that may constrain stability, power and lifetime. In this work, the case of fuel starvation is examined. The anode potential may rise to levels compatible with the oxidization of water. If water is not available, oxidation of the carbon support will accelerate catalyst sintering. Diagnostics methods used for in-situ and ex-situ analysis of PEM fuel cells are selected in order to better categorize irreversible changes of the cell. Electrochemical Impedance Spectroscopy (EIS) is found instrumental in the identification of fuel cell flooding conditions and membrane dehydration associated to mass transport limitations / reactant starvation and protonic conductivity decrease, respectively. Furthermore, it indicates that water electrolysis might happen at the anode. Cross sections of the membrane catalyst and gas diffusion layers examined by scanning electron microscopy indicate electrode thickness reduction as a result of reactions taking place during hydrogen starvation. Catalyst particles are found to migrate outwards and located on carbon backings. Membrane degradation in fuel cell environment is analyzed in terms of the mechanism for fluoride release which is considered an early predictor of membrane degradation. (orig.)

  16. Mechanical behavior of alternative multicrystalline silicon for solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Teresa Orellana

    2013-05-22

    The usage of more inexpensive silicon feedstock for the crystallization of multicrystalline silicon blocks promises cost reduction for the photovoltaic industry. Less expensive substrates made out of metallurgical silicon (MG-Si) are used as a mechanical support for the epitaxial solar cell. Moreover, conventional inert solar cells can be produced from up-graded metallurgical silicon (UMG-Si). This feedstock has higher content of impurities which influences cell performance and mechanical strength of the wafers. Thus, it is of importance to know these effects in order to know which impurities should be preferentially removed or prevented during the crystallization process. Solar cell processing steps can also exert a change in the values of mechanical strength of processed multicrystalline silicon wafers until the fabrication of a solar cell. Bending tests, fracture toughness and dynamic elastic modulus measurements are performed in this work in order to research the mechanical behavior of multicrystalline silicon crystallized with different qualities of silicon feedstock. Bending tests and residual stress measurements allows the quantification of the mechanical strength of the wafers after every solar cell processing step. The experimental results are compared with theoretical models found in the classical literature about the mechanical properties of ceramics. The influence of second phase particles and thermal processes on the mechanical strength of silicon wafers can be predicted and analyzed with the theoretical models. Metals like Al and Cu can decrease the mechanical strength due to micro-cracking of the silicon matrix and introduction of high values of thermal residual stress. Additionally, amorphous silicon oxide particles (SiOx) lower the mechanical strength of multicrystalline silicon due to thermal residual stresses and elastic mismatch with silicon. Silicon nitride particles (Si3N4) reduce fracture toughness and cause failure by radial cracking in its

  17. Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to ‘composite’ blast.

    Directory of Open Access Journals (Sweden)

    VictorPrima

    2012-02-01

    Full Text Available A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position towards blast generated by an external shock tube. In this study, we further characterized blast producing moderate TBI and defined ‘composite’ blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast, but negligible skull movement upon peak overpressure exposure off-axis (primary blast. Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, sICAM, and L-selectin along with neurotrophic factor NGF-beta were increased in serum within 6 hours post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2 were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast setups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with

  18. Mechanical Response of Single Plant Cells to Cell Poking: A Numerical Simulation Model

    Institute of Scientific and Technical Information of China (English)

    Rong Wang; Qun-Ying Jiao; De-Qiang Wei

    2006-01-01

    Cell poking is an experimental technique that is widely used to study the mechanical properties of plant cells. A full understanding of the mechanical responses of plant cells to poking force is helpful for experimental work. The aim of this study was to numerically investigate the stress distribution of the cell wall,cell turgor, and deformation of plant cells in response to applied poking force. Furthermore, the locations damaged during poking were analyzed. The model simulates cell poking, with the cell treated as a spherical,homogeneous, isotropic elastic membrane, filled with incompressible, highly viscous liquid. Equilibrium equations for the contact region and the non-contact regions were determined by using membrane theory.The boundary conditions and continuity conditions for the solution of the problem were found. The forcedeformation curve, turgor pressure and tension of the cell wall under cell poking conditions were obtained.The tension of the cell wall circumference was larger than that of the meridian. In general, maximal stress occurred at the equator around. When cell deformation increased to a certain level, the tension at the poker tip exceeded that of the equator. Breakage of the cell wall may start from the equator or the poker tip,depending on the deformation. A nonlinear model is suitable for estimating turgor, stress, and stiffness,and numerical simulation is a powerful method for determining plant cell mechanical properties.

  19. 基底细胞癌的病理诊断分析及预后%Pathological Diagnosis and Prognostic of Basal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    杜晓敏

    2015-01-01

    目的:探讨基底细胞癌的病理诊断分析及预后。方法整群选取2010年10月—2014年5月在该病理科进行基底细胞癌的病理诊断的74例患者作为研究对象,并对其病理资料进行回顾性分析。结果74例基底细胞癌患者中,眶周部23例,占31.1%,峡部5例,占6.8%,额部9例,占12.2%,颧骨部7例,占9.4%,鼻翼部19例,占25.6%,上唇部6例,占8.1%,下颌部3例,占4.1%,背部2例,占2.7%。镜下可见瘤细胞团块状或巢状排列,细胞核大小不一,排列密集紊乱,胞浆少淡染,瘤细胞巢周围裂隙形成,间质慢性炎细胞浸润。结论基底细胞癌是皮肤科最常见的恶性肿瘤之一,及早进行病理诊断和治疗,预后较好,可以明显的提高患者的生命质量。%Objective To investigate the pathological diagnosis and the prognosis of basal cell carcinoma. Methods 74 patients who underwent pathological diagnosis of basal cell carcinoma in our hospital from October 2010 to May 2014 in the Department of Pathology of our hospital were selected as the research object and their pathological data were retrospectively analyzed. Results In all the 74 patients, basal cell carcinoma in periorbital region was found in 23 cases, accounting for 31.1%; in isthmus in 5 cases, accounting for 6.8%; in forehead in 9 cases, accounting for 12.2%, in the zygomatic in 7 cases, accounting for 9.4%, in alae nasi in 19 cases, accounting for 25.6%, in upper lip in 6 cases, accounting for 8.1%, in lower jaw in 3 cases, accounting for 4.1% and in back in 2 cases, accounted for 2.7%. Under the microscope, the tumor cells, of which the nucleus of difference size were ar-ranged dense and irregular, and of which the scanty cytoplasm was slightly stained, distributed in the form of round or spindle and of nest. Interstitial chronic inflammatory cell infiltration was developed in the fracture around tumor cells. Conclusion Basal cell carcinoma is one of

  20. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda;

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways of the...... establishing the positive feedback in glutamate release that is critical for the self-sustained activity of the postsynaptic neuron. This mechanism differs from the mechanisms of the astrocyte-neuron signaling previously reported....

  1. NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Wortham, Brian W; Eppert, Bryan L; Motz, Greg T; Flury, Jennifer L; Orozco-Levi, Mauricio; Hoebe, Kasper; Panos, Ralph J; Maxfield, Melissa; Glasser, Stephan W; Senft, Albert P; Raulet, David H; Borchers, Michael T

    2012-05-01

    Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or TLR ligands. In this article, we show that the activating receptor NKG2D is a key mediator for CS-stimulated NK cell hyperresponsiveness, because CS-exposed NKG2D-deficient mice (Klrk1(-/-)) did not exhibit enhanced effector functions as assessed by cytokine responsiveness. NK cell cytotoxicity against MHC class I-deficient targets was not affected in a COPD model. However, NK cells from CS-exposed mice exhibit greater cytotoxic activity toward cells that express the NKG2D ligand RAET1ε. We also demonstrate that NKG2D-deficient mice exhibit diminished airway damage and reduced inflammation in a model of viral COPD exacerbation, which do not affect viral clearance. Furthermore, adoptive transfer of NKG2D(+) NK cells into CS-exposed, influenza-infected NKG2D-deficient mice recapitulated the phenotypes observed in CS-exposed, influenza-infected wild-type mice. Our findings indicate that NKG2D stimulation during long-term CS exposure is a central pathway in the development of NK cell hyperresponsiveness and influenza-mediated exacerbations of COPD. PMID:22467655

  2. Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells

    DEFF Research Database (Denmark)

    Thit, Amalie; Selck, Henriette; Bjerregaard, Henning F.

    2015-01-01

    CuO NPs have previously been reported as toxic to a range of cell cultures including kidney epithelial cells from the frog, Xenopus laevis (A6). Here we examine the molecular mechanisms affecting toxicity of Cu in different forms and particle sizes. A6 cells were exposed to ionic Cu (Cu2+) or CuO...... particles of three different sizes: CuO NPs of 6 nm (NP6), larger Poly-dispersed CuO NPs of <100 nm (Poly) and CuO Micro particles of <5 μm (Micro), at 200 μM, equal to 12.7 mg Cu/L. Poly was significantly more toxic than NP6, Micro and Cu2+ to A6 cells, causing DNA damage, decreased cell viability and...

  3. Bithionol inhibits ovarian cancer cell growth In Vitro - studies on mechanism(s) of action

    International Nuclear Information System (INIS)

    Drug resistance is a cause of ovarian cancer recurrence and low overall survival rates. There is a need for more effective treatment approaches because the development of new drug is expensive and time consuming. Alternatively, the concept of ‘drug repurposing’ is promising. We focused on Bithionol (BT), a clinically approved anti-parasitic drug as an anti-ovarian cancer drug. BT has previously been shown to inhibit solid tumor growth in several preclinical cancer models. A better understanding of the anti-tumor effects and mechanism(s) of action of BT in ovarian cancer cells is essential for further exploring its therapeutic potential against ovarian cancer. The cytotoxic effects of BT against a panel of ovarian cancer cell lines were determined by Presto Blue cell viability assay. Markers of apoptosis such as caspases 3/7, cPARP induction, nuclear condensation and mitochondrial transmembrane depolarization were assessed using microscopic, FACS and immunoblotting methods. Mechanism(s) of action of BT such as cell cycle arrest, reactive oxygen species (ROS) generation, autotaxin (ATX) inhibition and effects on MAPK and NF-kB signalling were determined by FACS analysis, immunoblotting and colorimetric methods. BT caused dose dependent cytotoxicity against all ovarian cancer cell lines tested with IC50 values ranging from 19 μM – 60 μM. Cisplatin-resistant variants of A2780 and IGROV-1 have shown almost similar IC50 values compared to their sensitive counterparts. Apoptotic cell death was shown by expression of caspases 3/7, cPARP, loss of mitochondrial potential, nuclear condensation, and up-regulation of p38 and reduced expression of pAkt, pNF-κB, pIκBα, XIAP, bcl-2 and bcl-xl. BT treatment resulted in cell cycle arrest at G1/M phase and increased ROS generation. Treatment with ascorbic acid resulted in partial restoration of cell viability. In addition, dose and time dependent inhibition of ATX was observed. BT exhibits cytotoxic effects on various

  4. Molecule mechanism of stem cells in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Wenjin Zhang

    2014-01-01

    Full Text Available Plants possess the ability to continually produce new tissues and organs throughout their life. Unlike animals, plants are exposed to extreme variations in environmental conditions over the course of their lives. The vitality of plants is so powerful that they can survive several hundreds of years or even more making it an amazing miracle that comes from plant stem cells. The stem cells continue to divide to renew themselves and provide cells for the formation of leaves, stems, and flowers. Stem cells are not only quiescent but also immortal, pluripotent and homeostatic. Stem cells are the magic cells that repair tissues and regenerate organs. During the past decade, scholars around the world have paid more and more attention toward plant stem cells. At present, the major challenge is in relating molecule action mechanism to root apical meristem, shoot apical meristem and vascular system. The coordination between stem cells maintenance and differentiation is critical for normal plant growth and development. Elements such as phytohormones, transcription factors and some other known or unknown genes cooperate to balance this process. In this review, Arabidopsis thaliana as a pioneer system, we highlight recent developments in molecule modulating, illustrating how plant stem cells generate new mechanistic insights into the regulation of plants growth and development.

  5. Hyper-active non-homologous end joining selects for synthetic lethality resistant and pathological Fanconi anemia hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Du, Wei; Amarachintha, Surya; Wilson, Andrew F; Pang, Qishen

    2016-01-01

    The prominent role of Fanconi anemia (FA) proteins involves homologous recombination (HR) repair. Poly[ADP-ribose] polymerase1 (PARP1) functions in multiple cellular processes including DNA repair and PARP inhibition is an emerging targeted therapy for cancer patients deficient in HR. Here we show that PARP1 activation in hematopoietic stem and progenitor cells (HSPCs) in response to genotoxic or oxidative stress attenuates HSPC exhaustion. Mechanistically, PARP1 controls the balance between HR and non-homologous end joining (NHEJ) in double strand break (DSB) repair by preventing excessive NHEJ. Disruption of the FA core complex skews PARP1 function in DSB repair and led to hyper-active NHEJ in Fanca(-/-) or Fancc(-/-) HSPCs. Re-expression of PARP1 rescues the hyper-active NHEJ phenotype in Brca1(-/-)Parp1(-/-) but less effective in Fanca(-/-)Parp1(-/-) cells. Inhibition of NHEJ prevents myeloid/erythroid pathologies associated with synthetic lethality. Our results suggest that hyper-active NHEJ may select for "synthetic lethality" resistant and pathological HSPCs. PMID:26916217

  6. Mechanical Properties of Plant Cell Walls Probed by Relaxation Spectra

    DEFF Research Database (Denmark)

    Hansen, Steen Laugesen; Ray, Peter Martin; Karlsson, Anders Ola;

    2011-01-01

    type. This may be due to the plant’s ability to compensate for the wall modification or because the biophysical method that is often employed, determination of simple elastic modulus and breakstrength, lacks the resolving power necessary for detecting subtle mechanical phenotypes. Here, we apply a...... method, determination of relaxation spectra, which probes, and can separate, the viscoelastic properties of different cell wall components (i.e. those properties that depend on the elastic behavior of load-bearing wall polymers combined with viscous interactions between them). A computer program, Bayes......Relax, that deduces relaxation spectra from appropriate rheological measurements is presented and made accessible through a Web interface. BayesRelax models the cell wall as a continuum of relaxing elements, and the ability of the method to resolve small differences in cell wall mechanical properties is...

  7. Chemo-mechanical control of neural stem cell differentiation

    Science.gov (United States)

    Geishecker, Emily R.

    Cellular processes such as adhesion, proliferation, and differentiation are controlled in part by cell interactions with the microenvironment. Cells can sense and respond to a variety of stimuli, including soluble and insoluble factors (such as proteins and small molecules) and externally applied mechanical stresses. Mechanical properties of the environment, such as substrate stiffness, have also been suggested to play an important role in cell processes. The roles of both biochemical and mechanical signaling in fate modification of stem cells have been explored independently. However, very few studies have been performed to study well-controlled chemo-mechanotransduction. The objective of this work is to design, synthesize, and characterize a chemo-mechanical substrate to encourage neuronal differentiation of C17.2 neural stem cells. In Chapter 2, Polyacrylamide (PA) gels of varying stiffnesses are functionalized with differing amounts of whole collagen to investigate the role of protein concentration in combination with substrate stiffness. As expected, neurons on the softest substrate were more in number and neuronal morphology than those on stiffer substrates. Neurons appeared locally aligned with an expansive network of neurites. Additional experiments would allow for statistical analysis to determine if and how collagen density impacts C17.2 differentiation in combination with substrate stiffness. Due to difficulties associated with whole protein approaches, a similar platform was developed using mixed adhesive peptides, derived from fibronectin and laminin, and is presented in Chapter 3. The matrix elasticity and peptide concentration can be individually modulated to systematically probe the effects of chemo-mechanical signaling on differentiation of C17.2 cells. Polyacrylamide gel stiffness was confirmed using rheological techniques and found to support values published by Yeung et al. [1]. Cellular growth and differentiation were assessed by cell counts

  8. Interferon Regulator Factor 8 (IRF8) Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells

    Science.gov (United States)

    Yu, Cheng-Rong; He, Chang; Mahdi, Rashid M.; Chan, Chi-Chao; Wang, Hongsheng; Morse, Herbert C.; Egwuagu, Charles E.

    2016-01-01

    Interferon Regulatory Factor-8 (IRF8) is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO) to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1) infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG) and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC) in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye. PMID:27171004

  9. Interferon Regulator Factor 8 (IRF8 Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Lin Sun

    Full Text Available Interferon Regulatory Factor-8 (IRF8 is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1 infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye.

  10. Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics

    Science.gov (United States)

    Hwang, Jae Youn; Kim, Jihun; Park, Jin Man; Lee, Changyang; Jung, Hayong; Lee, Jungwoo; Shung, K. Kirk

    2016-06-01

    We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label-free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free.

  11. Tensegrity finite element models of mechanical tests of individual cells.

    Science.gov (United States)

    Bursa, Jiri; Lebis, Radek; Holata, Jakub

    2012-01-01

    A three-dimensional finite element model of a vascular smooth muscle cell is based on models published recently; it comprehends elements representing cell membrane, cytoplasm and nucleus, and a complex tensegrity structure representing the cytoskeleton. In contrast to previous models of eucaryotic cells, this tensegrity structure consists of several parts. Its external and internal parts number 30 struts, 60 cables each, and their nodes are interconnected by 30 radial members; these parts represent cortical, nuclear and deep cytoskeletons, respectively. This arrangement enables us to simulate load transmission from the extracellular space to the nucleus or centrosome via membrane receptors (focal adhesions); the ability of the model was tested by simulation of some mechanical tests with isolated vascular smooth muscle cells. Although material properties of components defined on the basis of the mechanical tests are ambiguous, modelling of different types of tests has shown the ability of the model to simulate substantial global features of cell behaviour, e.g. "action at a distance effect" or the global load-deformation response of the cell under various types of loading. Based on computational simulations, the authors offer a hypothesis explaining the scatter of experimental results of indentation tests. PMID:22508025

  12. Load measurement system with load cell lock-out mechanism

    Science.gov (United States)

    Le, Thang; Carroll, Monty; Liu, Jonathan

    1995-01-01

    In the frame work of the project Shuttle Plume Impingement Flight Experiment (SPIFEX), a Load Measurement System was developed and fabricated to measure the impingement force of Shuttle Reaction Control System (RCS) jets. The Load Measurement System is a force sensing system that measures any combination of normal and shear forces up to 40 N (9 lbf) in the normal direction and 22 N (5 lbf) in the shear direction with an accuracy of +/- 0.04 N (+/- 0.01 lbf) Since high resolution is required for the force measurement, the Load Measurement System is built with highly sensitive load cells. To protect these fragile load cells in the non-operational mode from being damaged due to flight loads such as launch and landing loads of the Shuttle vehicle, a motor driven device known as the Load Cell Lock-Out Mechanism was built. This Lock-Out Mechanism isolates the load cells from flight loads and re-engages the load cells for the force measurement experiment once in space. With this highly effective protection system, the SPIFEX load measurement experiment was successfully conducted on STS-44 in September 1994 with all load cells operating properly and reading impingement forces as expected.

  13. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration.

    Science.gov (United States)

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  14. Effects and mechanisms of silibinin on human hepatoma cell lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma (HCC) cell growth. METHODS: Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS: We demonstrated that silibinin significantly reduced the growth of HUH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly upregulated p21/CDK4 and p27/CDK4 complexes, downregulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and upregulated activated caspase-3 and -9. Silibinin's anti angiogenic effects were indicated by down-regulated metalloproteinase-2 (MMP2) and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and decreased p-Akt production, indicating the role of PTEN/ PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 (AC-H3 and AC-H4), indicating a possible role of altered histone acetylation in silibininreduced HCC cell proliferation.CONCLUSION: Our results defined silibinin's in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention.

  15. Mechanisms and chemical induction of aneuploidy in rodent germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Mailhes, J B; Marchetti, F

    2004-10-15

    The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be inidentified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) can induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.

  16. Atomic Force Microscopy Measurements of the Mechanical Properties of Cell Walls on Living Bacterial Cells

    Science.gov (United States)

    Bailey, Richard; Mullin, Nic; Turner, Robert; Foster, Simon; Hobbs, Jamie

    2014-03-01

    Staphylococcus aureus is a major cause of infection in humans, including the Methicillin resistant strain, MRSA. However, very little is known about the mechanical properties of these cells. Our investigations use AFM to examine live S. aureus cells to quantify mechanical properties. These were explored using force spectroscopy with different trigger forces, allowing the properties to be extracted at different indentation depths. A value for the cell wall stiffness has been extracted, along with a second, higher value which is found upon indenting at higher forces. This higher value drops as the cells are exposed to high salt, sugar and detergent concentrations, implying that this measurement contains a contribution from the internal turgor pressure. We have monitored these properties as the cells progress through the cell cycle. Force maps were taken over the cells at different stages of the growth process to identify changes in the mechanics throughout the progression of growth and division. The effect of Oxacillin has also been studied, to better understand its mechanism of action. Finally mutant strains of S. aureus and a second species Bacillus subtilis have been used to link the mechanical properties of the cell walls with the chain lengths and substructures involved.

  17. Hip-spine syndrome:pathological base and biomechanics mechanism%髋-腰综合征病理基础及生物力学机制

    Institute of Scientific and Technical Information of China (English)

    王强; 赵文杰; 张斌; 戴闽

    2015-01-01

    背景:研究发现,髋关节骨性关节炎患者全髋关节置换后下腰痛的症状得到一定缓解,提示下肢力线的改变对于腰痛症状具有明显的影响。目的:就髋-腰综合征的病理基础与生物力学机制进行综述并予以分析。方法:计算机检索1976年1月至2015年3月PubMed数据库、中国期刊全文数据库的相关文章,英文检索词“low back pain,hip-spine syndrome,hip osteoarthritis,total hip replacement,biomechanics,balance parameters”;中文检索词“下腰痛,髋-腰综合征,髋骨关节炎,髋关节置换,生物力学,平衡参数”。排除重复性研究及部分相关性较低的基础类文章。结果与结论:共计检索出145篇中英文文献,最终选择62篇文献进行综述。在病理生理中,肿瘤坏死因子α、白细胞介素1β和基质金属蛋白酶等对髋-腰综合征的发生发展起着十分重要的作用。而生物力学中,脊柱-骨盆-下肢平衡代偿过程成为髋-腰综合征的主要力学机制,其平衡参数可为髋-腰综合征的诊断,治疗及术后评估提供依据。%BACKGROUND:Low back pain in patients with hip osteoarthritis can be relieved to some extent after total hip arthroplasty, indicating the changes in limb line of force have obvious effects on low back pain. OBJECTIVE:To review and analysis the pathological base and biomechanics mechanism of hip-spine syndrome. METHODS: We retrieved PubMed database and China National Knowledge Infrastructure for related articles published from January 1976 to March 2015. The key words were “low back pain, hip-spine syndrome, hip osteoarthritis, total hip replacement, biomechanics, balance parameters” in English and Chinese, respectively. Repeated studies and unrelated articles were excluded. RESULTS AND CONCLUSION:A total of 145 articles were retrieved, and finaly 62 articles were enroled in result analysis. In the pathophysiology, tumor necrosis

  18. Tracking the mechanical dynamics of human embryonic stem cell chromatin

    Directory of Open Access Journals (Sweden)

    Hinde Elizabeth

    2012-12-01

    Full Text Available Abstract Background A plastic chromatin structure has emerged as fundamental to the self-renewal and pluripotent capacity of embryonic stem (ES cells. Direct measurement of chromatin dynamics in vivo is, however, challenging as high spatiotemporal resolution is required. Here, we present a new tracking-based method which can detect high frequency chromatin movement and quantify the mechanical dynamics of chromatin in live cells. Results We use this method to study how the mechanical properties of chromatin movement in human embryonic stem cells (hESCs are modulated spatiotemporally during differentiation into cardiomyocytes (CM. Notably, we find that pluripotency is associated with a highly discrete, energy-dependent frequency of chromatin movement that we refer to as a ‘breathing’ state. We find that this ‘breathing’ state is strictly dependent on the metabolic state of the cell and is progressively silenced during differentiation. Conclusions We thus propose that the measured chromatin high frequency movements in hESCs may represent a hallmark of pluripotency and serve as a mechanism to maintain the genome in a transcriptionally accessible state. This is a result that could not have been observed without the high spatial and temporal resolution provided by this novel tracking method.

  19. Regulatory mechanisms of apoptosis in regularly dividing cells

    Directory of Open Access Journals (Sweden)

    Ribal S Darwish

    2010-08-01

    Full Text Available Ribal S DarwishDepartment of Anesthesiology, Division of Critical Care Medicine, University of Maryland Medical Center, Baltimore, Maryland, USAAbstract: The balance between cell survival and death is essential for normal development and homeostasis of organisms. Apoptosis is a distinct type of cell death with ultrastructural features that are consistent with an active, inherently controlled process. Abnormalities and ­dysregulation of apoptosis contribute to the pathophysiology of multiple disease processes. Apoptosis is strictly regulated by several positive and negative feedback mechanisms that regulate cell death and determine the final outcome after cell exposure to apoptotic stimuli. Mitochondria and caspases are central components of the regulatory mechanisms of ­apoptosis. Recently, noncaspase pathways of apoptosis have been explored through the studies of ­apoptosis-inducing factor and endonuclease G. Multiple difficulties in the apoptosis research relate to apoptosis detection and imaging. This article reviews current understanding of the regulatory mechanisms of apoptosis.Keywords: caspases, apoptosis-inducing factor, apoptosis inhibitory proteins, cytochrome c, mitochondria 

  20. Quantification of stromal vascular cell mechanics with a linear cell monolayer rheometer

    Energy Technology Data Exchange (ETDEWEB)

    Elkins, Claire M., E-mail: cma9@stanford.edu; Fuller, Gerald G. [Department of Chemical Engineering, Stanford University, Stanford, California 94305 (United States); Shen, Wen-Jun; Khor, Victor K.; Kraemer, Fredric B. [Division of Endocrinology, Gerontology and Metabolism, Stanford University, Stanford, California 94305 and Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304 (United States)

    2015-01-15

    Over the past few decades researchers have developed a variety of methods for measuring the mechanical properties of whole cells, including traction force microscopy, atomic force microscopy (AFM), and single-cell tensile testing. Though each of these techniques provides insight into cell mechanics, most also involve some nonideal conditions for acquiring live cell data, such as probing only one portion of a cell at a time, or placing the cell in a nonrepresentative geometry during testing. In the present work, we describe the development of a linear cell monolayer rheometer (LCMR) and its application to measure the mechanics of a live, confluent monolayer of stromal vascular cells. In the LCMR, a monolayer of cells is contacted on both top and bottom by two collagen-coated plates and allowed to adhere. The top plate then shears the monolayer by stepping forward to induce a predetermined step strain, while a force transducer attached to the top plate collects stress information. The stress and strain data are then used to determine the maximum relaxation modulus recorded after step-strain, G{sub r}{sup 0}, referred to as the zero-time relaxation modulus of the cell monolayer. The present study validates the ability of the LCMR to quantify cell mechanics by measuring the change in G{sub r}{sup 0} of a confluent cell monolayer upon the selective inhibition of three major cytoskeletal components (actin microfilaments, vimentin intermediate filaments, and microtubules). The LCMR results indicate that both actin- and vimentin-deficient cells had ∼50% lower G{sub r}{sup 0} values than wild-type, whereas tubulin deficiency resulted in ∼100% higher G{sub r}{sup 0} values. These findings constitute the first use of a cell monolayer rheometer to quantitatively distinguish the roles of different cytoskeletal elements in maintaining cell stiffness and structure. Significantly, they are consistent with results obtained using single-cell mechanical testing methods

  1. Mechanical behaviour of PEM fuel cell catalyst layers during regular cell operation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Baghdadi, Maher A.R. Sadiq [Fuel Cell Research Center, International Energy & Environment Foundation, Al-Najaf, P.O.Box 39 (Iraq)

    2010-07-01

    Damage mechanisms in a proton exchange membrane fuel cell are accelerated by mechanical stresses arising during fuel cell assembly (bolt assembling), and the stresses arise during fuel cell running, because it consists of the materials with different thermal expansion and swelling coefficients. Therefore, in order to acquire a complete understanding of the mechanical behaviour of the catalyst layers during regular cell operation, mechanical response under steady-state hygro-thermal stresses should be studied under real cell operating conditions and in real cell geometry (three-dimensional). In this work, full three-dimensional, non-isothermal computational fluid dynamics model of a PEM fuel cell has been developed to investigate the behaviour of the cathode and anode catalyst layers during the cell operation. A unique feature of the present model is to incorporate the effect of hygro and thermal stresses into actual three-dimensional fuel cell model. In addition, the temperature and humidity dependent material properties are utilize in the simulation for the membrane. The model is shown to be able to understand the many interacting, complex electrochemical, transport phenomena, and deformation that have limited experimental data.

  2. Mechanical behaviour of PEM fuel cell catalyst layers during regular cell operation

    Directory of Open Access Journals (Sweden)

    Maher A.R. Sadiq Al-Baghdadi

    2010-11-01

    Full Text Available Damage mechanisms in a proton exchange membrane fuel cell are accelerated by mechanical stresses arising during fuel cell assembly (bolt assembling, and the stresses arise during fuel cell running, because it consists of the materials with different thermal expansion and swelling coefficients. Therefore, in order to acquire a complete understanding of the mechanical behaviour of the catalyst layers during regular cell operation, mechanical response under steady-state hygro-thermal stresses should be studied under real cell operating conditions and in real cell geometry (three-dimensional. In this work, full three-dimensional, non-isothermal computational fluid dynamics model of a PEM fuel cell has been developed to investigate the behaviour of the cathode and anode catalyst layers during the cell operation. A unique feature of the present model is to incorporate the effect of hygro and thermal stresses into actual three-dimensional fuel cell model. In addition, the temperature and humidity dependent material properties are utilize in the simulation for the membrane. The model is shown to be able to understand the many interacting, complex electrochemical, transport phenomena, and deformation that have limited experimental data.

  3. Preventing effect of L-type calcium channel blockade on electrophysiological alterations in dentate gyrus granule cells induced by entorhinal amyloid pathology.

    Directory of Open Access Journals (Sweden)

    Hamid Gholami Pourbadie

    Full Text Available The entorhinal cortex (EC is one of the earliest affected brain regions in Alzheimer's disease (AD. EC-amyloid pathology induces synaptic failure in the dentate gyrus (DG with resultant behavioral impairment, but there is little known about its impact on neuronal properties in the DG. It is believed that calcium dyshomeostasis plays a pivotal role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on cellular properties of DG granule cells and also possible neuroprotective role of L-type calcium channel blockers (CCBs, nimodipine and isradipine, were investigated. The amyloid beta (Aβ 1-42 was injected bilaterally into the EC of male rats and one week later, electrophysiological properties of DG granule cells were assessed. Voltage clamp recording revealed appearance of giant sIPSC in combination with a decrease in sEPSC frequency which was partially reversed by CCBs in granule cells from Aβ treated rats. EC amyloid pathogenesis induced a significant reduction of input resistance (Rin accompanied by a profound decreased excitability in the DG granule cells. However, daily administration of CCBs, isradipine or nimodipine (i.c.v. for 6 days, almost preserved the normal excitability against Aβ. In conclusion, lower tendency to fire AP along with reduced Rin suggest that DG granule cells might undergo an alteration in the membrane ion channel activities which finally lead to the behavioral deficits observed in animal models and patients with early-stage Alzheimer's disease.

  4. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  5. Prognostic value of 18F-fluorodeoxyglucose positron emission tomography, computed tomography and magnetic resonance imaging in oral cavity squamous cell carcinoma with pathologically positive neck lymph node

    International Nuclear Information System (INIS)

    To evaluate the prognostic value of preoperative neck lymph node (LN) assessment with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), computed tomography (CT), and magnetic resonance imaging (MRI) in oral cavity squamous cell carcinoma (OSCC) patients with pathologically positive LN. In total, 47 OSCC patients with pathologically positive LN were retrospectively reviewed with preoperative 18F-FDG PET and CT/MRI. All patients underwent surgical resection, neck dissection and postoperative adjuvant radiotherapy and/or chemotherapy between March 2002 and October 2010. Histologic correlation was performed for findings of 18F-FDG PET and CT/MRI. Thirty-six (76.6%) of 47 cases were correctly diagnosed with neck LN metastasis by 18F-FDG PET and 32 (68.1%) of 47 cases were correctly diagnosed by CT/MRI. Follow-up ranged from 20 to 114 months (median, 56 months). Clinically negative nodal status evaluated by 18F-FDG PET or CT/MRI revealed a trend toward better clinical outcomes in terms of overall survival, disease-free survival, local recurrence-free survival, regional nodal recurrence-free survival, and distant metastasis-free survival rates even though the trends were not statistically significant. However, there was no impact of neck node standardized uptake value (SUVmax) on clinical outcomes. Notably, SUVmax showed significant correlation with tumor size in LN (p 2 = 0.62). PET and CT/MRI status of LN also had significant correlation with the size of intranodal tumor deposit (p 2 = 0.37 and p 2 = 0.48, respectively). 18F-FDG PET and CT/MRI at the neck LNs might improve risk stratification in OSCC patients with pathologically positive neck LN in this study, even without significant prognostic value of SUVmax.

  6. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial

    International Nuclear Information System (INIS)

    Background and purpose: To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC). Materials and methods: Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated. Results: Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis. Conclusions: Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable

  7. Investigating cell death mechanisms in Amyotrophic lateral sclerosis using transcriptomics

    Directory of Open Access Journals (Sweden)

    Paul Roy Heath

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis is a motor neuron disease characterised by degeneration and loss of upper and lower motor neurons from the motor cortex, brainstem and spinal cord although evidence is suggesting that there is further involvement of other cell types in the surrounding tissue. Transcriptomic analysis by gene expression profiling using microarray technology has enabled the determination of patterns of cell death in the degenerating tissues. This work has examined gene expression at the level of the tissue and individual cell types in both sporadic and familial forms of the disease. In addition, further studies have examined the differential vulnerability of neuronal cells in different regions of the central nervous system. Model systems have also provided further information to help unravel the mechanisms that lead to death of the motor neurons in disease and also provided novel insights. In this review we shall describe the methods that have been used in these investigations and describe how they have contributed to our knowledge of the cell death mechanisms in ALS.

  8. Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Elisabet Salas

    2014-01-01

    Full Text Available The ARF/INK4A (Cdkn2a locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin.

  9. Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

    Science.gov (United States)

    Salas, Elisabet; Rabhi, Nabil; Froguel, Philippe; Annicotte, Jean-Sébastien

    2014-01-01

    The ARF/INK4A (Cdkn2a) locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice) that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin. PMID:24672805

  10. Biophysical mechanism of cell inactivation by ionizing particles

    International Nuclear Information System (INIS)

    In radiobiological mechanism it is possible to distinguish the sequence of three different phases which can be denoted as physical, physico-chemical and biological. Mathematical models of the individual phases and their mutual interrelations are discussed. A special accent is given to the relation between the models of two non-biological phases and that of the biological one. Some detailed characteristics concerning DSB formation and repair and inactivation mechanisms in cells are analyzed with the help of the considered model chain. (author). 39 refs, 3 figs, 3 tabs

  11. Mechanical-Electrochemical-Thermal Simulation of Lithium-Ion Cells

    Energy Technology Data Exchange (ETDEWEB)

    Santhanagopalan, Shriram; Zhang, Chao; Sprague, Michael A.; Pesaran, Ahmad

    2016-06-01

    Models capture the force response for single-cell and cell-string levels to within 15%-20% accuracy and predict the location for the origin of failure based on the deformation data from the experiments. At the module level, there is some discrepancy due to poor mechanical characterization of the packaging material between the cells. The thermal response (location and value of maximum temperature) agrees qualitatively with experimental data. In general, the X-plane results agree with model predictions to within 20% (pending faulty thermocouples, etc.); the Z-plane results show a bigger variability both between the models and test-results, as well as among multiple repeats of the tests. The models are able to capture the timing and sequence in voltage drop observed in the multi-cell experiments; the shapes of the current and temperature profiles need more work to better characterize propagation. The cells within packaging experience about 60% less force under identical impact test conditions, so the packaging on the test articles is robust. However, under slow-crush simulations, the maximum deformation of the cell strings with packaging is about twice that of cell strings without packaging.

  12. Mechanism of yeast cell photoinactivation by visible light

    International Nuclear Information System (INIS)

    The nature of inactivation of visible light without sensitizers added to the cells has been investigated. In particular, the problem on the nature of intracellular sensitizers has been studied. Visible light is shown to inactivate the cells only in the presence of oxygen, that gives evidence that the process of photoinactivation is carried out according a photodynamic mechanism with participation of the endogenic sensitizer. The pigment - sensitizer is identified as the protoporphyrin on the basis of comparison of data obtained for the absorption spectrum structure and pigment fluorescence with the literature data on the spectral properties of porphyrin compounds

  13. On the Mechanism of Light Transmission by Muller Cells

    CERN Document Server

    Makarov, Vladimir; Khmelinskii, Igor; Inyushin, Mikhail

    2015-01-01

    We report that Muller cells contain bundles of long specialized intermediate filaments about 10 nm in diameter; most likely, these filaments are the channels providing light transmission to photoreceptor cells in mammalian and avian retinas. We interpret transmission of light in such channels using the notions of quantum confinement, describing energy transport in structures with electro-conductive walls and diameter much smaller than the wavelength of the respective photons. Model calculations produce photon transmission efficiency in such channels exceeding 0.8, in optimized geometry. We infer that protein molecules make up the channels, proposing a qualitative mechanism of light transmission by such structures.

  14. Pathologic assessment of myocardial cell necrosis and apoptosis after ischemia and reperfusion with molecular and morphological markers.

    Science.gov (United States)

    Takashi, E; Ashraf, M

    2000-02-01

    The present work illustrates the critical subcellular changes in the rat heart after 10-30 min of left coronary artery (LCA) occlusion and 120 min of reperfusion with a combination of several staining techniques. Triphenyltetrazolium chloride (TTC) to detect non-injured myocytes, horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) to detect necrotic and apoptotic cells were employed and electron microscopy (EM) was used to validate these changes. After 20 min of LCA occlusion, myocytes began to undergo necrosis whilst after 10 min occlusion, no myocyte underwent irreversible cell injury in the risk area. After 30 min of LCA occlusion and 120 min reperfusion, 36.3, 26.6 and 25% cells were normal, necrotic, and reversibly injured, respectively; the remaining 12.8% cells were apoptotic. Necrotic cells were strongly positive with HRP and negative for TTC and TUNEL. TUNEL-positive or apoptotic cells were slightly HRP-positive, indicating altered cell membrane permeability. Reversibly-injured myocytes were TTC-, HRP- and TUNEL-negative. These changes were more accurately defined in the 100- microm thick sections than in the traditional slices. It is concluded that: (1) TTC-staining of 100- microm thick sections is far superior and accurate for the detection of ischemic changes with shorter period of ischemia (10 min); (2) the combination of TTC-staining, HRP reaction and TUNEL method is excellent for demarcation of early ischemic changes; (3) TTC-negativity in ischemia less than 20 min does not indicate necrosis but only represents reversible changes; (4) the apoptosis is absent in early ischemia of 20 min with or without reperfusion at a time when sufficient ATP is present, and appears only after 30 min of coronary ligation and reperfusion; and (5) the apoptotic cells lose membrane integrity accompanied by decreased glycocalyx thickness and cell swelling as opposed to commonly known characteristics of apoptotic cells. PMID:10722798

  15. Fatigue and Mechanical Damage Propagation in Automotive PEM Fuel Cells

    Science.gov (United States)

    Banan, Roshanak

    Polymer electrolyte membrane (PEM) fuel cells are generally exposed to high magnitude road-induced vibrations and impact loads, frequent humidity-temperature loading cycles, and freeze/thaw stresses when employed in automotive applications. The resultant mechanical stresses can play a significant role in the evolution of mechanical defects in the membrane electrode assembly (MEA). The focus of this research is to investigate fatigue challenges due to humidity-temperature (hygrothermal) cycles and vibrations and their effects on damage evolution in PEM fuel cells. To achieve this goal, this thesis is divided into three parts that provide insight into damage propagation in the MEA under i) hygrothermal cycles, ii) external applied vibrations, and iii) a combination of both to simulate realistic automotive conditions. A finite element damage model based on cohesive zone theory was developed to simulate the propagation of micro-scale defects (cracks and delaminations) in the MEA under fuel cell operating conditions. It was found that the micro-defects can propagate to critical states under start-up and shut-down cycles, prior to reaching the desired lifespan of the fuel cell. The simultaneous presence of hygrothermal cycles and vibrations severely intensified damage propagation and resulted in considerably large defects within 75% of the fuel cell life expectancy. However, the order of generated damage was found to be larger under hygrothermal cycles than vibrations. Under hygrothermal cycles, membrane crack propagation was more severe compared to delamination propagation. Conversely, the degrading influence of vibrations was more significant on delaminations. The presence of an anode/cathode channel offset under the combined loadings lead to a 2.5-fold increase in the delamination length compared to the aligned-channel case. The developed model can be used to investigate the damage behaviour of current materials employed in fuel cells as well as to evaluate the

  16. Molecular mechanisms of cell death in intervertebral disc degeneration (Review).

    Science.gov (United States)

    Zhang, Fan; Zhao, Xueling; Shen, Hongxing; Zhang, Caiguo

    2016-06-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  17. Mechanisms of Dendritic Cell Lysosomal Killing of Cryptococcus

    Science.gov (United States)

    Hole, Camaron R.; Bui, Hoang; Wormley, Floyd L.; Wozniak, Karen L.

    2012-10-01

    Cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the CNS causing fatal meningitis in immunocompromised patients. Dendritic cells (DCs) phagocytose C. neoformans following inhalation. Following uptake, cryptococci translocate to the DC lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. DC lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. Our studies determined non-oxidative antifungal activity by DC lysosomal extract. We examined DC lysosomal killing of cryptococcal strains, anti-fungal activity of purified lysosomal enzymes, and mechanisms of killing against C. neoformans. Results confirmed DC lysosome fungicidal activity against all cryptococcal serotypes. Purified lysosomal enzymes, specifically cathepsin B, inhibited cryptococcal growth. Interestingly, cathepsin B combined with its enzymatic inhibitors led to enhanced cryptococcal killing. Electron microscopy revealed structural changes and ruptured cryptococcal cell walls following treatment. Finally, additional studies demonstrated that osmotic lysis was responsible for cryptococcal death.

  18. Mechanism of T-cell tolerance induced by myeloid-derived suppressor cells1

    OpenAIRE

    Nagaraj, Srinivas; Schrum, Adam G.; Cho, Hyun-Il; Celis, Esteban; Gabrilovich, Dmitry I.

    2010-01-01

    Antigen-specific T-cell tolerance plays a critical role in tumor escape. Recent studies implicated myeloid-derived suppressor cells (MDSC) in the induction of CD8+ T-cell tolerance in tumor-bearing hosts. However, the mechanism of this phenomenon remained unclear. We have found that incubation of antigen-specific CD8+ T cells, with peptide-loaded MDSC, did not induce signaling downstream of TCR. However, it prevented subsequent signaling from peptide-loaded dendritic cells. Using double TCR t...

  19. Mechanism of enhancement of microbial cell hydrophobicity by cationic polymers.

    OpenAIRE

    Goldberg, S; Doyle, R J; Rosenberg, M

    1990-01-01

    Polycationic polymers have been noted for their effects in promoting cell adhesion to various surfaces, but previous studies have failed to describe a mechanism dealing with this type of adhesion. In the present study, three polycationic polymers (chitosan, poly-L-lysine, and lysozyme) were tested for their effects on microbial hydrophobicity, as determined by adhesion to hydrocarbon and polystyrene. Test strains (Escherichia coli, Candida albicans, and a nonhydrophobic mutant, MR-481, derive...

  20. Cell-Autonomous Effector Mechanisms against Mycobacterium tuberculosis

    OpenAIRE

    MacMicking, John D.

    2014-01-01

    Few pathogens run the gauntlet of sterilizing immunity like Mycobacterium tuberculosis (Mtb). This organism infects mononuclear phagocytes and is also ingested by neutrophils, both of which possess an arsenal of cell-intrinsic effector mechanisms capable of eliminating it. Here Mtb encounters acid, oxidants, nitrosylating agents, and redox congeners, often exuberantly delivered under low oxygen tension. Further pressure is applied by withholding divalent Fe2+, Mn2+, Cu2+, and Zn2+, as well as...

  1. Role of ROBO4 Signalling in Developmental and Pathological Angiogenesis

    Directory of Open Access Journals (Sweden)

    Suresh Singh Yadav

    2014-01-01

    Full Text Available Transmembrane roundabout receptor family members (ROBO1–ROBO4 principally orchestrate the neuronal guidance mechanism of the nervous system. Secreted glycoprotein SLITs are the most appreciated ligands for ROBOs. Recently identified ROBO4 is the key mediator of SLIT-ROBO mediated developmental and pathological angiogenesis. Although SLIT2 has been shown to interact with ROBO4 as ligand, it remains an open question whether this protein is the physiologic partner of ROBO4. The purpose of this review is to summarise how reliable SLIT2 as ligand for ROBO4 is, if not what the other possible mechanisms demonstrated till date for ROBO4 mediated developmental and pathological angiogenesis are. We conclude that ROBO4 is expressed specially in vascular endothelial cells and maintains the vascular integrity via either SLIT2 dependent or SLIT2 independent manner. On the contrary, it promotes the pathological angiogenesis by involving different signalling arm(s/unknown ligand(s. This review explores the interactions SLIT2/ROBO1, SLIT2/ROBO1–ROBO4, ROBO1/ROBO4, and ROBO4/UNC5B which can be promising and potential therapeutic targets for developmental angiogenesis defects and pathological angiogenesis. Finally we have reviewed the ROBO4 signalling pathways and made an effort to elaborate the insight of this signalling as therapeutic target of pathological angiogenesis.

  2. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    International Nuclear Information System (INIS)

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart

  3. Bystander responses in cells models; targets, dosimetry and mechanisms

    International Nuclear Information System (INIS)

    The use of microbeam approaches has been a major advance in probing the relevance of bystander responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses induced in human or hamster cells even when radiation is deposited away from the nucleus in cytoplasmic targets either after charged particle or soft X-ray exposure. Importantly, the level of bystander effect, measured as cell killing was similar to that observed when the same amount of energy was deposited but targeted to the nucleus. In other studies, we have shown that underlying determination of the level of response is the energy deposited in a single cell rather than the number of cells hit. Also the overall response at low doses may be dominated by bystander signaling. These observations have significance for our understanding of radiation risk at low doses including those of environmental exposures and the applicability of the Linear Non Threshold model. The realization that cell to cell signaling is important for radiation response may also open up new therapeutic opportunities to either improve tumor cell kill or protect normal tissues if the pathways underpinning bystander signaling can be elucidated and controlled

  4. Mechanisms of Therapeutic Resistance in Cancer (Stem) Cells with Emphasis on Thyroid Cancer Cells

    OpenAIRE

    Hombach-Klonisch, Sabine; Natarajan, Suchitra; Thanasupawat, Thatchawan; Medapati, Manoj; PATHAK, ALOK; Ghavami, Saeid; Klonisch, Thomas

    2014-01-01

    The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to con...

  5. Study on the relationship between serum concentration of CYFRA21-1 and pathological staging in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To study the relationship between of serum concentrations of CYFRA21-1 and to pathological staging in patients with non-small cell lung cancer. Methods: Serum concentrations of CYFRA21-1 were determined with IRMA in 224 patients with non-small cell lung cancer. Results: The serum CYFRA21-1 levels in patients with non-small cell lung carcinoma increased gradually as the tumor size enlarged. Levels in patients of T2 and T3 stages were significantly higher than those in patients of T1 stage, but the difference between those in patients of T2 stage and T3 stage were not significant. The serum CYFRA21-1 levels also increased as the number of lymph nodes with metastasis increased. Differences of serum levels of CYFRA21-1 in patients of consecutive lymph node stages were all significant. Conclusion: Preoperative detection of the serum concentration of CYFRA21-1 in patient with non-small cell lung cancer has important clinical significance on the judgement of T, N stages. (authors)

  6. Mechanisms of cell accumulation induced by Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Octávio Menezes-de-Lima-Júnior

    1997-12-01

    Full Text Available Mycobacteria, specially Mycobacterium tuberculosis are among the micro-organisms that are increasing dramatically the number of infections with death, all over the world. A great number of animal experimental models have been proposed to investigate the mechanisms involved in the host response against these intracellular parasites. Studies of airway infection in guinea-pigs and rabbits, as well as, in mice intravenously infected with BCG have made an important contribution to our understanding of the virulence, pathogenesis and the immunology of mycobacterial infections. Although, there are few models to study the mechanisms of the initial inflammatory process induced by the first contact with the Mycobacteria, and the relevance of the acute generation of inflammatory mediators, cytokines and leukocyte infiltration to the development of the mycobacterial infection. In this work we reviewed our results obtained with a model of M. bovis BCG-induced pleurisy in mice, describing the mechanisms involved in the leukocyte influx induced by BCG at 24 hr. Different mechanisms appear to be related with the influx of neutrophils, eosinophils and mononuclear cells and distinct inflammatory mediators, cytokines and adhesion molecules are involved in the BCG-induced cell accumulation.

  7. Regenerating medicine related to the stem-cells and its mechanisms of action from adults cells

    International Nuclear Information System (INIS)

    Regenerating medicine is a branch of Medicine very developed in past years. Advances in this field have been closely linked with the new knowledge achieved on stem-cells and its ability to become in cells of different tissues. This type of medicine is based on the behaviors adopted by organism to substitute those damaged cells by the healthy ones by different processes in specific tissues. Therapeutic measures used may include the stem-cell transplantation, the use of soluble molecules, genic therapy and tissues engineering. Nowadays, the more used method is the adult stem-cells. However, is not well known the mechanisms by which the transplanted cells could to improve or to promote the tissue regeneration. To explain these mechanisms some hypotheses has been proposed including the cellular trans-differentiation, cells fusion, and the effects secondaries to cells release by cells of different soluble molecules with specific actions; in addition to the autocrine and paracrine effects that may have these soluble factors, it is suggested too the existence of a telecrine action. It is probable that more than one of these mechanisms be executed

  8. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara

    2016-01-01

    Tissue regeneration from transplanted mesenchymal stromal cells (MSC) either through transdifferentiation or cell fusion was originally proposed as the principal mechanism underlying their therapeutic action. However, several studies have now shown that both these mechanisms are very inefficient. The low MSC engraftment rate documented in injured areas also refutes the hypothesis that MSC repair tissue damage by replacing cell loss with newly differentiated cells. Indeed, despite evidence of preferential homing of MSC to the site of myocardial ischemia, exogenously administered MSC show poor survival and do not persist in the infarcted area. Therefore, it has been proposed that the functional benefits observed after MSC transplantation in experimental models of tissue injury might be related to the secretion of soluble factors acting in a paracrine fashion. This hypothesis is supported by pre-clinical studies demonstrating equal or even improved organ function upon infusion of MSC-derived conditioned medium (MSC-CM) compared with MSC transplantation. Identifying key MSC-secreted factors and their functional role seems a reasonable approach for a rational design of nextgeneration MSC-based therapeutics. Here, we summarize the major findings regarding both different MSC-mediated paracrine actions and the identification of paracrine mediators. PMID:27236669

  9. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Directory of Open Access Journals (Sweden)

    Wan Nurlina Wan Yahya

    2014-07-01

    Full Text Available Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

  10. Analysis of loss mechanisms in polycrystalline thin film solar cells

    Science.gov (United States)

    Sites, J. R.

    1990-08-01

    Our goal for thin-film polycrystalline solar cell analysis was to increase the useful information extracted from relatively straightforward electrical measurements. The strategy was to (1) systematize measurements and reporting, (2) organize results in terms of quantitative values for individual sources of current and voltage loss, and (3) evaluate possible analytical techniques to enhance precision and avoid pitfalls, and (4) insist on a viable physical explanation of each loss mechanism. Current-voltage, quantum efficiency, and capacitance measurements on CuInSe2 and CdTe solar cells from a variety of sources have been analyzed. In many cases losses were identified that may be lessened relatively easily. However, the operating voltage loss due to excessive forward recombination current throughout the depletion region remains the primary obstacle to efficiencies competitive with single crystal cells.

  11. Analysis of loss mechanisms in polycrystalline thin film solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sites, J.R. (Colorado State Univ., Fort Collins, CO (USA))

    1990-08-01

    Our goal for thin-film polycrystalline solar cell analysis was to increase the useful information extracted from relatively straightforward electrical measurements. The strategy was to (1) systematize measurements and reporting, (2) organize results in terms of quantitative values for individual sources of current and voltage loss, and (3) evaluate possible analytical techniques to enhance precision and avoid pitfalls, and (4) insist on a viable physical explanation of each loss mechanism. Current-voltage, quantum efficiency, and capacitance measurements on CuInSe{sub 2} and CdTe solar cells from a variety of sources have been analyzed. In many cases losses were identified that may be lessened relatively easily. However, the operating voltage loss due to excessive forward recombination current throughout the depletion region remains the primary obstacle to efficiencies competitive with single crystal cells. 1 tab., 4 figs., 26 refs.

  12. Cell Biological Mechanisms of Multidrug Resistance in Tumors

    Science.gov (United States)

    Simon, Sanford M.; Schindler, Melvin

    1994-04-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs.

  13. Chorein Sensitivity of Actin Polymerization, Cell Shape and Mechanical Stiffness of Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ioana Alesutan

    2013-09-01

    Full Text Available Background/Aims: Endothelial cell stiffness plays a key role in endothelium-dependent control of vascular tone and arterial blood pressure. Actin polymerization and distribution of microfilaments is essential for mechanical cell stiffness. Chorein, a protein encoded by the VPS13A gene, defective in chorea-acanthocytosis (ChAc, is involved in neuronal cell survival as well as cortical actin polymerization of erythrocytes and blood platelets. Chorein is expressed in a wide variety of further cells, yet nothing is known about the impact of chorein on cells other than neurons, erythrocytes and platelets. The present study explored whether chorein is expressed in human umbilical vein endothelial cells (HUVECs and addressed the putative role of chorein in the regulation of cytoskeletal architecture, stiffness and survival of those cells. Methods: In HUVECs with or without silencing of the VPS13A gene, VPS13A mRNA expression was determined utilizing quantitative RT-PCR, cytoskeletal organization visualized by confocal microscopy, G/F actin ratio and phosphorylation status of focal adhesion kinase quantified by western blotting, cell death determined by flow cytometry, mechanical properties studied by atomic force microscopy (AFM and cell morphology analysed by scanning ion conductance microscopy (SICM. Results: VPS13A mRNA expression was detectable in HUVECs. Silencing of the VPS13A gene attenuated the filamentous actin network, decreased the ratio of soluble G-actin over filamentous F-actin, reduced cell stiffness and changed cell morphology as compared to HUVECs silenced with negative control siRNA. These effects were paralleled by a significant decrease in FAK phosphorylation following VPS13A silencing. Moreover, silencing of the VPS13A gene increased caspase 3 activity and induced necrosis in HUVECs. Conclusions: Chorein is a novel regulator of cytoskeletal architecture, cell shape, mechanical stiffness and survival of vascular endothelial cells.

  14. Glomerulonephritis associated with marginal zone B-cell lymphoma: clinical, pathological characteristics of renal injury and treatment (clinical cases

    Directory of Open Access Journals (Sweden)

    B. T. Dzhumabaeva

    2015-12-01

    Full Text Available Glomerulonephritis associated with marginal zone B-cell lymphoma at the onset of disease is rarely diagnosed. In this article we reported two patient of the extranodal marginal zone B-cell lymphoma with kidney damage. The first patient with the extranodal marginal zone B-cell lymphoma involved the stomach, lymph nodes, bone marrow and associated with mesangioproliferative glomerulonephritis and renal failure. The second patient with the splenic form of marginal zone B-cell lymphoma associated with fibrillary glomerulonephritis and hepatitis C and involve the lymph nodes, liver, bone marrow, and synthesis monoclonal immunoglobulin (IgMκ, cryoglobulin type II. Glomerulonephritis of the both cases were established on the renal biopsies by the morphological investigation, immunofluorescence, and electron microscopy.Both patients received therapy with bendamustine and rituximab, which has resulted in complete remission for lymphatic tumors and improve of kidney function. Overall and event-free survival in the first case corresponds to 21 and 16 months, the second 29 and 20, respectively.These cases illustrates that the kidney may be initially involved by extranodal marginal zone B-cell lymphoma, and the need for expanded investigation of the possible dissemination. Combination of bendamustine and rituximab were effective and safety treatment in these cases.

  15. Molecular mechanisms regulating impaired neurogenesis of fragile X syndrome human embryonic stem cells.

    Science.gov (United States)

    Telias, Michael; Mayshar, Yoav; Amit, Ami; Ben-Yosef, Dalit

    2015-10-15

    Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the "GSK3β theory of FXS" for the first time in a human-based model. We found no evidence for a pathological increase in GSK3β protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system. PMID:26393806

  16. Pulmonary langerhans cell histiocytosis in adults: high-resolution CT - pathology comparisons and evolutional changes at CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Jin; Lee, Ho Yun; Kim, Tae Sung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Samsung Medical Center, Department of Radiology, Seoul (Korea, Republic of); Johkoh, Takeshi [Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Department of Radiology, Hyoko (Japan); Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2011-07-15

    To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH). We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 {+-} 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes. The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease. More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT. (orig.)

  17. Pulmonary langerhans cell histiocytosis in adults: high-resolution CT - pathology comparisons and evolutional changes at CT

    International Nuclear Information System (INIS)

    To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH). We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 ± 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes. The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease. More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT. (orig.)

  18. Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis

    DEFF Research Database (Denmark)

    Bäcklund, Johan; Treschow, Alexandra; Bockermann, Robert;

    2002-01-01

    Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA...

  19. Mechanically Stacked Four-Junction Concentrator Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Myles A.; Geisz, John F.; Ward, J. Scott; Garcia, Ivan; Friedman, Daniel J.; King, Richard R.; Chiu, Philip T.; France, Ryan M.; Duda, Anna; Olavarria, Waldo J.; Young, Michelle; Kurtz, Sarah R.

    2015-06-14

    Multijunction solar cells can be fabricated by bonding together component cells that are grown separately. Because the component cells are each grown lattice-matched to suitable substrates, this technique allows alloys of different lattice constants to be combined without the structural defects introduced when using metamorphic buffers. Here we present results on the fabrication and performance of four-junction mechanical stacks composed of GaInP/GaAs and GaInAsP/GaInAs tandems, grown on GaAs and InP substrates, respectively. The two tandems were bonded together with a low-index, transparent epoxy that acts as an omni-directional reflector to the GaAs bandedge luminescence, while simultaneously transmitting nearly all of the sub-bandgap light. As determined by electroluminescence measurements and optical modeling, the GaAs subcell demonstrates a higher internal radiative limit and thus higher subcell voltage, compared with GaAs subcells without enhanced internal optics; all four subcells exhibit excellent material quality. The device was fabricated with four contact terminals so that each tandem can be operated at its maximum power point, which raises the cumulative efficiency and decreases spectral sensitivity. Efficiencies exceeding 38% at one-sun have been demonstrated. Eliminating the series resistance is the key challenge for the concentrator cells. We will discuss the performance of one-sun and concentrator versions of the device, and compare the results to recently fabricated monolithic four-junction cells.

  20. Probing mechanical principles of cell-nanomaterial interactions

    Science.gov (United States)

    Gao, Huajian

    2014-01-01

    With the rapid development of nanotechnology, various types of nanoparticles, nanowires, nanofibers, nanotubes, and atomically thin plates and sheets have emerged as candidates for an ever increasing list of potential applications for next generation electronics, microchips, composites, barrier coatings, biosensors, drug delivery, and energy harvesting and conversion systems. There is now an urgent societal need to understand both beneficial and hazardous effects of nanotechnology which is projected to produce and release thousands of tons of nanomaterials into the environment in the coming decades. This paper aims to present an overview of some recent studies conducted at Brown University on the mechanics of cell-nanomaterial interactions, including the modeling of nanoparticles entering cells by receptor-mediated endocytosis and coarse-grained molecular dynamics simulations of nanoparticles interacting with cell membranes. The discussions will be organized around the following questions: Why and how does cellular uptake of nanoparticles depend on particle size, shape, elasticity and surface structure? In particular, we will discuss the effect of nanoparticle size on receptor-mediated endocytosis, the effect of elastic stiffness on cell-particle interactions, how high aspect ratio nanomaterials such as carbon nanotubes and graphenes enter cells and how different geometrical patterns of ligands on a nanoparticle can be designed to control the rate of particle uptake.

  1. Synergistically increased ILC2 and Th9 cells in lung tissue jointly promote the pathological process of asthma in mice.

    Science.gov (United States)

    Ying, Xinyu; Su, Zhaoliang; Bie, Qingli; Zhang, Pan; Yang, Huijian; Wu, Yumin; Xu, Yunyun; Wu, Jing; Zhang, Mengying; Wang, Shengjun; Xu, Huaxi

    2016-06-01

    In recent years, T helper (Th) 9 cells have been demonstrated to be key mediators in immune responses in asthmatic lungs, and innate lymphoid cells 2 (ILC2s) have been described as a novel type of innate immunocyte with the ability to enhance immunoglobulin E (IgE) production. However, the interaction between ILC2s and Th9 cells in the pulmonary system of a mouse model of asthma remains to be elucidated. In the present study, the response state of lung tissue with regards to Th9 and ILC2s in a mouse model of asthma was investigated by detecting Th9‑ and ILC2‑associated cytokine receptors. The present study also investigated the association between the expression levels of the cytokine receptors in lung tissue samples and the IgE levels in sera samples from mouse models of asthma. Results from the present study demonstrated that the frequency of ILC2s and Th9 cells was significantly increased in the lung tissue samples, indicating that a Th2-type immune response had occurred. In addition, high mRNA expression levels of RAR‑related orphan receptor α, interleukin 1 receptor‑like 1, transcription factor PU.1 and interleukin (IL)‑9 were observed. Furthermore, IL‑5Rα, IL‑13Rα2 and high‑affinity IgE receptor were increased in mouse models of asthma, and a positive association was observed between the expression levels of ILC2‑ or Th9‑associated receptors in tissue samples and IgE levels in the sera. This indicated that ILC2s and Th9 were in a state of polarization and may promote each other in the lung tissue of mouse models of asthma, and that the lung tissue was responding to the two types of cells via increased expression of receptors. PMID:27109139

  2. Matrix metalloproteinase-10 is a target of T and B cell responses that correlate with synovial pathology in patients with antibiotic-refractory Lyme arthritis.

    Science.gov (United States)

    Crowley, Jameson T; Strle, Klemen; Drouin, Elise E; Pianta, Annalisa; Arvikar, Sheila L; Wang, Qi; Costello, Catherine E; Steere, Allen C

    2016-05-01

    Infection-induced autoimmunity is thought to be a contributing factor in antibiotic-refractory Lyme arthritis, but studies of autoimmunity have been hindered by difficulty in identifying relevant autoantigens. We developed a novel approach that begins with the identification of T cell epitopes in synovial tissue using tandem mass spectrometry. Herein, we identified an immunogenic HLA-DR-presented peptide (T cell epitope) derived from the source protein matrix metalloproteinase-10 (MMP-10) from the synovium of a patient with antibiotic-refractory arthritis. This finding provided a bridge for the identification of autoantibody responses to MMP-10, the "first autoimmune hit" in a subgroup of patients with erythema migrans, the initial skin lesion of the infection. Months later, after priming of the immune response to MMP-10 in early infection, a subset of patients with antibiotic-responsive or antibiotic-refractory arthritis had MMP-10 autoantibodies, but only patients with antibiotic-refractory arthritis had both T and B cell responses to the protein, providing evidence for a "second autoimmune hit". Further support for a biologically relevant autoimmune event was observed by the positive correlation of anti-MMP-10 autoantibodies with distinct synovial pathology. This experience demonstrates the power of new, discovery-based methods to identify relevant autoimmune responses in chronic inflammatory forms of arthritis. PMID:26922382

  3. Pathology of the region of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Aufdermaur, M.

    1981-09-01

    Radiological, clinical and pathologic-anatomical findings seen in four types of disorders of the region of the knee jointare described. An attempt is made to explain the clinical symptomatology on the basis of pathologic-anatomical findings. It is demonstrated that the histology of a giant cell neoplasm does not permit conclusions as to prognosis. Etiology and pathogenesis of villonodular synovitis and of chondrocalcinosis are unexplained. Pathologic-anatomical findings of chondromalacia patellae are those of early osteoarthrosis.

  4. Probing mechanical properties of living cells by magnetopneumography.

    Science.gov (United States)

    Möller, W; Takenaka, S; Rust, M; Stahlhofen, W; Heyder, J

    1997-01-01

    Magnetopneumography (MPG) has been used to study long-term particle clearance from human lungs as well as cellular motility of pulmonary macrophages (PMs). This study describes an extension of the method enabling the measurement of mechanical properties of PM cells in vivo. Ferromagnetic microparticles are inhaled and then retained in the alveolar region of the lungs, where they are phagocytized within hours by PMs. The magnetic particles can be rotated in weak magnetic fields, and the response to this twisting shear (force) is detected as a macroscopic magnetic field producing a measure of cytoskeletal mechanics. Cytoplasmic viscosity is very high compared with that of water and is strongly non-Newtonian. Under rotational stresses from 0.4 to 6.4 Pa, it acts like a pseudoplastic fluid showing a characteristic shear rate dependence. The viscosity as well as the stiffness of the cytoskeleton increases with increasing shear stress as seems typical for living tissue and evidence for an intact cytoskeletal matrix. The particle recoil as measured by the amount of recoverable strain following a short twisting force describes a cytoplasmic elasticity that depends on both level and duration of stress. These investigations on the mechanical properties of living human cells are promising and should lead to better understanding of cellular dysfunction in disease as well as pathways for drug administration. PMID:10174196

  5. Correlation of Radiographic and Pathologic Findings of Dermal Lymphatic Invasion in Head and Neck Squamous Cell Carcinoma

    OpenAIRE

    Spector, Matthew E; Gallagher, K. Kelly; McHugh, Jonathan B; Mukherji, Suresh K.

    2011-01-01

    Head and neck squamous cell carcinoma (HNSCC) that involves the skin is able to invade the dermal lymphatic system. Currently there is no way to identify patients with dermal lymphatic invasion preoperatively. The purpose of this study is to determine if CT can predict dermal lymphatic invasion. Medical records, CT scans, and corresponding histopathologic slides were reviewed of HNSCC patients with skin resected as part of their treatment. Dermal lymphatic invasion was defined radiographicall...

  6. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

    Science.gov (United States)

    Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.

    2001-11-01

    Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

  7. Pathological Plasticity in Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Brandon S. Martin

    2012-01-01

    Full Text Available Deficits in neuronal plasticity are common hallmarks of many neurodevelopmental disorders. In the case of fragile-X syndrome (FXS, disruption in the function of a single gene, FMR1, results in a variety of neurological consequences directly related to problems with the development, maintenance, and capacity of plastic neuronal networks. In this paper, we discuss current research illustrating the mechanisms underlying plasticity deficits in FXS. These processes include synaptic, cell intrinsic, and homeostatic mechanisms both dependent on and independent of abnormal metabotropic glutamate receptor transmission. We place particular emphasis on how identified deficits may play a role in developmental critical periods to produce neuronal networks with permanently decreased capacity to dynamically respond to changes in activity central to learning, memory, and cognition in patients with FXS. Characterizing early developmental deficits in plasticity is fundamental to develop therapies that not only treat symptoms but also minimize the developmental pathology of the disease.

  8. Mechanical Instabilities of Biological Tubes

    Science.gov (United States)

    Hannezo, Edouard; Prost, Jacques; Joanny, Jean-François

    2012-07-01

    We study theoretically the morphologies of biological tubes affected by various pathologies. When epithelial cells grow, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated: varicose, dilated, sinuous, or sausagelike. They are all found in pathologies of tracheal, renal tubes, or arteries. The final shape depends crucially on the mechanical parameters of the tissues: Young’s modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.

  9. Regulatory mechanism of radiation-induced cancer cell death by the change of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Soo Jin; Jeong, Min Ho; Jang, Ji Yeon [College of Medicine, Donga Univ., Pusan (Korea, Republic of)

    2003-09-01

    cycle regulatory activites. In this study, we present a unique and reproducible model in which for investigating the mechanisms of various, radiation-induced, cancer cell death patterns. Further evaluation by using this model will provide a potent target for a new strategy of radiotherapy.

  10. Updates of pathologic myopia.

    Science.gov (United States)

    Ohno-Matsui, Kyoko; Lai, Timothy Y Y; Lai, Chi-Chun; Cheung, Chiu Ming Gemmy

    2016-05-01

    Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve. Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy. In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. PMID:26769165

  11. Forms of pathologization

    DEFF Research Database (Denmark)

    Brinkmann, Svend

    before, perhaps due to the malaises of modernity. Instead, we have learned to think and talk about human problems in new ways, viz. ways that involve pathologization. Pathologization, however, is not a unitary phenomenon, and the presentation gives an overview of four types of pathologization, which are...

  12. Time-dependent Mechanisms in Beta-cell Glucose Sensing

    OpenAIRE

    Vagn Korsgaard, Thomas; Colding-Jørgensen, Morten

    2006-01-01

    The relation between plasma glucose and insulin release from pancreatic beta-cells is not stationary in the sense that a given glucose concentration leads to a specific rate of insulin secretion. A number of time-dependent mechanisms appear to exist that modify insulin release both on a short and a longer time scale. Typically, two phases are described. The first phase, lasting up to 10 min, is a pulse of insulin release in response to fast changes in glucose concentration. The second phase i...

  13. Mechanical behavior of regular open-cell porous biomaterials made of diamond lattice unit cells.

    Science.gov (United States)

    Ahmadi, S M; Campoli, G; Amin Yavari, S; Sajadi, B; Wauthle, R; Schrooten, J; Weinans, H; Zadpoor, A A

    2014-06-01

    Cellular structures with highly controlled micro-architectures are promising materials for orthopedic applications that require bone-substituting biomaterials or implants. The availability of additive manufacturing techniques has enabled manufacturing of biomaterials made of one or multiple types of unit cells. The diamond lattice unit cell is one of the relatively new types of unit cells that are used in manufacturing of regular porous biomaterials. As opposed to many other types of unit cells, there is currently no analytical solution that could be used for prediction of the mechanical properties of cellular structures made of the diamond lattice unit cells. In this paper, we present new analytical solutions and closed-form relationships for predicting the elastic modulus, Poisson׳s ratio, critical buckling load, and yield (plateau) stress of cellular structures made of the diamond lattice unit cell. The mechanical properties predicted using the analytical solutions are compared with those obtained using finite element models. A number of solid and porous titanium (Ti6Al4V) specimens were manufactured using selective laser melting. A series of experiments were then performed to determine the mechanical properties of the matrix material and cellular structures. The experimentally measured mechanical properties were compared with those obtained using analytical solutions and finite element (FE) models. It has been shown that, for small apparent density values, the mechanical properties obtained using analytical and numerical solutions are in agreement with each other and with experimental observations. The properties estimated using an analytical solution based on the Euler-Bernoulli theory markedly deviated from experimental results for large apparent density values. The mechanical properties estimated using FE models and another analytical solution based on the Timoshenko beam theory better matched the experimental observations. PMID:24566381

  14. Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.

    Science.gov (United States)

    Bogusz, Agata M; Bagg, Adam

    2016-09-01

    Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations. The recent surge in next generation sequencing (NGS) technology has shed more light on the genetic landscape of SBCLs through characterization of numerous driver mutations including SF3B1 and NOTCH1 in CLL, ATM and CCND1 in MCL, KMT2D and EPHA7 in FL, MYD88 (L265P) in LPL, KLF2 and NOTCH2 in splenic MZL (SMZL) and BRAF (V600E) in HCL. The identification of distinct genetic lesions not only provides greater insight into the molecular pathogenesis of these disorders but also identifies potential valuable biomarkers for prognostic stratification, as well as specific targets for directed therapy. This review discusses the well-established and recently identified molecular lesions underlying the pathogenesis of SBCLs, highlights their clinical relevance and summarizes novel targeted therapies. PMID:27121112

  15. Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP

    Institute of Scientific and Technical Information of China (English)

    WANG Yan-ling; YAN Yun-li; ZHOU Na-jing; HAN Shuo; ZHAO Jun-xia; CAO Cui-li; Lü Yu-hong

    2010-01-01

    Background Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP.Methods The cell viability was measured by M∏ assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase Ⅱ (Topo Ⅱ) expressions in H446 and H446/VP cells after treated with or without VP-16.Results The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo Ⅱ were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo Ⅱ expressions, and increase bax expression in H446 cells compared with that of H446/VP cells.Conclusions The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo Ⅱ was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.

  16. Mechanism study of electrochemical oxidation in the terylene diaphragm cell

    Institute of Scientific and Technical Information of China (English)

    YU Xiu-juan; WANG Hui; SUN De-zhi; SONG Lai-wen; WU Lan

    2006-01-01

    By using a self-made carbon/polytetrafluoroethylene (C/PTFE) O2-fed as cathode and Ti/IrO2/RuO2 as anode, the effects of electrochemical oxidation of phenol and the coal-gas wastewater containing phenol were studied. The terylene diaphragm which kept pH>12 in cathodic compartment and pH<1 in the anodic compartment was selected in the experiment in comparison with the other ctron spin resonance spectrum(ESR) and the fluorescence spectra. Compared with pH, the accumulated H2O2 and the COD removal of the no-diaphragm cell, the mechanism of electrochemical oxidation in the terylene diaphragm cell was supposed. The degradation of by oxygen reduction at the cathode. The mineralization of phenol in the diaphragm cell was better than that in the no-diaphragm cell.When the coal-gas wastewater was treated by the electrolysis system with terylene diaphragm, the average removal efficiency of the volatile phenol and COD were 100% and 79.6%, respectively.

  17. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Lee J. Martin

    2010-03-01

    Full Text Available Alzheimer’s disease (AD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.

  18. Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy

    International Nuclear Information System (INIS)

    To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of residual lymph node status on overall survival (OS) and progression-free survival (PFS). Among the originally analyzed 296 patients, 100 (33.7 %) patients had ypT0, including 78 patients (78 %) with ypT0N0, and 22 patients (22 %) with ypT0N1. The 5-year OS of the total patients was 42.4 %. Patients with ypT0N0 have significant improved 5-year OS and PFS than ypT0N1 patients (OS: 50.7 % vs 13.6 %, P = 0.004; PFS: 49.6 % vs 13.6 %, P = 0.003). In multivariate analysis, residual lymph node status was also an independent prognostic factors for OS (HR: 0.406, 95 % CI: 0.240–0.686, P = 0.001) and PFS (HR: 0.427, 95 % CI: 0.248–0.734, P = 0.002). Our results indicate that patients with ypT0N0 after preoperative radiotherapy had significantly better OS and PFS than patients with ypT0N1 in ESCC. Residual nodal metastasis of ESCC patients with pathological complete response of the primary tumor after neoadjuvant radiotherapy does influence prognosis

  19. Functional role of regulatory T cells in B cell lymphoma and related mechanisms.

    Science.gov (United States)

    Wu, Wei; Wan, Jun; Xia, Ruixiang; Huang, Zhenqi; Ni, Jing; Yang, Mingzhen

    2015-01-01

    B cell lymphoma (BCL) has a higher degree of malignancy and complicated pathogenic mechanism. Regulatory T cells (Treg cells) are known to exert certain immune suppression functions, in addition to immune mediating effects. Recent studies have revealed the role of Treg cells in pathogenesis and progression of multiple malignant tumors. This study therefore investigated the functional role and related mechanism of Treg cells in BCL. A cohort of thirty patients who were diagnosed with BCL in our hospital between January 2013 and December 2014. Another thirty healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were separated and analyzed for the ratio of CD4+/CD25+ Treg cells. The mRNA expression levels of Foxp3, transforming growth factor (TGF)-β1 and interleukin (IL)-10 genes were quantified by real-time PCR, while their serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile all laboratory indexes for patients were monitored during the complete remission (CR) stage. BCL patients significantly elevated ratio of CD4+/CD25+ Treg cells, which were decreased at CR stage. mRNA levels of Foxp3, TGF-β1 and IL-10, in addition to protein levels of TGF-β1 and IL-10 were potentiated in lymphoma patients but decreased in CR patients (Pregulating cytokines, thereby facilitating the pathogenesis and progression of lymphoma. PMID:26464657

  20. Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells.

    Science.gov (United States)

    Shen, Ye; Xie, Chen; Gu, Yangshun; Li, Xiuyi; Tong, Jianping

    2016-04-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen

  1. The cell-stretcher: A novel device for the mechanical stimulation of cell populations

    Science.gov (United States)

    Seriani, S.; Del Favero, G.; Mahaffey, J.; Marko, D.; Gallina, P.; Long, C. S.; Mestroni, L.; Sbaizero, O.

    2016-08-01

    Mechanical stimulation appears to be a critical modulator for many aspects of biology, both of living tissue and cells. The cell-stretcher, a novel device for the mechanical uniaxial stimulation of populations of cells, is described. The system is based on a variable stroke cam-lever-tappet mechanism which allows the delivery of cyclic stimuli with frequencies of up to 10 Hz and deformation between 1% and 20%. The kinematics is presented and a simulation of the dynamics of the system is shown, in order to compute the contact forces in the mechanism. The cells, following cultivation and preparation, are plated on an ad hoc polydimethylsiloxane membrane which is then loaded on the clamps of the cell-stretcher via force-adjustable magnetic couplings. In order to show the viability of the experimentation and biocompatibility of the cell-stretcher, a set of two in vitro tests were performed. Human epithelial carcinoma cell line A431 and Adult Mouse Ventricular Fibroblasts (AMVFs) from a dual reporter mouse were subject to 0.5 Hz, 24 h cyclic stretching at 15% strain, and to 48 h stimulation at 0.5 Hz and 15% strain, respectively. Visual analysis was performed on A431, showing definite morphological changes in the form of cellular extroflections in the direction of stimulation compared to an unstimulated control. A cytometric analysis was performed on the AMVF population. Results show a post-stimulation live-dead ratio deviance of less than 6% compared to control, which proves that the environment created by the cell-stretcher is suitable for in vitro experimentation.

  2. Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus.

    Science.gov (United States)

    Panadero, Juan Alberto; Sencadas, Vitor; Silva, Sonia C M; Ribeiro, Clarisse; Correia, Vitor; Gama, Francisco M; Gomez Ribelles, José Luis; Lanceros-Mendez, Senentxu

    2016-02-01

    In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements. PMID:25772257

  3. Probing the mechanical properties of TNF-α stimulated endothelial cell with atomic force microscopy

    Directory of Open Access Journals (Sweden)

    Sei-Young Lee

    2011-01-01

    Full Text Available Sei-Young Lee1,2, Ana-Maria Zaske3, Tommaso Novellino1,4*, Delia Danila3, Mauro Ferrari1,5*, Jodie Conyers3, Paolo Decuzzi1,6*1Department of Nanomedicine and Biomedical Engineering, The University of Texas Medical School at Houston, Houston, TX, USA; 2Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA; 3CeTIR – Center for Translational Injury Research, The University of Texas Health Science Center at Houston, Houston, TX, USA; 4Department of Biomedical Engineering, Biomedical Campus University of Rome, Italy; 5MD Anderson Cancer Center, Houston, TX, USA; 6BioNEM – Center of Bio-Nanotechnology and Engineering for Medicine, University of Magna Graecia, Catanzaro, Italy; *Currently at Department of Nanomedicine and Biomedical Engineering, The Methodist Hospital Research Institute, Houston, TX, USAAbstract: TNF-α (tumor necrosis factor-α is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1 mechanical properties, employing atomic force microscopy; 2 cytoskeletal organization, through fluorescence microscopy; and 3 membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation with TNF-α (10 ng/mL for 20 h, for all three endothelial cells, the mechanical stiffness increased by about 50% with a mean apparent elastic modulus of E ~5 ± 0.5 kPa (~3.3 ± 0.35 kPa for the control cells; the density of F-actin filaments increased in the apical and median planes; and the ICAM-1 receptors were overexpressed compared with

  4. Biophysical response of living cells to boron nitride nanoparticles: uptake mechanism and bio-mechanical characterization

    Energy Technology Data Exchange (ETDEWEB)

    Rasel, Md. Alim Iftekhar; Li, Tong; Nguyen, Trung Dung; Singh, Sanjleena [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia); Zhou, Yinghong; Xiao, Yin [Queensland University of Technology (QUT), Institute of Health and Biomedical Innovation (Australia); Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia)

    2015-11-15

    Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

  5. Biophysical response of living cells to boron nitride nanoparticles: uptake mechanism and bio-mechanical characterization

    International Nuclear Information System (INIS)

    Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications

  6. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells

    DEFF Research Database (Denmark)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M;

    2015-01-01

    subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic...... analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular...... response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational...

  7. Early maturation and distinct tau pathology in induced pluripotent stem cell-derived neurons from patients with MAPT mutations.

    Science.gov (United States)

    Iovino, Mariangela; Agathou, Sylvia; González-Rueda, Ana; Del Castillo Velasco-Herrera, Martin; Borroni, Barbara; Alberici, Antonella; Lynch, Timothy; O'Dowd, Sean; Geti, Imbisaat; Gaffney, Daniel; Vallier, Ludovic; Paulsen, Ole; Káradóttir, Ragnhildur Thóra; Spillantini, Maria Grazia

    2015-11-01

    Tauopathies, such as Alzheimer's disease, some cases of frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, are characterized by aggregates of the microtubule-associated protein tau, which are linked to neuronal death and disease development and can be caused by mutations in the MAPT gene. Six tau isoforms are present in the adult human brain and they differ by the presence of 3(3R) or 4(4R) C-terminal repeats. Only the shortest 3R isoform is present in foetal brain. MAPT mutations found in human disease affect tau binding to microtubules or the 3R:4R isoform ratio by altering exon 10 splicing. We have differentiated neurons from induced pluripotent stem cells derived from fibroblasts of controls and patients with N279K and P301L MAPT mutations. Induced pluripotent stem cell-derived neurons recapitulate developmental tau expression, showing the adult brain tau isoforms after several months in culture. Both N279K and P301L neurons exhibit earlier electrophysiological maturation and altered mitochondrial transport compared to controls. Specifically, the N279K neurons show abnormally premature developmental 4R tau expression, including changes in the 3R:4R isoform ratio and AT100-hyperphosphorylated tau aggregates, while P301L neurons are characterized by contorted processes with varicosity-like structures, some containing both alpha-synuclein and 4R tau. The previously unreported faster maturation of MAPT mutant human neurons, the developmental expression of 4R tau and the morphological alterations may contribute to disease development. PMID:26220942

  8. Domoic Acid Toxicologic Pathology: A Review

    Directory of Open Access Journals (Sweden)

    Olga M. Pulido

    2008-05-01

    Full Text Available Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health.

  9. Domoic acid toxicologic pathology: a review.

    Science.gov (United States)

    Pulido, Olga M

    2008-01-01

    Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health. PMID:18728725

  10. Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

  11. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  12. CORRELATIONS AMONG EXPRESSION OF ANGIOPOIETIN-1 TO CLINICAL PATHOLOGICAL CHARACTERISTICS AN ANGIO- GENESIS IN ORAL SQUAMOUS CELL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    LI Chao; CHEN Jian-chao; WANG Zhao-hui; ZHANG Bing; LI Bin; SONG Yu-feng

    2006-01-01

    Objective: To study the expression and the significance of Angiopoietin-1 (Ang-1) through observing the correlations among the expression of Ang-1 to clinicopathologic characteristics and microvessel density (MVD) in oral squamous cell carcinoma (OSCC). Methods: Expressions of Angiopoietin-1 and CD34 in 41 human OSCC tissues, 30 adjacent noncancerous oral tissues and 10 normal oral mucosas were detected by immunohistochemical SABC method. MCD was also assessed. Results: Of the 41 OSCC tissues, 41.46% (17/41) was Ang-1 positive. The expression of Ang-1 was significantly lower in OSCC than that in adjacent noncancerous oral tissues (P<0.05) and normal oral mucosa (P<0.05). The Ang-1 expression was significantly higher in high differentiated tumor than that in moderately differentiated tumor (P<0.05). The MVD was significantly higher in Ang-1-negative OSCC than in Ang-1-positive OSCC (P<0.01), and negatively correlated with the expression of Ang-1 (r=-0.32, P<0.05). Conclusion: Down-regulated expression of Ang-1 may play a crucial role in the development of OSCC. It negatively regulated the angiogenesis of tumor.

  13. Adult T-cell leukemia-lymphoma: a clinico-pathologic study of twenty-six patients from Martinique.

    Science.gov (United States)

    Plumelle, Y; Pascaline, N; Nguyen, D; Panelatti, G; Jouannelle, A; Jouault, H; Imbert, M

    1993-01-01

    Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases. PMID:8113152

  14. Biosorption mechanism of Cr (Ⅵ) onto cells of Synechococcus sp.

    Institute of Scientific and Technical Information of China (English)

    SHEN Li; XIA Jin-lan; HE Huan; NIE Zhen-yuan; QIU Guan-zhou

    2007-01-01

    The biosorption mechanism of Cr (Ⅵ) ions on Synechococcus sp. biosorbent was studied by analyzing the biosorption kinetics as well as speciation change and bond formation during the biosorption process. The kinetics study shows that the adsorption process of Cr (Ⅵ) consists of a very fast stage in the first several minutes, in which more than half of the saturation adsorption is attained, and a slower stage that approximately follows the first order kinetic model, basically Freundlich isotherm models were observed. Comparative studies of FT-IR spectra of K2Cr2O7, free cells ofSynechococcus sp, and Cr-bound cells ofSynechococcus sp.show that the speciation of chromium that binds to the cells of Synechococcus sp. is Cr (Ⅲ), instead of Cr (Ⅵ), and the carboxylic,alcoholic, amido and amino groups may be involved in the binding of Cr (Ⅲ). Integrative analyses of the surface electric potential,the effect of pH value on adsorption behavior of Cr (Ⅵ), and the results of FT-IR show that the biosorption of Cr (Ⅵ) follows two subsequent steps, biosorption of Cr2O72- by electrostatical force at the protonated active sites and reduction of Cr2O72- to Cr3+ by the reductive groups on the surface of the biosorbents.

  15. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    Science.gov (United States)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  16. Adherens junction distribution mechanisms during cell-cell contact elongation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Gabrielle Goldenberg

    Full Text Available During Drosophila gastrulation, amnioserosa (AS cells flatten and spread as an epithelial sheet. We used AS morphogenesis as a model to investigate how adherens junctions (AJs distribute along elongating cell-cell contacts in vivo. As the contacts elongated, total AJ protein levels increased along their length. However, genetically blocking this AJ addition indicated that it was not essential for maintaining AJ continuity. Implicating other remodeling mechanisms, AJ photobleaching revealed non-directional lateral mobility of AJs along the elongating contacts, as well as local AJ removal from the membranes. Actin stabilization with jasplakinolide reduced AJ redistribution, and live imaging of myosin II along elongating contacts revealed fragmented, expanding and contracting actomyosin networks, suggesting a mechanism for lateral AJ mobility. Actin stabilization also increased total AJ levels, suggesting an inhibition of AJ removal. Implicating AJ removal by endocytosis, clathrin endocytic machinery accumulated at AJs. However, dynamin disruption had no apparent effect on AJs, suggesting the involvement of redundant or dynamin-independent mechanisms. Overall, we propose that new synthesis, lateral diffusion, and endocytosis play overlapping roles to populate elongating cell-cell contacts with evenly distributed AJs in this in vivo system.

  17. 基底细胞癌29例临床病理分析%Clinical and pathological analysis of 29 cases of basal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    周红; 陈敏慧

    2012-01-01

    Objective: To study the clinical features of skin basal cell carcinoma. Methods: Data of 29 cases of basal cell carcinoma was analyzed. Results: The ratio of male and female in these patients was 1: 1. 23. Age ranged from 36 to 81, patients over 50 - years - old of 24 patients was 82.76%. The most common type of nodules was solid (16 cases 55. 17% ). Conclusion: This disease developed more in old person with long term sun exposure.Pathological examination in the correct diagnosis, treatment and prognosis plays an important role.%目的:探讨皮肤基底细胞癌(basal cell carcinoma.BCC)临床病理特点及诱发因素,提高对该病的诊断水平.方法:对29例基底细胞癌患者的临床病理资料进行综合分析.结果:本组患者中男性13例,女性16例,男女比例1:1.23,年龄36 -81岁,其中≥50岁24例(82.76%),农民居多,以结节型(实性)最多见(16例,55.17%).结论:基底细胞癌的发病以中老年为主,好发于头面部等暴晒部位,基底细胞癌的发生与慢性长期日光照射密切相关,病理检查对该病的正确诊断、治疗及预后判断起着重要作用.

  18. Neuronal activity enhances tau propagation and tau pathology in vivo.

    Science.gov (United States)

    Wu, Jessica W; Hussaini, S Abid; Bastille, Isle M; Rodriguez, Gustavo A; Mrejeru, Ana; Rilett, Kelly; Sanders, David W; Cook, Casey; Fu, Hongjun; Boonen, Rick A C M; Herman, Mathieu; Nahmani, Eden; Emrani, Sheina; Figueroa, Y Helen; Diamond, Marc I; Clelland, Catherine L; Wray, Selina; Duff, Karen E

    2016-08-01

    Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies. PMID:27322420

  19. Controlling Self-Renewal and Differentiation of Stem Cells via Mechanical Cues

    OpenAIRE

    Nava, Michele M.; Raimondi, Manuela T.; Riccardo Pietrabissa

    2012-01-01

    The control of stem cell response in vitro, including self-renewal and lineage commitment, has been proved to be directed by mechanical cues, even in the absence of biochemical stimuli. Through integrin-mediated focal adhesions, cells are able to anchor onto the underlying substrate, sense the surrounding microenvironment, and react to its properties. Substrate-cell and cell-cell interactions activate specific mechanotransduction pathways that regulate stem cell fate. Mechanical factors, incl...

  20. Immunology Mechanism of CD4+ CD25 T Regulatory Cells Acting on Effector T Cells

    Institute of Scientific and Technical Information of China (English)

    FENGNing-han; WUHong-fei; WUJun; ZHANGWei; SUIYuan-gen; HEHou-guang; ZHANGChun-lei; ZHENGJun-song

    2004-01-01

    Objective: To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) and separating-cultured system(SCS). Methods: Detecting the percentage of CTLA4 and CD28 expressed on the Treg ceils and effector T ceils, and then adding Treg cells to mixed lymphocyte reaction(MLR) system in CCS and TransWeil Milliceil-PCF SCS, at the same time, adding or not adding anti-IL-10 or anti-TGF.II1 to the reacting systems, examining the inhibitory capacity of Treg ceils exerting on the MLR. Results: Compared with effector T cells, Treg cells expressed higher level CTLA4 and secreted much more IL-10 and TGF-β(P<0.01). The inhibitory capacity of Treg cells co-cultured with effector T ceils is much stronger than that in separating cultured group(P<0.01). Moreover, the inhibiting rate of Treg ceils exerting on effector T ceils through secretin_g IL-10 was more powerful than that through secreting TGF-β1 (P<0.01). Coaclusion: Both ceil-to-ceil contact and cytokines secretion mechanisms are involved in CD4+ CD25+ Treg ceils operating function. However, the former is more important. Intresfingly, we for the first time pointfound that IL-10 plays more powerful roles than TGF-β1 in the cytokines secretion mechanism.

  1. Frequency locking in hair cells: Distinguishing between distinct resonant mechanisms

    CERN Document Server

    Edri, Yuval; Yochelis, Arik

    2016-01-01

    The auditory system displays remarkable mechanical sensitivity and frequency discrimination. These attributes have been shown to rely on an amplification process, which requires biochemical feedback loops. In some systems, the active process was shown to lead to spontaneous oscillations of hair cell bundles. In the last decade, models that display proximity to an oscillatory onset (a.k.a. Hopf bifurcation) have gained increasing support due to many advantages in explaining the hearing phenomenology. Particularly, they exhibit resonant responses to distinct frequencies of incoming sound waves. Unlike previous studies, two types of driving forces are being examined: additive, in which the external forcing term does not couple directly on the systems observable (passive coupling), and parametric, in which the forcing term directly affects the observable and thus intrinsically modifies the systems properties (active coupling). By applying universal principles near the Hopf bifurcation onset, we find several funda...

  2. Chemical degradation mechanisms of membranes for alkaline membrane fuel cells

    International Nuclear Information System (INIS)

    Chemical degradation mechanisms of membranes for alkaline membrane fuel cells have been investigated using density functional theory (DFT). We have elucidated that the aryl-ether moiety of membranes is one of the weakest site against attack of hydroxide ions. The results of DFT calculations for hydroxide initiated aryl-ether cleavage indicated that the aryl-ether cleavage occurred prior to degradation of cationic functional group. Such a weak nature of the aryl-ether group arises from the electron deficiency of the aryl group as well as the low bond dissociation energy. The DFT results suggests that removal of the aryl-ether group in the membrane should enhance the stability of membranes under alkaline conditions. In fact, an ether fee poly(phenylene) membrane exhibits excellent stability against the attack from hydroxide ions

  3. Chemical degradation mechanisms of membranes for alkaline membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Yoong-Kee [National Institute of Advanced Industrial Science and Technology, Umezono 1-1-1, Tsukuba (Japan); Henson, Neil J.; Kim, Yu Seung [Los Alamos National Laboratory, Los Alamos, NM (United States)

    2015-12-31

    Chemical degradation mechanisms of membranes for alkaline membrane fuel cells have been investigated using density functional theory (DFT). We have elucidated that the aryl-ether moiety of membranes is one of the weakest site against attack of hydroxide ions. The results of DFT calculations for hydroxide initiated aryl-ether cleavage indicated that the aryl-ether cleavage occurred prior to degradation of cationic functional group. Such a weak nature of the aryl-ether group arises from the electron deficiency of the aryl group as well as the low bond dissociation energy. The DFT results suggests that removal of the aryl-ether group in the membrane should enhance the stability of membranes under alkaline conditions. In fact, an ether fee poly(phenylene) membrane exhibits excellent stability against the attack from hydroxide ions.

  4. Cell-autonomous effector mechanisms against mycobacterium tuberculosis.

    Science.gov (United States)

    MacMicking, John D

    2014-10-01

    Few pathogens run the gauntlet of sterilizing immunity like Mycobacterium tuberculosis (Mtb). This organism infects mononuclear phagocytes and is also ingested by neutrophils, both of which possess an arsenal of cell-intrinsic effector mechanisms capable of eliminating it. Here Mtb encounters acid, oxidants, nitrosylating agents, and redox congeners, often exuberantly delivered under low oxygen tension. Further pressure is applied by withholding divalent Fe²⁺, Mn²⁺, Cu²⁺, and Zn²⁺, as well as by metabolic privation in the form of carbon needed for anaplerosis and aromatic amino acids for growth. Finally, host E3 ligases ubiquinate, cationic peptides disrupt, and lysosomal enzymes digest Mtb as part of the autophagic response to this particular pathogen. It is a testament to the evolutionary fitness of Mtb that sterilization is rarely complete, although sufficient to ensure most people infected with this airborne bacterium remain disease-free. PMID:25081628

  5. Freezing osteoblast cells attached to hydroxyapatite discs and glass coverslips: Mechanisms of damage

    Institute of Scientific and Technical Information of China (English)

    McGRATH; John

    2007-01-01

    Damage mechanisms for osteoblast cells (OBs) attached to hydroxyapatite (HA) discs and glass coverslips were comprehensively investigated. Cell-cell, cell-matrix interaction altered the cryobiological properties of cells. Attached cells were sub- ject to more severe mechanical damage than isolated cells because attached cells had larger contacting area with ice and the three dimensional movements of iso- lated cells made them more flexible than attached cells that could only deform in one dimension. Results showed that the viability of attached OB cells decreased significantly compared with the viability of isolated OB cells under the same cryo- preservation procedure. Extracellular ice, differential thermal contraction, and mechanical stresses were the major damaging factors for OB cells attached to HA discs and glass coverslips.

  6. EXPRESSION OF P53 GENE IN ORAL SQUAMOUS CELL CARCINOMA AND ITS RELATION WITH CLINICAL AND PATHOLOGICAL PARAMETERS AND PROGNOSIS OF PATIENTS

    Institute of Scientific and Technical Information of China (English)

    毛驰; 卢勇; 赖钦声; 夏雨和; 杨橙

    1995-01-01

    One hundred and eleven cases of cral squamous cell carcinoma (OSCC) were examined for overexpression of p53 protein by using immunchistochemical technique.Association between p53 protein overexpression and clinical and pathological parameters as well as prognosis of patients were also analyzed. p53 protein overexpression was commonly observed (69.4%) in OSCC and may be used as a marker of carcinogenesis of OSCC.The level of p53 protein overexpression is correlated with the lowet three and five-year survival rate of OSCC.The presence of absence of p53 overexpression was not correlated with sex,age,site of tumor,size of tumor,degree of differentiation,node status,and clinical stage in OSCC.Single factor COX proportinoal hazards regression model analysis indicated that there was no significant association between p53 overexpression and prognosis of OSCC,Multivariable COX model analysis failed to establish effective life function of risk rate function,These showed that all the parameters analyzed in this study as well as p53 overexpression were not significant and effective risk factors of prognosis for patients wich OSCC.

  7. Methods for preclinical assessment of antipruritic agents and itch mechanisms independent of mast-cell histamine.

    Science.gov (United States)

    Kuraishi, Yasushi

    2015-01-01

    Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B4 released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B4, sphingosylphosphorylcholine, thromboxane A2, nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents. PMID:25947907

  8. Molecular mechanisms of pharmacological doses of ascorbate on cancer cells.

    Science.gov (United States)

    Venturelli, Sascha; Sinnberg, Tobias W; Niessner, Heike; Busch, Christian

    2015-06-01

    Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials. PMID:26065536

  9. The Mechanisms of Human Renal Epithelial Cell Modulation of Autologous Dendritic Cell Phenotype and Function.

    Directory of Open Access Journals (Sweden)

    Sandeep Sampangi

    Full Text Available Proximal tubule epithelial cells (PTEC of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC as the model system. We demonstrate that PTEC express three inhibitory molecules: (i cell surface PD-L1 that induces MoDC expression of PD-L1; (ii intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii soluble HLA-G (sHLA-G that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

  10. Diastolic function alteration mechanisms in physiologic hypertrophy versus pathologic hypertrophy are elucidated by model-based Doppler E-wave analysis

    Directory of Open Access Journals (Sweden)

    Simeng Zhu

    2014-12-01

    Full Text Available Athletic training can result in increased left ventricular (LV wall thickness, termed physiologic hypertrophy (PhH. By contrast, pathologic hypertrophy (PaH can be due to hypertension, aortic stenosis, or genetic mutation causing hypertrophic cardiomyopathy (HCM. Because morphologic (LV dimension, wall thickness, mass, etc. and functional index similarities (LV ejection fraction, cardiac output, peak filling rate, etc. limit diagnostic specificity, ability to differentiate between PhH and PaH is important. Conventional echocardiographic diastolic function (DF indexes have limited ability to differentiate between PhH and PaH and cannot provide information on chamber property (stiffness and relaxation. We hypothesized that kinematic model-based DF assessment can differentiate between PhH and PaH and, by providing chamber properties, has even greater value compared with conventional metrics. For validation, we assessed DF in the following three age-matched groups: pathologic (HCM hypertrophy (PaH, n = 14, PhH (Olympic rowers, PhH, n = 21, and controls (n = 21. Magnetic resonance imaging confirmed presence of both types of hypertrophy and determined LV mass and chamber size. Model-based indexes, chamber stiffness (k, relaxation/viscoelasticity (c, and load (xo and conventional indexes, Epeak (peak of E-wave, ratio of Epeak to Apeak (E/A, E-wave acceleration time (AT, and E-wave deceleration time (DT were computed. We analyzed 1588 E waves distributed as follows: 328 (PaH, 672 (athletes, and 588 (controls. Among conventional indexes, Epeak and E-wave DT were similar between PaH and PhH, whereas E/A and E-wave AT were lower in PaH. Model-based analysis showed that PaH had significantly higher relaxation/viscoelasticity (c and chamber stiffness (k than PhH. The physiologic equation of motion for filling-based derivation of the model provides a mechanistic understanding of the differences between PhH and PaH.

  11. Mechanisms of matrix metalloproteinase-2 (mmp-2 transcriptional repression by progesterone in jar choriocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Shalev Eliezer

    2009-05-01

    Full Text Available Abstract Background Although the MMP-2 promoter lacks a canonical progesterone response element (PRE, the hormone inhibits MMP-2 expression and is part of treatment protocols in gynecological invasive pathologies, including endometriosis and endometrial hyperplasia. This study aimed to explore the mechanism by which progesterone inhibits MMP-2 expression. Methods The effect of progesterone on MMP-2 expression in the JAR human choriocarcinoma cell line was analyzed by gelatin zymography. MMP-2 transcript expression was studied using Northern blot and semi-quantitative RT-PCR. Rat promoter deletion analysis, electrophoretic mobility shift and chromatin immuno-precipitation assays were performed in order to locate the DNA binding site and the transcription factors involved in MMP-2 regulation. Results Progesterone significantly decreased secretion of pro-MMP-2 and MMP-2 transcript expression level in a dose-dependent manner. Progesterone (1 microM significantly decreased both human and rat MMP-2 promoter activity (80.1% +/- 0.3 and 81.3% +/- 0.23, respectively. Progesterone acts through the SP1 family transcription factors-binding site, located between -1433 and -1342 bp region from the transcriptional start site of the rat MMP-2 promoter, which are present in the orthologous human MMP-2 promoter. Progesterone receptor (PR, SP2, SP3 and SP4 proteins are constitutively bound to this consensus sequence. Conclusion Progesterone reducesPR and SP4 binding to the MMP-2 promoter, thereby suppressing transcription. Progesterone also promotes SP4 degradation. These novel mechanisms of MMP-2 regulation by progesterone provide the biological rationale for the use of progesterone in clinical settings associated with increased MMP-2 expression.

  12. Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Yuan-Soon [School of Medical Technology, Taipei Medical University, Taipei (Taiwan); Liou, Hung-Bin; Lin, Yu-Ping; Guo, How-Ran; Ho, Sheng-Yow; Lee, Ching-Chang; Wang, Ying-Jan [Department of Environmental and Occupational Health, National Cheng Kung University Medical College, 138 Sheng-Li Road, Tainan (Taiwan); Lin, Jen-Kun; Pan, Min-Hsiung [Institute of Biochemistry, National Taiwan University, Medical College, Taipei (Taiwan); Jeng, Jiiang-Huei [School of Dentistry, National Taiwan University and Hospital, Medical College, Taipei (Taiwan)

    2002-08-01

    Nitric oxide (NO) is an environmental pollutant found in smog and cigarette smoke. Recently, NO has been discovered to act as a molecular messenger, mediating various physiological functions. However, when an excess of NO is present, cytotoxic and mutagenic effects can also be induced. The reaction of NO with superoxide results in the formation of peroxynitrite (ONOO{sup -}), which decomposes into the hydroxyl radical and nitrogen dioxide. Both of them are potent oxidant species that may initiate and propagate lipid peroxidation. In the present study, we examined the effects of NO and ONOO{sup -} on the induction of lipid peroxidation and cell death mechanisms in rats and in A549 pulmonary epithelial cells. The results showed that ONOO{sup -} is able to induce lipid peroxidation in pulmonary epithelial cells in a dose-dependent manner. 8-Epi-prostaglandin F{sub 2{alpha}} can serve as a good biomarker of lipid peroxidation both in vitro and in vivo. Postmitotic apoptosis was found in A549 cells exposed to NO, whereas ONOO{sup -} induced cell death more characteristic of necrosis than apoptosis. Apoptosis that occurred in cells may be related to the dysfunction of mitochondria, the release of cytochrome c into cytosol, and the activation of caspase-9. The relationship between caspase activation and the cleavage of other death substrates during postmitotic apoptosis in A549 cells needs further investigation. (orig.)

  13. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy

    OpenAIRE

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-01-01

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing ...

  14. Do long-lived mutant and calorie-restricted mice share common anti-aging mechanisms?—a pathological point of view

    OpenAIRE

    Ikeno, Yuji; Lew, Christie M.; Cortez, Lisa A.; Webb, Celeste R.; Lee, Shuko; Gene B Hubbard

    2006-01-01

    Rodent models are an invaluable resource for studying the mechanism of mammalian aging. In recent years, the availability of transgenic and knockout mouse models has facilitated the study of potential mechanisms of aging. Since 1996, aging studies with several long-lived mutant mice have been conducted. Studies with the long-lived mutant mice, Ames and Snell dwarf, and growth hormone receptor/binding protein knockout mice, are currently providing important clues regarding the role of the grow...

  15. Alzheimer’s Disease: Mechanism and Approach to Cell Therapy

    OpenAIRE

    Takashi Amemori; Pavla Jendelova; Jiri Ruzicka; Lucia Machova Urdzikova; Eva Sykova

    2015-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late...

  16. Do long-lived mutant and calorie-restricted mice share common anti-aging mechanisms?--a pathological point of view.

    Science.gov (United States)

    Ikeno, Yuji; Lew, Christie M; Cortez, Lisa A; Webb, Celeste R; Lee, Shuko; Hubbard, Gene B

    2006-06-01

    Rodent models are an invaluable resource for studying the mechanism of mammalian aging. In recent years, the availability of transgenic and knockout mouse models has facilitated the study of potential mechanisms of aging. Since 1996, aging studies with several long-lived mutant mice have been conducted. Studies with the long-lived mutant mice, Ames and Snell dwarf, and growth hormone receptor/binding protein knockout mice, are currently providing important clues regarding the role of the growth hormone/insulin like growth factor-1 axis in the aging process. Interestingly, these studies demonstrate that these long-lived mutant mice have physiological characteristics that are similar to the effects of calorie restriction, which has been the most effective experimental manipulation capable of extending lifespan in various species. However, a question remains to be answered: do these long-lived mutant and calorie-restricted mice extend their lifespan through a common underlying mechanism? PMID:19943137

  17. Comparative Transduction Mechanisms of Vestibular Otolith Hair Cells

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog vestibular otolith organs regenerate following aminoglycoside ototoxicity. Hair cells in these organs are differentially sensitive to gentamicin, with saccular hair cells and hair cells in the utricular striola being damaged at lower gentamicin concentrations than hair cells in the utricular extrastriola. Regenerating hair cells in these organs have short hair bundles and can be classified into a number of phenotypes using the same morphological criteria used to identify their mature counterparts. Our studies suggest that some supporting cells can convert, or transdifferentiate,into hair cells without an intervening cell division. By stimulating these processes in humans, clinicians may be able to alleviate human deafness and peripheral vestibular disorders by regenerating and replacing lost hair cells. In vivo and in vitro studies were done on cell proliferation and hair cell regeneration.

  18. Systematization of the Mechanism by Which Plasma Irradiation Causes Cell Growth and Tumor Cell Death

    Science.gov (United States)

    Shimizu, Nobuyuki

    2015-09-01

    New methods and technologies have improved minimally invasive surgical treatment and saved numerous patients. Recently, plasma irradiation has been demonstrated that might be useful in medical field and the plasma irradiation device is expected to become practically applicable. Mild plasma coagulator showed some advantages such as hemostasis and adhesion reduction in experimental animal model, but the mechanism of plasma irradiation remains unclear. Our study group aim to clarify the mechanism of plasma irradiation effects, mainly focusing on oxidative stress using cultured cell lines and small animal model. First, a study using cultured cell lines showed that the culture medium that was activated by plasma irradiation (we called this kind of medium as ``PAM'' -plasma activated medium-) induced tumor cell death. Although this effect was mainly found to be due to hydrogen peroxide, the remaining portion was considered as the specific effect of the plasma irradiation and we are now studying focusing on this effect. Second, we established a mouse intra-peritoneal adhesion model and checked biological reaction that occurred in the adhesion part. Histopathological study showed inflammatory cells infiltration into adhesion part and the expression of PTX3 that might involve tissue repair around adhesion part. We also confirmed that cytokines IL-6 and IL-10 might be useful as a marker of adhesion formation in this model. Applying ``PAM'' or mild plasma irradiation in this model, we examine the effects of plasma on inflamed cells. The samples in these experiments would be applied to targeted proteomics analysis, and we aim to demonstrate the systematization of the cell's reaction by plasma irradiation.

  19. Pathological review of late cerebral radionecrosis

    International Nuclear Information System (INIS)

    Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and glial fibrillary acidic protein (GFAP)-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions. (author)

  20. Pathology informatics fellowship training: Focus on molecular pathology

    OpenAIRE

    Diana Mandelker; Lee, Roy E.; Platt, Mia Y.; Gregory Riedlinger; Andrew Quinn; Luigi K F Rao; Klepeis, Veronica E.; Michael Mahowald; Lane, William J; Beckwith, Bruce A; Baron, Jason M.; David S McClintock; Kuo, Frank C.; Lebo, Matthew S.; Gilbertson, John R.

    2014-01-01

    Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology ...

  1. Progress on the pathologic mechanism and potential therapy of androgenic alopecia%脂溢性脱发的发生机制及治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    巫珊; 张海州

    2012-01-01

    Pathologic mechanism and therapeutic methods of androgenic alopecia were discussed. Pathological representations, pathogenesis and therapeutically active ingredients of androgenic alopecia were introduced, and the relationship between cytokines and androgenic alopecia was disclosed. The active ingredients which may inhibit or stimulate related cytokines with traditional treatment for hairloss are presented and its application prospect is also discussed.%综述了脂溢性脱发的发生机制及活性物治疗研究进展。主要介绍了脂溢性脱发的病理表现、发生机制以及治疗活性物的研究现状。重点揭示了相关细胞因子对脂溢性脱发的影响。提出将具有相应细胞因子激励或抑制作用的活性物与常规的功能性成分联合应用在防脱发个人护理品中,将充分发挥其治疗效果,并对其应用前景进行了展望。

  2. Cadmium (II) removal mechanisms in microbial electrolysis cells.

    Science.gov (United States)

    Colantonio, Natalie; Kim, Younggy

    2016-07-01

    Cadmium is a toxic heavy metal, causing serious environmental and human health problems. Conventional methods for removing cadmium from wastewater are expensive and inefficient for low concentrations. Microbial electrolysis cells (MECs) can simultaneously treat wastewater, produce hydrogen gas, and remove heavy metals with low energy requirements. Lab-scale MECs were operated to remove cadmium under various electric conditions: applied voltages of 0.4, 0.6, 0.8, and 1.0V; and a fixed cathode potential of -1.0V vs. Ag/AgCl. Regardless of the electric condition, rapid removal of cadmium was demonstrated (50-67% in 24h); however, cadmium concentration in solution increased after the electric current dropped with depleted organic substrate under applied voltage conditions. For the fixed cathode potential, the electric current was maintained even after substrate depletion and thus cadmium concentration did not increase. These results can be explained by three different removal mechanisms: cathodic reduction; Cd(OH)2 precipitation; and CdCO3 precipitation. When the current decreased with depleted substrates, local pH at the cathode was no longer high due to slowed hydrogen evolution reaction (2H(+)+2e(-)→H2); thus, the precipitated Cd(OH)2 and CdCO3 started dissolving. To prevent their dissolution, sufficient organic substrates should be provided when MECs are used for cadmium removal. PMID:26970043

  3. Mechanics of Cellulose Synthase Complexes in Living Plant Cells

    Science.gov (United States)

    Zehfroosh, Nina; Liu, Derui; Ramos, Kieran P.; Yang, Xiaoli; Goldner, Lori S.; Baskin, Tobias I.

    The polymer cellulose is one of the major components of the world's biomass with unique and fascinating characteristics such as its high tensile strength, renewability, biodegradability, and biocompatibility. Because of these distinctive aspects, cellulose has been the subject of enormous scientific and industrial interest, yet there are still fundamental open questions about cellulose biosynthesis. Cellulose is synthesized by a complex of transmembrane proteins called ``Cellulose Synthase A'' (CESA) in the plasma membrane. Studying the dynamics and kinematics of the CESA complex will help reveal the mechanism of cellulose synthesis and permit the development and validation of models of CESA motility. To understand what drives these complexes through the cell membrane, we used total internal reflection fluorescence microscopy (TIRFM) and variable angle epi-fluorescence microscopy to track individual, fluorescently-labeled CESA complexes as they move in the hypocotyl and root of living plants. A mean square displacement analysis will be applied to distinguish ballistic, diffusional, and other forms of motion. We report on the results of these tracking experiments. This work was funded by NSF/PHY-1205989.

  4. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ulf Geisen

    2015-07-01

    Full Text Available Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1. Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  5. Molecular mechanisms of mtal toxicity in neuronal cells

    OpenAIRE

    Rossi, Annamaria

    1996-01-01

    Modification of signal transduction by toxic agents can affect cell metabolism and physiological activity, impair cell capacity to adequately respond to hormones and growth stimuli and consequently compromise cell survival. This thesis describes studies on the interactions between toxic metals, at concentrations comparable to environmental exposure, and Ca2+ signalling in neuronal cells. Four tri-substituted organotin compounds (triethyltin (TET), trimethyltin (T...

  6. Self-Motion Mechanism Of Chained Spherical Grains Cells

    CERN Document Server

    Viridi, Sparisoma

    2013-01-01

    Cells are modeled with spherical grains connected each other. Each cell can shrink and swell by transporting its fluid content to other connected neighbor while still maintaining its density at constant value. As a spherical part of a cell swells it gains more pressure from its surrounding, while shrink state gains less pressure. Pressure difference between these two or more parts of cell will create motion force for the cell. For simplicity, cell is considered to have same density as its environment fluid and connections between parts of cell are virtually accommodated by a spring force. This model is also limited to 2-d case. Influence of parameters to cell motion will be presented. One grain cell shows no motion, while two and more grains cell can perform a motion.

  7. Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast

    OpenAIRE

    Svetlov, Stanislav I.; Prima, Victor; Glushakova, Olena; Svetlov, Artem; Kirk, Daniel R.; Gutierrez, Hector; Serebruany, Victor L.; Curley, Kenneth C.; Wang, Kevin K. W.; Hayes, Ronald L.

    2012-01-01

    A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. In this study, we further characterized blast producing moderate traumatic brain injury and defined “composite” blast and ...

  8. Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to ‘composite’ blast.

    OpenAIRE

    VictorPrima; StanislavI.Svetlov; DanielKirk; KennethCurley; VictorSerebruany

    2012-01-01

    A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position towards blast generated by an external shock tube. In this study, we further characterized blast producing moderate TBI and defined ‘composite’ blast and primary blast...

  9. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer;

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...... are twofold, both driven by the main hypothesis that PD patients who develop PG secondary to treatment with dopamine agonists have a decreased sensitivity towards dopamine and hence an increased demand for dopamine. The neurophysiological subproject 1 uses PET imaging to determine changes of dopamine...

  10. The Application of Micropipette Aspiration in Molecular Mechanics of Single Cells

    OpenAIRE

    Lee, Lap Man; Liu, Allen P.

    2014-01-01

    Micropipette aspiration is arguably the most classical technique in mechanical measurements and manipulations of single cells. Despite its simplicity, micropipette aspiration has been applied to a variety of experimental systems that span different length scales to study cell mechanics, nanoscale molecular mechanisms in single cells, bleb growth, and nucleus dynamics, to name a few. Enabled by micro/nanotechnology, several novel microfluidic devices have been developed recently with better ac...

  11. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

    Directory of Open Access Journals (Sweden)

    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  12. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  13. Discussion on Improvement of Toxicological Pathology Study

    Institute of Scientific and Technical Information of China (English)

    RenJin

    2003-01-01

    Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation procedure (SOP) for toxico-logical pathology assessment; emphasizing on immunotoxicology evaluation; adopting a new ex-periment model of replacement, featuring high speed and reliability; introducing new techniques and new models in toxicological mechanism re-search; and establishing a new appraisal system to screen innovative drug and rapid and high pre-cision methods for early security assessment, de-tection and measurement.

  14. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

    Science.gov (United States)

    Lopez, José I.; Cortes, Jesús M.

    2016-01-01

    Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection. PMID:27127618

  15. Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms

    Science.gov (United States)

    Scalea, Joseph R.; Tomita, Yusuke; Lindholm, Christopher R.; Burlingham, William

    2016-01-01

    Cell-based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types are being tested as possible routes to tolerance induction, in the absence of donor-derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, while avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here, we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in tolerance induction protocols. PMID:27014267

  16. Inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    李杰

    2012-01-01

    Objective To explore the inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia (CML) cells and its possible mechanism. Methods The effects of rapamycin at various concentrations on cell proliferation of CML cell line K562 cells were analyzed by MTT. The expressions

  17. Microfluidic artificial “vessels” for dynamic mechanical stimulation of mesenchymal stem cells

    OpenAIRE

    Zhou, Jing; Niklason, Laura E.

    2012-01-01

    Cells in the cardiovascular system are constantly exposed to complex mechanical stimulation due to the pulsatile nature of blood flow and the haemodynamic forces that are key to the regulation of vascular development, remodeling and pathophysiology. Mechanical stretch can also modulate the differentiation of stem cells toward vascular cell lineages (i.e., vascular smooth muscle cells), and represent a critical factor in vascular tissue engineering. Here we report on the development of a micro...

  18. Mechanical Properties of Living Adherent Cells :Relationship with Structure and Function

    Institute of Scientific and Technical Information of China (English)

    R.; FODIL; S.; Féréol; E.; PLANUS; V.M.; LAURENT; B.; LOUIS; D.; ISABEY

    2005-01-01

    1 IntroductionMechanical properties of living cells are dependent on a variety of intracellular and/or extracellular factors (e.g., spatial organization of cytoskeleton (CSK) elements; internal tension; actomyosin contraction; contribution of proximal and/or more distal environment...). Because these factors are involved in biological processes as important as cell adhesion, locomotion, cell contraction, signalization, understanding the relationships between cell mechanical properties, structure and functio...

  19. Effects of Chemotherapy-Induced Alterations in Cell Mechanical Properties on Cancer Metastasis

    Science.gov (United States)

    Prathivadhi, Sruti; Ekpenyong, Andrew; Nichols, Michael; Taylor, Carolyn; Ning, Jianhao

    Biological cells can modulate their mechanical properties to suit their functions and in response to changes in their environment. Thus, mechanical phenotyping of cells has been employed for tracking stem cell differentiation, bacterial infection, cell death, etc. Malignant transformation of cells also involves changes in mechanical properties. However, the extent to which mechanical properties of cancer cells contribute to metastasis is not well understood. Yet, more than 90% of all cancer deaths are directly related to metastasis. Transit of cells through the microcirculation is one of the key features of metastasis. We hypothesize that cancer treatment regimens do inadvertently alter cell mechanical properties in ways that might promote cancer metastasis. We use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that cancer cells treated with chemotherapeutic drugs such as daunorubicin, become more deformable at short timescales (0.1 s) and transit faster through the device. Our results are first steps in evaluating the pro- or anti-metastatic effects of chemotherapeutic drugs based on their induced alterations in cell mechanical properties.

  20. CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.

    Science.gov (United States)

    Lim, Tong Seng; Goh, James Kang Hao; Mortellaro, Alessandra; Lim, Chwee Teck; Hämmerling, Günter J; Ricciardi-Castagnoli, Paola

    2012-01-01

    Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force spectroscopy to characterize and compare the mechanical forces of interactions between DC:T-cells and B:T-cells. Following antigen stimulation, intercellular interactions of DC:T-cell conjugates were stronger than B:T-cell interactions. DCs induced higher levels of T-cell calcium mobilization and production of IL-2 and IFNγ than were elicited by B-cells, thus suggesting that tight intercellular contacts are important in providing mechanically stable environment to initiate T-cell activation. Blocking antibodies targeting surface co-stimulatory molecules CD80 or CD86 weakened intercellular interactions and dampen T-cell activation, highlighting the amplificatory roles of CD80/86 in regulating APC:T-cell interactions and T-cell functional activation. The variable strength of mechanical forces between DC:T-cells and B:T-cell interactions were not solely dependent on differential APC expression of CD80/86, since DCs were superior to B-cells in promoting strong interactions with T-cells even when CD80 and CD86 were inhibited. These data provide mechanical insights into the effects of co-stimulatory molecules in regulating APC:T-cell interactions. PMID:23024807

  1. CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.

    Directory of Open Access Journals (Sweden)

    Tong Seng Lim

    Full Text Available Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs, including dendritic cells (DCs and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force spectroscopy to characterize and compare the mechanical forces of interactions between DC:T-cells and B:T-cells. Following antigen stimulation, intercellular interactions of DC:T-cell conjugates were stronger than B:T-cell interactions. DCs induced higher levels of T-cell calcium mobilization and production of IL-2 and IFNγ than were elicited by B-cells, thus suggesting that tight intercellular contacts are important in providing mechanically stable environment to initiate T-cell activation. Blocking antibodies targeting surface co-stimulatory molecules CD80 or CD86 weakened intercellular interactions and dampen T-cell activation, highlighting the amplificatory roles of CD80/86 in regulating APC:T-cell interactions and T-cell functional activation. The variable strength of mechanical forces between DC:T-cells and B:T-cell interactions were not solely dependent on differential APC expression of CD80/86, since DCs were superior to B-cells in promoting strong interactions with T-cells even when CD80 and CD86 were inhibited. These data provide mechanical insights into the effects of co-stimulatory molecules in regulating APC:T-cell interactions.

  2. Mechanics governs single-cell signaling and multi-cell robustness in biofilm infections

    Science.gov (United States)

    Gordon, Vernita

    In biofilms, bacteria and other microbes are embedded in extracellular polymers (EPS). Multiple types of EPS can be produced by a single bacterial strain - the reasons for this redundancy are not well-understood. Our work suggests that different polymers may confer distinct mechanical benefits. Our model organism is Pseudomonas aeruginosa, an opportunistic human pathogen that forms chronic biofilm infections associated with increased antibiotic resistance and evasion of the immune defense. Biofilms initiate when bacteria attach to a surface, sense the surface, and change their gene expression. Changes in gene expression are regulated by a chemical signal, cyclic-di-GMP. We find that one EPS material, called ``PEL,'' enhances surface sensing by increasing mechanical coupling of single bacteria to the surface. Measurements of bacterial motility suggest that PEL may increase frictional interactions between the surface and the bacteria. Consistent with this, we show that bacteria increase cyclic-di-GMP signaling in response to mechanical shear stress. Mechanosensing has long been known to be important to the function of cells in higher eukaryotes, but this is one of only a handful of studies showing that bacteria can sense and respond to mechanical forces. For the mature biofilm, the embedding polymer matrix can protect bacteria both chemically and mechanically. P. aeruginosa infections in the cystic fibrosis (CF) lung often last for decades, ample time for the infecting strain(s) to evolve. Production of another EPS material, alginate, is well-known to tend to increase over time in CF infections. Alginate chemically protects biofilms, but also makes them softer and weaker. Recently, it is being increasingly recognized that bacteria in chronic CF infections also evolve to increase PSL production. We use oscillatory bulk rheology to determine the unique contributions of EPS materials to biofilm mechanics. Unlike alginate, increased PSL stiffens biofilms. Increasing both

  3. Widespread cytoskeletal pathology characterizes corticobasal degeneration.

    OpenAIRE

    Feany, M B; Dickson, D W

    1995-01-01

    Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized ...

  4. Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

    DEFF Research Database (Denmark)

    La Rocca, Rosanna; Tallerico, Rossana; Hassan, Almosawy Talib;

    2014-01-01

    treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells......In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were...... (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar5100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range...

  5. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells

    OpenAIRE

    Sahin, Aysegul Ocal; Buitenhuis, Miranda

    2012-01-01

    Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activit...

  6. Mechanisms of cell damage in agitated microcarrier tissue culture reactors

    Science.gov (United States)

    Cherry, Robert S.; Papoutsakis, E. Terry

    1986-01-01

    Cells growing on microcarriers may be damaged by collisions of the microcarrier against another microcarrier or the reactor agitator. Bead-bead collisions are caused by small-scale turbulence, which can also cause high local shear stress on the cells. The cells are also exposed to 10-20 Hz cyclic shear stress by bead rotation.

  7. Control mechanisms of cell proliferation in intestinal epithelium

    NARCIS (Netherlands)

    R.P.C. Rijke (Rudy)

    1977-01-01

    textabstractIn the adult organism some organs and tissues still contain proliferating and differentiating cells, whereas other organs only consist of non-dividing specialized cells. On the basis of their proliferative activity cell populations may be classified into three categories (135, 138,208).

  8. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  9. Universally Conserved Relationships between Nuclear Shape and Cytoplasmic Mechanical Properties in Human Stem Cells

    Science.gov (United States)

    Lozoya, Oswaldo A.; Gilchrist, Christopher L.; Guilak, Farshid

    2016-03-01

    The ability of cells to proliferate, differentiate, transduce extracellular signals and assemble tissues involves structural connections between nucleus and cytoskeleton. Yet, how the mechanics of these connections vary inside stem cells is not fully understood. To address those questions, we combined two-dimensional particle-tracking microrheology and morphological measures using variable reduction techniques to measure whether cytoplasmic mechanics allow for discrimination between different human adherent stem cell types and across different culture conditions. Here we show that nuclear shape is a quantifiable discriminant of mechanical properties in the perinuclear cytoskeleton (pnCSK) of various stem cell types. Also, we find the pnCSK is a region with different mechanical properties than elsewhere in the cytoskeleton, with heterogeneously distributed locations exhibiting subdiffusive features, and which obeys physical relations conserved among various stem cell types. Finally, we offer a prospective basis to discriminate between stem cell types by coupling perinuclear mechanical properties to nuclear shape.

  10. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo; Grauslund, Morten; Juhl, Birgitte Ravn; Jensen, Peter Buhl; Sehested, Maxwell

    2010-01-01

    similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing...... we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damagingreactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of...... topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin...

  11. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    2010-01-01

    similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing...... we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of...... topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin...

  12. CD80 and CD86 Differentially Regulate Mechanical Interactions of T-Cells with Antigen-Presenting Dendritic Cells and B-Cells

    OpenAIRE

    Tong Seng Lim; James Kang Hao Goh; Alessandra Mortellaro; Chwee Teck Lim; Hämmerling, Günter J.; Paola Ricciardi-Castagnoli

    2012-01-01

    Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force ...

  13. Cocaine mediated apoptosis of vascular cells as a mechanism for carotid artery dissection leading to ischemic stroke.

    Science.gov (United States)

    Dabbouseh, Noura M; Ardelt, Agnieszka

    2011-08-01

    In arterial dissection, blood may enter the arterial wall through an intimal tear, splitting the arterial wall and activating the coagulation cascade at the site of endothelial damage. Dissection of extracranial and intracranial vessels may lead to ischemic stroke through thromboembolic or hemodynamic mechanisms. Major blunt trauma or rapid acceleration-deceleration may cause dissection, but in patients with inherent arterial wall weakness, dissection can occur spontaneously or as a result of minor neck movement. Cocaine use has been associated with dissection of the aortic arch and coronary and renal arteries through cocaine-mediated hypertension. Recent preclinical studies have suggested, however, that cocaine may cause apoptosis of cells in the vascular wall. In this article, we postulate that cocaine may cause apoptosis of vascular endothelial and/or smooth muscle cells, thus weakening the vascular wall and resulting in a dissection-prone state. We review the literature and propose a biological basis for vasculopathy, vascular dissection, and ischemic stroke in the setting of cocaine use. Further research studies on vascular cells, as well as focused analysis of human pathological material, will be important in providing evidence for or against our hypotheses. PMID:21546166

  14. Molecular mechanism of extrinsic factors affecting antiagingof stem cells

    Institute of Scientific and Technical Information of China (English)

    Tzyy Yue Wong; Mairim Alexandra Solis; Ying-Hui Chen; Lynn Ling-Huei Huang

    2015-01-01

    Scientific evidence suggests that stem cells possessthe anti-aging ability to self-renew and maintaindifferentiation potentials, and quiescent state. Theobjective of this review is to discuss the microenvironmentwhere stem cells reside in vivo , thesecreted factors to which stem cells are exposed, thehypoxic environment, and intracellular factors includinggenome stability, mitochondria integrity, epigeneticregulators, calorie restrictions, nutrients, and vitaminD. Secreted tumor growth factor-β and fibroblastgrowth factor-2 are reported to play a role in stem cellquiescence. Extracellular matrices may interact withcaveolin-1, the lipid raft on cell membrane to regulatequiescence. N-cadherin, the adhesive protein on nichecells provides support for stem cells. The hypoxicmicro-environment turns on hypoxia-inducible factor-1to prevent mesenchymal stem cells aging throughp16 and p21 down-regulation. Mitochondria expressglucosephosphate isomerase to undergo glycolysisand prevent cellular aging. Epigenetic regulators suchas p300, protein inhibitors of activated Stats and H19help maintain stem cell quiescence. In addition, calorierestriction may lead to secretion of paracrines cyclicADP-ribose by intestinal niche cells, which help maintainintestinal stem cells. In conclusion, it is crucial tounderstand the anti-aging phenomena of stem cells atthe molecular level so that the key to solving the agingmystery may be unlocked.

  15. A systematic review of the parenting and outcomes experienced by offspring of mothers with borderline personality pathology: Potential mechanisms and clinical implications.

    Science.gov (United States)

    Eyden, Julie; Winsper, Catherine; Wolke, Dieter; Broome, Matthew R; MacCallum, Fiona

    2016-07-01

    There is growing interest in whether the parenting strategies and offspring outcomes of mothers with borderline personality disorder (BPD) differ from those of mothers without BPD. We searched PsychINFO, PubMed, EMBASE, Web of Science, Scopus and ASSIA databases for studies examining parenting skills and attitudes among mothers with BPD/BPD symptoms and/or offspring outcomes. PRISMA reporting guidelines were followed. Of 10,067 abstracts screened, 101 full-text articles were retrieved and 33 met pre-determined criteria for qualitative synthesis. Overall, studies suggest that mothers with BPD/BPD symptoms are more likely to engage in maladaptive interactions with their offspring characterised by insensitive, overprotective, and hostile parenting compared to mothers without BPD/BPD symptoms. Adverse offspring outcomes include BPD symptoms, internalising (including depression) and externalising problems, insecure attachment patterns, and emotional dysregulation. Findings suggest that vulnerability from mother to offspring may be partly transmitted via maladaptive parenting and maternal emotional dysfunction. Conclusions were limited by study heterogeneity in methodology and construct definitions, as well as a paucity of clinical comparison groups. Prospective studies of mothers with BPD and their offspring from pregnancy onwards may further elucidate mechanisms of transmission and identify resilience factors across development. Parenting behaviour awareness, improving attachment behaviours and emotional regulation strategies may be important intervention targets. PMID:27261413

  16. Vascular regulation of adult neurogenesis under physiological and pathological conditions

    Directory of Open Access Journals (Sweden)

    Masato eSawada

    2014-03-01

    Full Text Available Neural stem cells in the mammalian adult brain continuously produce new neurons throughout life. Accumulating evidence in rodents suggests that various aspects of adult neurogenesis, including the genesis, migration, and maturation of new neurons, are regulated by factors derived from blood vessels and their microenvironment. Brain injury enhances both neurogenesis and angiogenesis, thereby promoting the cooperative regeneration of neurons and blood vessels. In this paper, we briefly review the mechanisms for the vascular regulation of adult neurogenesis in the ventricular-subventricular zone under physiological and pathological conditions, and discuss their clinical potential for brain regeneration strategies.

  17. Mechanical Coupling of Smooth Muscle Cells Using Microengineered Substrates and Local Stimulation

    Science.gov (United States)

    Copeland, Craig; Hunter, David; Tung, Leslie; Chen, Christopher; Reich, Daniel

    2013-03-01

    Mechanical stresses directly affect many cellular processes, including signal transduction, growth, differentiation, and survival. Cells can themselves generate such stresses by activating myosin to contract the actin cytoskeleton, which in turn can regulate both cell-substrate and cell-cell interactions. We are studying mechanical forces at cell-cell and cell-substrate interactions using arrays of selectively patterned flexible PDMS microposts combined with the ability to apply local chemical stimulation. Micropipette ``spritzing'', a laminar flow technique, uses glass micropipettes mounted on a microscope stage to deliver drugs to controlled regions within a cellular construct while cell traction forces are recorded via the micropost array. The pipettes are controlled by micromanipulators allowing for rapid and precise movement across the array and the ability to treat multiple constructs within a sample. This technique allows for observing the propagation of a chemically induced mechanical stimulus through cell-cell and cell-substrate interactions. We have used this system to administer the acto-myosin inhibitors Blebbistatin and Y-27632 to single cells and observed the subsequent decrease in cell traction forces. Experiments using trypsin-EDTA have shown this system to be capable of single cell manipulation through removal of one cell within a pair configuration while leaving the other cell unaffected. This project is supported in part by NIH grant HL090747

  18. Mechanical properties of catalyst coated membranes: A powerful indicator of membrane degradation in fuel cells

    OpenAIRE

    Sadeghi Alavijeh, Alireza

    2015-01-01

    Mechanical durability of perfluorosulfonic acid (PFSA) ionomer membranes in polymer electrolyte fuel cells (PEFCs) is investigated in this thesis. This work contributes to a systematic characterization of the decay in mechanical properties of membranes and catalyst coated membranes (CCMs) that are subjected to controlled chemical and/or mechanical degradation mechanisms. During field operation of PEFCs, the membrane is subjected to a combination of chemical and mechanical degradation, resulti...

  19. Pathological and molecular mechanisms underlying resistance to recombinant human erythropoietin therapy in the remnant kidney rat model of chronic kidney disease associated anemia.

    Science.gov (United States)

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-06-01

    Anemia of chronic kidney disease (CKD) can be corrected by treatment with recombinant human erythropoietin (rHuEPO); however, some patients become hyporesponsive. The molecular mechanisms underlying this resistance remain to be elucidated. Our aim was to study hyporesponsiveness to rHuEPO therapy using the remnant kidney rat model of anemia associated with CKD induced by 5/6 nephrectomy. At starting, male Wistar rats were divided in 3 groups, for a 3-week protocol: Sham, CRF (vehicle) and two rHuEPO (200 k/kg body weight [BW]/week) treated groups; at the end of protocol, the rHuEPO treated rats were subdivided in responders (CRF200) and non-responders (CRF200NR), according to their hematologic response; blood, cellular and tissue studies were performed. The CRF200 group achieved correction of anemia, while the CRF200NR group developed anemia, after an initial response (1st week) to rHuEPO therapy. CRF and CRF200NR groups presented a trend to higher serum CRP levels; CRF200NR showed also high levels of renal inflammatory markers, such as interleukin (IL)-6, IL-1β, nuclear factor kappa B, connective tissue growth factor (CTGF) and transforming growth factor beta 1 (TGF-β1); no changes were found in iron metabolism. Our data suggest that the development of anemia/rHuEPO hyporesponsiveness is associated with a higher systemic and renal inflammatory condition, favoring hypoxia and triggering an increase in renal expression of HIF-1α, TGF-β1 and CTGF that will further aggravate renal fibrosis, which will enhance the inflammatory response, creating a cycle that promotes disease progression. New therapeutic strategies to reduce inflammation in CKD patients could improve the response to rHuEPO therapy and reduce hyporesponsiveness. PMID:27039028

  20. T-cell regulatory mechanisms in specific immunotherapy

    OpenAIRE

    Jutel, M; Akdis, C. A.

    2008-01-01

    Allergen-specific immunotherapy (SIT) is the only treatment which leads to a lifelong tolerance against previously disease-causing allergens due to restoration of normal immunity against allergens. The description of T-regulatory (Treg) cells being involved in prevention of sensitization to allergens has led to great interest whether they represent a major target for allergen-SIT and whether it would be possible to manipulate Treg cells to increase its efficacy. Activationinduced cell death, ...