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Sample records for columnar cell lesions

  1. Does flat epithelial atypia have rounder nuclei than columnar cell change/hyperplasia? A morphometric approach to columnar cell lesions of the breast.

    PubMed

    Yamashita, Yoshiko; Ichihara, Shu; Moritani, Suzuko; Yoon, Han-Seung; Yamaguchi, Masahiro

    2016-06-01

    Columnar cell lesions of the breast encompass columnar cell change/hyperplasia (CCC/CCH) and flat epithelial atypia (FEA). These have attracted researchers because emerging data suggest that FEA may represent the earliest histologically detectable non-obligate precursor of breast cancer. However, it is occasionally difficult to distinguish FEA from CCC/CCH because of similar histology. Although the nuclei of FEA are frequently described as relatively round compared with those of CCC/CCH, there are few morphometric studies to support this statement. The aim of this study was to provide objective data as to the nuclear shape in columnar cell lesions. As a shape descriptor, we adopted ellipticity that is defined by the formula 2b/2a, where a is the length of the long axis of the ellipse and b is the length of the short axis. Contrary to circularity, ellipticity reflects the overall configuration of an ellipse irrespective of surface irregularity. Our image analysis included generating whole slide images, extracting glandular cell nuclei, measuring nuclear ellipticity, and superimposing graded colors based on execution of results on the captured images. A total of 7917 nuclei extracted from 22 FEA images and 5010 nuclei extracted from 13 CCC/CCH images were analyzed. There was a significant difference in nuclear roundness between FEA and CCC/CCH with mean ellipticity values of 0.723 and 0.679, respectively (p < 0.001, Welch's t test). Furthermore, FEA with malignancy had significantly rounder nuclei than FEA without malignancy (p < 0.001). Our preliminary results suggest that nuclear ellipticity is a key parameter in reproducibly classifying columnar cell lesions of the breast.

  2. Solvent effect on columnar formation in solar-cell geometry

    NASA Astrophysics Data System (ADS)

    Park, J. H.; Sosa-Vargas, L.; Takanishi, Y.; Kim, K. H.; Kim, Y. S.; Park, Y. W.; Yamamoto, J.; Labardi, M.; Lagerwall, J. P. F.; Shimizu, Y.; Scalia, G.

    2016-03-01

    The efficiency of the conduction of photocurrent in discotic liquid crystals is known to depend on the quality of the columnar organization. Solvents have shown to be able to influence the formation of wire structures on substrates promoting very long and ordered wired formations or bulkier structures depending on the affinity of the solvent with parts of the molecular structure of discotics. Here we present a study on the effect of solvents when the liquid crystal is confined between two substrates with the columns running perpendicular to them, geometry used in solar cells. We focused on toluene and dodecane, solvents that have shown to promote on substrates the formation of aligned and long nanowires and bulk large and isolated fibers, respectively. The phase transition behavior indicates that toluene does not interfere with the columnar formation while dodecane strongly influence increasing the disorder in the structure.

  3. Anogenital Mammary-Like Glands: A Study of Their Normal Histology With Emphasis on Glandular Depth, Presence of Columnar Epithelial Cells, and Distribution of Elastic Fibers.

    PubMed

    Konstantinova, Anastasia M; Kyrpychova, Liubov; Belousova, Irena E; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal; Kerl, Katrin; Kazakov, Dmitry V

    2016-10-18

    The normal histology of anogenital mammary-like glands (AGMLG) has been studied previously, but some aspects, including glandular depth, presence of columnar epithelium resembling columnar cell change/hyperplasia as defined in mammary pathology, and distribution of elastic fibers, have not been previously investigated. To address these issues, we studied 148 AGMLG identified in 133 paraffin blocks sampled from 64 vulvar wide excision or vulvectomy specimens (64 patients, various indications for surgery). The depth of AGMLG ranged from 0.64 to 3.9 mm. Epithelial columnar cell change was noted in 33.1% of all AGMLG, whereas columnar cell hyperplasia was detected in 10.1%. Occasionally, combinations of cuboidal epithelium and columnar cell change were seen within 1 histological section. Of 22 specimens stained for elastic fibers, in only 6 (27.3%) cases were elastic fibers found around glands. Periductal elastic fibers were demonstrated around 3 of the only 5 ducts, which were available for analysis in slides stained for elastic fibers. The depth of AGMLG should be taken into account when planning topical and surgical therapies for lesions derived or evolving from AGMLG. Alterations identical to columnar cell change may represent a normal variation of AGMLG.

  4. Columnar cell variant of papillary thyroid carcinoma: A diagnostic dilemma in fine-needle aspiration cytology.

    PubMed

    Verma, Ritu; Paul, Paramita

    2016-10-01

    Columnar cell variant of papillary thyroid carcinoma (PTC) is an uncommon variant with an aggressive course as compared to classic papillary carcinoma. Cytologic diagnosis of these tumors is difficult due to absence of characteristic nuclear features of classic pattern of papillary carcinoma. We present a case of columnar cell variant in a young female misdiagnosed on aspiration cytology. A 21-year-old female presented with solitary nodule in the left aspect of thyroid. A diagnosis of medullary thyroid carcinoma was rendered. The resected thyoroidectomy specimen revealed a columnar cell variant of PTC which was further supported by immunohistochemical staining. Diagn. Cytopathol. 2016;44:816-819. © 2016 Wiley Periodicals, Inc.

  5. Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions.

    PubMed

    Huckfeldt, Rachel M; Schubert, Timm; Morgan, Josh L; Godinho, Leanne; Di Cristo, Graziella; Huang, Z Josh; Wong, Rachel O L

    2009-01-01

    Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories that show little overlap, or tiling. Repulsive homotypic interactions underlie such patterns in cell organization in invertebrate neurons. It is unclear how dendro-dendritic repulsive interactions can produce a nonrandom distribution of cells and their spatial territories in mammalian retinal horizontal cells, as mature horizontal cell dendrites overlap substantially. By imaging developing mouse horizontal cells, we found that these cells transiently elaborate vertical neurites that form nonoverlapping columnar territories on reaching their final laminar positions. Targeted cell ablation revealed that the vertical neurites engage in homotypic interactions that result in tiling of neighboring cells before the establishment of their dendritic fields. This developmental tiling of transient neurites correlates with the emergence of a nonrandom distribution of the cells and could represent a mechanism that organizes neighbor relationships and territories of neurons before circuit assembly.

  6. Does Cell Lineage in the Developing Cerebral Cortex Contribute to its Columnar Organization?

    PubMed Central

    Costa, Marcos R.; Hedin-Pereira, Cecilia

    2010-01-01

    Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone (VZ) could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighboring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell–cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits. PMID:20676384

  7. Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state

    PubMed Central

    Patani, R.; Hollins, A. J.; Wishart, T. M.; Puddifoot, C. A.; Álvarez, S.; de Lera, A. R.; Wyllie, D. J. A.; Compston, D. A. S.; Pedersen, R. A.; Gillingwater, T. H.; Hardingham, G. E.; Allen, N. D.; Chandran, S.

    2011-01-01

    A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro. PMID:21364553

  8. The Ingestion of Proteins and Colloidal Materials by Columnar Absorptive Cells of the Small Intestine in Suckling Rats and Mice

    PubMed Central

    Clark, Sam L.

    1959-01-01

    Proteins and colloidal materials, administered orally to suckling rats and mice, were ingested by columnar absorptive cells of the jejunum and ileum, but not of the duodenum. Bovine gamma globulin and ovalbumin were identified in the apical cytoplasm by staining with fluorescent antibody; trypan blue, Evans blue, saccharated iron oxide, and colloidal gold were detected intracellularly by their color, specific staining, and appearance in the electron microscope. Each substance was segregated in membrane-enclosed vacuoles, apparently part of a system of potentially interconnecting vacuoles and tubules in the apical cytoplasm which is continuous in places with the apical cell membrane. We postulate that ingestion of foreign materials was accomplished by pinocytosis, that is, by invagination of the apical cell membrane to form vacuoles containing material from the intestinal lumen. Approximately 18 days after birth columnar absorptive cells lost the ability to ingest proteins and colloids, and no longer contained large vacuoles and numerous tubules. At this age rats and mice lose the ability to absorb antibodies from the intestine in an immunologically intact form, and we conclude that cellular ingestion is part of the mechanism of absorption of intact proteins in suckling animals. Particulate fat apparently is absorbed in both newborn and adult animals by micropinocytosis. Thus adult animals may not have lost the capacity for pinocytosis, but rather have become selective as to what substances provoke it. Cortisone acetate, administered subcutaneously to rats 8 to 10 days old alters the columnar absorptive cells within 72 hours so that they resemble the cells in adult animals and no longer ingest proteins. PMID:13630932

  9. Dielectrophoretic columnar focusing device

    DOEpatents

    James, Conrad D.; Galambos, Paul C.; Derzon, Mark S.

    2010-05-11

    A dielectrophoretic columnar focusing device uses interdigitated microelectrodes to provide a spatially non-uniform electric field in a fluid that generates a dipole within particles in the fluid. The electric field causes the particles to either be attracted to or repelled from regions where the electric field gradient is large, depending on whether the particles are more or less polarizable than the fluid. The particles can thereby be forced into well defined stable paths along the interdigitated microelectrodes. The device can be used for flow cytometry, particle control, and other process applications, including cell counting or other types of particle counting, and for separations in material control.

  10. Experimental columnar metaplasia in the canine oesophagus.

    PubMed

    Gillen, P; Keeling, P; Byrne, P J; West, A B; Hennessy, T P

    1988-02-01

    Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.

  11. Chemotaxis of Flavobacterium columnare: To Channel Catfish Mucus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the etiological agent of columnaris disease in fresh water fish. The disease is characterized by chronic skin lesions and severe mortality. The skin mucus constitutes a large portion of body and many infectious organisms including F. columnare, is believed to invade throu...

  12. Storage Lesion. Role of Red Cell Breakdown

    PubMed Central

    Kim-Shapiro, Daniel B.; Lee, Janet; Gladwin, Mark T.

    2011-01-01

    As stored blood ages intraerythrocytic energy sources are depleted resulting in reduced structural integrity of the membrane. Thus, stored red cells become less deformable and more fragile as they age. This fragility leads to release of cell-free hemoglobin and formation of microparticles, sub-micron hemoglobin-containing vesicles. Upon transfusion, it is likely that additional hemolysis and microparticle formation occurs due to breakdown of fragile red blood cells. Release of cell-free hemoglobin and microparticles leads to increased consumption of nitric oxide (NO), an important signaling molecule that modulates blood flow, and may promote inflammation. Stored blood may also be deficient in recently discovered blood nitric oxide synthase activity. We hypothesize that these factors play a potential role in the blood storage lesion. PMID:21496045

  13. GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

    NASA Technical Reports Server (NTRS)

    Shavers, M. R.; Atwell, W.; Cucinotta, F. A.; Badhwar, G. D. (Technical Monitor)

    1999-01-01

    Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of

  14. Three immobilized-cell columnar bioreactors for enhanced production of commodity chemicals

    SciTech Connect

    Davison, B.H.; Scott, C.D.; Kaufman, E.N.

    1993-07-01

    Immobilized-cell fluidized-bed bioreactors (FBRS) can be used with a variety of fermentations to increase production of fuels, solvents, organic acids, and other fermentation products. Part of the increased rates and yields are due to the immobilization of the biocatalyst at high concentrations. This FBR system with immobilized Zymomonas mobiles increased ethanol productivity more than tenfold with 99% conversion and near stoichiometric yields. FBRs also offer several additional modes of operation for simultaneous fermentation and separation to further increase production by removing the inhibitory products directly from the continuous fermentation. The production of lactic acid by immobilized Lactobacillus was augmented with the addition and removal of solid adsorbent particles to the FBR. An immiscible organic extractant also was used to extract butanol from the acetone-butanol fermentation by Clostridium acetobutylicum. Demonstrations with these FBR systems have already shown definite advantages by improved overall product yields (decreasing feed costs) and by increased rates (decreasing capital and operating costs). Further demonstration and scale-up continue.

  15. Giant-cell lesions of the facial bones

    SciTech Connect

    Som, P.M.; Lawson, W.; Cohen, B.A.

    1983-04-01

    Giant-cell lesions of the paranasal sinuses, including the giant-cell reparative granuloma, the brown tumor of hyperparathyroidism, the true giant-cell tumor, cherubism, and the aneurysmal bone cyst, are uncommon entities. Plain radiographic and computed-tomographic studies of these lesions are described and the differential diagnosis is discussed.

  16. Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

    PubMed

    Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

    2012-12-01

    Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma.

  17. Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

    PubMed Central

    Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.

    2015-01-01

    Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis. PMID:25764135

  18. The red cell storage lesion(s): of dogs and men.

    PubMed

    Klein, Harvey G

    2017-03-01

    The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the "storage lesion(s)". Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients.

  19. The red cell storage lesion(s): of dogs and men

    PubMed Central

    Klein, Harvey G.

    2017-01-01

    The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the “storage lesion(s)”. Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients. PMID:28263166

  20. Hippocampal place cell instability after lesions of the head direction cell network

    NASA Technical Reports Server (NTRS)

    Calton, Jeffrey L.; Stackman, Robert W.; Goodridge, Jeremy P.; Archey, William B.; Dudchenko, Paul A.; Taube, Jeffrey S.; Oman, C. M. (Principal Investigator)

    2003-01-01

    The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

  1. Expression and function of PDGF-α in columnar epithelial cells of age-related cataracts patients.

    PubMed

    Wei, J; Tang, H; Xu, Z Q; Li, B; Xie, L Q; Xu, G X

    2015-10-27

    We studied the expression and function of platelet-derived growth factor A (PDGF-α) in the lens epithelial cells of cataracts patients. Ninety age-related cataracts patients were recruited in our hospital between January 2012 and January 2014. The expression levels of platelet-derived growth factor receptor (PDGFR) in the anterior capsule of the lens at different degrees of turbidity, and PDGF-α in the aqueous humor were detected. A human lens epithelium cell line was also cultured and studied. To investigate its function, PDGF-α was used to treat a PDGFR-silenced human lens epithelium cell line to observe changes in the proliferation, transfer, and epithelial mesenchymal transition (EMT). The expression of PDGF-α and its receptor increased in patients with more serious cataracts. Lens epithelium cells stimulated by PDGF-α showed greater proliferation and migration. The degree of EMT was also upregulated in cells stimulated by PDGF-α. However, silencing the expression of PDGFR inhibited the effects. The development and severity of age-related cataracts was related to the secretion and expression of PDGF-α. This may be a new therapeutic target for cataracts treatment.

  2. Importance of mast cells in human periapical inflammatory lesions.

    PubMed

    Ledesma-Montes, Constantino; Garcés-Ortíz, Maricela; Rosales-García, Gilberto; Hernández-Guerrero, Juan Carlos

    2004-12-01

    The role of mast cells (MCs) in periapical inflammatory lesions is not well understood. The objective of this work was to quantify MC numbers in human periapical lesions with the aim to clarify their role in the pathogenesis of these lesions. We analyzed the slides of 64 human periapical inflammatory lesions stained with pH 8.0 toluidine blue technique, quantified the number of MCs, and evaluated any correlation with age, gender, size, and location. The results of this study suggest that MCs were more numerous in females (p < 0.01); MC numbers were higher in biopsies from granulomas with proliferating epithelium and lower in biopsies from chronic apical abscesses; MC counts did not correlate with patients' age or size. MCs were observed more commonly in areas containing inflammatory infiltrate and degranulation was a frequent finding in these zones. Our results suggest that MCs play an active role in the pathogenesis of the periapical inflammatory lesions. The potential role of MCs related with the initiation, development, and persistence of the periapical inflammatory process are discussed.

  3. Flavobacterium columnare: Chemotaxis and adhesion to channel catfish mucus is mediated by lectin-like capsular substances

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is an important Gram-negative pathogen of fresh water fish that may cause chronic skin lesions and severe mortality. Isolates of F. columnare belong to either the virulent genomovar II or the less virulent genomovar I. Chemotaxis and adhesion assays were conducted in vitro...

  4. Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells

    PubMed Central

    JOHNSON, SARA D.; LEVINGSTON, CORINNE; YOUNG, M. RITA I.

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4+ T cell expression of the IL-2 receptor CD25 and CD8+ T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID:27354582

  5. The transcriptomes of columnar and standard type apple trees (Malus x domestica) - a comparative study.

    PubMed

    Krost, Clemens; Petersen, Romina; Schmidt, Erwin R

    2012-05-01

    Columnar apple trees (Malus x domestica) provide several economic advantages due to their specific growth habit. The columnar phenotype is the result of the dominant allele of the gene Co and is characterized by thick stems with short internodes and reduced lateral branching. Co is located on chromosome 10 and often appears in a heterozygous state (Co/co). The molecular explanation of columnar growth is not well established. Therefore, we studied the transcriptomes of columnar and standard type apple trees using 454 and Illumina next generation sequencing (NGS) technologies. We analyzed the transcriptomes of shoot apical meristems (SAMs) because we expect that these organs are involved in forming the columnar growth phenotype. The results of the comparative transcriptome analysis show significant differences in expression levels of hundreds of genes. Many of the differentially expressed genes are associated with membrane and cell wall growth or modification and can be brought in line with the columnar phenotype. Additionally, earlier findings on the hormonal state of shoots of columnar apples could be affirmed. Our study resulted in a large number of genes differentially expressed in columnar vs. standard type apple tree SAMs. Although we have not unraveled the nature of the Co gene, we could show that the modified expression of these genes, most likely due to the presence of Co, can determine the columnar phenotype. Furthermore, the usefulness of NGS for the analysis of the molecular basis of complex phenotypes is discussed.

  6. Chemotactic factors of Flavobacterium columnare to skin mucus of healthy channel catfish (Ictalurus punctatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To gain insight into chemotactic factors involved in chemotaxis, we exposed a virulent strain of Flavobacterium columnare to various treatments followed by analysis of its chemotactic activity. Chemotactic activity of F. columnare was significantly (p < 0.05) inhibited when cells were pretreated by ...

  7. Chemotactic factors of Flavobacterium columnare to skin mucus of healthy channel catfish (Ictalurus punctatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To gain insight into chemotactic factors involved in chemotaxis, we exposed a virulent strain of Flavobacterium columnare to various treatments followed by analysis of its chemotactic activity. The chemotactic activity of F. columnare was significantly (p < 0.05) inhibited when cells were pretreated...

  8. Composition of Extracellular Polymeric Substances (EPS) produced by Flavobacterium columnare isolated from tropical fish in Brazil

    PubMed Central

    de Alexandre Sebastião, Fernanda; Pilarski, Fabiana; Lemos, Manoel Victor Franco

    2013-01-01

    Thirty nine isolates of Flavobacterium columnare from Brazilian fish farms had their carbohydrate composition of EPS evaluated by high efficiency liquid chromatography, using the phenol-sulfuric acid method of EPS. The occurrence of capsules on F. columnare cells was not directly related to biofilm formation, and the predominant monosaccharide is glucose. PMID:24516426

  9. Carcinogenic HPV infection in the cervical squamo-columnar junction.

    PubMed

    Mirkovic, Jelena; Howitt, Brooke E; Roncarati, Patrick; Demoulin, Stephanie; Suarez-Carmona, Meggy; Hubert, Pascale; McKeon, Frank D; Xian, Wa; Li, Anita; Delvenne, Philippe; Crum, Christopher P; Herfs, Michael

    2015-07-01

    Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16(ink4), Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16(ink4) and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16(ink4) immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16(ink4) expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ.

  10. Laboratory experiments on columnar jointing

    NASA Astrophysics Data System (ADS)

    Goehring, L.; Morris, S. W.

    2003-12-01

    The mechanism causing columnar jointing has remained an enticing mystery since the basalt columns of the Giant's Causeway in N. Ireland were first reported to science in the 17th century. This phenomenon, in which shrinkage cracks form a quasi-hexagonal arrangement, has been shown to produce columns in starch, glass, coal, sandstone, and ice, as well as in a variety of lava flows. This suggests that this pattern-forming process is very general in nature. However, most studies of columnar jointing have been confined to field studies of basalt flows. Following Muller, we have experimented with desiccating corn starch in an effort to understand this pattern from a more general point of view. The diffusion and evaporation of water in starch is thought to be analogous to the diffusion and extraction of heat from a basalt flow. By combining direct sampling and x-ray tomography, fully 3D descriptions of columnar jointing were obtained with starch samples. We have characterized the pattern with several statistical indices, which describe its structure and relative disorder. These methods can resolve the ordering of the colonnade near the free surface. We identified two distinct mechanisms by which the mean column area increases during pattern evolution. We found both a slow, almost power-law increase in column area, as well as episodes of sudden catastrophic jumps in scale. The latter suggests that the column scale is not a simple single-valued function of drying rate, but rather a metastable state subject to hysteresis. Such metastable behaviour might explain a fundamental question about columnar jointing -- why the columns are so regular in the direction of their growth. Moreover, these experiments may help discriminate between the various theoretical models of this pattern forming process. Finally, our results lead to predictions that could be tested by field measurements on basaltic colonnades.

  11. Mid-Esophagus Columnar Metaplasia: What Is the Biopathogenic Pathway?

    PubMed

    Rolim, Inês; Rodrigues, Rita Vale; Bettencourt, António; Barros, Rita; Camilo, Vânia; Dias Pereira, António; Almeida, Raquel; Chaves, Paula

    2016-10-05

    We report a case of metaplastic columnar epithelium in the mid-esophagus in a patient with history of caustic ingestion. A cardiac-type gastric phenotype, with early signs of intestinalization, was confirmed by immunohistochemistry studies (MUC5AC, MUC6, SOX2, and CDX2). Nonmetaplastic mucosa had histologic evidence of gastroesophageal reflux. In this case, esophageal reepithelization seems to have been modulated by acidic gastroesophageal reflux, which might activate transcription factors leading to phenotypic reprogramming of the regenerative epithelium. Most interestingly, it is a clinical example showcasing the origin of columnar metaplasia from stem cells located within the esophageal epithelium.

  12. Gene mutations and actionable genetic lesions in mantle cell lymphoma

    PubMed Central

    Ahmed, Makhdum; Zhang, Leo; Nomie, Krystle; Lam, Laura; Wang, Michael

    2016-01-01

    Mutations and epigenetic alterations are key events in transforming normal cells to cancer cells. Mantle cell lymphoma (MCL), a non-Hodgkin's lymphoma of the B-cell, is an aggressive malignancy with poor prognosis especially for those patients who are resistant to the frontline drugs. There is a great need to describe the molecular basis and mechanism of drug resistance in MCL to develop new strategies for treatment. We reviewed frequent somatic mutations and mutations involving the B-cell pathways in MCL and discussed clinical trials that attempted to disrupt these gene pathways and/or epigenetic events. Recurrent gene mutations were discussed in the light of prognostic and therapeutic opportunity and also the challenges of targeting these lesions. Mutations in the ATM, CCND1, TP53, MLL2, TRAF2 and NOTCH1 were most frequently encountered in mantle cell lymphoma. Translational models should be built that would assess mutations longitudinally to identify important compensatory, pro-survival and anti-apoptic pathways and actionable genetic targets. PMID:27449094

  13. Aggregatibacter actinomycetemcomitans induces Th17 cells in atherosclerotic lesions.

    PubMed

    Jia, Ru; Hashizume-Takizawa, Tomomi; Du, Yuan; Yamamoto, Masafumi; Kurita-Ochiai, Tomoko

    2015-04-01

    Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in atherosclerosis remains poorly understood. We previously reported that Aggregatibacter actinomycetemcomitans (Aa) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether Aa promotes the Th17 inducing pathway in Aa-challenged Apoe(shl) mice. Mice were intravenously injected with live Aa HK1651 or vehicles. Time-course analysis of splenic IL-17(+)CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-β and IL-1β levels, the mRNA expression of Th17-related molecules such as IL-1β, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-β and RORγt, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with Aa time dependently induced tropism of Th17 cells in the spleen and increase in atheromatous lesions in the aortic sinus of Apoe(shl) mice. Serum IL-17, IL-6, TGF-β and IL-1β levels were significantly enhanced by Aa. The gene expression of IL-1β, IL-6, IL-17RA, IL-21, IL-23, TGF-β, STAT3, RORγt, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of Aa-challenged mice. Furthermore, Aa challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that Aa stimulates Th17 induction that affects the progression of Aa-accelerated atherosclerosis.

  14. The discovery of columnar jointing on Mars

    USGS Publications Warehouse

    Milazzo, M.P.; Keszthelyi, L.P.; Jaeger, W.L.; Rosiek, M.; Mattson, S.; Verba, C.; Beyer, R.A.; Geissler, P.E.; McEwen, A.S.; ,

    2009-01-01

    We report on the discovery of columnar jointing in Marte Valles, Mars. These columnar lavas were discovered in the wall of a pristine, 16-km-diameter impact crater and exhibit the features of terrestrial columnar basalts. There are discontinuous outcrops along the entire crater wall, suggesting that the columnar rocks covered a surface area of at least 200 km2, assuming that the rocks obliterated by the impact event were similarly jointed. We also see columns in the walls of other fresh craters in the nearby volcanic plains of Elysium Planitia–Amazonis Planitia, which include Marte Vallis, and in a well-preserved crater in northeast Hellas.

  15. Columnar Jointing Thermo-Mechanics

    NASA Astrophysics Data System (ADS)

    Iddon, Fiona; Hornby, Adrian; Kendrick, Jackie; Wadsworth, Fabian; von Aulock, Felix; Lavallée, Yan

    2014-05-01

    Thermo-mechanical effects, common to a wide range of geological phenomena, are integral to the formation of columnar joints during cooling and crystallisation of lava flows. The process, and resultant geometry, relies on a complex inter-play between heat distribution, contraction and tensile strength, yet the kinetics of their formation remains elusive. Results are presented from a combination of field survey, thermo-analytical characterisation and mechanical investigation to constrain conditions favourable for columnar jointing. Columnar joints from Seljavallir, Iceland, produce quadratic to heptagonal cross sectional patterns with column widths ranging from 20 to 70 cm in size. The fracture surfaces are characterised by striae of which spacing (between 1 to 6 cm) appear to share a positive linear relationship to the joint spacing. The striae exhibit both a smooth and rough portion, interpreted to express a change in deformation regime from fully brittle, mode-I fracture propagation to an increasingly ductile response of the lava with tensile fracture dissipation as the fracture event wanes. The contraction of the basalts has been investigated via the expansion coefficient determined in a dilatometer (at 3mN of normal stress and a rate of 2 °C/min). The expansion coefficient has been constrained to 10-5/°C and the onset of melting (and completion of natural crystallisation) at 1150°C. Experiments are currently being conducted to assess the effect of cooling rate and normal stress on the properties of the Seljavallir basalts. The mechanical properties of the rock in tension have been tested at room temperature in a uniaxial press (high-temperature tests are also scheduled). During true-tension pull test at a strain rate of 10-4 s-1, elastic deformation agrees to a Young's modulus of 6.3 GPa. Tensile failure initiated after 0.35% strain with the generation of a large crack at a peak stress of 2.2 MPa. The fracture induced a stress drop and upon stress build-up to

  16. Buoyancy-Induced, Columnar Vortices

    NASA Astrophysics Data System (ADS)

    Simpson, Mark; Glezer, Ari

    2015-11-01

    Free buoyancy-induced, columnar vortices (dust devils) that are driven by thermal instabilities of ground-heated, stratified air in areas with sufficient insolation convert the potential energy of low-grade heat in the surface air layer into a vortex flow with significant kinetic energy. A variant of the naturally-occurring vortex is deliberately triggered and anchored within an azimuthal array of vertical, stator-like flow vanes that form an open-top enclosure and impart tangential momentum to the radially entrained air. This flow may be exploited for power generation by coupling the vortex to a vertical-axis turbine. The fundamental mechanisms associated with the formation, evolution, and dynamics of an anchored, buoyancy-driven columnar vortex within such a facility are investigated experimentally using a heated ground plane. Specific emphasis is placed on the manipulation of the vortex formation and structure and the dependence of the vorticity production and sustainment mechanisms on the thermal resources and characteristic scales of the anchoring flow vanes using stereo-PIV. It is shown that manipulation of the formation and advection of vorticity concentrations within the enclosure can be exploited for increasing the available kinetic energy. Supported by ARPA-E.

  17. Flavobacterium columnare chemotaxis to channel catfish mucus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is a Gram-negative pathogen of many species of wild and cultured fish, especially channel catfish (Ictalurus punctatus). This motile microbe is responsible for severe economic losses to the catfish industry. Flavobacterium columnare isolates from diseased channel catfish b...

  18. Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.

    PubMed

    Karouni, Mirna; Kurban, Mazen; Abbas, Ossama

    2016-09-01

    Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

  19. Microglial cell activation in demyelinating canine distemper lesions.

    PubMed

    Stein, Veronika M; Czub, Markus; Schreiner, Nicole; Moore, Peter F; Vandevelde, Marc; Zurbriggen, Andreas; Tipold, Andrea

    2004-08-01

    Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.

  20. Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults.

    PubMed Central

    Katsuda, S.; Boyd, H. C.; Fligner, C.; Ross, R.; Gown, A. M.

    1992-01-01

    There have been only limited immunocytochemical studies of the cell composition of the early lesions of human atherosclerosis, and none that incorporate a comprehensive panel of antibodies to various cell types and subsets. The authors thus performed a prospective study of 27 lesions from 16 different individuals ranging in age from 15 to 34 years. These were all lesions that appeared grossly as slightly raised, yellow fatty streaks in the posterior ascending aorta, but on histologic examination had varying degrees of round-cell, spindle-cell, and foam-cell accumulation. Using a panel of antibodies, including monoclonal antibodies specific for smooth muscle cells [HHF35], human macrophages [HAM56], endothelial cells [monoclonal antibodies to F. VIII related antigen], lymphocytes [anti-CD45, anti-CD20, anti-CD45RO, anti-T-cell receptor], it was revealed that the predominant cell type in these early lesions was the smooth muscle cell, including the vast majority of the foam cells, which tended to appear in the deeper regions of the lesions. There were variable numbers of smooth muscle cells and lymphocytes; the latter were exclusively T cells. It is concluded that in atherosclerotic lesions of young adults, which may represent various stages of fatty streak formation and advanced fatty streaks, smooth muscle cell accumulation may be an early event. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1562051

  1. Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions.

    PubMed Central

    Ylä-Herttuala, S; Lipton, B A; Rosenfeld, M E; Goldberg, I J; Steinberg, D; Witztum, J L

    1991-01-01

    Lipoprotein lipase (LPL; EC 3.1.1.34) may promote atherogenesis by producing remnant lipoproteins on the endothelial surface and by acting on lipoproteins in the artery wall. In vitro, smooth muscle cells and macrophages synthesize LPL, but in human carotid lesions only a few smooth muscle cells were reported to contain LPL protein. Endothelial cells do not synthesize LPL in vitro, but in normal arteries intense immunostaining for LPL is present on the endothelium. We used Northern blot analysis, in situ hybridization, and immunocytochemistry of human and rabbit arteries to determine cellular distribution and the site of the synthesis of LPL in atherosclerotic lesions. Northern blot analysis showed that LPL mRNA was detectable in macrophage-derived foam cells isolated from arterial lesions of "ballooned" cholesterol-fed rabbits. In situ hybridization studies of atherosclerotic lesions with an antisense riboprobe showed a strong hybridization signal for LPL mRNA in some, but not all, lesion macrophages, which were mostly located in the subendothelial and edge areas of the lesions. Also, some smooth muscle cells in lesion areas also expressed LPL mRNA. Immunocytochemistry of frozen sections of rabbit lesions with a monoclonal antibody to human milk LPL showed intense staining for LPL protein in macrophage-rich intimal lesions. The results suggest that lesion macrophages and macrophage-derived foam cells express LPL mRNA and protein. Some smooth muscle cells in the lesion areas also synthesize LPL. These data are consistent with an important role for LPL in atherogenesis. Images PMID:1719546

  2. DNA lesions, inducible DNA repair, and cell division: Three key factors in mutagenesis and carcinogenesis

    SciTech Connect

    Ames, B.N.; Shigenaga, M.K.; Gold, L.S.

    1993-12-01

    DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 10{sup 6} oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants).

  3. Evaluation of mast cell counts and microvessel density in reactive lesions of the oral cavity

    PubMed Central

    Kouhsoltani, Maryam; Moradzadeh Khiavi, Monir; Tahamtan, Shabnam

    2016-01-01

    Background. Reliable immunohistochemical assays to assess the definitive role of mast cells (MCs) and angiogenesis in the pathogenesis of oral reactive lesions are generally not available. The aim of the present study was to evaluate mast cell counts (MCC) and microvessel density (MVD) in oral reactive lesions and determine the correlation between MCC and MVD. Methods. Seventy-five cases of reactive lesions of the oral cavity, including pyogenic granuloma, fibroma, peripheral giant cell granuloma, inflammatory fibrous hyperplasia, peripheral ossifying fibroma (15 for each category) were immunohisto-chemically stained with MC tryptase and CD31. Fifteen cases of normal gingival tissue were considered as the control group. The mean MCC and MVD in superficial and deep connective tissues were assessed and total MCC and MVD was computed for each lesion. Results. Statistically significant differences were observed in MCC and MVD between the study groups (P < 0.001). MC tryptase and CD31 expression increased in the superficial connective tissue of each lesion in comparison to the deep con-nective tissue. A significant negative correlation was not found between MCC and MVD in oral reactive lesions (P < 0.001, r = -0.458). Conclusion. Although MCs were present in the reactive lesions of the oral cavity, a direct correlation between MCC and MVD was not found in these lesions. Therefore, a significant interaction between MCs and endothelial cells and an active role for MCs in the growth of oral reactive lesions was not found in this study. PMID:28096950

  4. Chromaffin cell grafts to rat cerebral cortex reverse lesion-induced memory deficits.

    PubMed

    Welner, S A; Koty, Z C; Boksa, P

    1990-09-10

    Adrenal chromaffin cells were isolated from donor adult rats and transplanted to the cerebral cortex of bilaterally nucleus basalis magnocellularis-lesioned rats. Chromaffin cell grafts to lesioned animals completely reversed the spatial memory deficit seen in lesioned alone animals on a T-maze alternation task. Although chromaffin cell grafts have been used previously to reverse motor abnormalities arising from defective nigro-striatal aminergic transmission, the present report is the first evidence that chromaffin cell transplants can reverse deficits in memory function. Grafts also enhanced cortical acetylcholinesterase staining.

  5. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

    PubMed

    Ye, Li-Juan; Bian, Hui; Fan, Yao-Dong; Wang, Zheng-Bo; Yu, Hua-Lin; Ma, Yuan-Ye; Chen, Feng

    2016-09-01

    Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 10(5) cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  6. Clustered DNA lesion repair in eukaryotes: relevance to mutagenesis and cell survival

    PubMed Central

    Sage, Evelyne; Harrison, Lynn

    2011-01-01

    A clustered DNA lesion, also known as a multiply damaged site, is defined as ≥ 2 damages in the DNA within 1–2 helical turns. Only ionizing radiation and certain chemicals introduce DNA damage in the genome in this non-random way. What is now clear is that the lethality of a damaging agent is not just related to the types of DNA lesions introduced, but also to how the damage is distributed in the DNA. Clustered DNA lesions were first hypothesized to exist in the 1990’s, and work has progressed where these complex lesions have been characterized and measured in irradiated as well as in non-irradiated cells. A clustered lesion can consist of single as well as double strand breaks, base damage and abasic sites, and the damages can be situated on the same strand or opposing strands. They include tandem lesions, double strand break (DSB) clusters and non-DSB clusters, and base excision repair as well as the DSB repair pathways can be required to remove these complex lesions. Due to the plethora of oxidative damage induced by ionizing radiation, and the repair proteins involved in their removal from the DNA, it has been necessary to study how repair systems handle these lesions using synthetic DNA damage. This review focuses on the repair process and mutagenic consequences of clustered lesions in yeast and mammalian cells. By examining the studies on synthetic clustered lesions, and the effects of low vs high LET radiation on mammalian cells or tissues, it is possible to extrapolate the potential biological relevance of these clustered lesions to the killing of tumor cells by radiotherapy and chemotherapy, and to the risk of cancer in non-tumor cells, and this will be discussed. PMID:21185841

  7. Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections

    PubMed Central

    2012-01-01

    Central giant cell lesions are benign intraosseous proliferative lesions that have considerable local aggressiveness. Nonsurgical treatment methods, such as intralesional corticosteroid injections, systemic calcitonin and interferon have been reported. Recently, bisphosphonates have been used to treat central giant cell lesions. A case of a 36-year-old male with a central giant cell lesion crossing the mandibular midline was treated with intralesional corticosteroids combined with alendronate sodium for the control of systemic bone resorption. The steroid injections and the use of bisphosphonates were stopped after seven months when further needle penetration into the lesion was not possible due to new bone formation. After two years, the bony architecture was near normal, and only minimal radiolucency was present around the root apices of the involved teeth. The patient was followed up for four years, and panoramic radiography showed areas of new bone formation. Thus far, neither recurrence nor side effects of the medication have been detected. PMID:22913518

  8. Discovery of columnar jointing on Mars

    USGS Publications Warehouse

    Milazzo, M.P.; Keszthelyi, L.P.; Jaeger, W.L.; Rosiek, M.; Mattson, S.; Verba, C.; Beyer, R.A.; Geissler, P.E.; McEwen, A.S.

    2009-01-01

    We report on the discovery of columnar jointing in Marte Valles, Mars. These columnar lavas were discovered in the wall of a pristine, 16-km-diameter impact crater and exhibit the features of terrestrial columnar basalts. There are discontinuous outcrops along the entire crater wall, suggesting that the columnar rocks covered a surface area of at least 200 km2, assuming that the rocks obliterated by the impact event were similarly jointed. We also see columns in the walls of other fresh craters in the nearby volcanic plains of Elysium Planitia-Amazonis Planitia, which include Marte Vallis, and in a well-preserved crater in northeast Hellas. ?? 2009 The Geological Society of America.

  9. Langerhans cell histiocytosis: recurrent lesions affecting mandible in a 10-year-old patient.

    PubMed

    Loducca, S V; Mantesso, A; Araújo, N S; Magalhães, M H

    2001-01-01

    Hand-Schuller-Christian disease is a multifocal variant of eosinophilic granuloma, characterised by the classical triad of bony lesions, exophthalmos and diabetes insipidus. This case relates recurrent Langerhans' cell histiocytosis lesions presented as destruction of periodontal support associated with diabetes in a 10-year-old patient. Medical history suggests that the case represents a case of Hand-Schuller Christian disease.

  10. Nucleosome repeat lengths and columnar chromatin structure.

    PubMed

    Trifonov, Edward N

    2016-06-01

    Thorough quantitative study of nucleosome repeat length (NRL) distributions, conducted in 1992 by J. Widom, resulted in a striking observation that the linker lengths between the nucleosomes are quantized. Comparison of the NRL average values with the MNase cut distances predicted from the hypothetical columnar structure of chromatin (this work) shows a close correspondence between the two. This strongly suggests that the NRL distribution, actually, reflects the dominant role of columnar chromatin structure common for all eukaryotes.

  11. Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients.

    PubMed

    Yamaguchi, Sayaka; Miyagi, Takuya; Sogabe, Yoko; Yasuda, Masahito; Kanazawa, Nobuo; Utani, Atsushi; Izaki, Seiichi; Uezato, Hiroshi; Takahashi, Kenzo

    2017-02-28

    Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction. The aim of this study was to examine changes in the number of Langerhans cells and other dendritic cells, and maturation of epidermal Langerhans cells in the lesional and adjacent non-lesional skin in pellagra patients. Seven pellagra patients and 10 healthy individuals who served as controls were included. The number and distribution of dendritic cells and other cutaneous cells were examined by immunohistochemistry. Epidermal Langerhans cells decreased considerably in the skin lesions of pellagra patients, whereas other dendritic cells did not change. The decrease in the number of Langerhans cells was positively correlated with the histological severity of skin lesions. As the number of Langerhans cells was not reduced in the undisturbed neighboring skin, the depletion of epidermal Langerhans cells did not precede skin damage but was a cause of prolonged severe inflammation.

  12. Intranodal leiomyoma in a young child: report of a rare spindle cell lesion.

    PubMed

    Girhotra, Manish; Virk, Shehbaaz Singh; Verma, Sarika; Bansal, Kalpana; Gupta, Ruchika

    2014-01-01

    ABSTRACT Primary spindle cell lesions of lymph nodes, with the exception of Kaposi's sarcoma, are rare. Intranodal palisaded myofibroblastoma has been described as a spindle cell tumor with prominent amianthoid fibers, intralesional hemorrhage, and intracellular or extracellular inclusions. Another spindle cell lesion, intranodal leiomyoma, has been reported only occasionally. We report the case of a 6-year-old boy with a mass in the neck without other systemic complaints. Excision biopsy of the lymph node revealed a spindle cell tumor with lymph nodal tissue at the periphery. The tumor showed features of smooth muscle differentiation with focally high mitotic index. The classical features of myofibroblastoma were not present. A final pathologic diagnosis of intranodal leiomyoma was rendered. The child has been free of recurrence in the follow-up period. Intranodal leiomyoma is a rare primary spindle cell lesion of the lymph nodes and should be considered in the differential diagnosis of the same.

  13. Apoptotic Index and Proliferative Index in Premalignant and Malignant Squamous Cell Lesions of the Oral Cavity

    PubMed Central

    Viswanathan, Vidya; Juluri, Ravichandra; Goel, Seema; Madan, Jyotsna; Mitra, Subir K; Gopalakrishnan, Dharmarajan

    2015-01-01

    Background: Oral squamous cell lesions are most commonly diagnosed lesions in India. Both premalignant and malignant lesions are frequently encountered. In this study, we evaluated the role and significance of apoptotic indices (AI) and proliferative indices (PI) in premalignant and malignant squamous cell lesions of the oral cavity. Materials and Methods: A total of 62 histologically proven cases of premalignant and malignant oral squamous cell lesions were analyzed. The biopsies were stained with hematoxylin and eosin and also with monoclonal antibody Ki-67. AI and PI were assessed using a light microscope. Results: AI was found to increase gradually from normal to dysplasia to carcinoma. The highest AI was seen in well-differentiated squamous cell carcinomas (SCCs). PI also was found to increase significantly from normal to dysplasia to carcinoma. The highest PI was seen in poorly differentiated SCC. Conclusion: AI in conjunction with the PI offers an accurate idea as to the nature and course of the lesion and may help to plan timely surgical intervention that results in better clinical prognosis and outcome. PMID:25709366

  14. DNA lesions in hyperthermic cell killing: effects of thermotolerance, procaine, and erythritol.

    PubMed

    Jorritsma, J B; Konings, A W

    1986-04-01

    When HeLa S3 cells were subjected to 45 degrees C hyperthermia, DNA lesions were detected by the use of the alkaline unwinding/hydroxylapatite method. The number of lesions formed was not affected when the cells were made thermotolerant by either an acute (15 min 44 degrees C + 5 h 37 degrees C) or a chronic (5 h 42 degrees C) pretreatment before 45 degrees C hyperthermia. The presence of 10 mM procaine (heat sensitizer) or 0.5 M erythritol (heat protector) during hyperthermia also had no effect on the rate of formation of heat-induced alkali labile DNA lesions. These observations do not support a concept where DNA lesions are considered to be the ultimate cause of hyperthermic cell killing. Both drugs, however, influenced the rate of repair of radiation-induced strand breaks when present during preirradiation heat treatment. We conclude that the initial number of heat-induced alkali labile DNA lesions is not directly related to cell survival. It cannot be excluded, however, that differences in posthyperthermic repair of these lesions may lead to a positive correlation between residual DNA damage and survival after the different experimental conditions.

  15. Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression.

    PubMed

    Subramanian, Manikandan; Proto, Jonathan D; Matsushima, Glenn K; Tabas, Ira

    2016-12-13

    AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl(-/-) or wild-type mice were transplanted into lethally irradiated Ldlr(-/-) mice. These chimeric mice were then fed the Western-type diet (WD) for 17 weeks. We demonstrate that lesional macrophages in WT mice express Axl but that Axl deficiency in bone marrow-derived cells does not affect lesion size, cellularity, necrosis, or inflammatory parameters in advanced atherosclerotic plaques. Moreover, apoptosis of lesional cells was unaffected, and we found no evidence of defective lesional efferocytosis. In contrast to previously reported findings with MerTK deficiency, hematopoietic cell-Axl deficiency in WD-fed Ldlr(-/-) mice does not affect the progression of advanced atherosclerosis or lesional processes associated with TAM receptor signaling. These findings suggest a heretofore unappreciated TAM receptor hierarchy in advanced atherosclerosis.

  16. Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression

    PubMed Central

    Subramanian, Manikandan; Proto, Jonathan D.; Matsushima, Glenn K.; Tabas, Ira

    2016-01-01

    AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl−/− or wild-type mice were transplanted into lethally irradiated Ldlr−/− mice. These chimeric mice were then fed the Western-type diet (WD) for 17 weeks. We demonstrate that lesional macrophages in WT mice express Axl but that Axl deficiency in bone marrow-derived cells does not affect lesion size, cellularity, necrosis, or inflammatory parameters in advanced atherosclerotic plaques. Moreover, apoptosis of lesional cells was unaffected, and we found no evidence of defective lesional efferocytosis. In contrast to previously reported findings with MerTK deficiency, hematopoietic cell-Axl deficiency in WD-fed Ldlr−/− mice does not affect the progression of advanced atherosclerosis or lesional processes associated with TAM receptor signaling. These findings suggest a heretofore unappreciated TAM receptor hierarchy in advanced atherosclerosis. PMID:27958361

  17. Effects of gastric vagotomy on visceral cell proliferation induced by ventromedial hypothalamic lesions: role of vagal hyperactivity.

    PubMed

    Kintaka, Yuri; Osaka, Toshimasa; Suzuki, Yoko; Hashiguchi, Takeo; Niijima, Akira; Kageyama, Haruaki; Fumiko, Takenoya; Shioda, Seiji; Inoue, Shuji

    2009-07-01

    In rats, ventromedial hypothalamic (VMH) lesions induce cell proliferation in the visceral organs (stomach, small intestine, liver, and pancreas) due to hyperactivity of the vagus nerve. To investigate the effects of selective gastric vagotomy on VMH lesion-induced cell proliferation and secretion of gastric acid, we assessed the mitotic index (the number of proliferating cell nuclear antigen (PCNA)-immunopositive cells per 1,000 cells in the gastric mucosal cell layer) and measured the volume of secreted basal gastric acid. Furthermore, to explore whether or not ethanol-induced acute gastric mucosal lesions (AGML) lead to ulcer formation in VMH-lesioned rats, we assessed the ulcer index of both sham-operated and VMH-lesioned rats after administration of ethanol. VMH lesions resulted in an increased mitotic index and thickness of the gastric mucosal cell layer and gave rise to the hypersecretion of gastric acid. Selective gastric vagotomy restored these parameters to normal without affecting cell proliferation in other visceral organs. Ethanol-induced AGML caused ulcers in sham VMH-lesioned rats, whereas VMH-lesioned rats were less likely to exhibit such ulcers. These results suggest that VMH lesion-induced vagally mediated cell proliferation in the visceral organs is associated with hyperfunction in these organs, and VMH lesion-induced resistance to ethanol may be due to thickening of the gastric mucosal cell layer resulting from cell proliferation in the gastric mucosa-this in turn is due to hyperactivity of the vagus nerve.

  18. Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

    PubMed Central

    Lu, Song; White, John V.; Lin, Wan Lu; Zhang, Xiaoying; Solomides, Charalambos; Evans, Kyle; Ntaoula, Nectaria; Nwaneshiudu, Ifeyinwa; Gaughan, John; Monos, Dimitri S.; Oleszak, Emilia L.

    2014-01-01

    Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease. PMID:24752442

  19. Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions

    SciTech Connect

    Maguire, G.W.; Smith, E.L. III

    1985-06-01

    Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography with electrochemical detection of endogenous dopamine content and by (/sup 3/H)dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced (/sup 3/H)dopamine uptake compared with that of their matched controls. Normal appearing (/sup 3/H)GABA and (/sup 3/H)-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry.

  20. Stem cell therapy: A novel treatment approach for oral mucosal lesions

    PubMed Central

    Suma, G. N.; Arora, Madhu Pruthi; Lakhanpal, Manisha

    2015-01-01

    Stem cells have enormous potential to alleviate sufferings of many diseases that currently have no effective therapy. The research in this field is growing at an exponential rate. Stem cells are master cells that have specialized capability for self-renewal, potency and capability to differentiate to many cell types. At present, the adult mesenchymal stem cells are being used in the head and neck region for orofacial regeneration (including enamel, dentin, pulp and alveolar bone) in lieu of their proliferative and regenerative properties, their use in the treatment of oral mucosal lesions is still in budding stages. Moreover, there is scanty literature available regarding role of stem cell therapy in the treatment of commonly seen oral mucosal lesions like oral submucous fibrosis, oral lichen planus, oral ulcers and oral mucositis. The present review will focus on the current knowledge about the role of stem cell therapies in oral mucosal lesions and could facilitate new advancements in this area (articles were obtained from electronic media like PubMed, EBSCO, Cochrane and Medline etc., from year 2000 to 2014 to review the role of stem cell therapy in oral mucosal lesions). PMID:25709329

  1. Clear-cell melanocytic lesions with balloon-cell and sebocyte-like melanocytes: a unifying concept.

    PubMed

    Kazlouskaya, Viktoryia; Guo, Ying; Maia-Cohen, Sandra; Mones, Joan

    2014-05-01

    Melanocytes may assume unique shapes and sizes but rarely have clear cytoplasm. We studied 28 melanocytic lesions that contained clear-cell melanocytes of the balloon-cell and sebocyte-like types. Clear-cell melanocytes were found more commonly in females (64%) than in males (36%), with predominance in females younger than 50 years (79%) and predominance in males older than 50 years (67%). They were distributed evenly throughout the body but were not found on acral sites. Clear-cell melanocytes were most prevalent in congenital nevi (18 or 72%) but were also found in 5 Clark nevi, 2 Meischer nevi, 1 Unna nevus, 1 atypical intra-epidermal proliferation, and 1 melanoma. The clear cells were distributed diffusely in 86% of the lesions and focally in 14%. The overall percentage of clear-cell melanocytes was 56%. The percentage of balloon cells was 57% and sebocyte-like melanocytes 32%. Clear cells with morphologic features of both balloon cells and sebocyte-like melanocytes, that is, intermediate cells, were present in all lesions with an overall percentage of 12%. The presence of melanocytes of both the balloon-cell and sebocyte-like types and the finding of clear-cell melanocytes with intermediate features in all lesions lends support to the theory that balloon-cell and sebocyte-like melanocytes may represent morphologic expressions of the same alteration in melanogenesis.

  2. Genome sequence of the fish pathogen Flavobacterium columnare ATCC 49512

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is a Gram-negative, rod shaped, motile, and highly prevalent fish pathogen causing columnaris disease in freshwater fish worldwide. Here, we present the complete genome sequence of F. columnare strain ATCC 49512. ...

  3. Parasitism enhances tilapia susceptibility to Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, a Gram-negative bacterium, is the causative agent of columnaris disease. Many commercially important freshwater fish worldwide are susceptible to columnaris disease that can result in high fish mortality. Ichthyophthirius multifiliis (Ich) is a protozoan parasite in many ...

  4. Reduced gravity favors columnar crystal growth

    NASA Technical Reports Server (NTRS)

    Kattamis, T. Z.; Papazian, J. M.

    1981-01-01

    In zero gravity, alined columnar microstructures form at expense of equiaxed growth. Preferential crystal growth occurs in solidification chamber consisting of semicylindrical copper chill block brazed to stainless steel top plate. Method is best utilized in castings where directional dependence of physical properties is beneficial, as in turbine blades.

  5. One-step bone marrow-derived cell transplantation in talarosteochondral lesions: mid-term results

    PubMed Central

    BUDA, ROBERTO; VANNINI, FRANCESCA; CAVALLO, MARCO; BALDASSARRI, MATTEO; NATALI, SIMONE; CASTAGNINI, FRANCESCO; GIANNINI, SANDRO

    2013-01-01

    Purpose to verify the capability of scaffold-supported bone marrow-derived cells to be used in the repair of osteochondral lesions of the talus. Methods using a device to concentrate bone marrow-derived cells, a scaffold (collagen powder or hyaluronic acid membrane) for cell support and platelet gel, a one-step arthroscopic technique was developed for cartilage repair. In a prospective clinical study, we investigated the ability of this technique to repair talar osteochondral lesions in 64 patients. The mean follow-up was 53 months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scale score. We also considered the influence of scaffold type, lesion area, previous surgery, and lesion depth. Results the mean preoperative AOFAS scale score was 65.2 ± 13.9. The clinical results peaked at 24 months, before declining gradually to settle at a score of around 80 at the maximum follow-up of 72 months. Conclusions the use of bone marrow-derived cells supported by scaffolds to repair osteochondral lesions of the talus resulted in significant clinical improvement, which was maintained over time. Level of Evidence level IV, therapeutic case series. PMID:25606518

  6. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes

    PubMed Central

    Cohen, Isadora S.; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

    2015-01-01

    DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

  7. Giant Cell Lesions in Noonan Syndrome: Case Report and Review of The Literature

    PubMed Central

    Bufalino, Andreia; Carrera, Manoela; Carlos, Roman

    2010-01-01

    Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS) is a rare condition with phenotypic overlap with Noonan syndrome (NS). Once thought to be a specific and separate entity, it is now suggested to be a variant of the NS spectrum. We report a patient with classical cardinal features of NS, including short stature, mild ptosis, hypertelorism, down-slating palpebral fissures, low-set and posteriorly angulated ears, short neck, pectus excavatum, widely spaced nipples and cryptochidism, which were associated with bilateral central giant cell lesions in the mandible and germ-line mutation (C218T, Thr73Ile) in the exon 3 of the PTPN11 gene. The similar clinical and genetic aspects support the observation that NS/MGCLS is a variant of NS and giant cell lesions are an integrant part of this disorder. PMID:20383758

  8. Pre-existing smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions

    PubMed Central

    Yang, Pu; Hong, Michael S.; Fu, Chunhua; Schmit, Bradley M.; Su, Yunchao; Berceli, Scott A.; Jiang, Zhihua

    2015-01-01

    Background With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell-lineage composition across models, but the animal-to-animal difference has not attracted much attention though the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. Methods The R26R+;Myh11-CreER+ and R26R+;Scl-CreER+ mice were utilized to attach LacZ tags to the pre-existing smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). Results LacZ-tagged SMCs were physically relocated from media to neointima and changed to a de-differentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5–70% and 0–85%, with an average at low levels of 27% and 29% in CCA (n=15) and FA (n=15) lesions, respectively. Bone marrow cells, while able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Pre-existing ECs were located in the sub-endothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal-transition (EndoMT), however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n=7) and FA (n=7) lesions, respectively. ECs located on the luminal surface exhibited little evidence for EndoMT. Conclusion Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell-lineage composition. PMID:26387788

  9. Gentiana asclepiadea protects human cells against oxidation DNA lesions.

    PubMed

    Hudecová, Alexandra; Hašplová, Katarína; Miadoková, Eva; Magdolenová, Zuzana; Rinna, Alessandra; Collins, Andrew R; Gálová, Eliška; Vaculčíková, Dagmar; Gregáň, Fridrich; Dušinská, Mária

    2012-03-01

    The objectives of this study were to examine whether the methanolic and aqueous extracts from the haulm and flower of Gentiana asclepiadea exhibited free radical scavenging and protective (antigenotoxic) effect against DNA oxidation induced by H(2)O(2) in human lymphocytes and human embryonic kidney cells (HEK 293). All four extracts exhibited high scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radicals at concentrations 2.5 and 25 mg ml(-1). The level of DNA damage was measured using the alkaline version of single-cell gel electrophoresis (comet assay). Challenge with H(2)O(2) shows that the pre-treatment of the cells with non-genotoxic doses of Gentiana extracts protected human DNA-either eliminated or significantly reduced H(2)O(2) induced DNA damage. The genotoxic activity of H(2)O(2) was most effectively decreased after 30 min of pre-incubation with 0.05 mg ml(-1) (range, 93.5%-96.3% of reduction in lymphocytes) and 0.25 mg ml(-1) (range, 59.5%-71.4% and 52.7%-66.4% of reduction in lymphocytes and HEK 293 cells, respectively) of G. asclepiadea extracts. These results suggest that the tested G. asclepiadea extracts could be considered as an effective natural antioxidant source.

  10. T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells?

    PubMed Central

    2010-01-01

    Anti-neutrophil cytoplasmic antibody (ANCA) - associated vasculitis (AAV) is a life-threatening autoimmune disease characterized by an antibody-mediated glomerulonephritis and necrotizing vasculitis. Apart from antibodies, T cells are also involved in disease pathogenesis. This review stresses the hallmarks of T cell-mediated pathology in AAV and highlights the characteristics of lesional and circulating T cells in the immune response in AAV. Circulating effector T-cell populations are expanded and are in a persistent state of activation. Circulating regulatory T-cell subsets are less well characterized but seem to be impaired in function. Lesional effector T cells are present in granulomas, vasculitic lesions, and nephritis. Lesional T cells usually show pro-inflammatory properties and promote granuloma formation. Apart from T cells, dendritic cells are abundantly present at the sites of inflammation and locally orchestrate the immune response. Targeting the above-mentioned T cell-mediated disease mechanisms will potentially provide powerful therapeutic tools for AAV. PMID:20236453

  11. Expression of Stem Cell Markers in Preinvasive Tubal Lesions of Ovarian Carcinoma

    PubMed Central

    Chene, G.; Ouellet, V.; Rahimi, K.; Barres, V.; Meunier, L.; De Ladurantaye, M.; Provencher, D.; Mes-Masson, A. M.

    2015-01-01

    In order to better understand the ovarian serous carcinogenic process with tubal origin, we investigated the expression of stem cell markers in premalignant tubal lesions (serous tubal intraepithelial carcinoma or STIC). We found an increased stem cell marker density in the normal fallopian tube followed by a high CD117 and a low ALDH and CD44 expression in STICs raising the question of the role of the stem cell markers in the serous carcinogenic process. PMID:26504831

  12. Electron microscopic demonstration of lesions in target cell membranes associated with antibody-dependent cellular cytotoxicity.

    PubMed Central

    Dourmashkin, R R; Deteix, P; Simone, C B; Henkart, P

    1980-01-01

    To test the hypothesis that complement-mediated cell lysis and cell-mediated cytotoxicity operate by analogous mechanisms, cell membranes from two antibody-dependent cytotoxicity systems were examined by electron microscopy after negative staining. Ring-shaped membrane lesions generally similar to, but larger than, those previously described for complement lysis were observed. These findings are in agreement with recent measurements of larger functional pores for ADCC than complement. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7214742

  13. Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and Pathologic Findings

    PubMed Central

    Cauley, Christy E; Pitman, Martha B; Zhou, Jiahua; Perkins, James; Kuleman, Birte; Liss, Andrew S; Castillo, Carlos Fernandez-del; Warshaw, Andrew L; Lillemoe, Keith D; Thayer, Sarah P

    2015-01-01

    Background Circulating epithelial cell (CEC) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, pre-malignant, and malignant pancreatic lesions using a size-selective filtration device. Study Design Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell® devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathological data and clinical outcomes of these patients were obtained from medical records over a one year follow-up period. Results Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. CECs were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas (PDAC) (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions (p=0.41). In addition, CECs findings in PDAC patients were not associated with poor prognosis. Conclusions While CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is not diagnostic of malignancy, nor is it prognostic for patients with PDAC. PMID:26209458

  14. Complementary DNA sequences of the constant regions of T-cell antigen receptors α, β and γ in mandarin fish, Siniperca chuatsi Basilewsky, and their transcriptional changes after stimulation with Flavobacterium columnare.

    PubMed

    Tian, J Y; Qi, Z T; Wu, N; Chang, M X; Nie, P

    2014-02-01

    In this study, the constant-region genes (Cα, Cβ and Cγ) that encode the T-cell antigen receptor (TCR) α, β and γ chains were cloned from mandarin fish, Siniperca chuatsi Basilewsky, an important freshwater fish species in China. The complementary DNA sequences of Cα, Cβ and Cγ were 843, 716 and 906 base pairs (bp) in length and had a 465-, 289- and 360-bp 3' untranslated region, encoding 125, 142 and 182 amino acids, respectively. The amino-acid sequences of the constant regions of mandarin fish TCR α, β and γ chains (encoded by Cα, Cβ and Cγ, respectively) were most similar to those of their teleost counterparts, showing 60% similarity with pufferfish, 48% similarity with Atlantic salmon and 57% similarity with flounder, respectively. The phylogenetic analysis revealed that the mandarin fish Cα, Cβ and Cγ were clustered, respectively, with their vertebrate counterparts. The mandarin fish Cα, Cβ and Cγ could also be separated into four domains: immunoglobulin; connecting peptide (CP); transmembrane (TM); and cytoplasmic tail. Several conserved features in mammalian TCRs were also found in those of mandarin fish, such as a conserved cysteine residue in the CP domain of Cα, necessary for creating an interchain disulphide bond with the TCR β chain, and a conserved antigen receptor TM motif in Cα and Cβ. Meanwhile, transcripts of Cα, Cβ and Cγ were detectable in all examined organs, with a stronger signal observed in lymphoid organs. In addition, the temporal transcriptional changes for Cα and Cγ were investigated, 1, 2, 3, 4, 5, 6 and 8 weeks after stimulation with Flavobacterium columnare, in head kidney, spleen, blood, thymus, gill and intestine, using real-time polymerase chain reaction. The results demonstrated stimulation-dependent up-regulations in almost all tissues examined, which indicates that T cells may play important roles in preventing mandarin fish from bacterial invasion. In particular, apart from thymus, T cells were

  15. [Intravascular large B-cell lymphoma with massive pulmonary lesions].

    PubMed

    Higashiyama, Asumi; Hashino, Satoshi; Onozawa, Masahiro; Takahata, Mutsumi; Okada, Kohei; Kahata, Kaoru; Taniguchi, Natsuko; Nasuhara, Yasuyuki; Kubota, Kanako; Fujimoto, Nozomu; Matsuno, Yoshihiro; Nishimura, Masahiro; Asaka, Masahiro

    2010-05-01

    A 61-year-old man was admitted to our hospital with dyspnea on effort. Neither computed tomography scan nor chest X-ray film detected any specific findings that could explain hypoxemia. Since (67)Ga scintigraphy showed abnormal uptake in the bilateral lungs, transbronchial lung biopsy (TBLB) was performed. The TBLB specimen was diagnosed as intravascular large B-cell lymphoma (IVLBCL). There was no involvement of any other organ considered typical of IVLBCL. In cases showing clinical findings such as hypoxia despite mild pulmonary radiographic changes, a definitive diagnosis should be made using methods such as TBLB with consideration given to the possibility of IVLBCL.

  16. Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions.

    PubMed

    Saadoun, Samira; Bridges, Leslie R; Verkman, A S; Papadopoulos, Marios C

    2012-12-19

    Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin+ cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin+ cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica.

  17. Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

    PubMed

    Bedoya, Astrid M; Jaramillo, Roberto; Baena, Armando; Castaño, Jorge; Olaya, Natalia; Zea, Arnold H; Herrero, Rolando; Sanchez, Gloria I

    2013-04-01

    Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

  18. Proliferative lesions of intra-epidermal cytokeratin CAM5.2-positive cells in canine nipples.

    PubMed

    Yasuno, K; Nishiyama, S; Kobayashi, R; Yoshimura, H; Takahashi, K; Omachi, T; Kamiie, J; Shirota, K

    2014-01-01

    Non-keratinocyte cells with clear or vacuolated cytoplasm are frequently observed in the epidermis of canine nipples. Most of these cells express cytokeratin (CK) CAM5.2, a marker of luminal epithelial cells. The morphological and immunohistochemical characteristics of these clear cells were investigated. Nipple tissue from 36 dogs of both sexes was collected and labelled immunohistochemically for CAM5.2, CK7, CK14, CK18, CK20, α-smooth muscle actin, p63, melan-A, E-cadherin, epidermal growth factor receptor and oestrogen receptor (OR). The intra-epidermal CAM5.2(+) clear cells were present singly or as small clusters, mostly within the basal layer, in 22 dogs (61%). These cells also expressed CK7, CK18, E-cadherin and OR. Electron microscopy revealed that some of these cells had surface microvilli. Multifocal proliferative lesions consisting of these cells were observed in the nipples of four dogs. In these lesions, proliferating cells formed bilayered tubules with CAM5.2(+) inner and CK14/p63(+) outer cells. This is the first report describing intra-epidermal CAM5.2(+) clear cells, distinct from melanocytes and Merkel cells in dog nipples. These cells might arise from the luminal epithelium of the papillary duct.

  19. Male breast cancer precursor lesions: analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

    PubMed

    Doebar, Shusma C; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H; Bartlett, John Ms; Tryfonidis, Konstantinos; Dijkstra, Nizet H; Schröder, Caroline P; van Asperen, Christi J; Linderholm, Barbro; Benstead, Kim; Dinjens, Winan Nm; van Marion, Ronald; van Diest, Paul J; Martens, John Wm; van Deurzen, Carolien Hm

    2017-04-01

    In men, data regarding breast cancer carcinogenesis are limited. The aim of our study was to describe the presence of precursor lesions adjacent to invasive male breast cancer, in order to increase our understanding of carcinogenesis in these patients. Central pathology review was performed for 1328 male breast cancer patients, registered in the retrospective joint analysis of the International Male Breast Cancer Program, which included the presence and type of breast cancer precursor lesions. In a subset, invasive breast cancer was compared with the adjacent precursor lesion by immunohistochemistry (n=83) or targeted next generation sequencing (n=7). Additionally, we correlated the presence of ductal carcinoma in situ with outcome. A substantial proportion (46.2%) of patients with invasive breast cancer also had an adjacent precursor lesion, mainly ductal carcinoma in situ (97.9%). The presence of lobular carcinoma in situ and columnar cell-like lesions were very low (<1%). In the subset of invasive breast cancer cases with adjacent ductal carcinoma in situ (n=83), a complete concordance was observed between the estrogen receptor, progesterone receptor, and HER2 status of both components. Next generation sequencing on a subset of cases with invasive breast cancer and adjacent ductal carcinoma in situ (n=4) showed identical genomic aberrations, including PIK3CA, GATA3, TP53, and MAP2K4 mutations. Next generation sequencing on a subset of cases with invasive breast cancer and an adjacent columnar cell-like lesion showed genomic concordance in two out of three patients. A multivariate Cox model for survival showed a trend that the presence of ductal carcinoma in situ was associated with a better overall survival, in particular in the Luminal B HER2+ subgroup. In conclusion, ductal carcinoma in situ is the most commonly observed precursor lesion in male breast cancer and its presence seems to be associated with a better outcome, in particular in Luminal B HER2+ cases

  20. Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab.

    PubMed

    O'Connell, John Edward; Bowe, Conor; Murphy, Colm; Toner, Mary; Kearns, Gerard J

    2015-11-01

    Giant cell lesions (GCLs), previously referred to as giant cell granulomas, are benign tumors of the jaws of unknown etiology. Surgical management of aggressive GCLs is challenging, as these lesions demonstrate a tendency to recur following surgical removal. In addition, surgical treatment can be associated with significant morbidity. In an attempt to reduce both the extent of morbidity and the recurrence rate following surgery, a number of pharmacologic therapies have been advocated on the basis of assumptions about the predominant cell types and receptors, for the management of these lesions. This report describes the use of denosumab, an agent originally used for its anti-resorptive effects, in the management of an aggressive GCL of the mandible in an older patient, who was unsuitable for extensive surgery and in whom treatment with intralesional triamcinolone had proved unsuccessful. Denosumab may be a viable alternative or adjunct to surgery in the management of GCLs of the jaws.

  1. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

    PubMed Central

    Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

    2009-01-01

    The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

  2. Nonequilibrium scale selection mechanism for columnar jointing

    PubMed Central

    Goehring, Lucas; Mahadevan, L.; Morris, Stephen W.

    2009-01-01

    Crack patterns in laboratory experiments on thick samples of drying cornstarch are geometrically similar to columnar joints in cooling lava found at geological sites such as the Giant's Causeway. We present measurements of the crack spacing from both laboratory and geological investigations of columnar jointing, and show how these data can be collapsed onto a single master scaling curve. This is due to the underlying mathematical similarity between theories for the cracking of solids induced by differential drying or by cooling. We use this theory to give a simple quantitative explanation of how these geometrically similar crack patterns arise from a single dynamical law rooted in the nonequilibrium nature of the phenomena. We also give scaling relations for the characteristic crack spacing in other limits consistent with our experiments and observations, and discuss the implications of our results for the control of crack patterns in thin and thick solid films. PMID:19129495

  3. Columnar self-assembly of colloidal nanodisks.

    PubMed

    Saunders, Aaron E; Ghezelbash, Ali; Smilgies, Detlef-M; Sigman, Michael B; Korgel, Brian A

    2006-12-01

    The self-assembly of sterically stabilized colloidal copper sulfide nanodisks, 14-20 nm in diameter and 5-7 nm thick, was studied. The nanodisks were observed by electron microscopy and small-angle X-ray scattering to form columnar arrays when evaporated as thin films from concentrated dispersions. These superstructured nanomaterials might give rise to technologically useful properties, such as anisotropic electrical transport and electrorheological and optical properties.

  4. Neutrophil Elastase Is Produced by Pulmonary Artery Smooth Muscle Cells and Is Linked to Neointimal Lesions

    PubMed Central

    Kim, Yu-Mee; Haghighat, Leila; Spiekerkoetter, Edda; Sawada, Hirofumi; Alvira, Cristina M.; Wang, Lingli; Acharya, Swati; Rodriguez-Colon, Gabriela; Orton, Andrew; Zhao, Mingming; Rabinovitch, Marlene

    2011-01-01

    Previously, we reported that murine gammaherpesvirus-68 (M1-MHV-68) induces pulmonary artery (PA) neointimal lesions in S100A4-overexpressing, but not in wild-type (C57), mice. Lesions were associated with heightened lung elastase activity and PA elastin degradation. We now investigate a direct relationship between elastase and PA neointimal lesions, the nature and source of the enzyme, and its presence in clinical disease. We found an association exists between the percentage of PAs with neointimal lesions and elastin fragmentation in S100A4 mice 6 months after viral infection. Confocal microscopy documented the heightened susceptibility of S100A4 versus C57 PA elastin to degradation by elastase. A transient increase in lung elastase activity occurs in S100A4 mice, 7 days after M1-MHV-68, unrelated to inflammation or viral load and before neointimal lesions. Administration of recombinant elafin, an elastase-specific inhibitor, ameliorates early increases in serine elastase and attenuates later development of neointimal lesions. Neutrophils are the source of elevated elastase (NE) in the S100A4 lung, and NE mRNA and protein levels are greater in PA smooth muscle cells (SMC) from S100A4 mice than from C57 mice. Furthermore, elevated NE is observed in cultured PA SMC from idiopathic PA hypertension versus that in control lungs and localizes to neointimal lesions. Thus, PA SMC produce NE, and heightened production and activity of NE is linked to experimental and clinical pulmonary vascular disease. PMID:21763677

  5. PCNA--a cell proliferation marker in vocal chord cancer. Part I: Premalignant laryngeal lesions.

    PubMed

    Pignataro, L D; Broich, G; Lavezzi, A M; Biondo, B; Ottaviani, F

    1995-01-01

    Laryngeal hyperkeratotic lesions can progress to fully developed malignant carcinoma in some cases. These premalignant lesions are proliferative disorders whose potential for further tumour progression is perhaps difficult to assess by mere histology. Immunostaining with PCNA, a protein correlated with cell proliferation, has been used to study tissue behavior in 30 cases of premalignant laryngeal vocal chord lesions treated by epithelial stripping in microlaryngoscopy, 15 of whom had no progression and 15 had recurrence and final development of full malignancy. The results showed a statistically significantly higher PCNA-index in the cases which underwent further tumour progression towards malignancy. PCNA testing may thus be suggested as a marker for tumour progression potential and help in determining clinical treatment choices.

  6. Differentiation of focal intrahepatic lesions with /sup 99m/Tc-red blood cell imaging

    SciTech Connect

    Engel, M.A.; Marks, D.S.; Sandler, M.A.; Shetty, P.

    1983-03-01

    The appearance of focal hepatic lesions on /sup 99m/Tc-sulfur colloid images is nonspecific. As it is important to distinguish hemangiomas from other lesions prior to biopsy, a prospective study was performed using /sup 99m/Tc-labeled red blood cells. Dynamic perfusion and delayed blood-pool images (1-2 hours) were obtained and lesion activity categorized as increased, equal, or decreased compared with the liver. Of 21 patients studied, 9 (43%) had one or more hepatic hemangiomas, and 8 of these 9 patients (89%) demonstrated increased blood-pool activity. The 12 nonhemangiomatous lesions consisted of 7 metastatic tumors, 2 hepatomas, 1 cirrhotic nodule, and 2 hepatic cysts. None of these 12 patients had increased activity on delayed blood-pool images. Early dynamic images of hepatic hemangiomas demonstrated variable activity (vascularity) and were not useful in differentiating hemangiomas from other lesions. Sensitivity was 89% and specificity 100%. Although liver enzymes are usually normal with hepatic hemangiomas, they may also be normal in metastatic disease. The authors recommend that delayed blood-pool imaging be performed prior to biopsy, particularly in patients without a known primary tumor or those with normal liver enzyme levels.

  7. Differentiation of focal intrahepatic lesions with 99mTc-red blood cell imaging

    SciTech Connect

    Engel, M.A.; Marks, D.S.; Sandler, M.A.; Shetty, P.

    1983-03-01

    The appearance of focal hepatic lesions on 99mTc-sulfur colloid images is nonspecific. As it is important to distinguish hemangiomas from other lesions prior to biopsy, a prospective study was performed using 99mTc-labeled red blood cells. Dynamic perfusion and delayed blood-pool images (1-2 hours) were obtained and lesion activity categorized as increased, equal, or decreased compared with the liver. Of 21 patients studied, 9 (43%) had one or more hepatic hemangiomas, and 8 of these 9 patients (89%) demonstrated increased blood-pool activity. The 12 nonhemangiomatous lesions consisted of 7 metastatic tumors, 2 hepatomas, 1 cirrhotic nodule, and 2 hepatic cysts. None of these 12 patients had increased activity on delayed blood-pool images. Early dynamic images of hepatic hemangiomas demonstrated variable activity (vascularity) and were not useful in differentiating hemangiomas from other lesions. Sensitivity was 89% and specificity 100%. Although liver enzymes are usually normal with hepatic hemangiomas, they may also be normal in metastatic disease. The authors recommend that delayed blood-pool imaging be performed prior to biopsy, particularly in patients without a known primary tumor or those with normal liver enzyme levels.

  8. Medial entorhinal cortex lesions only partially disrupt hippocampal place cells and hippocampus-dependent place memory

    PubMed Central

    Hales, Jena B; Schlesiger, Magdalene I; Leutgeb, Jill K; Squire, Larry R; Leutgeb, Stefan; Clark, Robert E

    2014-01-01

    SUMMARY Entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired at acquiring the watermaze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, MEC is not necessary for all types of spatial coding, nor for all types of hippocampus-dependent memory, but is necessary for the normal acquisition of place memory. PMID:25437546

  9. Multinucleate Giant Cells in FNAC of Benign Breast Lesions: Its Significance

    PubMed Central

    R, Kalyani; Murthy V, Srinivasa

    2014-01-01

    Background: Multinucleate giant cells are described in breast aspirates. However, due to its rarity very few cases have been described cytologically. Hence recognition and correct interpretation of their presence is difficult, yet crucial for accurate diagnosis. Materials and Methods: The prospective study of FNAC (fine needle aspirate cytology) of breast lumps was conducted for a period of six months. Direct smears were prepared from the material aspirated. In case of fluid aspirates, centrifuge done and cell sediment was used for making smears. Smears were alcohol fixed and stained with PAP/H&E or air dried smears were stained with Leishman stain. Further smears were subjected to immunocytochemistry using vimentin and CD34 markers to know the origin of multinucleate giant cells. Results: We have reported 11 cases of breast lesions, which showed multinucleate giant cells on FNAC. Out of the 11 cases, Cytologically six cases showed granuloma debris with relative proportion of epithelioid histiocytes, lymphocytes, neutrophils and multinucleate giant cells. Two cases were diagnosed as acute suppurative granulomatous mastitis. Two cases of fibroadenoma and one case of fat necrosis showed multinucleate giant cells. Immunocytochemistry showed vimentin positivity in both stromal and histiocytic type of multinucleate giant cells and in isolated histiocytes. CD34 was focally positive in histiocytic type of giant cells. Conclusion: An effort is made to distinguish between the stromal and histiocytic type giant cells in non-neoplastic breast lesions. Further molecular studies have to be done to know the exact histogenesis and role of these multinucleate giant cells in benign lesions. PMID:25653953

  10. Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells

    PubMed Central

    Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter; Young, Antony R.

    2011-01-01

    Photochemotherapy—in which a photosensitizing drug is combined with ultraviolet or visible radiation—has proven therapeutic effectiveness. Existing approaches have drawbacks, however, and there is a clinical need to develop alternatives offering improved target cell selectivity. DNA substitution by 4-thiothymidine (S4TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we demonstrate that UVA photoactivation of DNA S4TdR does not generate reactive oxygen or cause direct DNA breakage and is only minimally mutagenic. In an organotypic human skin model, UVA penetration is sufficiently robust to kill S4TdR-photosensitized epidermal cells. We have investigated the DNA lesions responsible for toxicity. Although thymidine is the predominant UVA photoproduct of S4TdR in dilute solution, more complex lesions are formed when S4TdR-containing oligonucleotides are irradiated. One of these, a thietane/S5-(6-4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py] photoproducts induced by UVB/C radiation. These lesions are detectable in DNA from S4TdR/UVA-treated cells and are excised from DNA more efficiently by keratinocytes than by leukaemia cells. UVA irradiation also induces DNA interstrand crosslinking of S4TdR-containing duplex oligonucleotides. Cells defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are extremely sensitive to S4TdR/UVA indicating that these lesions contribute significantly to S4TdR/UVA cytotoxicity. PMID:21890905

  11. Systemic B-cell lymphoma presenting as an isolated lesion on the ear.

    PubMed

    Darvay, A; Russell-Jones, R; Acland, K M; Lampert, I; Chu, A C

    2001-03-01

    We report a case of systemic B-cell lymphoma that presented as an isolated cutaneous lesion on the ear, mimicking a primary cutaneous B-cell lymphoma. Although there was no clinical evidence of systemic disease, bone marrow involvement was found on further investigation and subsequent immunoglobulin gene analysis revealed an identical clone in the skin lesion and bone marrow aspirate. Evidence of a t(14 : 18) translocation was not identified. This case is unusual for several reasons. First, involvement of the pinna as a presenting feature of systemic lymphoma has not been reported previously. Second, the cutaneous lesion had been present for 3 years prior to diagnosis and there has been no clinical progression of systemic lymphoma during 2 years of follow-up. Third, the lymphoma does not correspond exactly to any of the entities in the REAL classification of systemic B-cell lymphoma. This case underlines the indolent nature of some systemic B-cell lymphomas and the need to investigate thoroughly patients with disease apparently confined to the skin.

  12. [Observation of cells tolerant of tobacco mosaic virus in virus-induced local lesions in Datura stramonium L. leaves].

    PubMed

    Reunov, A V; Lega, S N; Nagorskaia, V P; Lapshina, L A

    2011-01-01

    Ultrastructural examination of tobacco mosaic virus-induced local lesions developing in leaves of Datura stramonium plants demonstrated that, in the central area of the lesions, the cell response to viral invasion was not uniform. Most cells exhibited an acute hypersensitive reaction and underwent rapid and complete necrosis. However, some cells, despite considerable virus accumulation and immediate contact with completely collapsed cells, maintained a certain degree of structural integrity. Analysis performed showed that the proportion of collapsed and uncollapsed cells in the lesion centre 3 to 5 days after infection did not change essentially. These data suggest that the absence of hypersensitive response in some cells in the lesion centre is not due to an early stage of infection but is likely caused by cell tolerance of the virus.

  13. BUBR1 expression in benign oral lesions and squamous cell carcinomas: correlation with human papillomavirus.

    PubMed

    Lira, Régia C P; Miranda, Fabiana A; Guimarães, Márcia C M; Simões, Renata T; Donadi, Eduardo A; Soares, Christiane P; Soares, Edson G

    2010-04-01

    Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, an important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also a significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence on BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC, but not in benign oral lesions.

  14. Glutathione Depletion and Carbon Ion Radiation Potentiate Clustered DNA Lesions, Cell Death and Prevent Chromosomal Changes in Cancer Cells Progeny

    PubMed Central

    Hanot, Maïté; Boivin, Anthony; Malésys, Céline; Beuve, Michaël; Colliaux, Anthony; Foray, Nicolas; Douki, Thierry; Ardail, Dominique; Rodriguez-Lafrasse, Claire

    2012-01-01

    Poor local control and tumor escape are of major concern in head-and-neck cancers treated by conventional radiotherapy or hadrontherapy. Reduced glutathione (GSH) is suspected of playing an important role in mechanisms leading to radioresistance, and its depletion should enable oxidative stress insult, thereby modifying the nature of DNA lesions and the subsequent chromosomal changes that potentially lead to tumor escape. This study aimed to highlight the impact of a GSH-depletion strategy (dimethylfumarate, and l-buthionine sulfoximine association) combined with carbon ion or X-ray irradiation on types of DNA lesions (sparse or clustered) and the subsequent transmission of chromosomal changes to the progeny in a radioresistant cell line (SQ20B) expressing a high endogenous GSH content. Results are compared with those of a radiosensitive cell line (SCC61) displaying a low endogenous GSH level. DNA damage measurements (γH2AX/comet assay) demonstrated that a transient GSH depletion in resistant SQ20B cells potentiated the effects of irradiation by initially increasing sparse DNA breaks and oxidative lesions after X-ray irradiation, while carbon ion irradiation enhanced the complexity of clustered oxidative damage. Moreover, residual DNA double-strand breaks were measured whatever the radiation qualities. The nature of the initial DNA lesions and amount of residual DNA damage were similar to those observed in sensitive SCC61 cells after both types of irradiation. Misrepaired or unrepaired lesions may lead to chromosomal changes, estimated in cell progeny by the cytome assay. Both types of irradiation induced aberrations in nondepleted resistant SQ20B and sensitive SCC61 cells. The GSH-depletion strategy prevented the transmission of aberrations (complex rearrangements and chromosome break or loss) in radioresistant SQ20B only when associated with carbon ion irradiation. A GSH-depleting strategy combined with hadrontherapy may thus have considerable advantage in the

  15. Glutathione depletion and carbon ion radiation potentiate clustered DNA lesions, cell death and prevent chromosomal changes in cancer cells progeny.

    PubMed

    Hanot, Maïté; Boivin, Anthony; Malésys, Céline; Beuve, Michaël; Colliaux, Anthony; Foray, Nicolas; Douki, Thierry; Ardail, Dominique; Rodriguez-Lafrasse, Claire

    2012-01-01

    Poor local control and tumor escape are of major concern in head-and-neck cancers treated by conventional radiotherapy or hadrontherapy. Reduced glutathione (GSH) is suspected of playing an important role in mechanisms leading to radioresistance, and its depletion should enable oxidative stress insult, thereby modifying the nature of DNA lesions and the subsequent chromosomal changes that potentially lead to tumor escape.This study aimed to highlight the impact of a GSH-depletion strategy (dimethylfumarate, and L-buthionine sulfoximine association) combined with carbon ion or X-ray irradiation on types of DNA lesions (sparse or clustered) and the subsequent transmission of chromosomal changes to the progeny in a radioresistant cell line (SQ20B) expressing a high endogenous GSH content. Results are compared with those of a radiosensitive cell line (SCC61) displaying a low endogenous GSH level. DNA damage measurements (γH2AX/comet assay) demonstrated that a transient GSH depletion in resistant SQ20B cells potentiated the effects of irradiation by initially increasing sparse DNA breaks and oxidative lesions after X-ray irradiation, while carbon ion irradiation enhanced the complexity of clustered oxidative damage. Moreover, residual DNA double-strand breaks were measured whatever the radiation qualities. The nature of the initial DNA lesions and amount of residual DNA damage were similar to those observed in sensitive SCC61 cells after both types of irradiation. Misrepaired or unrepaired lesions may lead to chromosomal changes, estimated in cell progeny by the cytome assay. Both types of irradiation induced aberrations in nondepleted resistant SQ20B and sensitive SCC61 cells. The GSH-depletion strategy prevented the transmission of aberrations (complex rearrangements and chromosome break or loss) in radioresistant SQ20B only when associated with carbon ion irradiation. A GSH-depleting strategy combined with hadrontherapy may thus have considerable advantage in the

  16. Identification of candidate microbial sequences from inflammatory lesion of giant cell arteritis.

    PubMed

    Gordon, Lynn K; Goldman, Melissa; Sandusky, Hallie; Ziv, Nurit; Hoffman, Gary S; Goodglick, Todd; Goodglick, Lee

    2004-06-01

    Giant cell arteritis (GCA) is a granulomatous inflammatory disease of medium and large arteries which is prevalent in the elderly population. The etiology of GCA is unknown, although the immunologic features suggest the possible presence of a microorganism. Our group has examined whether microbial DNA fragments were present at GCA lesions and whether such microbial fragments could be associated with disease pathogenesis. Initial identification of microbial sequences was performed using genomic representational difference analysis (RDA). Laser dissecting microscopy was used to isolate cells from GCA lesions and adjacent uninvolved temporal artery. Using genomic RDA, we isolated 10 gene fragments; three of these sequences had high homology with prokaryotic genes and were considered high-priority candidates for further study. An examination of serum from GCA(+) individuals (in contrast to healthy age-matched controls) showed the presence of IgG which recognized in vitro translated proteins from these clones.

  17. Anomalous columnar order of charged colloidal platelets.

    PubMed

    Morales-Anda, L; Wensink, H H; Galindo, A; Gil-Villegas, A

    2012-01-21

    Monte Carlo computer simulations are carried out for a model system of like-charged colloidal platelets in the isothermal-isobaric ensemble (NpT). The aim is to elucidate the role of electrostatic interactions on the structure of synthetic clay systems at high particle densities. Short-range repulsions between particles are described by a suitable hard-core model representing a discotic particle. This potential is supplemented with an electrostatic potential based on a Yukawa model for the screened Coulombic potential between infinitely thin disklike macro-ions. The particle aspect-ratio and electrostatic parameters were chosen to mimic an aqueous dispersion of thin, like-charged, rigid colloidal platelets at finite salt concentration. An examination of the fluid phase diagram reveals a marked shift in the isotropic-nematic transition compared to the hard cut-sphere reference system. Several statistical functions, such as the pair correlation function for the center-of-mass coordinates and structure factor, are obtained to characterize the structural organization of the platelets phases. At low salinity and high osmotic pressure we observe anomalous hexagonal columnar structures characterized by interpenetrating columns with a typical intercolumnar distance corresponding to about half of that of a regular columnar phase. Increasing the ionic strength leads to the formation of glassy, disordered structures consisting of compact clusters of platelets stacked into finite-sized columns. These so-called "nematic columnar" structures have been recently observed in systems of charge-stabilized gibbsite platelets. Our findings are corroborated by an analysis of the static structure factor from a simple density functional theory.

  18. Function of Sox2 in ependymal cells of lesioned spinal cords in adult zebrafish.

    PubMed

    Ogai, Kazuhiro; Nakatani, Kumi; Hisano, Suguru; Sugitani, Kayo; Koriyama, Yoshiki; Kato, Satoru

    2014-11-01

    The sex-determining region Y-box 2 (Sox2) is related not only to pluripotency, but also to cell proliferation. Zebrafish can regain their motor function after spinal cord injury (SCI). Following SCI, new motor neurons are produced from proliferating ependymal cells. Here, we investigated the expression and function of Sox2 after SCI in zebrafish. Sox2 was upregulated as early as 1 day post-lesion (dpl) in ependymal cells, which was followed by cell proliferation. Sox2 knockdown significantly decreased the number of proliferating cells at 5dpl. The results of this study suggest a role of Sox2 as one of the proliferation initiators in ependymal cells after SCI.

  19. Perivascular inflammatory cells in ovine Visna/maedi encephalitis and their possible role in virus infection and lesion progression.

    PubMed

    Polledo, Laura; González, Jorge; Benavides, Julio; Martínez-Fernández, Beatriz; Ferreras, Ma Carmen; Marín, Juan F García

    2012-12-01

    We examined the distribution in the perivascular spaces of Visna/maedi antigen, T cells (CD3+, CD4+ and CD8+), B cells and macrophages by immunohistochemistry in 22 natural cases of Visna/maedi encephalitis. Sheep showed lymphocytic or histiocytic lesions. In mild lymphocytic lesions, the viral antigen was detected in perivascular cuffs where CD8+ T cells predominated, but in severe lymphocytic lesions, sparse antigen was identified, and CD8+/CD4+ T cells appeared in a similar proportion in multilayer perivascular sleeves. In histiocytic lesions, vessels were surrounded by macrophages with abundant viral antigen, with CD8+/CD4+ T cells and B cells in the periphery. These results could reflect different stages of virus neuroinvasion and clarify the neuropathogenesis of Visna/maedi encephalitis.

  20. Cytometric measurement of cell proliferation in echo-guided biopsies from focal lesions of the liver.

    PubMed

    Faccioli, S; Chieco, P; Gramantieri, L; Stecca, B A; Bolondi, L

    1996-02-01

    Increased proliferative activity determined in surgical specimens of hepatocellular carcinoma (HCC) has been associated with tumor grade and patient survival. The measurement of cell proliferation in echo-guided biopsies of small focal liver lesions might provide useful information for the early recognition of malignancy and for predicting the aggressiveness of small HCCs. We assessed the diagnostic and prognostic value of cell proliferation in 91 echo-guided needle biopsies of focal liver lesions using the monoclonal antibody Ki-67, which detects a human nuclear antigen that is present in proliferating cells. Measurements were performed by image cytometry as the percentage of Ki-67 positive hepatocytes nuclei over total hepatocyte nuclei in the biopsy. At the histological examination, 27 lesions were diagnosed as chronic hepatitis, 10 as cirrhosis, 11 as macroregenerative nodule, and 43 as HCC in cirrhotic liver. Although the highest Ki-67 values (> 20%) were found in less-differentiated HCCs, most well-differentiated HCCs and nine borderline nodules were completely devoid of Ki-67-positive hepatocytes. A sustained Ki-67 labeling (up to 16%) was found in hepatitis and cirrhosis, similar to that found in several malignant tumors. In the HCC subset, Ki-67 labeling was strongly correlated to the Edmondson-Steiner histological grade. However, survival analysis did not indicate a better outcome for those patients with low-proliferating tumors.

  1. Diminished number or complete loss of myoepithelial cells associated with metaplastic and neoplastic apocrine lesions of the breast.

    PubMed

    Tramm, Trine; Kim, Jee-Yeon; Tavassoli, Fattaneh A

    2011-02-01

    The presence of myoepithelial (ME) cells is considered an important feature in the vast majority of benign breast lesions. Recently, a case showing the absence of myoepithelium in a mammary duct with apocrine metaplasia was reported. To investigate the status of ME cells associated with apocrine metaplasia, the distribution of ME cells in 59 metaplastic and intraductal proliferative apocrine lesions was evaluated using immunohistochemical expression of p63 and Calponin. p63 showed a diminished number of ME cells and increased intermyoepithelial nuclear distance in ducts with all variants of apocrine metaplasia and proliferation compared with normal glands. In the majority of cases, Calponin showed a continuous ME layer. In 6 cases, including an apocrine papilloma, there were definitive ME gaps confirmed by both markers, in the absence of atypia and with preservation of the basement membrane. In all cases, there was frequent heterogeneity in the distribution of ME cells in ducts harboring apocrine cells and even in various papillae within papillary lesions. In summary, benign and noninvasive apocrine lesions can show reduction and occasional complete loss of ME cells. This observation is particularly important when evaluating apocrine papillary proliferations, in which the absence of ME cells may lead to overdiagnosis of atypia and/or malignancy. The observation suggests that at least 2 ME markers should be used when evaluating apocrine lesions, and that a malignant diagnosis should be based on features of the proliferating cells until more data become available on the significance, if any, of the absence of ME cells in apocrine lesions.

  2. Squamous cell carcinoma arising from an oral lichenoid lesion: a case report.

    PubMed

    Taghavi Zenouz, Ali; Mehdipour, Masoumeh; Attaran, Rana; Bahramian, Ayla; Emamverdi Zadeh, Paria

    2012-01-01

    Lichenoid reactions represent a family of lesions with different etiologic factors and a common clinical and histologic ap-pearance. Lichen planus is included with lichenoid reactions and is a relatively common chronic mucocutaneous disorder. The most important complication of lichenoid reactions is the possibility of malignant transformation. That is why it has been considered a precancerous condition. Although the malignant transformation rate varies widely in the literature, from 0.4 to 6.5 percent, in most studies it does not exceed 1%. The aim of this paper is to report a rare case of squamous cell car-cinoma (SCC) arising within an oral lichenoid lesion in a 17-year-old woman, where SCC is very uncommon. The patient did not have any risk factors and was healthy. The lesion was located on the border of the tongue. In view of thecommon occurrence of OLP (oral lichen planus) and the unresolved issues regarding its premalignant potential, this case report illus-trates the need for histologic confirmation and a close follow-up of clinical lesions with lichenoid features.

  3. Langerhans cell histiocytosis with multifocal bone lesions: comparative clinical features between single and multi-systems.

    PubMed

    Imashuku, Shinsaku; Kinugawa, Naoko; Matsuzaki, Akinobu; Kitoh, Toshiyuki; Ohki, Kentaro; Shioda, Yoko; Tsunematsu, Yukiko; Imamura, Toshihiko; Morimoto, Akira

    2009-11-01

    Langerhans cell histiocytosis (LCH) can be a single system or multi-system disease. Both disease types can be associated with multi-focal bone lesions, but their bone involvement patterns have not been compared systematically. Of the new pediatric LCH cases enrolled into the JLSG-02 study during 2002-2007, 67 cases of single system multifocal bone (SMFB) LCH and 97 cases of multi-system bone (MSB) LCH were analyzed to determine if the bone involvement patterns differ in these two types, and whether these differences correlate with outcome. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and other measures. Onset ages were higher for SMFB (P < 0.001), but the two types did not differ in the number of bone lesions per patient. The skull was most frequently affected in both types, followed by the spine. Lesions in the temporal bone (P = 0.002), ear-petrous bone (P < 0.001), orbita (P = 0.003), and zygomatic bone (P = 0.016) were significantly more common in MSB. The two types did not differ in response to treatment, but MSB was associated with a significantly higher incidence of diabetes insipidus (DI) (P < 0.001). Novel measures are required in preventing the development of DI in MSB-type LCH patients with "risk" bone lesions.

  4. Molluscum Contagiosum Virus Transcriptome in Abortively Infected Cultured Cells and a Human Skin Lesion

    PubMed Central

    Mendez-Rios, Jorge D.; Yang, Zhilong; Erlandson, Karl J.; Cohen, Jeffrey I.; Martens, Craig A.; Bruno, Daniel P.; Porcella, Stephen F.

    2016-01-01

    ABSTRACT Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model or a cell culture replication system. We used next-generation sequencing to analyze and compare polyadenylated RNAs from abortive MOCV infections of several cell lines and a human skin lesion. Viral RNAs were detected for 14 days after MOCV infection of cultured cells; however, there was little change in the RNA species during this time and a similar pattern occurred in the presence of an inhibitor of protein synthesis, indicating a block preventing postreplicative gene expression. Moreover, a considerable number of MOCV RNAs mapped to homologs of orthopoxvirus early genes, but few did so to homologs of intermediate or late genes. The RNAs made during in vitro infections represent a subset of RNAs detected in human skin lesions which mapped to homologs of numerous postreplicative as well as early orthopoxvirus genes. Transfection experiments using fluorescent protein and luciferase reporters demonstrated that vaccinia virus recognized MOCV intermediate and late promoters, indicating similar gene regulation. The specific recognition of the intermediate promoter in MOCV-infected cells provided evidence for the synthesis of intermediate transcription factors, which are products of early genes, but not for late transcription factors. Transcriptome sequencing (RNA-seq) and reporter gene assays may be useful for testing engineered cell lines and conditions that ultimately could provide an in vitro replication system. IMPORTANCE The inability to propagate molluscum contagiosum virus, which causes benign skin lesions in young children and more extensive infections in immunosuppressed adults, has constrained our understanding of the biology of this human

  5. β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

    PubMed Central

    Zwolanek, Daniela; Flicker, Magdalena; Kirstätter, Elisabeth; Zaucke, Frank; van Osch, Gerjo J.V.M.; Erben, Reinhold G.

    2015-01-01

    Abstract Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a β1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely β1 integrin-mediated, whereby both RGD- and collagen-binding integrins are involved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future. PMID:26309781

  6. The incomplete ordering of columnar fracture

    NASA Astrophysics Data System (ADS)

    Goehring, Lucas; Morris, Stephen

    2004-03-01

    Columnar fracture has been studied for centuries, and occurs in a wide range of media, from lava, to glass and starch. The best known examples of such fracture patterns include the basalts of the Giant's Causeway in N. Ireland, and the Devil's Postpile in California. Recently, we have performed experiments on columnar fracture in corn starch, which have lead to a fully three dimensional characterization of this pattern. It has been traditionally believed that a colonnade, in cross-section, tends toward a perfectly ordered hexagonal lattice (Budkewitsch & Robin, 1993), or some nearby local minima in energy (Jagla and Rojo, 2002). However, we show that the disorder in this pattern does not vanish, but tends toward a large, limiting value. Statistical quantification of this residual disorder, in two very different systems, desiccated starch and convectively cooled lava, tend toward identical, constant values. We can demonstrate that there is a strong ordering process for patterns that are more disordered than this limiting case. This suggests that residual disorder is inherent to this natural pattern.

  7. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

    PubMed Central

    Dartois, Véronique

    2015-01-01

    For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. However, most currently used anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution, and this has contributed to the long duration and limited success of current therapies. In this Progress article, I describe new methods to quantify and image drug distribution in infected lung tissue and in mycobacterial cells, and I explore how this technology could be used to design optimized multidrug regimens. PMID:24487820

  8. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  9. Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

    PubMed

    González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

    2008-01-01

    It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.

  10. /sup 99m/Tc red blood cell scintigraphy in evaluating focal liver lesions

    SciTech Connect

    Rabinowitz, S.A.; McKusick, K.A.; Strauss, H.W.

    1984-07-01

    To determine the accuracy of blood-pool imaging in the diagnosis of hepatic hemangiomas, 39 patients with various focal hepatic lesions were studied. The diagnoses in these patients were made by biopsy, angiography, surgical exploration, or clinical stability for a minimum of 14 months. The diagnoses were: hemangiomas (13 patients), hepatoma (three), metastases (19), abscesses (two), and liver cysts (two). After modified in vivo labeling of red blood cells with 20 mCi (740 MBq) of /sup 99m/Tc pertechnetate, an initial flow study and early (1-15 min) and delayed (1-2 hr) static images were obtained. Increased blood-pool activity with a discordant flow pattern was seen in 11 of 13 patients with hemangiomas. False-negative scans occurred in two hemangiomas with extensive fibrosis. None of the metastatic, abscess, or cystic lesions had increased blood-pool activity at any time after injection. It is concluded that /sup 99m/Tc red blood cell imaging can distinguish hemangiomas from other focal liver lesions.

  11. 99mTc red blood cell scintigraphy in evaluating focal liver lesions

    SciTech Connect

    Rabinowitz, S.A.; McKusick, K.A.; Strauss, H.W.

    1984-07-01

    To determine the accuracy of blood-pool imaging in the diagnosis of hepatic hemangiomas, 39 patients with various focal hepatic lesions were studied. The diagnoses in these patients were made by biopsy, angiography, surgical exploration, or clinical stability for a minimum of 14 months. The diagnoses were: hemangiomas (13 patients), hepatoma (three), metastases (19), abscesses (two), and liver cysts (two). After modified in vivo labeling of red blood cells with 20 mCi (740 MBq) of 99mTc pertechnetate, an initial flow study and early (1-15 min) and delayed (1-2 hr) static images were obtained. Increased blood-pool activity with a discordant flow pattern was seen in 11 of 13 patients with hemangiomas. False-negative scans occurred in two hemangiomas with extensive fibrosis. Two of three hepatomas had increased blood-pool activity associated with increased flow in a pattern identical to the increased blood-pool activity. None of the metastatic, abscess, or cystic lesions had increased blood-pool activity at any time after injection. It is concluded that 99mTc red blood cell imaging can distinguish hemangiomas from other focal liver lesions.

  12. Metabolites of the biocide o-phenylphenol generate oxidative DNA lesions in V 79 cells.

    PubMed

    Henschke, P; Almstadt, E; Lüttgert, S; Appel, K E

    2000-01-01

    Incubation of the o-phenylphenol (OPP) metabolites, o-phenylhydroquinone (PHQ) and o-phenylbenzoquinone (PBQ) with V 79 Chinese hamster cells led to a significant enhancement of the amount of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in nuclear DNA. With OPP no distinct induction of this lesion could be observed. In addition, PHQ and PBQ were able to generate DNA single-strand breaks (DNA SSB), while OPP failed to induce this lesion. All incubations were performed for 1 h without exogenous metabolic activations and the lowest effective concentration tested was 20 microM. It is concluded that these metabolites may contribute to the carcinogenicity of OPP and sodium o-phenylphenolate (SOPP) observed in rats, by generating reactive oxygen species (ROS) through their redox cycling properties.

  13. A Comparative Study of Immunohistochemical Myoepithelial Cell Markers in Cutaneous Benign Cystic Apocrine Lesions.

    PubMed

    Wood, Andrew; Houghton, Sinatra L; Biswas, Asok

    2016-07-01

    The use of immunohistochemical markers for myoepithelial cells (MEC) is a useful tool in the distinction of benign from malignant epithelial neoplasms. Although their use in breast tumors is well recognized, little is known concerning its application in comparable cutaneous lesions. Using benign cutaneous cystic apocrine lesions as a study model, the aim of this study was to compare 5 immunohistochemical markers [calponin, p63, smooth muscle actin (SMA), cytokeratin 14, and CD10] in their effectiveness to highlight MEC. Cases of apocrine hidrocystoma and cystadenoma (n = 44) were reviewed with a particular emphasis on proliferative features and apocrine change. The MEC staining pattern and the intensity and distribution scores in proliferative (n = 29) and nonproliferative (n = 15) lesions were assessed, and the differences between the 2 groups were statistically analyzed using Fisher exact test. Calponin and SMA stained MEC in the most consistent manner. Being a nuclear stain, p63 was easy to interpret but typically showed discontinuous staining. Cytokeratin 14 not only effectively highlighted MEC but also stained some luminal epithelial cells in an unpredictable manner. Because of prominent background dermal fibroblast staining, CD10 was often difficult to interpret. Only SMA and p63 showed a statistically significant difference in MEC staining intensity scores between the proliferative and nonproliferative groups. Our results show that immunohistological staining for MEC in benign cystic apocrine lesions of the skin is variable. The authors recommend that a panel of markers that includes calponin and p63 be used and highlight the need for awareness of specific caveats associated with individual markers.

  14. VIRULENCE OF Flavobacterium columnare GENOMOVARS IN RAINBOW TROUT (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the causative agent of columnaris disease and is responsible for significant economic losses in aquaculture. F. columnare is a Gram-negative bacterium, and five genetic types or genomovars have been described based on restriction fragment length polymorphism of the 16S rR...

  15. Virulence of Flavobacterium columnare genomovars in rainbow trout Oncorhynchus mykiss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the causative agent for columnaris disease and responsible for significant economic loss in the aquaculture industry. F. columnare is a gram negative bacteria with several genomovar classifications, based on the restriction fragment length polymorphism of the 16S rDNA gen...

  16. Multiplex PCR for rapid genotyping of Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, caused by the Gram-negative bacterium Flavobacterium columnare, is one of the leading causes of disease losses to the catfish industry in the Southeast USA. Recent research in our laboratory has deciphered the genetic diversity among F. columnare isolates through whole genome seq...

  17. Genomovars and genomes: Deciphering the genetic diversity of Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, caused by the Gram-negative bacterium Flavobacterium columnare, is one of the leading causes of disease losses to the catfish industry in the Southeast USA. An exceptionally high level of genetic diversity among isolates of F. columnare has long been recognized, yet very little h...

  18. Parasite treatment reduced Flavobacterium columnare infection in tilapia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterium Flavobacterium columnare and parasite Trichodina are common pathogens of cultured fish. The authors conducted a study to evaluate whether treatment of Trichodina parasitized tilapia with formalin would improve fish survival and reduce F. columnare infection in fish. Tilapia parasitized by...

  19. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions.

    PubMed

    Rhim, Andrew D; Thege, Fredrik I; Santana, Steven M; Lannin, Timothy B; Saha, Trisha N; Tsai, Shannon; Maggs, Lara R; Kochman, Michael L; Ginsberg, Gregory G; Lieb, John G; Chandrasekhara, Vinay; Drebin, Jeffrey A; Ahmad, Nuzhat; Yang, Yu-Xiao; Kirby, Brian J; Stanger, Ben Z

    2014-03-01

    Hematogenous dissemination is thought to be a late event in cancer progression. We recently showed in a genetic model of pancreatic ductal adenocarcinoma that pancreas cells can be detected in the bloodstream before tumor formation. To confirm these findings in humans, we used microfluidic geometrically enhanced differential immunocapture to detect circulating pancreas epithelial cells in patient blood samples. We captured more than 3 circulating pancreas epithelial cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These findings indicate that cancer cells are present in the circulation of patients before tumors are detected, which might be used in risk assessment.

  20. Effects of Cultured Adrenal Chromaffin Cell Implants on Hindlimb Reflexes of the 6-OHDA Lesioned Rat

    PubMed Central

    Pulford, Bruce E.; Mihajlov, Andrea R.; Nornes, Howard O.; Whalen, L. Ray

    1994-01-01

    The effects of implantation of cultured adrenal medullary cells on the recovery of neurotransmitter specific reflex activity were studied in the rat spinal cord using electrophysiological testing methods. Cell suspensions of cultured neonatal adrenal medullary chromaffin (AM) cells (which produce catecholamines), or Schwann (Sc) cells (controls) were implanted into the lumbar region of the spinal cord 2 weeks after catecholamine (CA) denervation by intracisternal injection of 6-hydroxydopamine (6-OHDA). All cells were taken from 7 day neonates and cultured for 10 days in the presence of nerve growth factor (NGF). Three months after implantation, the extent of implant-associated recovery of reflex activity was determined by measuring electromyogram (EMG) activity and force associated with the long latency component of the hindlimb withdrawal reflex (which is CA modulated). After the electrophysiological testing, rats were anesthetized, and the spinal cords were rapidly removed and frozen. Spinal cords were sectioned longitudinally, and implanted cells were visualized using glyoxylic acid techniques. Labelled sections were examined to determine cell survival. Results indicate that 1) chromaffin cells survive for 3 months in the segments of the cord into which they have been implanted and 2) rats implanted with AM cells have significantly more forceful withdrawal reflexes than those that received Sc cells or received no implant after lesioning. PMID:7703294

  1. Histological Lesions, Cell Cycle Arrest, Apoptosis and T Cell Subsets Changes of Spleen in Chicken Fed Aflatoxin-contaminated Corn

    PubMed Central

    Peng, Xi; Zhang, Keying; Bai, Shiping; Ding, Xuemei; Zeng, Qiufeng; Yang, Jun; Fang, Jing; Chen, Kejie

    2014-01-01

    The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen. PMID:25141002

  2. Omics markers of the red cell storage lesion and metabolic linkage

    PubMed Central

    D’Alessandro, Angelo; Nemkov, Travis; Reisz, Julie; Dzieciatkowska, Monika; Wither, Matthew J.; Hansen, Kirk C.

    2017-01-01

    The introduction of omics technologies in the field of Transfusion Medicine has significantly advanced our understanding of the red cell storage lesion. While the clinical relevance of such a lesion is still a matter of debate, quantitative and redox proteomics approaches, as well quantitative metabolic flux analysis and metabolic tracing experiments promise to revolutionise our understanding of the role of blood processing strategies, inform the design and testing of novel additives or technologies (such as pathogen reduction), and evaluate the clinical relevance of donor and recipient biological variability with respect to red cell storability and transfusion outcomes. By reviewing existing literature in this rapidly expanding research endeavour, we highlight for the first time a correlation between metabolic markers of the red cell storage age and protein markers of haemolysis. Finally, we introduce the concept of metabolic linkage, i.e. the appreciation of a network of highly correlated small molecule metabolites which results from biochemical constraints of erythrocyte metabolic enzyme activities. For the foreseeable future, red cell studies will advance Transfusion Medicine and haematology by addressing the alteration of metabolic linkage phenotypes in response to stimuli, including, but not limited to, storage additives, enzymopathies (e.g. glucose 6-phosphate dehydrogenase deficiency), hypoxia, sepsis or haemorrhage. PMID:28263171

  3. Computer-aided vaccine designing approach against fish pathogens Edwardsiella tarda and Flavobacterium columnare using bioinformatics softwares

    PubMed Central

    Mahendran, Radha; Jeyabaskar, Suganya; Sitharaman, Gayathri; Michael, Rajamani Dinakaran; Paul, Agnal Vincent

    2016-01-01

    Edwardsiella tarda and Flavobacterium columnare are two important intracellular pathogenic bacteria that cause the infectious diseases edwardsiellosis and columnaris in wild and cultured fish. Prediction of major histocompatibility complex (MHC) binding is an important issue in T-cell epitope prediction. In a healthy immune system, the T-cells must recognize epitopes and induce the immune response. In this study, T-cell epitopes were predicted by using in silico immunoinformatics approach with the help of bioinformatics tools that are less expensive and are not time consuming. Such identification of binding interaction between peptides and MHC alleles aids in the discovery of new peptide vaccines. We have reported the potential peptides chosen from the outer membrane proteins (OMPs) of E. tarda and F. columnare, which interact well with MHC class I alleles. OMPs from E. tarda and F. columnare were selected and analyzed based on their antigenic and immunogenic properties. The OMPs of the genes TolC and FCOL_04620, respectively, from E. tarda and F. columnare were taken for study. Finally, two epitopes from the OMP of E. tarda exhibited excellent protein–peptide interaction when docked with MHC class I alleles. Five epitopes from the OMP of F. columnare had good protein–peptide interaction when docked with MHC class I alleles. Further in vitro studies can aid in the development of potential peptide vaccines using the predicted peptides. PMID:27284239

  4. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

    PubMed

    Ufimtseva, Elena

    2015-01-01

    Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

  5. Myelin-specific T cells induce interleukin-1beta expression in lesion-reactive microglial-like cells in zones of axonal degeneration.

    PubMed

    Grebing, Manuela; Nielsen, Helle H; Fenger, Christina D; T Jensen, Katrine; von Linstow, Christian U; Clausen, Bettina H; Söderman, Martin; Lambertsen, Kate L; Thomassen, Mads; Kruse, Torben A; Finsen, Bente

    2016-03-01

    Infiltration of myelin-specific T cells into the central nervous system induces the expression of proinflammatory cytokines in patients with multiple sclerosis (MS). We have previously shown that myelin-specific T cells are recruited into zones of axonal degeneration, where they stimulate lesion-reactive microglia. To gain mechanistic insight, we used RNA microarray analysis to compare the transcript profile in hippocampi from perforant pathway axonal-lesioned mice with and without adoptively transferred myelin-specific T cells 2 days postlesion, when microglia are clearly lesion reactive. Pathway analysis revealed that, among the 1,447 differently expressed transcripts, the interleukin (IL)-1 pathway including all IL-1 receptor ligands was upregulated in the presence of myelin-specific T cells. Quantitative polymerase chain reaction showed increased mRNA levels of IL-1β, IL-1α, and IL-1 receptor antagonist in the T-cell-infiltrated hippocampi from axonal-lesioned mice. In situ hybridization and immunohistochemistry showed a T-cell-enhanced lesion-specific expression of IL-1β mRNA and protein, respectively, and induction of the apoptosis-associated speck-like protein, ASC, in CD11b(+) cells. Double in situ hybridization showed colocalization of IL-1β mRNA in a subset of CD11b mRNA(+) cells, of which many were part of cellular doublets or clusters, characteristic of proliferating, lesion-reactive microglia. Double-immunofluorescence showed a T-cell-enhanced colocalization of IL-1β to CD11b(+) cells, including lesion-reactive CD11b(+) ramified microglia. These results suggest that myelin-specific T cells stimulate lesion-reactive microglial-like cells to produce IL-1β. These findings are relevant to understand the consequences of T-cell infiltration in white and gray matter lesions in patients with MS.

  6. Mesenchymal stem cells in post-surgical cavities of large maxillary bone lesions

    PubMed Central

    Bertolai, Roberto; Catelani, Carlo; Signorini, Mattia; Rossi, Alessandro; Giannini, Domenico

    2016-01-01

    Summary Background Recent studies have highlighted that MSCs are capable of regenerating large bone defects when used in combination with bone substitutes and increasing allo-graft osteointegration. We investigated the hypothesis that autologous MSCs may lead to increased bone regeneration and reduced healing time in post-surgical cavities of large maxillary bone lesions. Methods This study involved 10 patients (TEST GROUP) (6 males and 4 females). All patients had expansive mandibular lesions larger than 3 cm. From the surgical point of view, the 10 patients were treated with MSCs (withdrawal of the iliac crest bone marrow BMMSs) directly into the post-surgical cavity, without the addition of filler. Results and radiological data, in the postoperative, were compared to those of patients who did not receive any grafting of MSCs. The 7 patients with mandibular lesions showed a rapid and very good healing with an 85–90% ossification of the major defect at 12 months. Conclusions Through the use of stem cells a greater ossification of the residual cavity (85–90%) was observed at 12 months after surgical enucleation in contenitive defects. PMID:28228785

  7. Squamous cell carcinoma developing in a cutaneous lichen planus lesion: a rare case.

    PubMed

    Ghosh, Saptarshi; Kotne, Sivasankar; Ananda Rao, P B; Turlapati, S P V; Kumar Soren, Dillip

    2014-01-01

    Lichen planus is a benign disorder characterized by an itchy, noninfectious skin rash. Though lichen planus is a common papulosquamous disorder affecting about 1-2% of the population, neoplastic transformation of cutaneous lichen planus lesions occurs very rarely and should be borne in mind while treating nonhealing longstanding lesions of lichen planus. Studies suggest an estimated 0.3-3% risk of malignancy in patients with oral lichen planus, however, cutaneous lichen planus does not carry an increased risk of malignant degeneration. We present a case of a 36-year-old male with a 10-year-long history of hypertrophic lichen planus who presented with a nonhealing ulcer in the left popliteal fossa. The patient underwent wide local excision with superficial skin grafting. Postoperative histopathological examination revealed verrucous squamous cell carcinoma complicating lichen planus. In view of underlying structure involvement, adjuvant radiation therapy was given. This case is being reported to emphasize the infrequent possibility of development of malignancy in cutaneous lichen planus, especially if it presents as a longstanding, nonhealing, itchy lesion with patchy areas of depigmentation in the lower limbs.

  8. Squamous cell carcinoma-like and pox lesions occurring simultaneously in chorioallantoic membranes of chicken embryos inoculated with materials from squamous cell carcinoma and pox lesions in broiler chickens.

    PubMed

    Fallavena, L C; Rodrigues, N C; Moraes, H L; Salle, C T; da Silva, A B; Nascimento, V P; Rodrigues, O

    1997-01-01

    The finding of closely associated squamous cell carcinoma (SCC)-like lesions and pox lesions in chorioallantoic membranes (CAMs) inoculated with skin and palate samples taken from broilers is described. The samples were obtained from two broilers coming from different flocks that were not vaccinated against fowl pox. Both birds presented skin lesions, which were diagnosed in one bird as fowl pox, and in the other as SCC. After inoculation of CAMs with fresh tissues from both birds, histologic examination revealed, in all CAMs, lesions that were characteristic of fowl pox together with lesions consistent with those seen in the skin of broilers affected with SCC. This finding was unexpected and may shed some light on the etiology of SCC.

  9. Columnar liquid crystals in cylindrical nanoconfinement.

    PubMed

    Zhang, Ruibin; Zeng, Xiangbing; Kim, Bongseock; Bushby, Richard J; Shin, Kyusoon; Baker, Patrick J; Percec, Virgil; Leowanawat, Pawaret; Ungar, Goran

    2015-02-24

    Axial orientation of discotic columnar liquid crystals in nanopores of inorganic templates, with the columns parallel to the axis of the nanochannels, is considered desirable for applications such as production of molecular wires. Here, we evaluate experimentally the role of the rigidity of the LC columns in achieving such orientation in nanopores where the planar anchoring (i.e., columns parallel to wall surface) is enforced. We studied the columnar phase of several discotic compounds with increasing column rigidity in the following order: dendronized carbazole, hexakis(hexyloxy)triphenylene (HAT6), a 1:1 HAT6-trinitrofluorenone (TNF) complex, and a helicene derivative. Using 2-D X-ray diffraction, AFM, grazing incidence diffraction, and polarized microscopy, we observed that the orientation of the columns changes from circular concentric to axial with increasing column rigidity. Additionally, when the rigidity is borderline, increasing pore diameter can change the configuration from axial back to circular. We derive expressions for distortion free energy that suggest that the orientation is determined by the competition between, on the one hand, the distortion energy of the 2-d lattice and the mismatch of its crystallographic facets with the curved pore wall in the axial orientation and, on the other hand, the bend energy of the columns in the circular configuration. Furthermore, the highly detailed AFM images of the core of the disclinations of strength +1 and +1/2 in the center of the pore reveal that the columns spiral down to the very center of the disclination and that there is no amorphous or misaligned region at the core, as suggested previously.

  10. Predictive value of red blood cell distribution width for coronary artery lesions in patients with Kawasaki disease.

    PubMed

    Xu, Haiyan; Fu, Songling; Wang, Wei; Zhang, Qing; Hu, Jian; Gao, Lichao; Zhu, Weihua; Gong, Fangqi

    2016-08-01

    Recent studies have shown that elevated red blood cell distribution width is associated with poor outcome in cardiovascular diseases. In order to assess the predictive value of red blood cell distribution width, before treatment with intravenous immunoglobulins, for coronary artery lesions in patient with Kawasaki disease, we compared 83 patients with coronary artery lesions and 339 patients without coronary artery lesions before treatment with intravenous immunoglobulin. Clinical, echocardiographic, and biochemical values were evaluated along with red blood cell distribution width. A total of 422 consecutive patients with Kawasaki disease were enrolled into our study. According to receiver operating characteristic curve analysis, the optimal red blood cell distribution width cut-off value for predicting coronary artery lesions was 14.55% (area under the curve was 0.721; p=0.000); eighty-three patients (19.7%) had coronary artery lesions, and 70% of the patients with coronary artery lesions had red blood cell distribution width level >14.55%. Logistic regression analysis revealed that fever duration >14 days (odds ratio was 3.42, 95% confidence interval was 1.27-9.22; p=0.015), intravenous immunoglobulin resistance (odds ratio was 2.33, 95% confidence interval was 1.02-5.29; p=0.04), and red blood cell distribution width >14.55% (odds ratio was 3.49, 95% confidence interval was 2.01-6.05; p=0.000) were independent predictors of coronary artery lesions in patients with Kawasaki disease. In Conclusion, red blood cell distribution width may be helpful for predicting coronary artery lesions in patients with Kawasaki disease.

  11. Gene Deletion Strategy To Examine the Involvement of the Two Chondroitin Lyases in Flavobacterium columnare Virulence

    PubMed Central

    Li, Nan; Qin, Ting; Zhang, Xiao Lin; Huang, Bei; Liu, Zhi Xin; Xie, Hai Xia; Zhang, Jin; McBride, Mark J.

    2015-01-01

    Flavobacterium columnare is an important bacterial pathogen of freshwater fish that causes high mortality of infected fish and heavy economic losses in aquaculture. The pathogenesis of this bacterium is poorly understood, in part due to the lack of efficient methods for genetic manipulation. In this study, a gene deletion strategy was developed and used to determine the relationship between the production of chondroitin lyases and virulence. The F. johnsoniae ompA promoter (PompA) was fused to sacB to construct a counterselectable marker for F. columnare. F. columnare carrying PompA-sacB failed to grow on media containing 10% sucrose. A suicide vector carrying PompA-sacB was constructed, and a gene deletion strategy was developed. Using this approach, the chondroitin lyase-encoding genes, cslA and cslB, were deleted. The ΔcslA and ΔcslB mutants were both partially deficient in digestion of chondroitin sulfate A, whereas a double mutant (ΔcslA ΔcslB) was completely deficient in chondroitin lyase activity. Cells of F. columnare wild-type strain G4 and of the chondroitin lyase-deficient ΔcslA ΔcslB mutant exhibited similar levels of virulence toward grass carp in single-strain infections. Coinfections, however, revealed a competitive advantage for the wild type over the chondroitin lyase mutant. The results indicate that chondroitin lyases are not essential virulence factors of F. columnare but may contribute to the ability of the pathogen to compete and cause disease in natural infections. The gene deletion method developed in this study may be employed to investigate the virulence factors of this bacterium and may have wide application in many other members of the phylum Bacteroidetes. PMID:26253667

  12. Gene deletion strategy to examine the involvement of the two chondroitin lyases in Flavobacterium columnare virulence.

    PubMed

    Li, Nan; Qin, Ting; Zhang, Xiao Lin; Huang, Bei; Liu, Zhi Xin; Xie, Hai Xia; Zhang, Jin; McBride, Mark J; Nie, Pin

    2015-11-01

    Flavobacterium columnare is an important bacterial pathogen of freshwater fish that causes high mortality of infected fish and heavy economic losses in aquaculture. The pathogenesis of this bacterium is poorly understood, in part due to the lack of efficient methods for genetic manipulation. In this study, a gene deletion strategy was developed and used to determine the relationship between the production of chondroitin lyases and virulence. The F. johnsoniae ompA promoter (PompA) was fused to sacB to construct a counterselectable marker for F. columnare. F. columnare carrying PompA-sacB failed to grow on media containing 10% sucrose. A suicide vector carrying PompA-sacB was constructed, and a gene deletion strategy was developed. Using this approach, the chondroitin lyase-encoding genes, cslA and cslB, were deleted. The ΔcslA and ΔcslB mutants were both partially deficient in digestion of chondroitin sulfate A, whereas a double mutant (ΔcslA ΔcslB) was completely deficient in chondroitin lyase activity. Cells of F. columnare wild-type strain G4 and of the chondroitin lyase-deficient ΔcslA ΔcslB mutant exhibited similar levels of virulence toward grass carp in single-strain infections. Coinfections, however, revealed a competitive advantage for the wild type over the chondroitin lyase mutant. The results indicate that chondroitin lyases are not essential virulence factors of F. columnare but may contribute to the ability of the pathogen to compete and cause disease in natural infections. The gene deletion method developed in this study may be employed to investigate the virulence factors of this bacterium and may have wide application in many other members of the phylum Bacteroidetes.

  13. Live or let die - retinal ganglion cell death and survival during development and in the lesioned adult CNS.

    PubMed

    Bähr, M

    2000-10-01

    Programmed cell death or apoptosis is a common and widespread phenomenon that is important for proper development of the nervous system. In the adult CNS, however, apoptosis contributes to secondary cell loss after various types of lesions. The retino-tectal system has been successfully used as a convenient model system to study the molecular mechanisms of neuronal apoptosis and survival during development and in the lesioned adult CNS. This review describes the current knowledge about the interactions of cell death and survival pathways in general and for retinal ganglion cells specifically.

  14. Predicting drug susceptibility of non–small cell lung cancers based on genetic lesions

    PubMed Central

    Sos, Martin L.; Michel, Kathrin; Zander, Thomas; Weiss, Jonathan; Frommolt, Peter; Peifer, Martin; Li, Danan; Ullrich, Roland; Koker, Mirjam; Fischer, Florian; Shimamura, Takeshi; Rauh, Daniel; Mermel, Craig; Fischer, Stefanie; Stückrath, Isabel; Heynck, Stefanie; Beroukhim, Rameen; Lin, William; Winckler, Wendy; Shah, Kinjal; LaFramboise, Thomas; Moriarty, Whei F.; Hanna, Megan; Tolosi, Laura; Rahnenführer, Jörg; Verhaak, Roel; Chiang, Derek; Getz, Gad; Hellmich, Martin; Wolf, Jürgen; Girard, Luc; Peyton, Michael; Weir, Barbara A.; Chen, Tzu-Hsiu; Greulich, Heidi; Barretina, Jordi; Shapiro, Geoffrey I.; Garraway, Levi A.; Gazdar, Adi F.; Minna, John D.; Meyerson, Matthew; Wong, Kwok-Kin; Thomas, Roman K.

    2009-01-01

    Somatic genetic alterations in cancers have been linked with response to targeted therapeutics by creation of specific dependency on activated oncogenic signaling pathways. However, no tools currently exist to systematically connect such genetic lesions to therapeutic vulnerability. We have therefore developed a genomics approach to identify lesions associated with therapeutically relevant oncogene dependency. Using integrated genomic profiling, we have demonstrated that the genomes of a large panel of human non–small cell lung cancer (NSCLC) cell lines are highly representative of those of primary NSCLC tumors. Using cell-based compound screening coupled with diverse computational approaches to integrate orthogonal genomic and biochemical data sets, we identified molecular and genomic predictors of therapeutic response to clinically relevant compounds. Using this approach, we showed that v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations confer enhanced Hsp90 dependency and validated this finding in mice with KRAS-driven lung adenocarcinoma, as these mice exhibited dramatic tumor regression when treated with an Hsp90 inhibitor. In addition, we found that cells with copy number enhancement of v-abl Abelson murine leukemia viral oncogene homolog 2 (ABL2) and ephrin receptor kinase and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) kinase family genes were exquisitely sensitive to treatment with the SRC/ABL inhibitor dasatinib, both in vitro and when it xenografted into mice. Thus, genomically annotated cell-line collections may help translate cancer genomics information into clinical practice by defining critical pathway dependencies amenable to therapeutic inhibition. PMID:19451690

  15. Activities of wogonin analogs and other flavones against Flavobacterium columnare.

    PubMed

    Tan, Cheng-Xia; Schrader, Kevin K; Khan, Ikhlas A; Rimando, Agnes M

    2015-02-01

    In our on-going pursuit to discover natural products and natural product-based compounds to control the bacterial species Flavobacterium columnare, which causes columnaris disease in channel catfish (Ictalurus punctatus), we synthesized flavone and chalcone analogs, and evaluated these compounds, along with flavonoids from natural sources, for their antibacterial activities against two isolates of F. columnare (ALM-00-173 and BioMed) using a rapid bioassay. The flavonoids chrysin (1a), 5,7-dihydroxy-4'-methoxyflavone (11), isorhamnetin (26), luteolin (27), and biochanin A (29), and chalcone derivative 8b showed strong antibacterial activities against F. columnare ALM-00-173 based on minimum inhibition concentration (MIC) results. Flavonoids 1a, 8, 11, 13 (5,4'-dihydroxy-7-methoxyflavone), 26, and 29 exhibited strong antibacterial activities against F. columnare BioMed based upon MIC results. The 24-h 50% inhibition concentration (IC50 ) results revealed that 27 and 29 were the most active compounds against F. columnare ALM-00-173 (IC50 of 7.5 and 8.5 mg/l, resp.), while 26 and 29 were the most toxic compound against F. columnare BioMed (IC50 of 9.2 and 3.5 mg/l, resp.). These IC50 results were lower than those obtained for wogonin against F. columnare ALM-00-173 and F. columnare BioMed (28.4 and 5.4 mg/l, resp.). However, based on MIC results, none of the compounds evaluated in this study were as active as wogonin (MIC 0.3 mg/l for each F. columnare isolate). Further modification of the wogonin structure to enhance antibacterial is of interest.

  16. Advanced lytic lesion is a poor mobilization factor in peripheral blood stem cell collection in patients with multiple myeloma.

    PubMed

    Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2014-12-01

    This study examined the incidence and predictors of peripheral blood stem cell (PBSC) mobilization failure in patients with multiple myeloma (MM). Retrospective data for 104 patients who received granulocyte colony-stimulating factor (G-CSF) alone or with cyclophosphamide as mobilization regimens were analyzed. The rates of mobilization failure using two definitions of failure (< 2 × 10(6) and < 4 × 10(6) CD34(+) cells/kg) following the first collection attempt were 16.3 and 33.7%, respectively. Predictors of mobilization failure were evaluated using logistic regression analysis which included age, advanced osteolytic lesions, bone marrow cellularity before mobilization, platelet count, body mass index before mobilization, and mobilization method. Lytic bone lesions were assessed using a conventional skeletal survey, and advanced osteolytic lesions were defined as lytic lesions in more than three skeletal sites regardless of the number of lytic lesions. On multivariate analysis, advanced osteolytic lesions [hazard ratio (HR) = 10.95, P = 0.001] and age ≥60 years (HR = 5.45, P = 0.016) were associated with a PBSC yield < 2 × 10(6) CD34(+) cells/kg, and advanced osteolytic lesions (HR = 5.08, P = 0.006), white blood cell count ≤4,000/µL before mobilization (HR = 4.72, P = 0.005), and G-CSF only mobilization (HR 10.52, P < 0.001) were associated with PBSC yield < 4 × 10(6) CD34(+) cells/kg. The data suggest that an advanced osteolytic lesion is a significant predictor of mobilization failure in MM patients.

  17. Gene Therapy Inhibiting Neointimal Vascular Lesion: In vivo Transfer of Endothelial Cell Nitric Oxide Synthase Gene

    NASA Astrophysics Data System (ADS)

    von der Leyen, Heiko E.; Gibbons, Gary H.; Morishita, Ryuichi; Lewis, Neil P.; Zhang, Lunan; Nakajima, Masatoshi; Kaneda, Yasufumi; Cooke, John P.; Dzau, Victor J.

    1995-02-01

    It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as β-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessel. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.

  18. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium.

    PubMed

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, José; Anderson, Kathryn V

    2016-01-26

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis.

  19. Human DNA polymerase β, but not λ, can bypass a 2-deoxyribonolactone lesion together with proliferating cell nuclear antigen

    PubMed Central

    Crespan, Emmanuele; Pasi, Emanuela; Imoto, Shuhei; Hübscher, Ulrich; Greenberg, Marc M.; Maga, Giovanni

    2012-01-01

    The C1′-oxidized lesion 2-deoxyribonolactone (L) is induced by free radical attack of DNA. This lesion is mutagenic, inhibits base excision repair, and can lead to strand scission. In double stranded DNA L is repaired by long-patch base excision repair, but it induces replication fork arrest in a single-strand template. Translesion synthesis requires a specialized DNA polymerase (Pol). In E. coli, Pol V is responsible for bypassing L, while in yeast Pol ζ has been shown to be required for efficient bypass. Very little is known about the identity of human Pols capable of bypassing L. For instance, the activity of family X enzymes has never been investigated. We examined the ability of different family X Pols: Pols β, λ and TdT from human cells and Pol IV from S. cerevisiae to act on DNA containing an isolated 2-deoxyribonolactone, as well as when the lesion comprises the 5′-component of a tandem lesion. We show that Pol β, but not Pol λ, can bypass a single L lesion in the template, and its activity is increased by the auxiliary protein proliferating cell nuclear antigen (PCNA), while both enzymes were completely blocked by a tandem lesion. Yeast Pol IV was able to bypass the single L and the tandem lesion but with little nucleotide insertion specificity. Finally, L did not affect the polymerization activity of the template-independent enzyme TdT. PMID:23101935

  20. Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: III. Inhibition of intracellular migration of membrane glycoproteins in rat intestinal columnar cells and hepatocytes as visualized by light and electron-microscope radioautography after 3H-fucose injection

    SciTech Connect

    Bennett, G.; Carlet, E.; Wild, G.; Parsons, S.

    1984-08-01

    In the present work, the effects of these drugs on migration of membrane glycoproteins have been examined at the ultrastructural level in duodenal villous columnar cells and hepatocytes. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In duodenal villous columnar cells, 3H-fucose labeling of the apical plasma membrane was reduced by 51% after colchicine and by 67% after vinblastine treatment; but there was little change in labeling of the lateral plasma membrane. Labeling of the Golgi apparatus increased. This suggests that labeled glycoproteins destined for the apical plasma membrane were inhibited from leaving the Golgi region, while migration to the lateral plasma membrane was not impaired. In hepatocytes, labeling of the sinusoidal plasma membrane was reduced by 83% after colchicine and by 85% after vinblastine treatment. Labeling of the lateral plasma membrane also decreased, although not so dramatically. Labeling of the Golgi apparatus and neighboring secretory vesicles increased. This indicates that the drugs inhibited migration of membrane glycoproteins from the Golgi region to the various portions of the plasma membrane. Accumulation of secretory vesicles at the sinusoidal front suggests that exocytosis may also have been partially inhibited. In both cell types, microtubules almost completely disappeared after drug treatment. Microtubules may, therefore, be necessary for intracellular transport of membrane glycoproteins, although the possibility of a direct action of these drugs on Golgi or plasma membranes must also be considered.

  1. Differences between tangential geostrophy and columnar flow

    NASA Astrophysics Data System (ADS)

    Amit, Hagay; Pais, Maria Alexandra

    2013-07-01

    Core flows inverted from time-dependent geomagnetic field models image the geodynamo at the top of its generation region, the Earth's outer core. Physical assumptions incorporated in these inversions affect the resulting flows. Based on rapid rotation dominance, two assumptions similar in form yet different in essence have been proposed: tangential geostrophy (TG, LeMouël 1984) and columnar flow (CF, Amit & Olson 2004). We recall that CF is theoretically consistent with the quasi-geostrophy (QG) theory for an incompressible fluid with spherical solid boundaries whereas TG is not. As such, we highlight the importance of applying the CF assumption when inverting geomagnetic data for interior core (columnar) flows that can be used in kinematic dynamo and thermal convection models in the Boussinesq approximation. Next we evaluate the non-uniqueness associated with CF flows. The areas of ambiguous patches at the core surface where invisible TG or CF flows reside are roughly comparable. The spatial distribution of ambiguous patches for both TG and CF is quite asymmetric about the equator, so assuming equatorial symmetry is expected to reduce the non-uniqueness significantly. In fact, for assumed equatorial symmetry, the only possible non-unique flows will be those along hypothetical ζ-contours in the opposite hemispheres that their equatorial plane projections are parallel. TG flows exhibit a strong Atlantic/Pacific hemispheric dichotomy and a well-defined eccentric gyre whereas in CF flows the dichotomy between these two hemispheres is weaker and the gyre is less clear suggesting that the eccentric gyre might not conserve mass. Both TG and CF upwelling/downwelling patterns are strongly localized in the equatorial region. In addition, in both cases upwelling/downwelling is correlated with equatorward/poleward flow respectively, as expected for QG convection. CF upwelling is more intense than TG upwelling but the magnitude ratio is smaller than the factor 2

  2. Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

    PubMed Central

    Zhang, Hao; Li, Hao; Ma, Qing; Yang, Fang-Yan; Diao, Tao-Yu

    2016-01-01

    AIM To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis. METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions. RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH. CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions. PMID:27818592

  3. Water hardness influences Flavobacterium columnare pathogenesis in channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies were conducted to determine aspects of water chemistry responsible for large differences in pathogenesis and mortality rates in challenges of channel catfish Ictalurus punctatus with Flavobacterium columnare; challenges were conducted in water supplying the Stuttgart National Aquaculture Res...

  4. Giant Cell Lesions of Lungs: A Histopathological and Morphometric Study of Seven Autopsy Cases

    PubMed Central

    Natarajan, M.; Biligi, Dayananda S; Raghupathi, A.R

    2015-01-01

    Introduction Macrophages undergo fusion to form multinucleated giant cells (MGC) in several pathologic conditions. The exact mechanism of their generation is still unclear. MGC are a common feature of granulomas that develop during various inflammatory reactions. Aim To study the histopathological features of giant cell lesions in lungs and correlate the characteristics of giant cells with other histopathological findings. Also, to determine the utility of morphometry to differentiate foreign body and Langhans MGC. Materials and Methods Seven cases were analysed. Specimen of lungs was grossed, sectioned and processed. Routinely, tissue sections were stained by Haematoxylin and Eosin (H&E) stain. Polarizing microscopy and special stains were employed in selected cases. Granulomas and MGC were counted and measured. Several other parameters like location, distribution, type and number of MGC, associated predominant inflammatory component and nature of granulomas were analysed. Results Five patterns of lesions were observed in seven cases. Aspiration pneumonia was seen in three cases (42.85%) and constituted the most common pattern. However, aspiration pneumonia as the only cause of MGC was seen in only one case (14.28%). Pulmonary tuberculosis and asteroid bodies constituted two cases (28.57%) each. Cryptococcal pneumonia and cholesterol clefts constituted one case (14.28%) each. Crypococci were demonstrated to be positively birefringent by polarized microscopy on Ziehl-Neelsen stained sections. Based on statistical analysis of morphometric data, a new index (NP index) was proposed to statistically categorize MGC into foreign body type and Langhans type. NP index value of ≤0.016 was found to be statistically significant (p<0.005) in foreign body MGC. It had high sensitivity and efficacy. Conclusion MGC may not be always associated with granulomas. The mechanisms that lead to the occurrence of MGC, independent of granuloma needs to be elucidated. Morphometry may

  5. Erythropoietin reduces storage lesions and decreases apoptosis indices in blood bank red blood cells

    PubMed Central

    Penuela, Oscar Andrés; Palomino, Fernando; Gómez, Lina Andrea

    2015-01-01

    Background Recent evidence shows a selective destruction of the youngest circulating red blood cells (neocytolysis) trigged by a drop in erythropoietin levels. Objective The aim of this study was to evaluate the effect of recombinant human erythropoietin beta on the red blood cell storage lesion and apoptosis indices under blood bank conditions. Methods Each one of ten red blood cell units preserved in additive solution 5 was divided in two volumes of 100 mL and assigned to one of two groups: erythropoietin (addition of 665 IU of recombinant human erythropoietin) and control (isotonic buffer solution was added). The pharmacokinetic parameters of erythropoietin were estimated and the following parameters were measured weekly, for six weeks: Immunoreactive erythropoietin, hemolysis, percentage of non-discocytes, adenosine triphosphate, glucose, lactate, lactate dehydrogenase, and annexin-V/esterase activity. The t-test or Wilcoxon's test was used for statistical analysis with significance being set for a p-value <0.05. Results Erythropoietin, when added to red blood cell units, has a half-life >6 weeks under blood bank conditions, with persistent supernatant concentrations of erythropoietin during the entire storage period. Adenosine triphosphate was higher in the Erythropoietin Group in Week 6 (4.19 ± 0.05 μmol/L vs. 3.53 ± 0.02 μmol/L; p-value = 0.009). The number of viable cells in the Erythropoietin Group was higher than in the Control Group (77% ± 3.8% vs. 71% ± 2.3%; p-value <0.05), while the number of apoptotic cells was lower (9.4% ± 0.3% vs. 22% ± 0.8%; p-value <0.05). Conclusions Under standard blood bank conditions, an important proportion of red blood cells satisfy the criteria of apoptosis. Recombinant human erythropoietin beta seems to improve storage lesion parameters and mitigate apoptosis. PMID:26969770

  6. Protonospheric columnar electron content determination. I - Analysis.

    NASA Technical Reports Server (NTRS)

    Almeida, O. G.

    1973-01-01

    A combination of phase-path length difference and Faraday rotation angle data obtained from geostationary satellite transmissions is used to determine the integration constant necessary to convert phase-path length difference information into absolute values of total slant columnar electron content. The total content thus determined, which is the sum of the ionospheric and protonospheric contents, is measured with uncertainties about one order of magnitude smaller than the value of the protonospheric content. It is thus, in principle, possible to determine the latter by subtracting from the measurement the so-called 'Faraday content.' This idea, proposed by several authors in the past, is critically examined in the present paper. It is impossible to totally eliminate the ionospheric contribution to the measurements; however, it is shown that the degree of elimination depends on the type of distribution of the longitudinal component of the geomagnetic field along the path of observation. Satisfactory minimization of the ionospheric contribution can be accomplished only under certain geometries of observation.

  7. Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma

    PubMed Central

    Asakura, Takanori; Ishii, Makoto; Kikuchi, Taku; Kameyama, Kaori; Namkoong, Ho; Nakata, Noboru; Sugita, Kayoko; Tasaka, Sadatomo; Shimizu, Takayuki; Hoshino, Yoshihiko; Okamoto, Shinichiro; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Abstract Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma. A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein–Barr virus-encoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because

  8. Characterization of keratin and cell cycle protein expression in cell lines from squamous intraepithelial lesions progressing towards a malignant phenotype.

    PubMed Central

    Hietanen, S.; Syrjänen, K.; Syrjänen, S.

    1998-01-01

    Two cell lines derived from vaginal intraepithelial neoplasias (VAINs) expressing human papillomavirus (HPV) 33 (VAIN I, UT-DEC-1) and 16 (VAIN II, UT-DEC-2) E6-E7 mRNA were studied in organotypic culture for their keratins and cell cycle regulatory proteins in relation to replicative aging. Early-passage UT-DEC-1 and UT-DEC-2 cells reproduced epithelial patterns consistent with VAIN. Cells from later passages resembled full-thickness intraepithelial neoplasia (UT-DEC-1) and microinvasive cancer (UT-DEC-2). The morphological changes were compatible with these cell lines' ability for anchorage-independent growth at later passages. Simple epithelial keratins were aberrantly expressed in both cell lines. K18 (absent in normal vaginal keratinocytes) and K17 expression increased in UT-DEC-1 and UT-DEC-2 cells at late passages. No marked differences in expression of p53 (wild type in both cell lines), mdm-2 or PCNA were detected in parallel with progression. The expression of p21WAF1/cip1 localized mostly to the upper half of the epithelium at early passage and was more intense in the HPV 16-positive UT-DEC-2 cell line expressing K10. In Northern blot analyses, the transcription pattern of the HPV 33 E6-E7 of the UT-DEC-1 cell line changed during later passages, whereas that of the HPV 16 E6-E7 of the UT-DEC-2 cell line remained unaltered. The present characterization of the phenotype of these cell lines derived from natural squamous intraepithelial lesions shows an association between simple epithelial-type keratin expression and progressive changes in growth and morphology, but fails to demonstrate consistent changes in the expression of cell cycle regulatory proteins studied in parallel with progression. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9514056

  9. Recruitment of CD8+ T cells expressing granzymeA is associated with lesion progression in human cutaneous leishmaniasis

    PubMed Central

    Faria, D.R.; Souza, P.E.A.; Durães, F.V; Carvalho, E.M.; Gollob, K.J.; Machado, P.R.; Dutra, W.O.

    2009-01-01

    Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from non-ulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a five-fold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzymeA than E-CL. Interestingly, granzymeA expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-γ+ and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+granzymeA+ T-cells is involved in lesion progression in human CL. PMID:19646207

  10. Tracing a key player in the regulation of plant architecture: the columnar growth habit of apple trees (Malus × domestica).

    PubMed

    Petersen, Romina; Krost, Clemens

    2013-07-01

    Plant architecture is regulated by a complex interplay of some key players (often transcription factors), phytohormones and other signaling molecules such as microRNAs. The columnar growth habit of apple trees is a unique form of plant architecture characterized by thick and upright stems showing a compaction of internodes and carrying short fruit spurs instead of lateral branches. The molecular basis for columnar growth is a single dominant allele of the gene Columnar, whose identity, function and gene product are unknown. As a result of marker analyses, this gene has recently been fine-mapped to chromosome 10 at 18.51-19.09 Mb [according to the annotation of the apple genome by Velasco (2010)], a region containing a cluster of quantitative trait loci associated with plant architecture, but no homologs to the well-known key regulators of plant architecture. Columnar apple trees have a higher auxin/cytokinin ratio and lower levels of gibberellins and abscisic acid than normal apple trees. Transcriptome analyses corroborate these results and additionally show differences in cell membrane and cell wall function. It can be expected that within the next year or two, an integration of these different research methodologies will reveal the identity of the Columnar gene. Besides enabling breeders to efficiently create new apple (and maybe related pear, peach, cherry, etc.) cultivars which combine desirable characteristics of commercial cultivars with the advantageous columnar growth habit using gene technology, this will also provide new insights into an elevated level of plant growth regulation.

  11. Columnar aerosol characterization over Scandinavia and Svalbard

    NASA Astrophysics Data System (ADS)

    Toledano, C.; Cachorro, V. E.; Ortiz de Galisteo, J. P.; Bennouna, Y.; Berjón, A.; Torres, B.; Fuertes, D.; González, R.; de Frutos, A. M.

    2013-05-01

    An overview of sun photometer measurements of aerosol properties in Scandinavia and Svalbard was provided by Toledano et al. (2012) thanks to the collaborative effort of various research groups from different countries that maintain a number of observation sites in the European Arctic and sub-Arctic regions. The spatial coverage of this kind of data has remarkably improved in the last years, thanks, among other things, to projects carried out within the framework of the International Polar Year 2007-08. The data from a set of operational sun photometer sites belonging either to national or international measurement networks (AERONET, GAW-PFR) were evaluated. The direct sun observations provided spectral aerosol optical depth (AOD) and Ångström exponent (AE), that are parameters with sufficient long-term records for a first characterization at all sites. At the AERONET sites, microphysical properties derived from inversion of sun-sky radiance data were also examined. AOD (500nm) ranged from 0.08 to 0.10 in Arctic and sub-Arctic sites whereas the aerosol load was higher in more populated areas in Southern Scandinavia (average AOD about 0.10-0.12 at 500 nm). On the Norwegian coast, aerosols showed larger mean size than in continental areas. Columnar particle size distributions and related parameters were used to evaluate aerosol volume efficiencies. The aerosol optical depth characterization revealed that the seasonal patterns in the high Arctic (with the typical hazy spring), in the sub-Arctic region and Southern Scandinavia are all different. The clean continental, polluted continental and maritime aerosols constitute the three main aerosol types, although persistent (Asian) dust was also detected in Svalbard.

  12. Differences between tangential geostrophy and columnar flow

    NASA Astrophysics Data System (ADS)

    Amit, Hagay; Pais, M. Alexandra

    2013-04-01

    Core flows inverted from time-dependent geomagnetic field models image the geodynamo at the top of its generation region, the Earth's outer core. Physical assumptions incorporated in these inversions may affect the resulting flows. Based on rapid rotation dominance, two assumptions similar in form yet different in essence were proposed: Tangential geostrophy (TG, LeMouël, 1984) and columnar flow (CF, Amit and Olson, 2004). We show that CF is theoretically consistent with the quasi-geostrophy (QG) theory for an incompressible fluid with spherical solid boundaries, whereas TG is not. The areas of ambiguous patches at the core surface where invisible TG or CF flows reside are roughly comparable. The spatial distribution of ambiguous patches for both TG and CF is quite asymmetric about the equator, so assuming equatorial symmetry may hypothetically reduce the non-uniqueness significantly. TG flows exhibit a strong Atlantic/Pacific hemispheric dichotomy and a well-defined eccentric gyre, whereas in CF flows the dichotomy between these two hemispheres is weaker and the gyre is less clear, suggesting that the eccentric gyre might not conserve mass. Both TG and CF upwelling/downwelling patterns are strongly localized in the equatorial region. In addition, in both cases upwelling/downwelling is correlated with equatorward/poleward flow respectively, as expected for QG convection. CF upwelling is more intense than TG upwelling but the magnitude ratio is smaller than the factor 2 distinguishing the analytical expressions of the two assumptions due to the dominance of magnetic field advection by toroidal core flow in the geomagnetic secular variation.

  13. Differences between tangential geostrophy and columnar flow

    NASA Astrophysics Data System (ADS)

    Amit, H.; Pais, M. A.

    2012-12-01

    Core flows inverted from time-varying geomagnetic field models image the geodynamo at the top of its generation region, the Earth's outer core. Physical assumptions incorporated in these inversions may affect the resulting flows. Based on rapid rotation dominance, two assumptions similar in form yet different in essence were proposed: Tangential geostrophy (TG; LeMouël, 1984) and columnar flow (CF; Amit and Olson, 2004). We show that CF is theoretically consistent with the quasi-geostrophy theory for an incompressible fluid with spherical solid boundaries, whereas TG is not. The low-latitude ageostrophic belt associated with CF is broader than that associated with TG, but the global non-uniqueness reduction of TG and CF is roughly comparable. The spatial distribution of ambiguous patches for both TG and CF is quite asymmetric about the equator, so assuming equatorial symmetry may reduce the non-uniqueness significantly. TG flows exhibit a strong Atlantic/Pacific hemispheric dichotomy and a well-defined eccentric gyre, whereas in CF flows the dichotomy between these two hemispheres is weaker and the gyre is less clear, suggesting that the eccentric gyre might not conserve mass. Both TG and CF upwelling patterns are strongly localized in the equatorial region. In addition, in both TG and CF upwelling/downwelling is correlated with poleward/equatorward flow respectively. CF upwelling is more intense than TG upwelling, but the magnitude ratio is smaller than the expected value based on purely analytical arguments, perhaps indicating that the poloidal flow is constrained by the geomagnetic secular variation.

  14. The early history of odontogenic ghost cell lesions: from Thoma to Gorlin.

    PubMed

    Ide, Fumio; Kikuchi, Kentaro; Miyazaki, Yuji; Kusama, Kaoru; Saito, Ichiro; Muramatsu, Takashi

    2015-03-01

    To reappraise the early history of odontogenic ghost cell lesions (OGCL), the extensive world literature published from 1838 to 1962 was reviewed. In light of the long history of OGCL, the term "calcifying epithelioma of Malherbe" first appeared in a 1931 French report, and the term "ghost cells" had its origin in two American seminal articles by Thoma and Goldman in 1946. Although Gorlin et al. coined the term "calcifying odontogenic cyst" (COC) in 1962, this type of cyst was initially reported three decades earlier by Rywkind in Russia, and almost concurrently by Blood good in the United States and Sato in Japan. In 1948, Willis provided the initial histological evidence of a peripheral COC in his British pathology textbook. Credit for the earliest clinical presentation of odontoma associated calcifying cystic odontogenic tumor belongs to the American radiology textbook by Thoma in 1917. A Scandinavian journal report published in 1953 by Husted and Pindborg was the first to address a dentinogenic ghost cell tumor, and its peripheral counterpart was originally reported in the Swiss literature 7 years later. The current concept of COC was undoubtedly established by Gorlin et al. but the history of OGCL really started with Thoma's pioneering work about a century ago.

  15. Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion

    PubMed Central

    Yamamoto, Yusuke; Wang, Xia; Bertrand, Denis; Kern, Florian; Zhang, Ting; Duleba, Marcin; Srivastava, Supriya; Khor, Chiea Chuen; Hu, Yuanyu; Wilson, Lane H.; Blaszyk, Hagen; Rolshud, Daniil; Teh, Ming; Liu, Jianjun; Howitt, Brooke E.; Vincent, Matthew; Crum, Christopher P.; Nagarajan, Niranjan; Ho, Khek Yu; McKeon, Frank; Xian, Wa

    2016-01-01

    The precancerous lesion known as Barrett's oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett's stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma. PMID:26783136

  16. Optimizing modulation frequency for structured illumination in a fiber-optic microendoscope to image nuclear morphometry in columnar epithelium

    PubMed Central

    Keahey, P. A.; Tkaczyk, T. S.; Schmeler, K. M.; Richards-Kortum, R. R.

    2015-01-01

    Fiber-optic microendoscopes have shown promise to image the changes in nuclear morphometry that accompany the development of precancerous lesions in tissue with squamous epithelium such as in the oral mucosa and cervix. However, fiber-optic microendoscopy image contrast is limited by out-of-focus light generated by scattering within tissue. The scattering coefficient of tissues with columnar epithelium can be greater than that of squamous epithelium resulting in decreased image quality. To address this challenge, we present a small and portable microendoscope system capable of performing optical sectioning using structured illumination (SI) in real-time. Several optical phantoms were developed and used to quantify the sectioning capabilities of the system. Columnar epithelium from cervical tissue specimens was then imaged ex vivo, and we demonstrate that the addition of SI achieves higher image contrast, enabling visualization of nuclear morphology. PMID:25798311

  17. Lipoprotein(a) Promotes Smooth Muscle Cell Proliferation and Dedifferentiation in Atherosclerotic Lesions of Human Apo(a) Transgenic Rabbits

    PubMed Central

    Ichikawa, Tomonaga; Unoki, Hiroyuki; Sun, Huijun; Shimoyamada, Hiroaki; Marcovina, Santica; Shikama, Hisataka; Watanabe, Teruo; Fan, Jianglin

    2002-01-01

    Elevated plasma lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the mechanism underlying Lp(a) atherogenicity is unclear. Recently, we demonstrated that Lp(a) may potentially be proatherogenic in transgenic rabbits expressing human apolipoprotein(a) [apo(a)]. In this study, we further investigated atherosclerotic lesions of transgenic rabbits by morphometry and immunohistochemistry. On a cholesterol diet, human apo(a) transgenic rabbits had more extensive atherosclerotic lesions of the aorta, carotid artery, iliac artery, and coronary artery than did nontransgenic littermate rabbits as defined by increased intimal lesion area. Enhanced lesion development in transgenic rabbits was characterized by increased accumulation of smooth muscle cells, that was often associated with the Lp(a) deposition. To explore the possibility that Lp(a) may be involved in the smooth-muscle cell phenotypic modulation, we stained the lesions using a panel of monoclonal antibodies against smooth-muscle myosin heavy-chain isoforms (SM1, SM2, and SMemb) and basic transcriptional element binding protein-2 (BTEB2). We found that a large number of smooth muscle cells located in the apo(a)-containing areas of transgenic rabbits were positive for SMemb and BTEB2, suggesting that these smooth muscle cells were either immature or in the state of activation. In addition, transgenic rabbits showed delayed fibrinolytic activity accompanied by increased plasma plasminogen activator inhibitor-1. We conclude that Lp(a) may enhance the lesion development by mediating smooth muscle cell proliferation and dedifferentiation possibly because of impaired fibrinolytic activity. PMID:11786416

  18. Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

    PubMed Central

    Campbell, T. Mark; Churchman, Sarah M.; Gomez, Alejandro; McGonagle, Dennis; Conaghan, Philip G.; Ponchel, Frederique

    2016-01-01

    Objective In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non‐BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences. Methods Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI‐determined BML and non‐BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony‐forming unit–fibroblast (CFU‐F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture‐expanded CD271+ cells were analyzed for tripotentiality and gene expression. Results BML regions were associated with greater trabecular bone area and cartilage damage compared with non‐BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non‐BML regions (median difference 5.6‐fold; P < 0.001); the CFU‐F assay showed a similar trend (median difference 4.3‐fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up‐regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone. Conclusion This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target. PMID

  19. Use of autologous bone marrow mononuclear cells and cultured bone marrow stromal cells in dogs with orthopaedic lesions.

    PubMed

    Crovace, A; Favia, A; Lacitignola, L; Di Comite, M S; Staffieri, F; Francioso, E

    2008-09-01

    The aim of the study is to evaluate the clinical application in veterinary orthopedics of bone marrow mononuclear cells (BMMNCs) and cultured bone marrow stromal cells (cBMSCs) for the treatment of some orthopaedic lesions in the dog. The authors carried out a clinical study on 14 dogs of different breed, age and size with the following lesions: 1 bone cyst of the glenoid rime; 2 nonunion of the tibia; 3 nonunion of the femur; 2 lengthening of the radius; 1 large bone defect of the distal radius;1 nonunion with carpus valgus; 4 Legg-Calvé-Perthés disease. In 9 cases the BMMCNs were used in combination with a three dimensional resorbable osteogenic scaffold the chemical composition and size of which facilitates the ingrowth of bone. In these cases the BMMNCs were suspended in an adequate amount of fibrin glue and then distribuited uniformly on a Tricalcium-Phosphate (TCP) scaffold onto which were also added some drops of thrombin. In 1 case of nonunion of the tibia and in 3 cases of Legg-Calvè-Perthés (LCP) disease the cultured BMSCs were used instead because of the small size of the dogs and of the little amount of aspirated bone marrow. X-ray examinations were performed immediately after the surgery. Clinical, ultrasounds and X-ray examinations were performed after 20 days and then every month. Until now the treated dogs have shown very good clinical and X-ray results. One of the objectives of the study was to use the BMMNCs in clinical application in orthopaedic lesions in the dog. The advantages of using the cells immediately after the bone marrow is collected, are that the surgery can be performed the same day, the cells do not need to be expanded in vitro, they preserve their osteogenic potential to form bone and promote the proper integration of the implant with the bone and lastly, the technique is easier and the costs are lower.

  20. Benign and malignant papillary lesions of the breast. A cytomorphologic study.

    PubMed

    Jeffrey, P B; Ljung, B M

    1994-04-01

    Fine-needle aspiration cytology of benign and malignant papillary lesions of the breast has been infrequently described. To define the cytologic features of benign and malignant papillary breast lesions better, the authors retrospectively reviewed the fine-needle aspiration cytology of five cases of histologically proven intracystic papillary carcinoma (IPC) and six cases of histologically proven papilloma. Clinical information was obtained from the medical records in each case. Intracystic papillary carcinoma tended to present as a larger tumor (average, 5 cm) in older women (average, 65.4 years). Papilloma, however, tended to present as a smaller tumor (average, 1.5 cm) in younger women (average, 43 years). Eighty percent of the IPC cases (4/5) and 50% of the papilloma cases (3/6) yielded highly cellular aspirates with complex vascular papillae and single columnar cells. Macrophages were a constant feature of IPC and were present in all but one case of papilloma. Although cellular atypia was not a prominent feature in either IPC or papilloma, moderate atypia was noted in one case of IPC and two cases of papilloma. Severe atypia was noted in a single case of IPC. Although IPC tended to yield a harvest with higher cellularity and single intact cells, no single feature or constellation of findings was consistently reliable in distinguishing IPC from papilloma. The authors found that papillary lesions of the breast demonstrate a distinct cytomorphology characterized by complex vascular papillae, columnar cells, and macrophages. They concluded, however, that, in the absence of overt cytologic malignancy, distinguishing between benign and malignant papillary breast lesions is difficult, if not impossible.

  1. Clonal Expansions of Cd8+ T Cells Dominate the T Cell Infiltrate in Active Multiple Sclerosis Lesions as Shown by Micromanipulation and Single Cell Polymerase Chain Reaction

    PubMed Central

    Babbe, Holger; Roers, Axel; Waisman, Ari; Lassmann, Hans; Goebels, Norbert; Hohlfeld, Reinhard; Friese, Michael; Schröder, Roland; Deckert, Martina; Schmidt, Stephan; Ravid, Rivka; Rajewsky, Klaus

    2000-01-01

    Clonal composition and T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level of single cells. Individual CD4+ or CD8+ T cells were isolated from frozen sections of lesional tissue by micromanipulation and subjected to single target amplification of TCR-β gene rearrangements. This strategy allows the assignment of a TCR variable region (V region) sequence to the particular T cell from which it was amplified. Sequence analysis revealed that in both cases investigated, the majority of CD8+ T cells belonged to few clones. One of these clones accounted for 35% of CD8+ T cells in case 1. V region sequence comparison revealed signs of selection for common peptide specificities for some of the CD8+ T cells in case 1. In both cases, the CD4+ T cell population was more heterogeneous. Most CD4+ and CD8+ clones were represented in perivascular infiltrates as well as among parenchymal T cells. In case 2, two of the CD8+ clones identified in brain tissue were also detected in peripheral blood. Investigation of the antigenic specificities of expanded clones may help to elucidate their functional properties. PMID:10934227

  2. Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

    PubMed

    Zhang, Yan-Qiang; Li, Peng; Zhang, Feng-Qin; Sun, Shao-Jun; Cao, Yin-Guang

    2016-12-09

    Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5(+) cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5(+) cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

  3. A Giant-Cell Lesion with Cellular Cannibalism in the Mandible: Case Report and Review of Brown Tumors in Hyperparathyroidism

    PubMed Central

    Cimetti, Laura; Annoni, Matteo; Anselmi, Diego; Tettamanti, Lucia; Tagliabue, Angelo

    2017-01-01

    A small radiolucent area in the mandible was discovered in a 58-year-old woman with no oral complaints. The patient's history included only hypertension. The lesion was considered as an inflammatory cyst and was enucleated. Three months later, a CT revealed the presence of a cyst-like lesion in the mandible with thin expanded buccal cortical plate, localized erosion, and a polylobate appearance on the lingual aspect of the cortical plate. The histological diagnosis of the lesion was central giant-cell granuloma (CGCG). The lesion was thoroughly enucleated. Nevertheless, another X-ray carried out six months later revealed multiple bilateral osteolytic areas throughout the jaw. In addition, widespread cortical plate erosion was observed, as well as signs of root resorption and periodontal enlargement. There was no sign of neurological involvement, although the nerves appeared to be dislocated. After full blood chemistry analysis and detailed collection of radiographs, the final diagnosis was brown tumors in primary hyperparathyroidism. This case report demonstrates how dental clinicians may be the first-line specialists who identify a complex systemic disease before other clinicians. Finally, it highlights the role of cellular cannibalism in predicting the clinical aggressiveness of brown tumors as well as in other giant-cell lesions. PMID:28280638

  4. A Giant-Cell Lesion with Cellular Cannibalism in the Mandible: Case Report and Review of Brown Tumors in Hyperparathyroidism.

    PubMed

    Azzi, Lorenzo; Cimetti, Laura; Annoni, Matteo; Anselmi, Diego; Tettamanti, Lucia; Tagliabue, Angelo

    2017-01-01

    A small radiolucent area in the mandible was discovered in a 58-year-old woman with no oral complaints. The patient's history included only hypertension. The lesion was considered as an inflammatory cyst and was enucleated. Three months later, a CT revealed the presence of a cyst-like lesion in the mandible with thin expanded buccal cortical plate, localized erosion, and a polylobate appearance on the lingual aspect of the cortical plate. The histological diagnosis of the lesion was central giant-cell granuloma (CGCG). The lesion was thoroughly enucleated. Nevertheless, another X-ray carried out six months later revealed multiple bilateral osteolytic areas throughout the jaw. In addition, widespread cortical plate erosion was observed, as well as signs of root resorption and periodontal enlargement. There was no sign of neurological involvement, although the nerves appeared to be dislocated. After full blood chemistry analysis and detailed collection of radiographs, the final diagnosis was brown tumors in primary hyperparathyroidism. This case report demonstrates how dental clinicians may be the first-line specialists who identify a complex systemic disease before other clinicians. Finally, it highlights the role of cellular cannibalism in predicting the clinical aggressiveness of brown tumors as well as in other giant-cell lesions.

  5. Radiating columnar joints in Gyeongju, Korea as a educational site

    NASA Astrophysics Data System (ADS)

    Woo, H.; Kim, J. H.; Jang, Y. D.

    2015-12-01

    Gyeongju is located in the central eastern part of South Korea. There are various directional columnar joint sets in Tertiary trachytic basalt formation along the shore. In particular, rare radiating columnar joints occur in this area. Columnar joints are parallel, prismatic columns that are formed as a result of contraction during the rapid cooling of lava flow, forming a three dimensional fracture network. In general, the radius and direction of the rock column represent the cooling rate and surface respectively. Radiating direction of columns here indicates that dome- or lobe-shaped lava was cooled from its surface to the core during the viscous lava flow. The fact that the trachytic textures of plagioclase laths are indistinct suggests that the radiating columnar joints are equivalent to the frontal end of the lava lobes. This area is currently has a shore trail course, which is being developed into a picturesque educational park. There are corresponding information boards on the trail near each type of columnar joints to explain not only the forming process and geological mechanisms but the importance of nature conservation to visitors, especially students. A variety of educational materials and educational programs linked to regular school curriculum are also being developed.

  6. Measurement of oxidatively-induced clustered DNA lesions using a novel adaptation of single cell gel electrophoresis (comet assay).

    PubMed

    Georgakilas, Alexandros G; Holt, Stewart M; Hair, Jessica M; Loftin, Charles W

    2010-12-01

    The two basic groups of complex DNA damage are double-strand breaks (DSBs) and non-DSB oxidatively-induced clustered DNA lesions (OCDLs). The single-cell gel electrophoresis (SCGE) or comet assay has been widely used for the detection of low levels of various types of DNA lesions including single-strand breaks (SSBs), DSBs, and oxidized bases per individual cell. There are limited data on the use of the comet assay for the detection of non-DSB clustered DNA lesions using different repair enzymes as enzymatic probes. This unit discusses a novel adaptation of the comet assay used to measure these unique types of lesions. Until now OCDL yields have been measured using primarily pulsed-field agarose gel electrophoresis. The advantages offered by the current approach are: (1) measurement of OCDL levels per individual cell; (2) use of a small number of cells (∼10,000) and relatively low doses of ionizing radiation (1 to 2 Gy) or low levels of oxidative stress, which are not compatible with standard agarose gel electrophoresis; and finally, (3) the assay is fast and allows direct comparison with pulsed-field gel electrophoresis results.

  7. Increased numbers of CD4+ and CD8+ T cells in lesional skin of cats with allergic dermatitis.

    PubMed

    Roosje, P J; van Kooten, P J; Thepen, T; Bihari, I C; Rutten, V P; Koeman, J P; Willemse, T

    1998-07-01

    The aim of this study was to characterize T cells in the skin of cats with an allergic dermatitis histologically compatible with atopic dermatitis, since T cells play an important role in the pathogenesis of atopic dermatitis in humans. We observed a significantly greater number of T cells in lesional skin of domestic short-haired cats with allergic dermatitis (n = 10; median age 5.8 years) than in the skin of healthy control animals (n = 10; median age 5.0 years). In the skin of the healthy control animals, one or two CD4+ cells and no CD8+ cells were found. A predominant increase of CD4+ T cells and a CD4+/CD8+ ratio (mean +/- SD: 3.9 +/- 2.0) was found in the lesional skin of 10 cats with allergic dermatitis. The CD4+/CD8+ cell ratio in the skin of healthy control animals could not be determined because of the absence of CD8+ cells. The CD4+/CD8+ cell ratio in the peripheral blood of 10 cats with allergic dermatitis (mean +/- SD: 1.9 +/- 0.4) did not differ significantly from that in 10 healthy control animals (2.2 +/- 0.4). The CD4+/CD8+ cell ratio and predominance of CD4+ T cells in the lesional skin of cats with allergic dermatitis is comparable to that found in atopic dermatitis in humans. In addition, the observed increase of CD4+ T cells in the nonlesional skin of cats with allergic dermatitis compared to the skin of healthy cats is similar to what is seen in humans. Cytokines produced by T cells and antigen-specific T cells are important mediators in the inflammatory cascade resulting in atopic dermatitis in humans. This study is a first step to investigate their role in feline allergic dermatitis.

  8. The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions.

    PubMed

    Alexandre, Ariane Fernandes; Quaresma, Juarez Antonio Simões; Barboza, Tânia Cristina; de Brito, Arival Cardoso; Xavier, Marília Brasil; de Oliveira, Clivia Maria Moraes; Unger, Deborah Aben Athar; Kanashiro-Galo, Luciane; Sotto, Mirian Nacagami; Duarte, Maria Irma Seixas; Pagliari, Carla

    2017-02-01

    Jorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus.

  9. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

    PubMed

    Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

    2015-09-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined.

  10. A type 2 papillary renal cell carcinoma presenting as an intracystic necrotic lesion: A case report

    PubMed Central

    FU, ZHENYU; SUN, LIGUO; HUANG, YUHUA; ZHANG, JIE; ZHANG, ZICHAO; WANG, LIJUN; WANG, SHENGYU; ZHANG, GE

    2013-01-01

    Papillary renal carcinoma (papillary RCC) is a histological subtype of the renal carcinoma, which in turn, has two morphological subtypes that correlate with prognosis. The present study reported an unexpected finding of type 2 papillary renal cell carcinoma (papillary RCC) presenting intracystic necrosis cavity. A cystic renal lesion was identified incidentally in a 66-year-old man during an abdominal computed tomography (CT) scan performed for the evaluation of a gastrointestinal stromal tumor. Subsequent contrast material-enhanced CT scan and magnetic resonance imaging (MRI) examination labeled the mass as category III degree on the basis of the Bosniak classification scheme. Surgical exploration by laparoscopic radical nephrectomy was performed to determine the diagnosis. Definitive pathological study confirmed a type 2 papillary RCC with an intracystic necrosis cavity. To the best of our knowledge, this case demonstrated for the first time a cavity within a papillary RCC, supporting the hypothesis that type 2 papillary RCC could develop cavity avascular necrosis during its cystic degeneration. PMID:24649168

  11. High frequency columnar silicon microresonators for mass detection

    SciTech Connect

    Kehrbusch, J.; Ilin, E. A.; Hullin, M.; Oesterschulze, E.

    2008-07-14

    A simple but effective technological scheme for the fabrication of high frequency silicon columnar microresonators is presented. With the proposed technique the dimensions of the microresonators are controlled on a scale of at least 1 {mu}m. Characterization of the mechanical properties of silicon columns gave resonant frequencies of the lowest flexural mode of 3-7 MHz with quality factors of up to 2500 in air and {approx}8800 under vacuum condition. Columnar microresonators were operated as mass balance with a sensitivity of 1 Hz/fg. A mass detection limit of 25 fg was deduced from experiments.

  12. Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation Is Essential for Functional Regeneration

    PubMed Central

    Tscherter, Anne; Heidemann, Martina; Kleinlogel, Sonja; Streit, Jürg

    2016-01-01

    Presently there exists no cure for spinal cord injury (SCI). However, transplantation of embryonic tissue into spinal cord (SC) lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated SC circuits. We tested the two hypotheses in an in vitro SC lesion model that is based on propagation of activity between two rat organotypic SC slices in culture. Transplantation of dissociated cells from E14 rat SC or forebrain (FB) re-established the relay of activity over the lesion site and thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays (MEAs) we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse FB cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated SC circuits. In contrast, transplantation of neurospheres (NS) induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated SC circuits. PMID:27708562

  13. Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size.

    PubMed

    Devlin, Cecilia M; Kuriakose, George; Hirsch, Emmet; Tabas, Ira

    2002-04-30

    Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.

  14. Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys.

    PubMed

    Barefoot, H C; Baker, H F; Ridley, R M

    2002-02-01

    Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.

  15. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.

    PubMed

    Regnell, Christine Elisabeth; Hildrestrand, Gunn Annette; Sejersted, Yngve; Medin, Tirill; Moldestad, Olve; Rolseth, Veslemøy; Krokeide, Silje Zandstra; Suganthan, Rajikala; Luna, Luisa; Bjørås, Magnar; Bergersen, Linda H

    2012-09-27

    Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

  16. Phenotypic characterization and genetic diversity of Flavobacterium columnare isolated from red tilapia, Oreochromis sp. in Thailand

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the etiologic agent of columnaris disease and severely affects various freshwater aquaculture fish species worldwide. The objectives of this study were to determine the phenotypic characteristics and genetic variability among F. columnare isolates isolated from red tilapi...

  17. Gastrointestinal tract spindle cell lesions--just like real estate, it's all about location.

    PubMed

    Voltaggio, Lysandra; Montgomery, Elizabeth A

    2015-01-01

    Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

  18. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

    PubMed

    Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark

    2003-04-01

    Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

  19. Research Note Mesenchymal stem cells from skin lesions of psoriasis patients promote proliferation and inhibit apoptosis of HaCaT cells.

    PubMed

    Liu, R F; Wang, F; Wang, Q; Zhao, X C; Zhang, K M

    2015-12-22

    Psoriasis is an inflammatory skin disease characterized by excessive proliferation and abnormal differentiation and apoptosis of keratinocytes (KCs). Mesenchymal stem cells (MSCs) from skin lesions of psoriasis patients demonstrate abnormal cytokine secretion, which may affect KC proliferation and apoptosis. Here, we explored how MSCs from skin lesions of psoriasis patients affect HaCaT cell proliferation and apoptosis. First, flow cytometry and multipotent differentiation methods were used to identify skin MSCs, which were then co-cultured with HaCaT cells. HaCaT cell proliferation was analyzed in real-time, and cell cycle progression and apoptosis were assessed by flow cytometry. Cell morphologies and multipotencies of skin MSCs were similar between the psoriasis group and healthy control group, with high levels of CD29, CD44, CD73, CD90, and CD105 and limited expression of CD34, CD45, and HLA-DR. MSCs from skin lesions of psoriasis patients promote KC proliferation more potently and are less capable of inducing KC apoptosis. This may underlie KC proliferation and abnormal apoptosis in psoriasis skin lesions, which results in abnormal thickening of the epidermis.

  20. Ungeremine and its hemisynthetic analogues as bactericides against Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Gram-negative bacterium Flavobacterium columunare is the cause of colmunaris disease in channel catfish (Ictalurus punctatus). In a previous study, the betaine-type alkaloid ungeremine, 1 obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. ...

  1. Chemotactic response of Flavobacterium columnare to channel catfish mucus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has demonstrated that genomovar II Flavobacterium columnare isolates are more pathogenic for channel catfish (Ictalurus punctatus) and have a higher capacity for adhesion than genomovar I isolates. To begin to define the basis for this, the objectives of the present study were to determine...

  2. Activities of wogonin analogs and other flavones against Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In our continuing pursuit to discover natural products and natural product-based compounds for the control of the bacterial species Flavobacterium columnare which causes columnaris disease in channel catfish (Ictalurus punctatus), we synthesized eighteen flavone and three chalcone analogues and thes...

  3. Columnar organization of orientation domains in V1

    NASA Astrophysics Data System (ADS)

    Liedtke, Joscha; Wolf, Fred

    In the primary visual cortex (V1) of primates and carnivores, the functional architecture of basic stimulus selectivities appears similar across cortical layers (Hubel & Wiesel, 1962) justifying the use of two-dimensional cortical models and disregarding organization in the third dimension. Here we show theoretically that already small deviations from an exact columnar organization lead to non-trivial three-dimensional functional structures. We extend two-dimensional random field models (Schnabel et al., 2007) to a three-dimensional cortex by keeping a typical scale in each layer and introducing a correlation length in the third, columnar dimension. We examine in detail the three-dimensional functional architecture for different cortical geometries with different columnar correlation lengths. We find that (i) topological defect lines are generally curved and (ii) for large cortical curvatures closed loops and reconnecting topological defect lines appear. This theory extends the class of random field models by introducing a columnar dimension and provides a systematic statistical assessment of the three-dimensional functional architecture of V1 (see also (Tanaka et al., 2011)).

  4. Antibacterial activity of acylglucinol derivatives against Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease is one of the most common bacterial diseases of pond-raised channel catfish (Ictalurus punctatus) in the southeastern United States of America. The Gram-negative, rod-shaped bacterium Flavobacterium columnare is the cause of columnaris disease. Direct economic losses to catfish pr...

  5. Parasitism by Ich enhanced susceptibility of tilapia to Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In aquaculture systems, fish are commonly infected by two or more pathogens. Bacterium Flavobacterium columnare and parasite Ichthyophthirius multifiliis (Ich) are two common pathogens of cultured fish and result in heavy economic losses for aquaculture. There is no published information available ...

  6. Suppression of Medulloblastoma Lesions by Forced Migration of Preneoplastic Precursor Cells with Intracerebellar Administration of the Chemokine Cxcl3

    PubMed Central

    Ceccarelli, Manuela; Micheli, Laura; Tirone, Felice

    2016-01-01

    Medulloblastoma (MB), tumor of the cerebellum, remains a leading cause of cancer-related mortality in childhood. We previously showed, in a mouse model of spontaneous MB (Ptch1+/-/Tis21-/-), that a defect of the migration of cerebellar granule neuron precursor cells (GCPs) correlates with an increased frequency of MB. This occurs because GCPs, rather than migrating internally and differentiating, remain longer in the proliferative area at the cerebellar surface, becoming targets of transforming insults. Furthermore, we identified the chemokine Cxcl3 as responsible for the inward migration of GCPs. As it is known that preneoplastic GCPs (pGCPs) can still migrate and differentiate like normal GCPs, thus exiting the neoplastic program, in this study we tested the hypothesis that pGCPs within a MB lesion could be induced by Cxcl3 to migrate and differentiate. We observed that the administration of Cxcl3 for 28 days within the cerebellum of 1-month-old Ptch1+/-/Tis21-/- mice, i.e., when MB lesions are already formed, leads to complete disappearance of the lesions. However, a shorter treatment with Cxcl3 (2 weeks) was ineffective, suggesting that the suppression of MB lesions is dependent on the duration of Cxcl3 application. We verified that the treatment with Cxcl3 causes a massive migration of pGCPs from the lesion to the internal granular layer, where they differentiate. Thus, the induction of migration of pGCPs in MB lesions may open new ways to treat MB that exploit the plasticity of the pGCPs, forcing their differentiation. It remains to be tested whether this plasticity continues at advanced stages of MB. If so, these findings would set a potential use of the chemokine Cxcl3 as therapeutic agent against MB development in human preclinical studies. PMID:28018222

  7. Insights into red blood cell storage lesion: Toward a new appreciation.

    PubMed

    Antonelou, Marianna H; Seghatchian, Jerard

    2016-12-01

    Red blood cell storage lesion (RSL) is a multifaceted biological phenomenon. It refers to deterioration in RBC quality that is characterized by lethal and sub-lethal, reversible and irreversible defects. RSL is influenced by prestorage variables and it might be associated with variable clinical outcomes. Optimal biopreservation conditions are expected to offer maximum levels of RBC survival and acceptable functionality and bioreactivity in-bag and in vivo; consequently, full appraisal of RSL requires understanding of how RSL changes interact with each other and with the recipient. Recent technological innovation in MS-based omics, imaging, cytometry, small particle and systems biology has offered better understanding of RSL contributing factors and effects. A number of elegant in vivo and in vitro studies have paved the way for the identification of quality control biomarkers useful to predict RSL profile and posttransfusion performance. Moreover, screening tools for the early detection of good or poor "storers" and donors have been developed. In the light of new perspectives, storage time is not the touchstone to rule on the quality of a packed RBC unit. At least by a biochemical standpoint, the metabolic aging pattern during storage may not correspond to the currently fresh/old distinction of stored RBCs. Finally, although each unit of RBCs is probably unique, a metabolic signature of RSL across storage variables might exist. Moving forward from traditional hematologic measures to integrated information on structure, composition, biochemistry and interactions collected in bag and in vivo will allow identification of points for intervention in a transfusion meaningful context.

  8. Skin lesion removal

    MedlinePlus

    ... removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; Mole - removal; Nevus - removal; ... can remove: Benign or pre-malignant skin lesions Warts Moles Sunspots Hair Small blood vessels in the ...

  9. Mechanistic modelling suggests that the size of preneoplastic lesions is limited by intercellular induction of apoptosis in oncogenically transformed cells

    PubMed Central

    Kundrát, Pavel; Bauer, Georg; Jacob, Peter; Friedland, Werner

    2012-01-01

    Selective removal of oncogenically transformed cells by apoptosis induced via signalling by surrounding cells has been suggested to represent a natural anticarcinogenic process. To investigate its potential effect in detail, a mechanistic model of this process is proposed. The model is calibrated against in vitro data on apoptosis triggered in transformed cells by defined external inducers as well as through signalling by normal cells under coculture conditions. The model predicts that intercellular induction of apoptosis is capable of balancing the proliferation of oncogenically transformed cells and limiting the size of their populations over long times, even if their proliferation per se were unlimited. Experimental research is desired to verify whether the predicted stable population of transformed cells corresponds to a kind of dormancy during early-stage carcinogenesis (dormant preneoplastic lesions), and how this process relates to other anticarcinogenic mechanisms taking place under in vivo conditions. PMID:22045028

  10. FoxP3+ T regulatory cells in oral lichen planus and its correlation with the distinct clinical appearance of the lesions

    PubMed Central

    Pereira, Joabe S; Monteiro, Bárbara V; Nonaka, Cassiano F; Silveira, Éricka J; Miguel, Márcia C

    2012-01-01

    The aim of this study was to evaluate the presence of FoxP3+ cells in oral lichen planus (OLP) and to correlate the findings with clinical and histopathological features of these lesions. The sample consisted of 32 cases of OLP (17 reticular and 15 erosive cases) and 10 cases of inflammatory fibrous hyperplasia (IFH). Clinical examination, histopathological and histomorphometric analysis, and immunohistochemistry (anti-FoxP3 antibody) were performed. Cells were counted in juxtaepithelial and intraepithelial regions of the lesions, and the results are expressed as the mean and range. Most erosive lesions were keratinized and exhibited epithelial atrophy, whereas most reticular lesions were hyperkeratinized. Mean epithelial thickness and mean density of the inflammatory infiltrate were higher in reticular lesions than in erosive OLP. Juxtaepithelial FoxP3+ cells were slightly more frequent in erosive lesions (mean: 1.7 and range: 0–9.4) than in reticular lesions (mean: 1.5 and range: 0–8.3). There was a significant difference in the frequency of these cells between OLP (mean: 1.6 and range: 0–9.4) and IFH (mean: 0.5 and range: 0–1.4) (P < 0.05). The number of intraepithelial FoxP3+ cells was higher in reticular OLP and IFH when compared with erosive lesions. The larger number of juxtaepithelial FoxP3+ cells in OLP compared to IFH might be related to the distinct etiopathogenesis of these lesions. High disease activity or action of the oral microbiota may explain the slightly higher frequency of FoxP3+ cells in erosive lesions. PMID:22804765

  11. Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal vascular lesion in patients with lupus nephritis.

    PubMed

    Yao, G H; Liu, Z H; Zhang, X; Zheng, C X; Chen, H P; Zeng, C H; Li, L S

    2008-08-01

    Currently, the detection of renal vascular lesions (VLS) in lupus nephritis (LN) mainly depends on biopsy examination, and lack surrogate biomarkers for clinical dynamic evaluation. The aim of the present study is to explore the correlation between circulatory endothelial damage biomarkers and VLS. Soluble E-selectin, thrombomodulin (TM) and vascular cell adhesion molecule-1 (VCAM-1) were measured by ELISA. TM and VCAM-1 levels both were significantly elevated in LN with VLS than in LN without VLS (P < 0.01). However, the serum E-selectin was not significantly changed in LN patients with and without VLS. A positive correlation was found between TM and serum creatinine (r = 0.617, P < 0.05) in patients with vascular lesions. In order to further analyse the relationship between TM level and severity degree of vascular lesions in LN patients, we subdivided the patients with vascular lesions into two groups: with thrombotic microangiopathy (TMA) and without TMA. TM level of the patients with TMA is significantly higher than those without TMA (P < 0.01). In conclusion, combined with renal pathological examination, monitoring the circulatory levels of TM and VCAM-1, can provide circulating biomarkers of VLS in LN patients.

  12. Effective staining method with iodine for leukoplakia and lesions surrounding squamous cell carcinomas of the tongue assessed by colorimetric analysis.

    PubMed

    Maeda, Keiko; Yamashiro, Masashi; Michi, Yasuyuki; Suzuki, Tetsuo; Ohyama, Yoshio; Okada, Norihiko; Amagasa, Teruo

    2009-12-01

    To determine whether staining with iodine solution provides an efficient criterion for determining the area of resection for the lesions surrounding squamous cell carcinoma (SCC) and leukoplakia of the tongue, we determined the optimum density of iodine solution and staining procedure and analyzed the color of lightly stained lesions (LSLs) in relation to the histopathologic findings. Sixty-five patients with SCC or leukoplakia of the tongue were divided into two groups: lesions stained with 3% Lugol solution and restained with either 5% Lugol solution (n=38) or 10% iodine glycerin (n=27). Among the lesions stained with 5% Lugol solution, significant differences were found in all color values. Color difference values (DeltaE*ab) using 3% and 5% Lugol solutions were significantly different between epithelial hyperplasia/mild epithelial dysplasia and moderate to severe dysplasia (P < 0.05). According to the evaluations of five clinicians in 46 LSLs, a distinctive boundary was most often obtained using 5% Lugol solution. These results suggest that the most effective method for obtaining a clear boundary and distinguishing moderate to severe dysplasia from mild or no epithelial dysplasia according to the measured color value was to stain with 3% followed by 5% Lugol solution.

  13. Natural and lesion-induced decrease in cell proliferation in the medial nucleus of the trapezoid body during hearing development.

    PubMed

    Saliu, Aminat; Adise, Shana; Xian, Sandy; Kudelska, Kamila; Rodríguez-Contreras, Adrián

    2014-04-01

    The functional interactions between neurons and glial cells that are important for nervous system function are presumably established during development from the activity of progenitor cells. In this study we examined proliferation of progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in the rat auditory brainstem. We performed DNA synthesis labeling experiments to demonstrate changes in cell proliferation activity during postnatal stages of development. An increase in cell proliferation correlated with MNTB growth and the presence of S100β-positive astrocytes among MNTB neurons. In additional experiments we analyzed the fate of newly born cells. At perinatal ages, newly born cells colabeled with the astrocyte marker S100β in higher numbers than when cells were generated at postnatal day 6. Furthermore, we identified newly born cells that were colabeled with caspase-3 immunohistochemistry and performed comparative experiments to demonstrate that there is a natural decrease in cell proliferation activity during postnatal development in rats, mice, gerbils, and ferrets. Lastly, we found that there is a stronger decrease in MNTB cell proliferation after performing bilateral lesions of the auditory periphery in rats. Altogether, these results identify important stages in the development of astrocytes in the MNTB and provide evidence that the proliferative activity of the progenitor cells is developmentally regulated. We propose that the developmental reduction in cell proliferation may reflect coordinated signaling between the auditory brainstem and the auditory periphery.

  14. [Femoral osteolytic lesions with soft tissue tumors and hypercalcemia as presentation form of a B-cell lymphoma].

    PubMed

    Hernández Hernández, J L; Olmos Martínez, J M; Figols Ladrón de Guevara, J; Riancho Moral, J A; González Macías, J

    2000-05-01

    Hypercalcemia associated with haematological neoplasms account for 15 to 20% of hipercalcemia in malignancy, and occurs usually in patients with multiple myeloma. However, its incidence in patients with linfoma is low, and it is observed usually in T-cell linfomas. Bone affectation is also uncommon in patients with non-Hodgkin linfoma. It usually is seen as a late manifestation of the disease, and its occurrence as the form of presentation is exceptional. We hereby report a patient with a B-cell non-Hodgkin linfoma presenting with hypercalcemia and femoral osteolytic lesions.

  15. Ultrastructural Characterization of Hyperactive Endothelial Cells, Pericytes and Fibroblasts in Hypertrophic and Nodular Port Wine Stain Lesions.

    PubMed

    Gao, L; Yin, R; Wang, H; Guo, W; Song, W; Nelson, J S; Tan, W; Wang, G

    2017-02-09

    Port wine stain (PWS) is a congenital vascular malformation of human skin involving the superficial vascular plexus,(1-4) but the molecular pathogenesis of these lesions remains incompletely understood.(5-8) We herein performed a transmission electron microscopy (TEM) study to determine the main pathological characteristics and ultrastructure of various cell types, including endothelial cells (ECs), pericytes, fibroblasts and keratinocytes, in hypertrophic and nodular PWS. The study was approved by the Investigational Review Board at the Xijing Hospital, Xi'an, China. This article is protected by copyright. All rights reserved.

  16. Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice

    PubMed Central

    Harry, Brian L.; Sanders, John M.; Feaver, Ryan E.; Lansey, Melissa; Deem, Tracy L.; Zarbock, Alexander; Bruce, Anthony C.; Pryor, Andrew W.; Gelfand, Bradley D.; Blackman, Brett R.; Schwartz, Martin A.; Ley, Klaus

    2009-01-01

    Objective Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) has recently been shown to form an essential element of a mechanosensory complex that mediates endothelial responses to fluid shear stress. The aim of this study was to determine the in vivo role of PECAM-1 in atherosclerosis. Methods and Results We crossed C57BL/6 Pecam1−/− mice with apolipoprotein E–deficient (Apoe−/−) mice. On a Western diet, Pecam1−/−Apoe−/− mice showed reduced atherosclerotic lesion size compared to Apoe−/− mice. Striking differences were observed in the lesser curvature of the aortic arch, an area of disturbed flow, but not in the descending thoracic or abdominal aorta. Vascular cell adhesion molecule-1 (VCAM-1) expression, macrophage infiltration, and endothelial nuclear NF-κB were all reduced in Pecam1−/−Apoe−/− mice. Bone marrow transplantation suggested that endothelial PECAM-1 is the main determinant of atherosclerosis in the aortic arch, but that hematopoietic PECAM-1 promotes lesions in the abdominal aorta. In vitro data show that siRNA-based knockdown of PECAM-1 attenuates endothelial NF-κB activity and VCAM-1 expression under conditions of atheroprone flow. Conclusion These results indicate that endothelial PECAM-1 contributes to atherosclerotic lesion formation in regions of disturbed flow by regulating NF-κB–mediated gene expression. PMID:18688018

  17. Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome

    PubMed Central

    Shin, Jessica; Monti, Stefano; Aires, Daniel J.; Duvic, Madeleine; Golub, Todd

    2007-01-01

    Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. PMID:17638852

  18. Agonistic Anti-TIGIT Treatment Inhibits T Cell Responses in LDLr Deficient Mice without Affecting Atherosclerotic Lesion Development

    PubMed Central

    Foks, Amanda C.; Ran, Ingrid A.; Frodermann, Vanessa; Bot, Ilze; van Santbrink, Peter J.; Kuiper, Johan; van Puijvelde, Gijs H. M.

    2013-01-01

    Objective Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. Methods and Results TIGIT was upregulated on CD4+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr−/− mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. Conclusions Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells. PMID:24376654

  19. Plasma cell dyscrasia with polyneuropathy--POEMS syndrome presenting with vasculitic skin lesions and responding to combination chemotherapy.

    PubMed

    Sharabi, Y; Raanani, P; Shenkar, A; Thaler, M; Grossman, E

    2000-12-01

    We report a 61-year-old male patient who presented with severe sensorimotor neuropathy, leg edema and skin lesions with M-paraprotein and 50% plasma cells in the bone marrow. The POEMS (Crow-Fukase) syndrome was diagnosed and the skin lesions were compatible with vasculitis according to the histopathology. The patient was treated with aggressive combined chemotherapy, which induced improvement in both the clinical and laboratory parameters of his disease. To the best of our knowledge this is the first report of a vasculitic process underlying the skin changes in the POEMS syndrome. Our findings may shed light on the unknown pathogenesis of this syndrome and the successful results of treatment support the adoption of an aggressive therapeutic approach in symptomatic patients.

  20. Cellular, columnar and modular organization of spatial representations in medial entorhinal cortex.

    PubMed

    Burgalossi, Andrea; Brecht, Michael

    2014-02-01

    Spatial discharge patterns in medial entorhinal cortex consist of grid, head direction, border and spatial-band cells. These firing patterns differ from the single-peaked fields of hippocampal place cells, in that they have well-defined geometries and extend throughout the available space. Such discharge properties could contribute to a metric representation of space. Both functional and anatomical evidence point to principal cell diversity, modularity and columnar organization, but linking entorhinal anatomy and physiology remains challenging. Layer 2 microcircuits consist of pyramidal neurons and a stellate cell network, which lacks recurrent excitation and is coupled by disynaptic inhibition. Intracellular recordings showed that periodic, grid-like firing emerges from depolarization ramps, whereas theta-oscillations determine spike timing. Interference with various inputs to entorhinal cortex abolishes grid activity, often without concomitant loss of hippocampal place activity.

  1. Adult Bone Marrow Neural Crest Stem Cells and Mesenchymal Stem Cells Are Not Able to Replace Lost Neurons in Acute MPTP-Lesioned Mice

    PubMed Central

    Neirinckx, Virginie; Marquet, Alice; Coste, Cécile

    2013-01-01

    Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC) or mesenchymal stem cells (MSC) survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management. PMID:23741377

  2. Columnar grown copper films on polyimides strained beyond 100%

    PubMed Central

    Sun, Jeong-Yun; Lee, Hae-Ryung; Hwan Oh, Kyu

    2015-01-01

    Many flexible electronic devices contain metal films on polymer substrates to satisfy requirements for both electrical conductivity and mechanical durability. Despite numerous trials to date, the stretchability of metal interconnects remains an issue. In this paper, we have demonstrated a stretchable metal interconnect through control of the texture of a copper film with columnar grown grains on a polyimide (PI) substrate. The columnar grown copper films (CGC films) were deposited by regulating radio frequency (RF) sputtering powers. CGC films were able to sustain their electrical conductivity at strains above 100%. Instead of ultimate electrical discontinuity by channel crack propagation, CGC films maintained their conductivity by forming ligament structures, or a ‘conductive net,’ through trapped micro-cracks. XRD, AFM and in situ SEM analysis were used to investigate these stretchable conductors. PMID:26337668

  3. Columnar mesophases of hexabenzocoronene derivatives. II. Charge carrier mobility

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, James; Marcon, Valentina; Kremer, Kurt; Nelson, Jenny; Andrienko, Denis

    2008-09-01

    Combining atomistic molecular dynamic simulations, Marcus-Hush theory description of charge transport rates, and master equation description of charge dynamics, we correlate the temperature-driven change of the mesophase structure with the change of charge carrier mobilities in columnar phases of hexabenzocoronene derivatives. The time dependence of fluctuations in transfer integrals shows that static disorder is predominant in determining charge transport characteristics. Both site energies and transfer integrals are distributed because of disorder in the molecular arrangement. It is shown that the contributions to the site energies from polarization and electrostatic effects are of opposite sign for positive charges. We look at three mesophases of hexabenzocoronene: herringbone, discotic, and columnar disordered. All results are compared to time resolved microwave conductivity data and show excellent agreement with no fitting parameters.

  4. Modular columnar supramolecular polymers as scaffolds for biomedical applications.

    PubMed

    Petkau-Milroy, Katja; Sonntag, Michael H; Brunsveld, Luc

    2013-08-12

    Self-assembly of discotic molecules into supramolecular polymers offers a flexible approach for the generation of multicomponent one-dimensional columnar architectures with tuneable biomedical properties. Decoration with ligands induces specific binding of the self-assembled scaffold to biological targets. The modular design allows the easy co-assembly of different discotics for the generation of probes for targeted imaging and cellular targeting with adjustable ligand density and composition.

  5. Ballistic performance of oriented columnar-grained tungsten polycrystals

    SciTech Connect

    Leonard, W.; Magness, L.S.; Dowding, R.J.; Trogolo, J.; Chung, M.; Kapoor, D.

    1996-06-01

    Prior ballistic tests have demonstrated that the crystallographic orientation of a single crystal tungsten penetrator with respect to the penetrator axis influences penetration performance. The difference in penetration performance is attributed to anisotropy of the flow and failure of the monocrystalline tungsten penetrators during the penetration of the armor target. In preliminary ballistic experiments, the performance and deformation behaviors of polycrystalline tungsten penetrators having columnar grains oriented in the [100], [110], or [111] crystallographic directions were explored.

  6. Virulence of Flavobacterium columnare genomovars in rainbow trout Oncorhynchus mykiss.

    PubMed

    Evenhuis, Jason P; LaFrentz, Benjamin R

    2016-08-09

    Flavobacterium columnare is the causative agent of columnaris disease and is responsible for significant economic losses in aquaculture. F. columnare is a Gram-negative bacterium, and 5 genetic types or genomovars have been described based on restriction fragment length polymorphism of the 16S rRNA gene. Previous research has suggested that genomovar II isolates are more virulent than genomovar I isolates to multiple species of fish, including rainbow trout Oncorhynchus mykiss. In addition, improved genotyping methods have shown that some isolates previously classified as genomovar I, and used in challenge experiments, were in fact genomovar III. Our objective was to confirm previous results with respect to genomovar II virulence, and to determine the susceptibility of rainbow trout to other genomovars. The virulence of 8 genomovar I, 4 genomovar II, 3 genomovar II-B, and 5 genomovar III isolates originating from various sources was determined through 3 independent challenges in rainbow trout using an immersion challenge model. Mean cumulative percent mortality (CPM) of ~49% for genomovar I isolates, ~1% for genomovar II, ~5% for the II-B isolates, and ~7% for the III isolates was observed. The inability of genomovar II isolates to produce mortalities in rainbow trout was unanticipated based on previous studies, but may be due to a number of factors including rainbow trout source and water chemistry. The source of fish and/or the presence of sub-optimal environment may influence the susceptibility of rainbow trout to different F. columnare genomovars.

  7. Large-scale columnar vortices in rotating turbulence

    NASA Astrophysics Data System (ADS)

    Yokoyama, Naoto; Takaoka, Masanori

    2016-11-01

    In the rotating turbulence, flow structures are affected by the angular velocity of the system's rotation. When the angular velocity is small, three-dimensional statistically-isotropic flow, which has the Kolmogorov spectrum all over the inertial subrange, is formed. When the angular velocity increases, the flow becomes two-dimensional anisotropic, and the energy spectrum has a power law k-2 in the small wavenumbers in addition to the Kolmogorov spectrum in the large wavenumbers. When the angular velocity decreases, the flow returns to the isotropic one. It is numerically found that the transition between the isotropic and anisotropic flows is hysteretic; the critical angular velocity at which the flow transitions from the anisotropic one to the isotropic one, and that of the reverse transition are different. It is also observed that the large-scale columnar structures in the anisotropic flow depends on the external force which maintains a statistically-steady state. In some cases, small-scale anticyclonic structures are aligned in a columnar structure apart from the cyclonic Taylor column. The formation mechanism of the large-scale columnar structures will be discussed. This work was partially supported by JSPS KAKENHI.

  8. Occurrence in vivo of sister chromatid exchanges at the same locus in successive cell divisions caused by nonrepairable lesions induced by gamma rays.

    PubMed

    Morales-Ramírez, P; Vallarino-Kelly, T; Rodríguez-Reyes, R

    1988-01-01

    The capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three-way differentiation of sister chromatids. Evidence was obtained that exposure to gamma radiation induces DNA lesions that result in the formation of SCE at the same locus in two successive cell divisions. The relevance of this observation with respect to DNA repair and mutagenesis is discussed.

  9. [Oral squamous cell carcinoma and lichen planus vs. lichenoid lesions. Case report].

    PubMed

    Esquivel-Pedraza, Lilly; Fernández-Cuevas, Laura; Ruelas-Villavicencio, Ana Lilia; Guerrero-Ramos, Brenda; Hernández-Salazar, Amparo; Milke-García, María Pilar; Méndez-Flores, Silvia

    2016-01-01

    Introducción: el desarrollo de carcinoma escamocelular a partir del liquen plano bucal es controversial. Describimos un caso con carcinoma escamocelular intrabucal, que cursa con lesiones de liquen plano bucal y se analizan las dificultades para distinguir los cambios incipientes del carcinoma escamocelular de las lesiones por liquen plano intrabucales que lleven a establecer un diagnóstico certero de ambas entidades. Caso clínico: hombre de 57 años, con antecedente de tabaquismo y hábito alcohólico crónico, que presenta lesión tumoral ulcerada en borde lateral izquierdo de lengua y placas blancas reticulares bilaterales en mucosa yugal, bordes laterales y vientre de lengua. El reporte histopatológico fue de carcinoma escamocelular invasor moderadamente diferenciado y liquen plano respectivamente. Conclusiones: la naturaleza premaligna del liquen plano bucal es controvertida, esto por inconsistencia en los criterios diagnóstico clínicos e histológicos que permitan diferenciar los casos de liquen plano bucal de otras lesiones como las reacciones liquenoides o displasias intraepiteliales con alto potencial de malignización. Posiblemente las reacciones liquenoides bucales tienen un mayor riesgo de transformación maligna al compararse con el clásico liquen plano bucal.

  10. Unraveling the Gordian knot: red blood cell storage lesion and transfusion outcomes

    PubMed Central

    Tzounakas, Vassilis L.; Kriebardis, Anastasios G.; Seghatchian, Jerard; Papassideri, Issidora S.; Antonelou, Marianna H.

    2017-01-01

    What is following the impressive progress that has been made? During the last couple of years several tremors have shaken the field of Transfusion Medicine. The epicentres of those tremors were located on novel insights into the RBC storage lesion, on emerging connections between storage lesion and post-transfusion performance and effects, and on acknowledging that storage time is only one (rather than the most prominent) of the parameters which contribute to the progression of storage lesion in any given unit of blood. The optimisation of bio-preservation conditions emerged at the same time with all-new scientific knowledge gained by advances in research tools, implementation of technological innovations, and application of elegant in vitro and in vivo models of transfusion. Simultaneously, one after another, all the reported randomised clinical trials concluded, with spectacular consensus, that there is no significant difference in the rate of adverse clinical events (including death) among patients who underwent transfusion with fresh (and presumably good) or standard of care (and presumably bad) blood. The comparative analysis and comprehension of the aforementioned data would set the context for the next generation of research in blood transfusion science, since the need for safer and more efficient transfusions remains. PMID:28263169

  11. Study of columnar-equiaxed transition and anaxial columnar dendrites growth of hypoeutectic alloy with synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Li, F. G.; Zhang, J.; Dong, Q.; Dai, Y. B.; Sun, B. D.; Xie, H. L.

    2013-10-01

    Among solidification processes, the columnar to equiaxed transition (CET) is critical component for formation either of microstructure or macrostructure. Directional solidification of Al-Cu alloy was performed at the BL13W beamline of Shanghai Synchrotron Radiation Facility (SSRF). The imaging results reveal that CET was provoked by external thermal disturbance. The fragment of dendrite tips were come from solute-rich-zone. And they floated to the mushy zone to form the equiaxed dendrites. As the conditions are suitable, a new dendrite morphology sprout and grow up, in which dendrites grow along <110> directions in a binary Al-Cu alloy. These dendrites have no obvious primary arms and were named anaxial columnar dendrites.

  12. Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

    PubMed

    Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

    2016-09-01

    Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy.

  13. Viral Infection Induces De Novo Lesions of Coronary Allograft Vasculopathy through a Natural Killer Cell-Dependent Pathway

    PubMed Central

    Graham, Jay A.; Wilkinson, Robert A.; Hirohashi, Tsutomu; Chase, Catharine M.; Colvin, Robert B.; Madsen, Joren C.; Fishman, Jay A.; Russell, Paul S.

    2009-01-01

    Viral infections including those due to cytomegalovirus (CMV) have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG−/−). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus (LCMV) but not in uninfected controls. This process was also dependent upon the presence of NK cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell dependent pathway in the absence of T- and B-lymphocytes. PMID:19843029

  14. Topology of ON and OFF inputs in visual cortex enables an invariant columnar architecture.

    PubMed

    Lee, Kuo-Sheng; Huang, Xiaoying; Fitzpatrick, David

    2016-05-05

    Circuits in the visual cortex integrate the information derived from separate ON (light-responsive) and OFF (dark-responsive) pathways to construct orderly columnar representations of stimulus orientation and visual space. How this transformation is achieved to meet the specific topographic constraints of each representation remains unclear. Here we report several novel features of ON-OFF convergence visualized by mapping the receptive fields of layer 2/3 neurons in the tree shrew (Tupaia belangeri) visual cortex using two-photon imaging of GCaMP6 calcium signals. We show that the spatially separate ON and OFF subfields of simple cells in layer 2/3 exhibit topologically distinct relationships with the maps of visual space and orientation preference. The centres of OFF subfields for neurons in a given region of cortex are confined to a compact region of visual space and display a smooth visuotopic progression. By contrast, the centres of the ON subfields are distributed over a wider region of visual space, display substantial visuotopic scatter, and have an orientation-specific displacement consistent with orientation preference map structure. As a result, cortical columns exhibit an invariant aggregate receptive field structure: an OFF-dominated central region flanked by ON-dominated subfields. This distinct arrangement of ON and OFF inputs enables continuity in the mapping of both orientation and visual space and the generation of a columnar map of absolute spatial phase.

  15. Topology of ON and OFF inputs in visual cortex enables an invariant columnar architecture

    PubMed Central

    Lee, Kuo-Sheng; Huang, Xiaoying; Fitzpatrick, David

    2016-01-01

    Circuits in visual cortex integrate the information derived from separate ON and OFF pathways to construct orderly columnar representations of orientation and visual space1–7. How this transformation is achieved to meet the specific topographic constraints of each representation remains unclear. Here we report several novel features of ON/OFF convergence visualized by mapping the receptive fields of layer 2/3 neurons in tree shrew visual cortex using two-photon imaging of GCaMP6 calcium signals. The spatially separate ON and OFF subfields of simple cells in layer 2/3 were found to exhibit topologically distinct relationships with the maps of visual space and orientation preference. The centers of OFF subfields for neurons in a given region of cortex were confined to a compact region of visual space and displayed a smooth visuotopic progression. In contrast, the centers of the ON subfields were distributed over a wider region of visual space, displayed significant visuotopic scatter, and an orientation-specific displacement consistent with orientation preference map structure. As a result, cortical columns exhibit an invariant aggregate receptive field structure: an OFF-dominated central region flanked by ON-dominated subfields. This distinct arrangement of ON- and OFF- inputs enables continuity in the mapping of both orientation and visual space and the generation of a columnar map of absolute spatial phase. PMID:27120162

  16. Amelioration of sensory attention and sensorimotor deficits by chromaffin cell grafts to the cerebral cortex of nucleus basalis magnocellularis lesioned rats.

    PubMed

    Welner, S A; Koty, Z C

    1993-12-31

    Rats that have received lesions to the nucleus basalis magnocellularis display with a variety of behavioral deficits; among these are decreases in performance of maze tests as well as deficiencies on measures of general health, sensory attention and sensorimotor abilities. We have previously shown that grafts of chromaffin cells placed in the cerebral cortex of nucleus basalis magnocellularis lesioned rats can ameliorate the lesion-induced deficits in performance of a task involving spatial memory. In the present study, we find that lesion-induced deficits in the sensory attention measure of exploration of the environment (head scanning) as well as the sensorimotor behavior involving a rat righting itself when placed nose down on an inclined grid are evident at 8 weeks post-lesion in lesioned-alone rats; these deficits are significantly ameliorated by chromaffin cell grafts in the cerebral cortex placed two weeks following the lesion procedure. These findings may have relevance to the use of chromaffin cells for grafting in neurodegenerative disorders in which sensorimotor or attention deficit components are involved.

  17. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

    PubMed Central

    Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

    2015-01-01

    The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C) (80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to vitamin D-sufficient +NTCU (SN)); DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -fold (p <0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

  18. Estradiol alters cell growth in nonmalignant colonocytes and reduces the formation of preneoplastic lesions in the colon.

    PubMed

    Weige, Charles C; Allred, Kimberly F; Allred, Clinton D

    2009-12-01

    Numerous clinical and animal studies show that hormone replacement therapy reduces the risk of colon tumor formation. However, the majority of experiments have shown that estradiol (E(2)) does not inhibit the growth of malignantly transformed colon epithelia. As such, the presented studies focused on evaluating the effects of E(2) in noncancerous colonocytes. E(2) treatments (0-10 nmol/L) reduced cell growth and increased apoptotic activity in young adult mouse colonocytes (YAMC), a nonmalignant cell line, in a dose-responsive manner. These effects were lost in the YAMC-Ras cells, an isogenic cell line with a single malignant transformation. Cotreatment with an estrogen receptor (ER) antagonist inhibited the physiologic effects of E(2) in YAMC cells, suggesting that the response is ER mediated. To further study the effect of E(2) on colonic epithelia, we evaluated the development of preneoplastic lesions in ovariectomized wild-type (WT) and ERbeta knockout (ERbetaKO) mice treated with either vehicle or E(2). WT E(2)-treated animals exhibited significantly fewer aberrant crypt foci and increased apoptotic activity in colonic epithelia when compared with WT control mice or ERbetaKO animals receiving either treatment. For the first time, we showed that E(2) alters the growth of nontransformed colonocytes in vitro and that, through an ERbeta-mediated mechanism, E(2) influences the physiology of noncancerous colonocytes, resulting in fewer preneoplastic lesions. Collectively, these data show that the protective actions of E(2) occur primarily during the initiation/promotion stages of disease development and identify the hormone as an important chemoprotective agent.

  19. Construction of two selectable markers for integrative/conjugative plasmids in Flavobacterium columnare

    NASA Astrophysics Data System (ADS)

    Zhang, Jin; Zou, Hong; Wang, Liangfa; Huang, Bei; Li, Nan; Wang, Guitang; Nie, Pin

    2012-03-01

    Flavobacterium columnare, the etiological agent of columnaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable markers (chloramphenicol and spectinomycin resistance) for gene transfer in F. columnare. These two new artificial selectable markers, which were created by placing the chloramphenicol or spectinomycin resistance gene under the control of the native acs regulatory region of F. columnare, were functional in both F. columnare and Escherichia coli. The integrative/conjugative plasmids constructed by using these markers were introduced into F. columnare G4 via electroporation or conjugation. The integrated plasmid DNA was confirmed by Southern blotting and PCR analysis. These two markers can be employed in future investigations into gene deletion and the pathogenicity of virulence factors in F. columnare.

  20. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases.

    PubMed

    Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique

    2015-11-01

    The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

  1. Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions

    PubMed Central

    JIA, HAI-YAN; SHI, YING; LUO, LONG-FEI; JIANG, GUAN; ZHOU, QIONG; XU, SHI-ZHENG; LEI, TIE-CHI

    2016-01-01

    Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis. When we analyzed template-DNA strand segregation in trypsin-dissociated human psoriatic keratinocytes using BrdU pulse-chase labeling, we found that the percentage of asymmetric segregation of BrdU was significantly increased in the cell pairs of psoriatic epidermal cells compared with normal epidermal cells. Furthermore, we also examined the effects of both interleukin (IL)-17A and IL-22 cytokines on the differentiation status of cultured human keratinocytes. The results indicated that both cytokines had synergistic effects on passage-one epidermal cell sheets derived from skin explants and also on cultured keratinocytes, were involved in the maintenance of the undifferentiated stem cell phenotype, and these results suggest an efficient mechanism for preventing the premature loss of basal stem-cell pools in the pro-inflammatory cytokine-enriched milieu of the psoriatic epidermis. Our findings suggest that inhibition of hyperactive stem cells represents a potential therapeutic target to combat recalcitrant epidermal hyperplasia in psoriasis. PMID:26707630

  2. Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

    PubMed

    Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

    2007-02-09

    Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward

  3. A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis

    PubMed Central

    Gao, Yanzhe; Mutter-Rottmayer, Elizabeth; Greenwalt, Alicia M.; Goldfarb, Dennis; Yan, Feng; Yang, Yang; Martinez-Chacin, Raquel C.; Pearce, Kenneth H.; Tateishi, Satoshi; Major, Michael B.; Vaziri, Cyrus

    2016-01-01

    Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell-specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer cells destabilizes RAD18. Conversely, ectopic expression of MAGE-A4 (in cell lines lacking endogenous MAGE-A4) promotes RAD18 stability. DNA-damage-induced mono-ubiquitination of the RAD18 substrate PCNA is attenuated by MAGE-A4 silencing. MAGE-A4-depleted cells fail to resume DNA synthesis normally following ultraviolet irradiation and accumulate γH2AX, thereby recapitulating major hallmarks of TLS deficiency. Taken together, these results demonstrate a mechanism by which reprogramming of ubiquitin signalling in cancer cells can influence DNA damage tolerance and probably contribute to an altered genomic landscape. PMID:27377895

  4. Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.

    PubMed

    Schrader, Kevin K; Avolio, Fabiana; Andolfi, Anna; Cimmino, Alessio; Evidente, Antonio

    2013-02-13

    The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.

  5. Use of a postlabelling assay to examine the removal of radiation-induced DNA lesions by purified enzymes and human cell extracts.

    PubMed

    Weinfeld, M; Lee, J; Ruiqi, G; Karimi-Busheri, F; Chen, D; Allalunis-Turner, J

    1997-08-01

    We have used a 32P-postlabelling assay to examine the activity of purified Esherichia coli endonuclease IV, human apurinic/apyrimidinic endonuclease I and human cell-free extracts towards irradiated DNA. The assay can detect thymine glycols, 3'-phosphoglycolate groups and at least one other major lesion that has yet to be fully characterized. It was observed that endonuclease IV removed the phosphoglycolates and the uncharacterized lesion(s) suggesting that the latter are abasic sites with modified deoxyribose residues. The purified human enzyme acted only on the phosphoglycolate residues. Cell-free extract, prepared from A549 lung carcinoma cells by sonication or treatment with toluene, efficiently removed the phosphoglycolate and unknown lesions, but was less reactive towards thymine glycols. The extract was completely inactivated by heating at 60 degrees C for 10 min. Removal of the unknown product and phosphoglycolate did not require magnesium, but 1 mM EDTA did inhibit release of the latter. The cell-free extract exhibited substantially more activity towards native than heat-denatured DNA. A comparison of extracts prepared from 4 cell lines displaying a range of radiosensitivities, including an ataxia telangiectasia cell line, showed that all contained similar levels of repair activity towards the detectable lesions.

  6. NIAM-Deficient Mice Are Predisposed to the Development of Proliferative Lesions including B-Cell Lymphomas

    PubMed Central

    Reed, Sara M.; Hagen, Jussara; Muniz, Viviane P.; Rosean, Timothy R.; Borcherding, Nick; Sciegienka, Sebastian; Goeken, J. Adam; Naumann, Paul W.; Zhang, Weizhou; Tompkins, Van S.; Janz, Siegfried; Meyerholz, David K.; Quelle, Dawn E.

    2014-01-01

    Nuclear Interactor of ARF and Mdm2 (NIAM, gene designation Tbrg1) is a largely unstudied inhibitor of cell proliferation that helps maintain chromosomal stability. It is a novel activator of the ARF-Mdm2-Tip60-p53 tumor suppressor pathway as well as other undefined pathways important for genome maintenance. To examine its predicted role as a tumor suppressor, we generated NIAM mutant (NIAMm/m) mice homozygous for a β-galactosidase expressing gene-trap cassette in the endogenous gene. The mutant mice expressed significantly lower levels of NIAM protein in tissues compared to wild-type animals. Fifty percent of aged NIAM deficient mice (14 to 21 months) developed proliferative lesions, including a uterine hemangioma, pulmonary papillary adenoma, and a Harderian gland adenoma. No age-matched wild-type or NIAM+/m heterozygous animals developed lesions. In the spleen, NIAMm/m mice had prominent white pulp expansion which correlated with enhanced increased reactive lymphoid hyperplasia and evidence of systemic inflammation. Notably, 17% of NIAM mutant mice had splenic white pulp features indicating early B-cell lymphoma. This correlated with selective expansion of marginal zone B cells in the spleens of younger, tumor-free NIAM-deficient mice. Unexpectedly, basal p53 expression and activity was largely unaffected by NIAM loss in isolated splenic B cells. In sum, NIAM down-regulation in vivo results in a significant predisposition to developing benign tumors or early stage cancers. These mice represent an outstanding platform for dissecting NIAM's role in tumorigenesis and various anti-cancer pathways, including p53 signaling. PMID:25393878

  7. E-cadherin Controls Bronchiolar Progenitor Cells and Onset of Preneoplastic Lesions in Mice12

    PubMed Central

    Ceteci, Fatih; Ceteci, Semra; Zanucco, Emanuele; Thakur, Chitra; Becker, Matthias; El-Nikhely, Nefertiti; Fink, Ludger; Seeger, Werner; Savai, Rajkumar; Rapp, Ulf R

    2012-01-01

    Although progenitor cells of the conducting airway have been spatially localized and some insights have been gained regarding their molecular phenotype, relatively little is known about the mechanisms regulating their maintenance, activation, and differentiation. This study investigates the potential roles of E-cadherin in mouse Clara cells, as these cells were shown to represent the progenitor/stem cells of the conducting airways and have been implicated as the cell of origin of human non-small cell lung cancer. Postnatal inactivation of E-cadherin affected Clara cell differentiation and compromised airway regeneration under injury conditions. In steady-state adult lung, overexpression of the dominant negative E-cadherin led to an expansion of the bronchiolar stem cells and decreased differentiation concomitant with canonical Wnt signaling activation. Expansion of the bronchiolar stem cell pool was associated with an incessant proliferation of neuroepithelial body.associated Clara cells that ultimately gave rise to bronchiolar hyperplasia. Despite progressive hyperplasia, only a minority of the mice developed pulmonary solid tumors, suggesting that the loss of E-cadherin function leads to tumor formation when additional mutations are sustained. The present study reveals that E-cadherin plays a critical role in the regulation of proliferation and homeostasis of the epithelial cells lining the conducting airways. PMID:23308049

  8. Chiral discotic columnar germs of nucleosome core particles.

    PubMed Central

    Livolant, F; Leforestier, A

    2000-01-01

    In concentrated solution and in the presence of high concentrations of monovalent cations, nucleosome core particles order into a discotic columnar mesophase. This phase is limited to finite-sized hexagonal germs that further divide into six coiled branches, following an iterative process. We show how the structure of the germs comes from the competition between hexagonal packing and chirality with a combination of dendritic facetting and double-twist configurations. Geometrical considerations lead us to suspect that the chirality of the eukaryotic chromosomes may originate from the same competition. PMID:10777768

  9. Architecture of Columnar Nacre, and Implications for Its Formation Mechanism

    SciTech Connect

    Metzler, Rebecca A.; Olabisi, Ronke M.; Coppersmith, Susan N.; Gilbert, P. U. P. A.; Abrecht, Mike; Frazer, Bradley H.; Ariosa, Daniel; Johnson, Christopher J.

    2007-06-29

    We analyze the structure of Haliotis rufescens nacre, or mother-of-pearl, using synchrotron spectromicroscopy and x-ray absorption near-edge structure spectroscopy. We observe imaging contrast between adjacent individual nacre tablets, arising because different tablets have different crystal orientations with respect to the radiation's polarization vector. Comparing previous data and our new data with models for columnar nacre growth, we find the data are most consistent with a model in which nacre tablets are nucleated by randomly distributed sites in the organic matrix layers.

  10. Insufficiency of bone scintigraphy in vertebral lesions of langerhans cell histiocytosis compared to f-18 fluorodeoxyglucose positron emission tomography/computed tomography and diagnostic computed tomography.

    PubMed

    Koç, Zehra Pınar; Şimşek, Selçuk; Akarsu, Saadet; Balcı, Tansel Ansal; Onur, Mehmet Ruhi; Kepenek, Ferat

    2015-02-05

    Langerhans cell histiocytosis (LCH) is a benign disorder related to the histiocytes which can infiltrate bone tissue. The most effective method for demonstrating severity of this disease is PET/CT and bone scintigraphy might show bone lesions. We present a seventeen year old male patient with disseminated LCH presented with exophtalmos and having multiple vertebral lesions which were identified by F-18 FDG PET/CT scan and diagnostic CT but not in the bone scintigraphy.

  11. Conditioned medium from mesenchymal stem cells induces cell death in organotypic cultures of rat hippocampus and aggravates lesion in a model of oxygen and glucose deprivation.

    PubMed

    Horn, Ana Paula; Frozza, Rudimar Luiz; Grudzinski, Patrícia Benke; Gerhardt, Daniéli; Hoppe, Juliana Bender; Bruno, Alessandra Nejar; Chagastelles, Pedro; Nardi, Nance Beyer; Lenz, Guido; Salbego, Christianne

    2009-01-01

    Cell therapy using bone marrow-derived mesenchymal stem cells (MSC) seems to be a new alternative for the treatment of neurological diseases, including stroke. In order to investigate the response of hippocampal tissue to factors secreted by MSC and if these factors are neuroprotective in a model of oxygen and glucose deprivation (OGD), we used organotypic hippocampal cultures exposed to conditioned medium from bone marrow-derived MSC. Our results suggest that the conditioned medium obtained from these cells aggravates lesion caused by OGD. In addition, the presence of the conditioned medium alone was toxic mainly to cells in the CA1, CA2 and CA3 areas of the hippocampal organotypic culture even in basal conditions. GABA stimulation and NMDA and AMPA receptors antagonists were able to reduce propidium iodide staining, suggesting that the cell death induced by the toxic factors secreted by MSC could involve these receptors.

  12. Brain Lesions

    MedlinePlus

    ... MRI scans, brain lesions appear as dark or light spots that don't look like normal brain tissue. Usually, a brain lesion is an incidental finding unrelated to the condition or symptom that led to the imaging test in the first place. ...

  13. Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

    PubMed

    Lacroix, Steve; Hamilton, Laura K; Vaugeois, Alexandre; Beaudoin, Stéfanny; Breault-Dugas, Christian; Pineau, Isabelle; Lévesque, Sébastien A; Grégoire, Catherine-Alexandra; Fernandes, Karl J L

    2014-01-01

    The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI) and multiple sclerosis (MS). Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC), and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE) model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE), remyelination (LPC) and significant locomotor defects (EAE). Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

  14. Involved-Lesion Radiation Therapy After Chemotherapy in Limited-Stage Head-and-Neck Diffuse Large B Cell Lymphoma

    SciTech Connect

    Yu, Jeong Il; Nam, Heerim; Ahn, Yong Chan; Kim, Won Seog; Park, Keunchil; Kim, Seok Jin

    2010-10-01

    Purpose: To report treatment outcomes after combined-modality therapy in patients with Stage I/II head-and-neck (HN) diffuse large B cell lymphoma (DLBL). Methods and Materials: Eighty-six eligible patients received sequential chemotherapy and involved-lesion radiation therapy from 1995 to 2006. After a median of four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-plus-CHOP chemotherapy, a median of 41.4 Gy was delivered to the known initial gross lesion with adequate margin (2 to 3 cm). Results: After a median follow-up of 57 months, eight treatment failures were observed: distant metastasis in 8 patients; and locoregional failure in 4 patients. Among the 4 patients with locoregional failure, 3 presented with in-field failures, and 1 both in-field and out-of-field failure (contralateral neck). Rates of overall survival (OS) and freedom from progression (FFP) at 10 years were 74.1% and 88.9%, respectively. There was no severe side effect except 1 patient with Grade 3 mucositis during and after completion of radiation therapy. Multivariate analyses showed that absence of B symptom (p = 0.022) and normal lactate dehydrogenase (p = 0.017) were related to favorable OS, age >60 years (p = 0.033) was related to favorable FFP, and international prognostic index of 0 or 1 was related to favorable OS (p = 0.003) and FFP (p = 0.03). Conclusion: This study demonstrated that patients with Stage I/II HN DLBL did not need whole-neck irradiation. Involved-lesion radiation therapy might reduce radiation toxicity with favorable treatment results.

  15. Paracoccidioides brasiliensis interacts with dermal dendritic cells and keratinocytes in human skin and oral mucosa lesions.

    PubMed

    Silva, Wellington Luiz Ferreira da; Pagliari, Carla; Duarte, Maria Irma Seixas; Sotto, Mirian N

    2016-05-01

    Paracoccidioidomycosis (PCM) is a systemic disease caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. In PCM the skin and oral mucosa are often affected. Dendritic cells and keratinocytes of the integument play a role in innate and adaptive immune response against pathogens, due to their function as antigen presenting cells. Aiming to verify the interaction of P. brasiliensis with these cell populations, we studied 52 skin and 47 oral mucosa samples taken from patients with proven diagnosis of PCM. The biopsies were subjected to immunohistochemical and/or immunofluorescence staining with anti-factor XIIIa (marker of dermal dendrocytes), anti-CD207 (marker of mature Langerhans cells), anti-pan cytokeratins (AE1-AE3) and anti-P. brasiliensis antibodies. Analyses with confocal laser microscopy were also performed for better visualization of the interaction between keratinocytes and the fungi. In sum, 42% of oral mucosa samples displayed yeast forms in Factor XIIIa dermal dendrocytes cytoplasm. Langerhans cells in skin and oral mucosa samples did not show yeast cells in their cytoplasm. In sum, 54% of skin and 60% of mucosal samples displayed yeast cells in the cytoplasm of keratinocytes. The parasitism of keratinocytes may represent a possible mechanism of evasion of the fungus to local immune mechanisms. Factor XIIIa dendrocytes and keratinocytes may be acting as antigen-presenting cells to fulfill the probably impaired function of Langerhans cells in skin and oral mucosa of human PCM.

  16. Addition of oligosaccharide decreases the freezing lesions on human red blood cell membrane in the presence of dextran and glucose.

    PubMed

    Quan, Guo Bo; Han, Ying; Liu, Min Xia; Fang, Lei; Du, Wei; Ren, Su Ping; Wang, Jie Xi; Wang, Yan

    2011-04-01

    Although incubation with glucose before freezing can increase the recovery of human red blood cells frozen with polymer, this method can also result in membrane lesions. This study will evaluate whether addition of oligosaccharide (trehalose, sucrose, maltose, or raffinose) can improve the quality of red blood cell membrane after freezing in the presence of glucose and dextran. Following incubation with glucose or the combinations of glucose and oligosaccharides for 3h in a 37°C water bath, red blood cells were frozen in liquid nitrogen for 24h using 40% dextran (W/V) as the extracellular protective solution. The postthaw quality was assessed by percent hemolysis, osmotic fragility, mean corpuscle volume (MCV), distribution of phosphatidylserine, the postthaw 4°C stability, and the integrity of membrane. The results indicated the loading efficiency of glucose or oligosaccharide was dependent on their concentrations. Moreover, addition of trehalose or sucrose could efficiently decrease osmotic fragility of red blood cells caused by incubation with glucose before freezing. The percentage of damaged cell following incubation with glucose was 38.04±21.68% and significantly more than that of the unfrozen cells (0.95±0.28%, P<0.01). However, with the increase of the concentrations of trehalose, the percentages of damaged cells were decreased steadily. When the concentration of trehalose was 400mM, the percentage of damaged cells was 1.97±0.73% and similar to that of the unfrozen cells (P>0.05). Moreover, similar to trehalose, raffinose can also efficiently prevent the osmotic injury caused by incubation with glucose. The microscopy results also indicated addition of trehalose could efficiently decrease the formation of ghosts caused by incubation with glucose. In addition, the gradient hemolysis study showed addition of oligosaccharide could significantly decrease the osmotic fragility of red blood cells caused by incubation with glucose. After freezing and thawing

  17. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.

    PubMed

    van de Nieuwenhof, Hedwig P; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G; Massuger, Leon F A G; van der Zee, Ate G J; de Hullu, Joanne A; van Kempen, Leon C L T

    2011-02-01

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n = 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (P < 0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P = 0.004), dyskeratosis (P < 0.001), hyperplasia (P = 0.048) and basal cellular atypia (P = 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.

  18. Atypical mucocutaneous leishmaniasis caused by Leishmania braziliensis in an acquired immunodeficiency syndrome patient: T-cell responses and remission of lesions associated with antigen immunotherapy.

    PubMed

    Da-Cruz, A M; Filgueiras, D V; Coutinho, Z; Mayrink, W; Grimaldi, G; De Luca, P M; Mendonca, S C; Coutinho, S G

    1999-01-01

    An atypical case of acquired immunodeficiency syndrome-associated mucocutaneous lesions due to Leishmania braziliensis is described. Many vacuolated macrophages laden with amastigote forms of the parasite were found in the lesions. Leishmanin skin test and serology for leishmaniasis were both negative. The patient was resistant to therapy with conventional drugs (antimonial and amphotericin B). Interestingly, remission of lesions was achieved after an alternative combined therapy of antimonial associated with immunotherapy (whole promastigote antigens). Peripheral blood mononuclear cells were separated and stimulated in vitro with Leishmania antigens to test the lymphoproliferative responses (LPR). Before the combined immunochemotherapy, the LPR to leishmanial antigens was negligible (stimulation index - SI=1.4). After the first course of combined therapy it became positive (SI=4.17). The antigen responding cells were predominantly T-cells (47.5%) most of them with CD8+ phenotype (33%). Very low CD4+ cells (2.2%) percentages were detected. The increased T-cell responsiveness to leishmanial antigens after combined therapy was accompanied by interferon-g (IFN-g) production as observed in the cell culture supernatants. In this patient, healing of the leishmaniasis lesions was associated with the induction of a specific T-cell immune response, characterized by the production of IFN-g and the predominance of the CD8+ phenotype among the Leishmania-reactive T-cells.

  19. Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway.

    PubMed

    Di, Ting-Ting; Ruan, Zhi-Tong; Zhao, Jing-Xia; Wang, Yan; Liu, Xin; Wang, Ying; Li, Ping

    2016-03-01

    The flavonoid astilbin is the major active component extracted from the rhizome of Smilax glabra, which has been widely used in China to treat inflammatory and autoimmune diseases, Psoriasis is a common chronic inflammatory disease in which T helper 17 (Th17) cells play an important role, provoking inflammation. We employed an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate the effect of astilbin in inflammation. Mice were administered 25 to 50mg/kg astilbin. Inflammation of psoriasis-like lesions was assessed by histology, circulating levels of T cells were assessed by flow cytometry and cytokines by bead-based immunoassay. Jak/Stat3 in isolated T cells was assessed by Western blotting and RORγt expression was assessed by RT-PCR. Administration of astilbin ameliorated IMQ-induced keratinocyte proliferation, infiltration of CD3+ cells to psoriatic lesions and ameliorated elevations in circulating CD4+ and CD8+ T cells and inflammatory cytokines (IL-17A, TNF-α, IL-6, IFN-γ and IL-2). In vitro, astilbin inhibited Th17 cell differentiation and IL-17 secretion of isolated T cells, and inhibited Jak/Stat3 signaling in Th17 cells, while up-regulating Stat3 inhibitor SCOSE3 expression in psoriatic lesions. Thus, astilbin likely alleviates psoriasis-like skin lesions by inhibiting Th17 related inflammation. Astilbin represents as an interesting candidate drug for immunoregulation of psoriasis.

  20. Activated myeloid dendritic cells accumulate and co-localize with CD3+ T cells in coronary artery lesions in patients with Kawasaki disease.

    PubMed

    Yilmaz, Atilla; Rowley, Anne; Schulte, Danica J; Doherty, Terence M; Schröder, Nicolas W J; Fishbein, Michael C; Kalelkar, Mitra; Cicha, Iwona; Schubert, Katja; Daniel, Werner G; Garlichs, Christoph D; Arditi, Moshe

    2007-08-01

    Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD.

  1. Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

    PubMed

    Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

    2015-09-01

    Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.

  2. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation.

    PubMed

    Wingard, John R; Hiemenz, John W; Jantz, Michael A

    2012-08-30

    Pulmonary nodules and nodular infiltrates occur frequently during treatment of hematologic malignancies and after hematopoietic cell transplantation. In patients not receiving active immunosuppressive therapy, the most likely culprits are primary lung cancer, chronic infectious or inactive granulomata, or even the underlying hematologic disease itself (especially in patients with lymphoma). In patients receiving active therapy or who are otherwise highly immunosuppressed, there is a wider spectrum of etiologies with infection being most likely, especially by bacteria and fungi. Characterization of the pulmonary lesion by high-resolution CT imaging is a crucial first diagnostic step. Other noninvasive tests can often be useful, but invasive testing by bronchoscopic evaluation or acquisition of tissue by one of several biopsy techniques should be performed for those at risk for malignancy or invasive infection unless contraindicated. The choice of the optimal biopsy technique should be individualized, guided by location of the lesion, suspected etiology, skill and experience of the diagnostic team, procedural risk of complications, and patient status. Although presumptive therapy targeting the most likely etiology is justified in patients suspected of serious infection while evaluation proceeds, a structured evaluation to determine the specific etiology is recommended. Interdisciplinary teamwork is highly desirable to optimize diagnosis and therapy.

  3. Columnar Jointing and Quasihexagonal Crack Patterns in Corn Starch

    NASA Astrophysics Data System (ADS)

    Goehring, Lucas; Morris, Stephen W.

    2003-03-01

    The well-known geophysical phenomenon of basaltic columnar jointing, occurring most spectacularly in the Giant's Causeway in N. Ireland, has inspired several theories describing the origin and evolution of quasihexagonal crack patterns (P. Budkewitsch and P-Y. Robin, J. Volcanol. Geotherm. Res., 59, 219 (1994); E. A. Jagla and A. G. Rojo, Phys. Rev. E, 65, 026203 (2002) for example). Field studies have not been able to distinguish between these theories. However, the desiccation of water-starch mixtures also produces quasihexagonal crack patterns (G. Müller, J. Geophys. Res. 103, 15239 (1998)). The diffusion and evaporation of water is thought to be analogous to the diffusion and extraction of heat from a basalt flow. To better understand hexagonal columnar jointing, we have desiccated corn starch under controlled conditions. We have studied the dynamics of the crack pattern, and measured several maturation indices. Such indices attempt to quantify how disordered cracks evolve into ordered hexagonal patterns. Our objective is to determine whether laboratory tests can discriminate between the theoretical models of this interesting geological pattern.

  4. Changes in the expression of stem cell markers in oral lichen planus and hyperkeratotic lesions.

    PubMed

    Köse, Osman; Lalli, Anand; Kutulola, Adegun O; Odell, Edward W; Waseem, Ahmad

    2007-06-01

    Despite the pivotal role of stem cells in homeostasis of oral epithelia the location of this cell population within the tissue is uncertain. How disease influences these cells in vivo also remains to be elucidated. In this study we have used six molecular markers to identify stem cells in normal and diseased buccal mucosa. Samples of normal oral mucosa (NOM), hyperkeratosis (OHK) and oral lichen planus (OLP) were immunostained for alpha6 and beta1 integrins, keratin 15 (K15), melanoma-associated chondroitin sulphate proteoglycan (MCSP), NG2 the rat homologue of human MCSP and notch 1. K15, NG2 and beta1 staining was continuous in the basal layer of NOM whilst alpha6 and MCSP were limited to basal cells at the tips of connective tissue papillae. K15 was downregulated in OLP whereas alpha6, beta1 and MCSP were upregulated in both OLP and OHK. NG2 remained unchanged and notch 1 was absent in all samples. Therefore, the stem cell phenotype in OLP and OHK maybe altered in response to pathological signaling. Classification of these changes is essential to understand the role of adult stem cells in the pathogenesis of oral diseases characterised by abnormal keratinocyte proliferation and differentiation.

  5. Brain transplantation of genetically engineered human neural stem cells globally corrects brain lesions in the mucopolysaccharidosis type VII mouse.

    PubMed

    Meng, Xing-Li; Shen, Jin-Song; Ohashi, Toya; Maeda, Hiroshi; Kim, Seung Up; Eto, Yoshikatsu

    2003-10-15

    In the present study, we investigated the feasibility of using human neural stem cells (NSCs) in the treatment of diffuse central nervous system (CNS) alterations in a murine model of mucopolysaccharidosis VII (MPS VII), a lysosomal storage disease caused by a genetic defect in the beta-glucuronidase gene. An immortalized NSC line derived from human fetal telencephalon was genetically engineered to overexpress beta-glucuronidase and transplanted into the cerebral ventricles of neonatal MPS VII mouse. Transplanted human NSCs were found to integrate and migrate in the host brain and to produce large amount of beta-glucuronidase. Brain contents of the substrates of beta-glucuronidase were reduced to nearly normal levels, and widespread clearing of lysosomal storage was observed in the MPS VII mouse brain at 25 days posttransplantation. The number of engrafted cells decreased markedly after the transplantation, and it appears that the major cause of the cell death was not the immune response of the host but apoptotic cell death of grafted human NSCs. Results showed that human NSCs would serve as a useful gene transfer vehicle for the treatment of diffuse CNS lesions in human lysosomal storage diseases and are potentially applicable in the treatment of patients suffering from neurological disorders.

  6. Assessment of regeneration in meniscal lesions by use of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

    PubMed

    González-Fernández, Maria L; Pérez-Castrillo, Saúl; Sánchez-Lázaro, Jaime A; Prieto-Fernández, Julio G; López-González, Maria E; Lobato-Pérez, Sandra; Colaço, Bruno J; Olivera, Elías R; Villar-Suárez, Vega

    2016-07-01

    OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans.

  7. HIV-1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion.

    PubMed

    Morén, Constanza; González-Casacuberta, Ingrid; Álvarez-Fernández, Carmen; Bañó, Maria; Catalán-Garcia, Marc; Guitart-Mampel, Mariona; Juárez-Flores, Diana Luz; Tobías, Ester; Milisenda, José; Cardellach, Francesc; Gatell, Josep Maria; Sánchez-Palomino, Sonsoles; Garrabou, Glòria

    2017-02-01

    To characterize mitochondrial/apoptotic parameters in chronically human immunodeficiency virus (HIV-1)-infected promonocytic and lymphoid cells which could be further used as therapeutic targets to test pro-mitochondrial or anti-apoptotic strategies as in vitro cell platforms to deal with HIV-infection. Mitochondrial/apoptotic parameters of U1 promonocytic and ACH2 lymphoid cell lines were compared to those of their uninfected U937 and CEM counterparts. Mitochondrial DNA (mtDNA) was quantified by rt-PCR while mitochondrial complex IV (CIV) function was measured by spectrophotometry. Mitochondrial-nuclear encoded subunits II-IV of cytochrome-c-oxidase (COXII-COXIV), respectively, as well as mitochondrial apoptotic events [voltage-dependent-anion-channel-1(VDAC-1)-content and caspase-9 levels] were quantified by western blot, with mitochondrial mass being assessed by spectrophotometry (citrate synthase) and flow cytometry (mitotracker green assay). Mitochondrial membrane potential (JC1-assay) and advanced apoptotic/necrotic events (AnexinV/propidium iodide) were measured by flow cytometry. Significant mtDNA depletion spanning 57.67% (P < 0.01) was found in the U1 promonocytic cells further reflected by a significant 77.43% decrease of mitochondrial CIV activity (P < 0.01). These changes were not significant for the ACH2 lymphoid cell line. COXII and COXIV subunits as well as VDAC-1 and caspase-9 content were sharply decreased in both chronic HIV-1-infected promonocytic and lymphoid cell lines (<0.005 in most cases). In addition, U1 and ACH2 cells showed a trend (moderate in case of ACH2), albeit not significant, to lower levels of depolarized mitochondrial membranes. The present in vitro lymphoid and especially promonocytic HIV model show marked mitochondrial lesion but apoptotic resistance phenotype that has been only partially demonstrated in patients. This model may provide a platform for the characterization of HIV-chronicity, to test novel therapeutic options or

  8. Effects of Electromagnetic Stimulation on Gene Expression of Mesenchymal Stem Cells and Repair of Bone Lesions

    PubMed Central

    Jazayeri, Maryam; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Bolouri, Bahram; Mirahmadi, Fereshteh; Farokhi, Mehdi

    2017-01-01

    Objective Most people experience bone damage and bone disorders during their lifetimes. The use of autografts is a suitable way for injury recovery and healing. Mesenchymal stem cells (MSCs) are key players in tissue engineering and regenerative medicine. Their proliferation potential and multipotent differentiation ability enable MSCs to be considered as appropriate cells for therapy and clinical applications. Differentiation of stem cells depends on their microenvironment and biophysical stimulations. The aim of this study is to analyze the effects of an electromagnetic field on osteogenic differentiation of stem cells. Materials and Methods In this experimental animal study, we assessed the effects of the essential parameters of a pulsatile electromagnetic field on osteogenic differentiation. The main purpose was to identify an optimum electromagnetic field for osteogenesis induction. After isolating MSCs from male Wistar rats, passage-3 (P3) cells were exposed to an electromagnetic field that had an intensity of 0.2 millitesla (mT) and frequency of 15 Hz for 10 days. Flow cytometry analysis confirmed the mesenchymal identity of the isolated cells. Pulsatile electromagnetic field-stimulated cells were examined by immunocytochemistry and real-time polymerase chain reaction (PCR). Results Electromagnetic field stimulation alone motivated the expression of osteogenic genes. This stimulation was more effective when combined with osteogenic differentiation medium 6 hours per day for 10 days. For the in vivo study, an incision was made in the cranium of each animal, after which we implanted a collagen scaffold seeded with stimulated cells into the animals. Histological analysis revealed bone formation after 10 weeks of implantation. Conclusion We have shown that the combined use of chemical factors and an electromagnetic field was more effective for inducing osteogenesis. These elements have synergistic effects and are beneficial for bone tissue engineering

  9. Regeneration of nigrostriatal dopaminergic axons after transplantation of olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation at the lesion site.

    PubMed

    Teng, Xichuan; Nagata, Isao; Li, Hong-Peng; Kimura-Kuroda, Junko; Sango, Kazunori; Kawamura, Koki; Raisman, Geoffrey; Kawano, Hitoshi

    2008-11-01

    The fibrotic scar formed after central nervous system injury has been considered an obstacle to axonal regeneration. The present study was designed to examine whether cell transplantation into a damaged central nervous system can reduce fibrotic scar formation and promote axonal regeneration. Nigrostriatal dopaminergic axons were unilaterally transected in rats and cultures of olfactory-ensheathing cells (OECs), and olfactory nerve fibroblasts were transplanted into the lesion site. In the absence of transplants, few tyrosine hydroxylase-immunoreactive axons extended across the lesion 2 weeks after the transection. Reactive astrocytes increased around the lesion, and a fibrotic scar containing type IV collagen deposits developed in the lesion center. The immunoreactivity of chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in and around the lesion. One and 2 weeks after transection and simultaneous transplantation, dopaminergic axons regenerated across the transplanted tissues, which consisted of p75-immunoreactive OECs and fibronectin-immunoreactive fibroblasts. Reactive astrocytes and chondroitin sulfate immunoreactivity increased around the transplants, whereas the deposition of type IV collagen and fibrotic scar formation were completely prevented at the lesion site. Transplantation of meningeal fibroblasts similarly prevented the formation of the fibrotic scar, although its effect on regeneration was less potent than transplantation of OECs and olfactory nerve fibroblasts. The present results suggest that elimination of the inhibitory fibrotic scar is important for neural regeneration.

  10. Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants.

    PubMed

    Nieto-Sampedro, Manuel

    2003-11-01

    Growth-promoting macroglia (aldynoglia) with growth properties and immunological markers similar to Schwann cells, are found in loci of the mammalian CNS where axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus-hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle freely with astrocytes and can migrate in brain and spinal cord. Transplantation of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal cord after multiple central rhizotomy, promoted sensory and central axon growth and partial functional restoration, judging by anatomical, electrophysiological and behavioural criteria. OEC transplants suppressed astrocyte reactivity, thus generally favouring axon growth after a lesion. However, the functional repair promoted by OEC transplants was partial in the best cases, depending on lesion type and location. Cyst formation after photochemical cord lesion was partially prevented but neither the corticospinal tract, interrupted by a mild contusion, nor the sectioned medial longitudinal fascicle, did regrow after OEC transplantation in the injured area.

  11. Cell Cycle Regulatory Proteins p27(kip), Cyclins Dl and E and Proliferative Activity in Oncocytic (Hurthle Cell) Lesions of the Thyroid.

    PubMed

    Maynes, Lincoln J.; Hutzler, Michael J.; Patwardhan, Nilima A.; Wang, Songtao; Khan, Ashraf

    2000-01-01

    Cyclins are prime cell-cycle regulators central to the control of cell proliferation in eukaryotic cells. The formation of cyclin/cyclin-dependent kinases (CDK) complexes activates the kinases and initiates a cascade of events, which directs cells through the cell cycle. CDK inhibitors (CDKIs) such as p27(kip1) inhibit cyclln-CDK complexes and function as negative regulators of the cell cycle. Previous studies have shown that p27(kip1) is decreased In malignant relative to benign thyroid tumors, but its role and Interaction with other cell cycle regulatory proteins have not been well established In oncocytic lesions of the thyroid. We studied the expression of p27(kip1), cyclins D1 and E, and Ki67 In 20 cases of oncocytic adenoma (AD). 6 cases of oncocytic carcinoma (CA). 8 cases of Hashimoto's thyroiditis (HT). and 9 cases of nodular goiter with oncocytic change (NG) by Immunohistochemlstry. In the latter two lesions only oncocytic cells were evaluated. The positive staining was stratified Into four groups. Statistical analysis was done using the Kruslcal-Wallis one-way analysis of variance test, and, when significant the Dunn multiple-comparisons procedure was used to determine pairwise differences. AllI 20 AD were p27(kip1) posItive, 10 were 4+, 2 were 3+, and the remaining 8 were 1+. In contrast all 6 CA showed 4+ p27(kip1) staining, of the 8 HT 2 were 4+, two 3+, three1+, and I was negative.All 9 NG were p27 positive, 7 showed 4+, one 3+, and one 1+ staining. On pairwise comparison differences in p27(kip1) staining between AD and CA and between HT and CA were statistically significant (p=0.0243 and p=0.0142, respectively). In all but one case Ki67 expression was either very low (<3%) or negative. No significant differences were seen in the expression of cyclin D1 or cyclin E among the groups observed. In conclusion, the increased p27(kip1) expression in malignant oncocytlc tumors relative to benign oncocytic lesions is unlike any other malignant progression

  12. Optimized reverse primer for 16S-RFLP analysis and genomovar assignment of Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the causative agent of columnaris disease which severely impacts channel catfish production in the USA and has emerged as an important pathogen in the US rainbow trout industry. Our laboratory previously standardized a genetic typing system for F. columnare in which a por...

  13. Basal polarization of the mucosal compartment in Flavobacterium columnare susceptible and resistant channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The freshwater bacterial pathogen, Flavobacterium columnare, infects a variety of ornamental and farmed fish species worldwide through mucosal attachment points on the gill and skin. While previous studies have demonstrated a chemotactic response of F. columnare to fish mucus, little is known about ...

  14. Genome sequence of the fish pathogen Flavobacterium columnare genomovar II strain 94-081

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Channel catfish is one of the most important commodities in Mississippi and the largest aquaculture industry in the United States. Columnaris disease, caused by Flavobacterium columnare, affects many commercially important freshwater fish species. F. columnare strain 94-081 was isolated from disease...

  15. Complete genome sequence of the fish pathogen Flavobacterium columnare strain C#2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is a Gram-negative bacterial pathogen that causes columnaris disease of freshwater fish. Flavobacterium columnare strain C#2 was isolated from a diseased warm water fish and is typed as genomovar II. The genome consists of a single 3.33 Mb circular chromosome with 2,689 pred...

  16. Isolation and characterization of Flavobacterium columnare strains infecting fishes inhabiting the Laurentian Great Lakes basin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, the etiological agent of columnaris disease, causes significant losses in fish worldwide. In this study, F. columnare infection prevalence was assessed in representative Great Lakes fish species. Over 2,000 wild, feral, and hatchery-propagated salmonids, percids, centrarc...

  17. Enhanced susceptibility of hybrid tilapia to Flavobacterium columnare after parasitism by Ichthyophthirius multifiliis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterium Flavobacterium columnare and protozoan Ichthyophthirius multifiliis are two common pathogens of cultured fish. The objective of this study was to evaluate the susceptibility of hybrid tilapia (Oreochromis spp.) to the bacterium F. columnare, including fish mortality and bacterial loads in ...

  18. Epstein–Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions

    PubMed Central

    Xiao, Hai-Juan; Li, Ji; Song, Hong-Mei; Li, Zheng-Hong; Dong, Mei; Zhou, Xiao-Ge

    2016-01-01

    Abstract Systemic Epstein–Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage). There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by

  19. Lesional accumulation of CD163-expressing cells in the gut of patients with inflammatory bowel disease.

    PubMed

    Franzè, Eleonora; Caruso, Roberta; Stolfi, Carmine; Sarra, Massimiliano; Cupi, Maria Laura; Caprioli, Flavio; Monteleone, Ivan; Zorzi, Francesca; De Nitto, Daniela; Colantoni, Alfredo; Biancone, Livia; Pallone, Francesco; Monteleone, Giovanni

    2013-01-01

    Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD), but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response.

  20. Progress and prospects in neurorehabilitation: clinical applications of stem cells and brain-computer interface for spinal cord lesions.

    PubMed

    Gongora, Mariana; Peressutti, Caroline; Machado, Sergio; Teixeira, Silmar; Velasques, Bruna; Ribeiro, Pedro

    2013-04-01

    Spinal cord injury (SCI) is a disease that affects millions of people worldwide, causing a temporary or permanent impairment of neuromotor functions. Mostly associated to traumatic lesions, but also to other forms of disease, the appropriate treatment is still unsure. In this review, several ongoing studies are presented that aim to provide methods of prevention that ensure quality of life, and rehabilitation trends to patients who suffer from this injury. Stem cell research, highlighted in this review, seeks to reduce damage caused to the tissue, as also provide spinal cord regeneration through the application of several types of stem cells. On the other hand, research using brain-computer interface (BCI) technology proposes the development of interfaces based on the interaction of neural networks with artificial tools to restore motor control and full mobility of the injured area. PubMed, MEDLINE and SciELO data basis analyses were performed to identify studies published from 2000 to date, which describe the link between SCI with stem cells and BCI technology.

  1. Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells

    PubMed Central

    Uchiyama, Shintaro; Saeki, Noritaka; Ogawa, Kazushige

    2015-01-01

    AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer. PMID:25593460

  2. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    PubMed

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  3. Columnar interactions determine horizontal propagation of recurrent network activity in neocortex

    PubMed Central

    Wester, Jason C.; Contreras, Diego

    2012-01-01

    The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential L4→L2/3→L5 sequence, followed by horizontal propagation with a leading front in supra and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supra and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supra and infragranular circuits with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo. PMID:22514308

  4. Effect of Packed Red Blood Cell Cryopreservation on Development of the Storage Lesion and Inflammation

    DTIC Science & Technology

    2015-09-01

    A. Schreiber, MD September 2015 Air Force Research Laboratory 711th Human Performance Wing U.S. Air Force School of Aerospace Medicine...under standard conditions, but the Food and Drug Administration currently restricts their use to 14 days after thawing. The effect of longer term...transfusion with previously cryopreserved packed red blood cells is superior to that of aged units stored under standard conditions, but the Food and

  5. A novel serrated columnar phased array ultrasonic transducer

    NASA Astrophysics Data System (ADS)

    Zou, Cheng; Sun, Zhenguo; Cai, Dong; Song, Hongwei; Chen, Qiang

    2016-02-01

    Traditionally, wedges are required to generate transverse waves in a solid specimen and mechanical rotation device is needed for interrogation of a specimen with a hollow bore, such as high speed railway locomotive axles, turbine rotors, etc. In order to eliminate the mechanical rotation process, a novel array pattern of phased array ultrasonic transducers named as serrated columnar phased array ultrasonic transducer (SCPAUT) is designed. The elementary transducers are planar rectangular, located on the outside surface of a cylinder. This layout is aimed to generate electrically rotating transverse waveforms so as to inspect the longitudinal cracks on the outside surface of a specimen which has a hollow bore at the center, such as the high speed railway locomotive axles. The general geometry of the SCPAUT and the inspection system are illustrated. A FEM model and mockup experiment has been carried out. The experiment results are in good agreement with the FEM simulation results.

  6. D2-D1 phase transition of columnar liquid crystals

    NASA Astrophysics Data System (ADS)

    Sun, Y. F.; Swift, J.

    1986-04-01

    The D2-D1 phase transition in columnar liquid crystals of the HAT series [e.g., HAT11 (triphenelene hexa-n-dodecanoate)] is discussed within the framework of Landau theory. The order parameters which describe the transition are abstracted from a tensor density function, and are associated with two irreducible representations of the symmetry group of the high-temperature D2 phase. A mechanism for a first-order transition is then suggested in accordance with both theoretical considerations and the experimental result for the D2-D1 transition. Two possible arrangements of the herringbone structure of the D1 phase are obtained, each of which gives six orientational states in the low-temperature D1 phase.

  7. Electronic structure of vortices pinned by columnar defects

    NASA Astrophysics Data System (ADS)

    Mel'Nikov, A. S.; Samokhvalov, A. V.; Zubarev, M. N.

    2009-04-01

    The electronic structure of a vortex line trapped by an insulating columnar defect in a type-II superconductor is analyzed within the Bogolubov-de Gennes theory. For quasiparticle trajectories with small impact parameters defined with respect to the vortex axis, the normal reflection of electrons and holes at the defect surface results in the formation of an additional subgap spectral branch. The increase in the impact parameter at this branch is accompanied by the decrease in the excitation energy. When the impact parameter exceeds the radius of the defect this branch transforms into the Caroli-de Gennes-Matricon one. As a result, the minigap in the quasiparticle spectrum increases with the increase in the defect radius. The scenario of the spectrum transformation is generalized for the case of arbitrary vorticity.

  8. Columnar epitaxy of hexagonal and orthorhombic silicides on Si(111)

    NASA Technical Reports Server (NTRS)

    Fathauer, R. W.; Nieh, C. W.; Xiao, Q. F.; Hashimoto, Shin

    1990-01-01

    Columnar grains of PtSi and CrSi2 surrounded by high-quality epitaxial silicon are obtained by ultrahigh vacuum codeposition of Si and metal in an approximately 10:1 ratio on Si(111) substrates heated to 610-840 C. This result is similar to that found previously for CoSi2 (a nearly-lattice-matched cubic-fluorite crystal) on Si(111), in spite of the respective orthorhombic and hexagonal structures of PtSi and CrSi2. The PtSi grains are epitaxial and have one of three variants of the relation defined by PtSi(010)/Si(111), with PtSi 001 line/Si 110 line type.

  9. Population genetic structure of Venezuelan chiropterophilous columnar cacti (Cactaceae).

    PubMed

    Nassar, Jafet M; Hamrick, J L; Fleming, Theodore H

    2003-11-01

    We conducted allozyme surveys of three Venezuelan self-incompatible chiropterophilous columnar cacti: two diploid species, Stenocereus griseus and Cereus repandus, and one tetraploid, Pilosocereus lanuginosus. The three cacti are pollinated by bats, and both bats and birds disperse seeds. Population sampling comprised two spatial scales: all Venezuelan arid zones (macrogeographic) and two arid regions in northwestern Venezuela (regional). Ten to 15 populations and 17-23 loci were analyzed per species. Estimates of genetic diversity were compared with those of other allozyme surveys in the Cactaceae to examine how bat-mediated gene dispersal affects the population genetic attributes of the three cacti. Genetic diversity was high for both diploid (P(s) = 94.1-100, P(p) = 56.7-72.3, H(s) = 0.182-0.242, H(p) = 0.161-0.205) and tetraploid (P(s) = 93.1, P(p) = 76.1, H(s) = 0.274, H(p) = 0.253) species. Within-population heterozygote deficit was detected in the three cacti at macrogeographic (F(IS) = 0.145-0.182) and regional (F(IS) = 0.057-0.174) levels. Low genetic differentiation was detected at both macrogeographic (G(ST) = 0.043-0.126) and regional (G(ST) = 0.009-0.061) levels for the three species, suggesting substantial gene flow among populations. Gene exchange among populations seems to be regulated by distance among populations. Our results support the hypothesis that bat-mediated gene dispersal confers high levels of genetic exchange among populations of the three columnar cacti, a process that enhances levels of genetic diversity within their populations.

  10. Evolving fracture patterns: columnar joints, mud cracks, and polygonal terrain

    NASA Astrophysics Data System (ADS)

    Goehring, L.

    2012-12-01

    Contraction cracks can form captivating patterns, such as the artistic craquelure sometimes found in pottery glazes, to the cracks in dried mud, or the polygonal networks covering the polar regions of Earth and Mars. Two types are frequently encountered: those with irregular rectilinear patterns, such as that formed by an homogeneous slurry when dried (or cooled) uniformly, and more regular hexagonal patterns, such as those typified by columnar joints. Once cracks start to form in a thin contracting layer, they will sequentially break the layer into smaller and smaller pieces. A rectilinear crack pattern encodes information about the order of cracks, as later cracks tend to intersect with earlier cracks at right angles. In this manner they relieve the stresses perpendicular to the pre-existing crack. In a hexagonal pattern, in contrast, the angles between all cracks at a vertex are near 120°. In this presentation it will be shown how both types of pattern can arise from identical forces, and that a rectilinear, T-junction dominated pattern will develop into to a hexagonal pattern, with Y-junctions, if allowed to. Such an evolution can be explained as the result of three conditions: (1) if cracks advance through space, or heal and recur, that the previous positions of a crack tip acts as a line of weakness, guiding the next iteration of cracking; (2) that the order of opening of cracks can change in each iteration; and (3) that crack tips curve to maximise the local strain energy release rate. The ordering of crack patterns are seen in a number of systems: columnar joints in starch and lava; desiccation cracks in clays that are repeatedly wetted and dried; cracks in eroding gypsum-cemented sand layers; and the cracks in permafrost known as polygonal terrain. These patterns will each be briefly explored, in turn, and shown to obey the above principles of crack pattern evolution.

  11. Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesions Development and Its Chemoattraction Manipulation as a Therapeutic Tool

    PubMed Central

    Francisconi, Carolina Favaro; Vieira, Andreia Espindola; Biguetti, Claudia Cristina; Glowacki, Andrew J; Favaro Trombone, Ana Paula; Letra, Ariadne; Menezes Silva, Renato; Sfeir, Charles S.; Little, Steven R.; Garlet, Gustavo Pompermaier

    2015-01-01

    Introduction The pathogenesis of periapical lesions is determined by the balance between host pro-inflammatory immune response and counteracting anti-inflammatory and reparative responses, which include regulatory T cells (Tregs) as potential immunoregulatory agents. In this study, we investigated (in a cause-and-effect manner) the involvement of CCL22-CCR4 axis in Tregs migration to the periapical area and the role of Tregs in the determination of outcomes in periapical lesions. Methods Periapical lesions were induced in C57Bl/6 (WT) and CCR4KO mice (pulp exposure and bacterial inoculation), and treated with anti-GITR to inhibit Tregs function or alternatively with CCL22-releasing, PLGA particles to induce site-specific migration of Tregs. Post treatment, lesions were analyzed for Tregs influx and phenotype, overall periapical bone loss and inflammatory/immunological and wound healing markers expression (analyzed by RealTimePCRarray). Results Tregs inhibition by anti-GITR or CCR4 depletion results in a significant increase in periapical lesions severity, associated with upregulation of proinflammatory, Th1, Th17 and tissue destruction markers in parallel with decreased Tregs and healing markers expression. The local release of CCL22 in the root canal system resulted in the promotion of Tregs migration in a CCR4-dependent manner, leading to the arrest of periapical lesions progression, associated with downregulation of pro-inflammatory, Th1, Th17 and tissue destruction markers in parallel with increased Tregs and healing markers expression. Conclusions Since the natural and CCL22 induced Tregs migration switch active lesion into inactivity phenotype, Tregs chemoattractant may be a promisor strategy for the clinical management of periapical lesions. PMID:26589811

  12. Primary Sarcomas of Thyroid Gland–Series of Three Cases with Brief Review of Spindle Cell Lesions of Thyroid

    PubMed Central

    Singh, Meeta; Rani, Poonam; Khurana, Nita; Mishra, Anurag

    2017-01-01

    Primary Malignant Fibrous Histiocytoma (MFH-T) and Leiomyosarcoma (LMS-T) of the thyroid gland are extremely rare tumors. Very few cases have been reported in the literature. Both entities occur more commonly in women than men. The closest clinical and histological differential diagnosis is anaplastic carcinoma of thyroid. We present three cases of rare primary sarcomas of thyroid gland. Case-1 was a 63-year-old woman and Case-2 was a 52-year-old woman. Both of them presented with a rapidly increasing thyroid mass clinically mimicking anaplastic carcinoma (AC-T). Both the patients developed pulmonary metastasis and succumbed to the illness soon after the diagnosis of MFH-T was made. Case 3 was 65-year-old woman with neck swelling since six months diagnosed as LMS-T. The present communication adds three new cases to the literature on sarcomas of thyroid gland with an emphasis on differential diagnosis of spindle cell lesions of thyroid. MFH-T and LMS-T needs to be differentiated from AC-T, metastatic sarcomas, spindle cell variant of medullary carcinoma, synovial sarcoma, fibrosarcoma; final diagnosis rests on histopathology and immunohistochemistry. PMID:28384879

  13. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

    PubMed

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-16

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  14. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    NASA Astrophysics Data System (ADS)

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  15. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    PubMed Central

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke. PMID:28091591

  16. Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions.

    PubMed Central

    Horvai, A; Palinski, W; Wu, H; Moulton, K S; Kalla, K; Glass, C K

    1995-01-01

    Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7777517

  17. Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series.

    PubMed

    Sivendran, Shanthi; Harvey, Harold; Lipton, Allan; Drabick, Joseph

    2011-06-01

    Langerhans cell histiocytosis (LCH) is a rare disease caused by a clonal proliferation of specialized dendritic (Langerhans) cells. Although uncommon, it is potentially fatal and carries significant morbidity. Bone involvement is particularly destructive and to date, no standard of care exists for management of both the disease and the significant bone pain as many of these patients experience. In the literature, 12 patients who had previously been heavily pretreated for their disease had their bone pain treated with a bisphosphonate as extrapolated from the cancer literature. Interestingly, these patients had a complete or near complete resolution of their pain, return of functional status and in 75% of cases radiographic evidence of reduction or regression of disease. Only 6 of these patients were treated with a newer generation bisphosphonate, zoledronic acid. In this paper, we report a case series of 2 patients with LCH bone involvement who received 4 mg of intravenous zoledronic acid monthly for 1 year with complete resolution in their bone pain. In addition, both patients demonstrated reduction in tumor burden after bisphosphonate treatment. Uniquely, our first case is the only reported case in the literature using a bisphosphonate as first line therapy in the treatment of LCH. This case demonstrates the potential role of zoledronic acid therapy in the first line setting for disease stabilization and symptomatic control in patients unable to receive conventional therapy.

  18. Pink lesions.

    PubMed

    Giacomel, Jason; Zalaudek, Iris

    2013-10-01

    Dermoscopy (dermatoscopy or surface microscopy) is an ancillary dermatologic tool that in experienced hands can improve the accuracy of diagnosis of a variety of benign and malignant pigmented skin tumors. The early and more accurate diagnosis of nonpigmented, or pink, tumors can also be assisted by dermoscopy. This review focuses on the dermoscopic diagnosis of pink lesions, with emphasis on blood vessel morphology and pattern. A 3-step algorithm is presented, which facilitates the timely and more accurate diagnosis of pink tumors and subsequently guides the management for such lesions.

  19. Growing large columnar grains of CH3NH3PbI3 using the solid-state reaction method enhanced by less-crystallized nanoporous PbI2 films

    NASA Astrophysics Data System (ADS)

    Zheng, Huifeng; Wang, Weiqi; Liu, Yangqiao; Sun, Jing

    2017-03-01

    Compact, pinhole-free and PbI2-free perovskite films, are desirable for high-performance perovskite solar cells (PSCs), especially if large columnar grains are obtained in which the adverse effects of grain boundaries will be minimized. However, the conventional solid-state reaction methods, originated from the two-step method, failed to grow columnar grains of CH3NH3PbI3 in a facile way. Here, we demonstrate a strategy for growing large columnar grains of CH3NH3PbI3, by less-crystallized nanoporous PbI2 (ln-PbI2) film enhanced solid-state reaction method. We demonstrated columnar grains were obtainable only when ln-PbI2 films were applied. Therefore, the replacement of compact PbI2 by ln-PbI2 in the solid-sate reaction, leads to higher power conversion efficiency, better reproducibility, better stability and less hysteresis. Furthermore, by systematically investigating the effects of annealing temperature and duration, we found that an annealing temperature ≥120 °C was also critical for growing columnar grains. With the optimal process, a champion efficiency of 16.4% was obtained and the average efficiency reached 14.2%. Finally, the mechanism of growing columnar grains was investigated, in which a VPb″ -assisted hooping model was proposed. This work reveals the origins of grain growth in the solid-state reaction method, which will contribute to preparing high quality perovskite films with much larger columnar grains.

  20. Mandibular intraosseous squamous cell carcinoma lesion associated with odontogenic keratocyst: a case report.

    PubMed

    Park, Han-Kyul; Kim, Tae-Seop; Geum, Dong-Ho; Yoon, Sang-Yong; Song, Jae-Min; Hwang, Dae-Seok; Cho, Yeong-Cheol; Kim, Uk-Kyu

    2015-04-01

    Squamous cell carcinoma (SCC) is the most common malignant tumor in the oral cavity, and it accounts for about 90% of all oral cancers. Several risk factors for oral SCC have been identified; however, SCC associated with odontogenic keratocysts have rarely been reported. The present study describes the case of a 36-year-old man with SCC of the right ramus of the mandible, which was initially diagnosed as a benign odontogenic cyst. He underwent enucleation at another hospital followed by segmental mandibulectomy and fibular free flap reconstruction at our institution. In this case, we introduce a patient with oral cancer associated with odontogenic cyst on the mandible and report a satisfactory outcome with wide resection and immediate free flap reconstruction.

  1. Mandibular intraosseous squamous cell carcinoma lesion associated with odontogenic keratocyst: a case report

    PubMed Central

    Kim, Tae-Seop; Geum, Dong-Ho; Yoon, Sang-Yong; Song, Jae-Min; Hwang, Dae-Seok; Cho, Yeong-Cheol

    2015-01-01

    Squamous cell carcinoma (SCC) is the most common malignant tumor in the oral cavity, and it accounts for about 90% of all oral cancers. Several risk factors for oral SCC have been identified; however, SCC associated with odontogenic keratocysts have rarely been reported. The present study describes the case of a 36-year-old man with SCC of the right ramus of the mandible, which was initially diagnosed as a benign odontogenic cyst. He underwent enucleation at another hospital followed by segmental mandibulectomy and fibular free flap reconstruction at our institution. In this case, we introduce a patient with oral cancer associated with odontogenic cyst on the mandible and report a satisfactory outcome with wide resection and immediate free flap reconstruction. PMID:25922819

  2. Detection of the Epstein-Barr virus and DNA-topoisomerase II- α in recurrent and nonrecurrent giant cell lesion of the jawbones.

    PubMed

    Zyada, Manal M; Salama, Nagla M

    2013-01-01

    The aims of this study were to determine whether the expression of Topo II-α correlates with presence of EBV in giant cell lesion of the jawbones and whether it is predictive of clinical biologic behavior of these lesions. Paraffin-embedded tissues from 8 recurrent and 7 nonrecurrent cases of bony GCLs and 9 peripheral giant cell lesions (PGCLs) as a control group were assessed for the expression of EBV and Topo II-α using immunohistochemistry. The results showed positive staining for Topo II-α in mononuclear stromal cells (MSCs) and multinucleated giant cells (MGCs). Student t-test showed that mean Topo II-α labelling index (LI) in recurrent cases was significantly higher than that in non-recurrent cases (P = 0.0001). Moreover, Spearman's correlation coefficients method showed a significant correlation between DNA Topo II-α LI and both of gender and site in these lesions. Moderate EBV expression in relation to the highest Topo II-α LI was observed in two cases of GCT. It was concluded that high Topo II-α LIs could be identified as reliable predicators for the clinical behavior of GCLs. Moreover, EBV has no etiological role in the benign CGCLs in contrast to its role in the pathogenesis of GCTs.

  3. Mouse bronchiolar cell carcinogenesis. Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2-chloroethyl) ureas.

    PubMed Central

    Rehm, S.; Lijinsky, W.; Singh, G.; Katyal, S. L.

    1991-01-01

    neoplastic lesions. N-nitroso-methyl-bis-chloroethylurea- and NTCU-induced mouse bronchiolar cell alterations could be an interesting new model to study mechanisms of bronchiolar cell differentiation and tumor formation. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 PMID:1651059

  4. Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

    PubMed

    Katada, C; Muto, M; Tanabe, S; Higuchi, K; Sasaki, T; Azuma, M; Ishido, K; Katada, N; Sakuramoto, S; Yamashita, K; Masaki, T; Nakayama, M; Okamoto, M; Koizumi, W

    2014-07-01

    Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal

  5. Premalignant Lesions of the Anal Canal and Squamous Cell Carcinoma of the Anal Canal

    PubMed Central

    Poggio, Juan Lucas

    2011-01-01

    Squamous cell carcinoma of the anus (SCCA) is a rare tumor. However, its incidence has been increasing in men and women over the past 25 years worldwide. Risk factors associated with this cancer are those behaviors that predispose individuals to human papillomavirus (HPV) infection and immunosuppression. Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus-positive men who have sex with men. High-risk patients may benefit from screening. The most common presentation is rectal bleeding, which is present in nearly 50% of patients. Twenty percent of patients have no symptoms at the time of presentation. Clinical staging of anal cancer requires a digital rectal exam and a positron emission tomography/computed tomography scan of the chest, abdomen, and pelvis. Endorectal/endoanal ultrasound appears to add more-specific staging information when compared with digital rectal examination alone. Treatment of anal cancer prior to the 1970s involved an abdominoperineal resection. However, the current standard of care for localized anal cancer is concurrent chemoradiation therapy, primarily because of its sphincter-saving and colostomy-sparing potential. Studies have addressed alternative chemoradiation regimens to improve the standard protocol of fluorouracil, misogynic, and radiation, but no alternative regimen has proven superior. Surgery is reserved for those patients with residual disease or recurrence. PMID:22942800

  6. PCNA--a cell proliferation marker in vocal cord cancer. Part II: Recurrence in malignant laryngeal lesions.

    PubMed

    Broich, G; Lavezzi, A M; Biondo, B; Pignataro, L D

    1996-01-01

    Laryngeal squamous cell carcinoma constitutes the most frequent carcinoma found in the head and neck region. A precise prediction for recurrence potential cannot be done on site, treatment and histologic grading. Since Proliferating Cell Nuclear Antigen (PCNA) and DNA-cytometry have shown a good correlation between premalignant lesions and their progressive potential towards full-fledged carcinoma in the larynx as described in part I of this work, we have analyzed the PCNA index and DNA cytometry in specimen taken from vocal chord carcinomas with a 5-year follow-up, in order to assess its relationship with the presence or absence of tumour progression. 42 cases with (21) and without (2) recurrence have been examined. The DNA-index ranged from 1.01 to 1.43 (mean 1.10) in the group without and from 1.02 to 1.59 (mean 1.38) in the group with recurrent carcinoma (p = 0.002). The PCNA-index ranged from 0.00% to 18.90% (mean 6.97%) in the nonrecurrent group and from 0.00 to 3g.50% (mean 16.35%) in the patients with recurrence (p = 0.001). Both indices also correlated in a highly significant way. From these data emerges a highly significant correlation between the cytometric indices of cell proliferation and PCNA immunostaining. Furthermore the high correction between PCNA and DNA-index is of special interest for single case assessment. High DNA aberration and PCNA-index in vocal chord carcinoma may indicate a higher cellular aggressiveness of the tumour, resulting in a greater overall risk of metastases and local recurrences. Our results support the thesis that the indices of cellular proliferation within some cancers can define subsets of patients of high risk and help in isolating a population in which a more aggressive clinical protocol may be proposed.

  7. Gap junctional communication between vascular cells. Induction of connexin43 messenger RNA in macrophage foam cells of atherosclerotic lesions.

    PubMed Central

    Polacek, D.; Lal, R.; Volin, M. V.; Davies, P. F.

    1993-01-01

    The structure and function of blood vessels depend on the ability of vascular cells to receive and transduce signals and to communicate with each other. One means by which vascular cells have been shown to communicate is via gap junctions, specifically connexin43. In atherosclerosis, the normal physical patterns of communication are disrupted by the subendothelial infiltration and accumulation of blood monocytes, which in turn can differentiate into resident foam cells. In this paper we report that neither freshly isolated human peripheral blood monocytes nor differentiated monocytes/macrophages exhibit functional gap junctional dye transfer in homo-cellular culture or in co-culture with endothelial cells or smooth muscle cells. By Northern analysis, neither freshly isolated blood monocytes nor pure cultures of differentiated monocyte/macrophages expressed gap junction messenger RNA. However, immunohistochemical staining followed by in situ hybridization on sections of human atherosclerotic carotid arteries revealed strong expression of gap junction connexin43 messenger RNA by macrophage foam cells. These results suggest that tissue-specific conditions present in atherosclerotic arteries induce expression of connexin43 messenger RNA in monocyte/macrophages. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8382009

  8. A composite neoplastic lesion of the vulva with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia containing multinucleated giant cells.

    PubMed

    Konstantinova, Anastasia M; Kacerovska, Denisa; Michal, Michal; Kazakov, Dmitry V

    2014-10-01

    Anogenital mammary-like glands (AGMLG) are nowadays considered a normal component of the anogenital area. Lesions affecting AGMLG are similar to those seen in breast. We present a case of a complex neoplastic lesion of the AGMLG with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia. Multinucleated cells were detected in the pseudoangiomatous stromal hyperplasia areas as seen in some patients with neurofibromatosis type 1. The neoplasm is similar to rare mammary composite neoplasms that feature simultaneously patterns of a fibroepithelial neoplasms and intraductal papilloma.

  9. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    PubMed Central

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  10. IL-4 induces the formation of multinucleated giant cells and expression of β5 integrin in central giant cell lesion

    PubMed Central

    Aghbali, Amirala; Rafieyan, Sona; Mohamed-Khosroshahi, Leila; Baradaran, Behzad; Shanehbandi, Dariush

    2017-01-01

    Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells. Key words:β5 integrin, giant cell, Il-4, monocyte, rank. PMID:27918730

  11. Enzyme-labeled Antigen Method: Development and Application of the Novel Approach for Identifying Plasma Cells Locally Producing Disease-specific Antibodies in Inflammatory Lesions

    PubMed Central

    Mizutani, Yasuyoshi; Shiogama, Kazuya; Onouchi, Takanori; Sakurai, Kouhei; Inada, Ken-ichi; Tsutsumi, Yutaka

    2016-01-01

    In chronic inflammatory lesions of autoimmune and infectious diseases, plasma cells are frequently observed. Antigens recognized by antibodies produced by the plasma cells mostly remain unclear. A new technique identifying these corresponding antigens may give us a breakthrough for understanding the disease from a pathophysiological viewpoint, simply because the immunocytes are seen within the lesion. We have developed an enzyme-labeled antigen method for microscopic identification of the antigen recognized by specific antibodies locally produced in plasma cells in inflammatory lesions. Firstly, target biotinylated antigens were constructed by the wheat germ cell-free protein synthesis system or through chemical biotinylation. Next, proteins reactive to antibodies in tissue extracts were screened and antibody titers were evaluated by the AlphaScreen method. Finally, with the enzyme-labeled antigen method using the biotinylated antigens as probes, plasma cells producing specific antibodies were microscopically localized in fixed frozen sections. Our novel approach visualized tissue plasma cells that produced 1) autoantibodies in rheumatoid arthritis, 2) antibodies against major antigens of Porphyromonas gingivalis in periodontitis or radicular cyst, and 3) antibodies against a carbohydrate antigen, Strep A, of Streptococcus pyogenes in recurrent tonsillitis. Evaluation of local specific antibody responses expectedly contributes to clarifying previously unknown processes in inflammatory disorders. PMID:27006517

  12. Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGF/{beta}/BMP cell signaling in Drosophila melanogaster

    SciTech Connect

    Wharton, K.; Ray, R.P.; Gelbart, W.M.

    1996-02-01

    We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-{beta} homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-{beta} superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embryonic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-{beta}-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila. 57 refs., 4 figs., 3 tabs.

  13. Studies of intestinal lymphoid tissue. VII. The secondary nature of lymphoid cell "activation" in the jejunal lesion of tropical sprue.

    PubMed Central

    Marsh, M. N.; Mathan, M.; Mathan, V. I.

    1983-01-01

    Morphometric techniques were used in the evaluation of lymphocyte morphology and activity in tropical sprue. jejunal biopsies from control subjects (8), patients with epidemic disease (7), patients with endemic disease (11), and subjects who had recovered from sprue (4) were analyzed blindly. In patients with sprue, lymphocytes were increased significantly within crypt (but not surface) epithelium. Immunoblasts (greater than 6 mu in diameter) were increased by 5% over control subjects. Group means for lymphocytic mitotic indexes were also significantly raised, while flux ratios only differed significantly between endemic sprue patients and control subjects. The lymphocytic infiltration was distributed focally in the upper crypt and crypt-villus interzones. Analysis of epidemic cases (presenting within 4-28 days) revealed detectable changes in lymphocyte behavior only after 3 weeks' illness, whereas mucosal lesions and malabsorption were already established during the first week. These data indicate that lymphocyte activation, suggestive of a local cell-mediated immune reaction, does occur in tropical sprue but is secondary to damage already inflicted on enterocytes and their function. Images Figure 3 Figure 4 Figure 5 PMID:6614143

  14. Human papillomavirus in oral lesions.

    PubMed

    González, Joaquín V; Gutiérrez, Rafael A; Keszler, Alicia; Colacino, Maria del Carmen; Alonio, Lidia V; Teyssie, Angelica R; Picconi, Maria Alejandra

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR) using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.

  15. Generation of biotechnology-derived Flavobacterium columnare ghosts by PhiX174 gene E-mediated inactivation and the potential as vaccine candidates against infection in grass carp.

    PubMed

    Zhu, Wenxing; Yang, Guiwen; Zhang, Yuyu; Yuan, Jinduo; An, Liguo

    2012-01-01

    Flavobacterium columnare is a bacterial pathogen causing high mortality rates for many freshwater fish species. Fish vaccination with a safe and effective vaccine is a potential approach for prevention and control of fish disease. Here, in order to produce bacterial ghost vaccine, a specific Flavobacterium lysis plasmid pBV-E-cat was constructed by cloning PhiX174 lysis gene E and the cat gene with the promoter of F. columnare into the prokaryotic expression vector pBV220. The plasmid was successfully electroporated into the strain F. columnare G4cpN22 after curing of its endogenous plasmid. F. columnare G4cpN22 ghosts (FCGs) were generated for the first time by gene E-mediated lysis, and the vaccine potential of FCG was investigated in grass carp (Ctenopharyngodon idellus) by intraperitoneal route. Fish immunized with FCG showed significantly higher serum agglutination titers and bactericidal activity than fish immunized with FKC or PBS. Most importantly, after challenge with the parent strain G4, the relative percent survival (RPS) of fish in FCG group (70.9%) was significantly higher than FKC group (41.9%). These results showed that FCG could confer immune protection against F. columnare infection. As a nonliving whole cell envelope preparation, FCG may provide an ideal alternative to pathogen-based vaccines against columnaris in aquaculture.

  16. Generation of Biotechnology-Derived Flavobacterium columnare Ghosts by PhiX174 Gene E-Mediated Inactivation and the Potential as Vaccine Candidates against Infection in Grass Carp

    PubMed Central

    Zhu, Wenxing; Yang, Guiwen; Zhang, Yuyu; Yuan, Jinduo; An, Liguo

    2012-01-01

    Flavobacterium columnare is a bacterial pathogen causing high mortality rates for many freshwater fish species. Fish vaccination with a safe and effective vaccine is a potential approach for prevention and control of fish disease. Here, in order to produce bacterial ghost vaccine, a specific Flavobacterium lysis plasmid pBV-E-cat was constructed by cloning PhiX174 lysis gene E and the cat gene with the promoter of F. columnare into the prokaryotic expression vector pBV220. The plasmid was successfully electroporated into the strain F. columnare G4cpN22 after curing of its endogenous plasmid. F. columnare G4cpN22 ghosts (FCGs) were generated for the first time by gene E-mediated lysis, and the vaccine potential of FCG was investigated in grass carp (Ctenopharyngodon idellus) by intraperitoneal route. Fish immunized with FCG showed significantly higher serum agglutination titers and bactericidal activity than fish immunized with FKC or PBS. Most importantly, after challenge with the parent strain G4, the relative percent survival (RPS) of fish in FCG group (70.9%) was significantly higher than FKC group (41.9%). These results showed that FCG could confer immune protection against F. columnare infection. As a nonliving whole cell envelope preparation, FCG may provide an ideal alternative to pathogen-based vaccines against columnaris in aquaculture. PMID:22719209

  17. Nodular lesions and mesangiolysis in diabetic nephropathy.

    PubMed

    Wada, Takashi; Shimizu, Miho; Yokoyama, Hitoshi; Iwata, Yasunori; Sakai, Yoshio; Kaneko, Shuichi; Furuichi, Kengo

    2013-02-01

    Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.

  18. Derivation of Aerosol Columnar Mass from MODIS Optical Depth

    NASA Technical Reports Server (NTRS)

    Gasso, Santiago; Hegg, Dean A.

    2003-01-01

    In order to verify performance, aerosol transport models (ATM) compare aerosol columnar mass (ACM) with those derived from satellite measurements. The comparison is inherently indirect since satellites derive optical depths and they use a proportionality constant to derive the ACM. Analogously, ATMs output a four dimensional ACM distribution and the optical depth is linearly derived. In both cases, the proportionality constant requires a direct intervention of the user by prescribing the aerosol composition and size distribution. This study introduces a method that minimizes the direct user intervention by making use of the new aerosol products of MODIS. A parameterization is introduced for the derivation of columnar aerosol mass (AMC) and CCN concentration (CCNC) and comparisons between sunphotometer, MODIS Airborne Simulator (MAS) and in-measurements are shown. The method still relies on the scaling between AMC and optical depth but the proportionality constant is dependent on the MODIS derived r$_{eff}$,\\eta (contribution of the accumulation mode radiance to the total radiance), ambient RH and an assumed constant aerosol composition. The CCNC is derived fkom a recent parameterization of CCNC as a function of the retrieved aerosol volume. By comparing with in-situ data (ACE-2 and TARFOX campaigns), it is shown that retrievals in dry ambient conditions (dust) are improved when using a proportionality constant dependent on r$ {eff}$ and \\eta derived in the same pixel. In high humidity environments, the improvement inthe new method is inconclusive because of the difficulty in accounting for the uneven vertical distribution of relative humidity. Additionally, two detailed comparisons of AMC and CCNC retrieved by the MAS algorithm and the new method are shown. The new method and MAS retrievals of AMC are within the same order of magnitude with respect to the in-situ measurements of aerosol mass. However, the proposed method is closer to the in-situ measurements than

  19. Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

    PubMed Central

    Cetindis, Marcel; Biegner, Thorsten; Lehman, Max; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar

    2015-01-01

    Background: Resistance to programmed cell death (apoptosis) is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Vitamin D (calcitriol) may overcome apoptosis resistance in tumor cells of OSCC. Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development. Material and Methods: Expression of VDR was analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen (n=42) by immunohistochemistry (IHC). Moreover, serum vitamin D levels were measured by 25(OH)D3 (calcidiol) in patients with OSCC (n=42) and correlated with IHC results. Results: Expression of VDR was significantly increased in precancerous and OSCC compared with normal tissue. Compared with SIN I-III lesions VDR expression significantly decreased in OSCC. Severe vitamin D deficiency was detected in our OSCC patient cohort but there was no significant correlation analyzed between serum vitamin D levels and corresponding immunohistochemically detected VDR expression in OSCC. Conclusions: Our survey provides the first evidence of VDR expression in precancerous lesions of OSCC. Apoptosis induction of VDR+ cells in oral precancerous lesions and OSCC by natural vitamin D or synthetic vitamin D compounds could be useful for chemoprevention. Moreover, systemically and/or locally applied, these compounds may act as sensitizers for apoptosis mediated by radio-, and chemotherapy treatment in OSCC. Key words:Oral cancer, oral precancer, lichen planus, leukoplakia, apoptosis, serum 25(OH)D3, vitamin D receptor, chemoprevention, multistep carcinogenesis. PMID:25662556

  20. Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle Cells

    PubMed Central

    Niu, Panpan; Yang, Mengya; Yang, Yilin; Zhao, Ying

    2016-01-01

    Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high- cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6Chigh monocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis. PMID:27043821

  1. Inhibition of hyaluronan synthesis in breast cancer cells by 4-methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo.

    PubMed

    Urakawa, Hiroshi; Nishida, Yoshihiro; Wasa, Junji; Arai, Eisuke; Zhuo, Lisheng; Kimata, Koji; Kozawa, Eiji; Futamura, Naohisa; Ishiguro, Naoki

    2012-01-15

    Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4-methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the progression of bone metastasis via inhibition of HA synthesis. Here, we investigated the effects of MU on HA expression in MDA-MB-231 breast cancer cell line in addition to their tumorigenicity in vitro and in vivo. HAS2 mRNA expression was downregulated after 6 and 24 hr treatment with MU. Quantitative analysis of HA revealed that MU significantly inhibited the intracellular and cell surface HA. MU significantly inhibited cell growth and induced apoptosis as determined by cell proliferation and TUNEL assays, respectively. Phosphorylation of Akt was suppressed after 12 and 24 hr treatment with MU. MU treatment also inhibited cell motility as well as cell invasiveness. MU also inhibited cell growth and motility in murine fibroblast cell line NIH3T3. In vivo, administration of MU inhibited the expansion of osteolytic lesions on soft X-rays in mouse breast cancer xenograft models. HA accumulation in bone metastatic lesions was perturbed peripherally. These data suggest that MU might be a therapeutic candidate for bone metastasis of breast cancer via suppression of HA synthesis and accumulation.

  2. Cu2+ removal and recovery by Spi SORB: batch stirred and up-flow packed bed columnar reactor systems.

    PubMed

    Vannela, Raveender; Verma, Sanjay Kumar

    2006-06-01

    The biosorption of Cu(2+) by free and poly acrylamide gel (PAG) immobilized Spirulina platensis (SpiSORB) was characterized under batch and continuous packed bed columnar reaction systems. The biosorption of Cu(2+) was shown to be highest at pH of 6.0 for both types of biomass. The PAG immobilization process did not interfere with the Cu(2+) binding sites present on biomass leading to cent percent (ca. 250 mg g(-1) of dry biomass) retention of biosorption as compared to free cells. Transmission electron microscopy on Cu(2+) localization revealed that majority of metal is being sequestered by the cell wall only. The infrared spectrum of metal treated S. platensis biomass indicated the possible involvement of amide, amino, and carboxyl groups in metal binding. Up-flow packed bed columnar reactor containing 2.0 g of PAG immobilized S. platensis shown a maximum of 143-fold volume reduction factor at the residence time of 4.6 min for Cu(2+) alone and found to decrease dramatically when Zn(2+ )is present in a bimetallic solution.

  3. Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells

    PubMed Central

    1996-01-01

    Peripheral nerve injury is followed by Wallerian degeneration which is characterized by cellular and molecular events that turn the degenerating nerve into a tissue that supports nerve regeneration. One of these is the removal, by phagocytosis, of myelin that contains molecules which inhibit regeneration. We have recently documented that the scavenger macrophage and Schwann cells express the galactose- specific lectin MAC-2 which is significant to myelin phagocytosis. In the present study we provide evidence for a mechanism leading to the augmented expression of cell surface MAC-2. Nerve lesion causes noneuronal cells, primarily fibroblasts, to produce the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF). In turn, GM- CSF induces Schwann cells and macrophages to up-regulate surface expression of MAC-2. The proposed mechanism is based on the following novel observations. GM-CSF mRNA was detected by PCR in in vitro and in vivo degenerating nerves, but not in intact nerves. The GM-CSF molecule was detected by ELISA in medium conditioned by in vitro and in vivo degenerating peripheral nerves as of the 4th h after injury. GM-CSF activity was demonstrated by two independent bioassays, and repressed by activity blocking antibodies. Significant levels of GM-CSF were produced by nerve derived fibroblasts, but neither by Schwann cells nor by nerve derived macrophages. Mouse rGM-CSF enhanced MAC-2 production in nerve explants, and up-regulated cell surface expression of MAC-2 by Schwann cells and macrophages. Interleukin-1 beta up-regulated GM-CSF production thus suggesting that injury induced GM-CSF production may be mediated by interleukin-1 beta. Our findings highlight the fact that fibroblasts, by producing GM-CSF and thereby affecting macrophage and Schwann function, play a significant role in the cascade of molecular events and cellular interactions of Wallerian degeneration. PMID:8601605

  4. Hodgkin-like peripheral T-cell lymphoma (PTCL) with preserved Hodgkin-like lesions at autopsy: a case report with an interesting clinical course.

    PubMed

    Mori, Daisuke; Matsuishi, Eijo; Akashi, Michiaki; Shibaki, Masami; Hirano, Takayuki; Ide, Mikiko; Tsutsumi, Yoko; Tsukiji, Hidenori; Gondo, Hisashi

    2015-01-01

    The presence of the so-called Hodgkin and Reed-Sternberg (H-RS) like cells may occur in T-cell non-Hodgkin lymphoma. Reported herein is the autopsy case of Hodgkin-like peripheral T-cell lymphoma (PTCL) in a 77-year-old male with gradual submandibular lymph node enlargement. The first biopsy showed Hodgkin-like PTCL, initially misdiagnosed as classical Hodgkin lymphoma. Although he was treated with a regimen of ABVD, his disease recurred with cervical lymph node enlargement. A second biopsy showed angioimmunoblastic T-cell lymphoma (AITL) and H-RS like cells became obscure. Despite treatment with the CHOP regimen, he died. An autopsy confirmed that only Hodgkin-like lesions preserved while the AITL component had disappeared. This clinical course is very interesting in that only the Hodgkin-like lesions were systematically exacerbated and became the main cause of death. There are no reports of Hodgkin-like PTCL following AITL and finally preserved Hodgkin-like lesions in autopsy.

  5. Growth of columnar hydrogel colloidal crystals in water-organic solvent mixture.

    PubMed

    Zhou, Jun; Cai, Tong; Tang, Shijun; Marquez, Manuel; Hu, Zhibing

    2006-01-31

    A novel emulsion method has been demonstrated to grow columnar hydrogel colloidal crystals by mixing an aqueous suspension of poly-N-isopropylacrylamide-co-allylamine microgels with organic solvent, driven by the coalescence of micelles consisting of organic oil droplets coated by many microgels. This method leads to microgel colloidal crystals of several centimeters growing from the top to the bottom along the gravity direction. Both temperature and polymer concentration play critical roles for the formation of columnar crystals. A phase diagram has been determined, and it can be used as a guide to selectively grow different crystals, including columnar crystals and randomly oriented crystals, and enable the coexistence of columnar crystals and randomly oriented crystals.

  6. Formalin treatment of Trichondina sp. reduced Flavobacterium columnare infection in tilapia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterium Flavobacterium columnare and protozoan Trichodina spp. are common pathogens of cultured fish. Recent studies on parasite-bacterium interaction show evidence that concurrent infections increase severity of some infectious diseases, especially bacterial diseases. The effect of parasite treat...

  7. Sickeningly sweet: L-rhamnose stimulates Flavobacterium columnare biofilm formation and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, the causative agent of columnaris disease causes substantial mortality worldwide in numerous freshwater finfish species. Due to its global significance and impact on the aquaculture industry continual efforts to better understand basic mechanisms that contribute to disease ...

  8. Assessment of Flavobacterium columnare from golden shiners Notemingonus crysoleucas subject to crowding stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intensive aquaculture practices and exposure to environmental stressors can trigger outbreaks of Flavobacterium columnare, a bacterial pathogen that causes columnaris disease in commercially important fish including Golden Shiners. A rapid assessment of the bacterial load is essential to prevent out...

  9. Polypeptide synthesis in columnar and squamous explants of human uterine cervix.

    PubMed

    Cowan, M E; Ward, K; Woodman, C B; Skinner, G R

    1982-10-01

    There were quantitative and qualitative differences in the in-vitro synthesis of 3 polypeptides between squamous and columnar epithelial explants of human cervix. One cross-linked keratin-like polypeptide of mol. wt 50,000 was synthesized and phosphorylated by squamous but not by columnar explants; a second cross-linked keratin-like polypeptide of mol. wt 52,000, which was present in larger amounts in squamous than columnar explants, was both glycosylated and phosphorylated during in-vitro explantation of squamous tissue; a third polypeptide of mol. wt 25,200 which was keratin-like but not cross-linked, was synthesized in squamous-tissue explants but in only 4% of columnar-tissue explants.

  10. Polypeptide synthesis in columnar and squamous explants of human uterine cervix.

    PubMed Central

    Cowan, M. E.; Ward, K.; Woodman, C. B.; Skinner, G. R.

    1982-01-01

    There were quantitative and qualitative differences in the in-vitro synthesis of 3 polypeptides between squamous and columnar epithelial explants of human cervix. One cross-linked keratin-like polypeptide of mol. wt 50,000 was synthesized and phosphorylated by squamous but not by columnar explants; a second cross-linked keratin-like polypeptide of mol. wt 52,000, which was present in larger amounts in squamous than columnar explants, was both glycosylated and phosphorylated during in-vitro explantation of squamous tissue; a third polypeptide of mol. wt 25,200 which was keratin-like but not cross-linked, was synthesized in squamous-tissue explants but in only 4% of columnar-tissue explants. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6184064

  11. Numerical Investigation of Synthetic Buoyancy-Induced Columnar Vortices

    NASA Astrophysics Data System (ADS)

    Malaya, Nicholas; Stogner, Roy; Moser, Robert

    2015-11-01

    Much of the solar energy incident on the Earth's surface is absorbed into the ground, which in turn heats the air layer above the surface. This buoyant air layer contains considerable gravitational potential energy. The energy can drive the formation of columnar vortices (``Dust-Devils'') which arise naturally in the atmosphere. These ``Dust-Devils'' occur over a wide range of scales in many different locations across the Earth, as well as on Mars. A new energy harvesting approach makes use of this ubiquitous process by creating and anchoring the vortices artificially and extracting energy from them. In this talk we explore the characteristics of these vorticies through numerical simulation. Computational models of the turning vane system used to generate the vortex have been developed. We will discuss the formulation of these models and their validation against available experimental measurements. We will also describe the use of these simulations to optimize the turning vane configuration to maximize the power extraction, as well as serving as a vehicle to probe the dynamics of the underlying physical processes. Finally, this talk will conclude with comparisons between the synthetic vorticies and the naturally occurring phenomena. This work supported by the Department of Energy [ARPA-E] under Award Number [DE-FOA-0000670].

  12. N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ neural stem cell niche into demyelinated lesions.

    PubMed

    Klingener, Michael; Chavali, Manideep; Singh, Jagdeep; McMillan, Nadia; Coomes, Alexandra; Dempsey, Peter J; Chen, Emily I; Aguirre, Adan

    2014-07-16

    Discrete cellular microenvironments regulate stem cell pools and their development, as well as function in maintaining tissue homeostasis. Although the signaling elements modulating neural progenitor cells (NPCs) of the adult subventricular zone (SVZ) niche are fairly well understood, the pathways activated following injury and the resulting outcomes, are less clear. In the present study, we used mouse models of demyelination and proteomics analysis to identify molecular cues present in the adult SVZ niche during injury, and analyzed their role on NPCs in the context of promoting myelin repair. Proteomic analysis of SVZ tissue from mice with experimental demyelination identified several proteins that are known to play roles in NPC proliferation, adhesion, and migration. Among the proteins found to be upregulated were members of the N-cadherin signaling pathway. During the onset of demyelination in the subcortical white matter (SCWM), activation of epidermal growth factor receptor (EGFR) signaling in SVZ NPCs stimulates the interaction between N-cadherin and ADAM10. Upon cleavage and activation of N-cadherin signaling by ADAM10, NPCs undergo cytoskeletal rearrangement and polarization, leading to enhanced migration out of the SVZ into demyelinated lesions of the SCWM. Genetically disrupting either EGFR signaling or ADAM10 inhibits this pathway, preventing N-cadherin regulated NPC polarization and migration. Additionally, in vivo experiments using N-cadherin gain- and loss-of-function approaches demonstrated that N-cadherin enhances the recruitment of SVZ NPCs into demyelinated lesions. Our data revealed that EGFR-dependent N-cadherin signaling physically initiated by ADAM10 cleavage is the response of the SVZ niche to promote repair of the injured brain.

  13. Multiple regression analysis in modeling of columnar ozone in Peninsular Malaysia.

    PubMed

    Tan, K C; Lim, H S; Mat Jafri, M Z

    2014-06-01

    This study aimed to predict monthly columnar ozone (O3) in Peninsular Malaysia by using data on the concentration of environmental pollutants. Data (2003-2008) on five atmospheric pollutant gases (CO2, O3, CH4, NO2, and H2O vapor) retrieved from the satellite Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) were employed to develop a model that predicts columnar ozone through multiple linear regression. In the entire period, the pollutants were highly correlated (R = 0.811 for the southwest monsoon, R = 0.803 for the northeast monsoon) with predicted columnar ozone. The results of the validation of columnar ozone with column ozone from SCIAMACHY showed a high correlation coefficient (R = 0.752-0.802), indicating the model's accuracy and efficiency. Statistical analysis was utilized to determine the effects of each atmospheric pollutant on columnar ozone. A model that can retrieve columnar ozone in Peninsular Malaysia was developed to provide air quality information. These results are encouraging and accurate and can be used in early warning of the population to comply with air quality standards.

  14. Silicon crystals: Process for manufacturing wafer-like silicon crystals with a columnar structure

    NASA Technical Reports Server (NTRS)

    Authier, B.

    1978-01-01

    Wafer-like crystals suitable for making solar cells are formed by pouring molten Si containing suitable dopants into a mold of the desired shape and allowing it to solidify in a temperature gradient, whereby the large surface of the melt in contact with the mold is kept at less than 200 D and the free surface is kept at a temperature of 200-1000 D higher, but below the melting point of Si. The mold can also be made in the form of a slit, whereby the 2 sides of the mold are kept at different temperatures. A mold was milled in the surface of a cylindrical graphite block 200 mm in diameter. The granite block was induction heated and the bottom of the mold was cooled by means of a water-cooled Cu plate, so that the surface of the mold in contact with one of the largest surfaces of the melt was held at approximately 800 D. The free surface of the melt was subjected to thermal radiation from a graphite plate located 2 mm from the surface and heated to 1500 D. The Si crystal formed after slow cooling to room temperature had a columnar structure and was cut with a diamond saw into wafers approximately 500 mm thick. Solar cells prepared from these wafers had efficiencies of 10 to 11%.

  15. DNA alkylation lesions and their repair in human cells: modification of the comet assay with 3-methyladenine DNA glycosylase (AlkD).

    PubMed

    Hašplová, Katarína; Hudecová, Alexandra; Magdolénová, Zuzana; Bjøras, Magnar; Gálová, Eliška; Miadoková, Eva; Dušinská, Mária

    2012-01-05

    3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows assessment of specific DNA alkylation lesions. The resulting baseless sugars are alkali-labile, and under the conditions of the alkaline comet assay they appear as DNA strand breaks. The alkylating agent methyl methanesulfonate (MMS) was used to induce alkylation lesions and to optimize conditions for the modified comet assay method with AlkD on human lymphoblastoid (TK6) cells. We also studied cellular and in vitro DNA repair of alkylated bases in DNA in TK6 cells after treatment with MMS. Results from cellular repair indicate that 50% of DNA alkylation is repaired in the first 60 min. The in vitro repair assay shows that while AlkD recognises most alkylation lesions after 60 min, a cell extract from TK6 cells recognises most of the MMS-induced DNA adducts already in the first 15 min of incubation, with maximum detection of lesions after 60 min' incubation. Additionally, we tested the in vitro repair capacity of human lymphocyte extracts from 5 individuals and found them to be able to incise DNA alkylations in the same range as AlkD. The modification of the comet assay with AlkD can be useful for in vitro and in vivo genotoxicity studies to detect alkylation damage and repair and also for human biomonitoring and molecular epidemiology studies.

  16. Weissella cibaria WIKIM28 ameliorates atopic dermatitis-like skin lesions by inducing tolerogenic dendritic cells and regulatory T cells in BALB/c mice

    PubMed Central

    Lim, Seul Ki; Kwon, Min-Sung; Lee, Jieun; Oh, Young Joon; Jang, Ja-Young; Lee, Jong-Hee; Park, Hae Woong; Nam, Young-Do; Seo, Myung-Ji; Roh, Seong Woon; Choi, Hak-Jong

    2017-01-01

    The occurrence of atopic dermatitis (AD), a chronic inflammatory skin disease, has been increasing steadily in children and adults in recent decades. In this study, we evaluated the ability of the lactic acid bacterium Weissella cibaria WIKIM28 isolated from gatkimchi, a Korean fermented vegetable preparation made from mustard leaves, to suppress the development of AD induced by 2,4-dinitrochlorobenzene in a murine model. Oral administration of W. cibaria WIKIM28 reduced AD-like skin lesions, epidermal thickening, and serum immunoglobulin E levels. Furthermore, the production of type 2 helper T (Th2) cytokines such as interleukin (IL)-4, IL-5, and IL-13 decreased in peripheral lymph node cells. Moreover, the intake of W. cibaria WIKIM28 increased the proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells in mesenteric lymph nodes (MLNs) and IL-10 levels in polyclonally stimulated MLN cells. In conclusion, the oral administration of W. cibaria WIKIM28 isolated from gatkimchi ameliorated AD-like symptoms by suppressing allergic Th2 responses and inducing Treg responses. These results suggest that W. cibaria WIKIM28 may be applicable as a probiotic for the prevention and amelioration of AD. PMID:28067304

  17. Microwave treatment of eight seconds protects cells of Isatis indigotica from enhanced UV-B radiation lesions.

    PubMed

    Chen, Yi-Ping

    2006-01-01

    To determine the role of microwaves in the stress resistance of plants to enhanced ultraviolet-B (UV-B) radiation, Isatis indigotica Fort. seeds were subjected to microwave radiation for 8 s (wavelength 125 mm, power density 1.26 mW mm(-2), 2450 MHz). Afterwards they were cultivated in plastic pots in an artificial-glass greenhouse maintained at 25 degrees C, 70% relative humidity, and 400 micromol mol(-1) CO2, under visible-light conditions of 1500 micromol m(-2) s(-1) for 8 h day(-1). When the seedlings were 10 days old, they were subjected to 10.08 kJ m(-2) UV-B (PAR: 220 micromol m(-2) s(-1)) radiation for 8 days. Changes in a number of physiological and biochemical characteristics and in the thermal decomposition enthalpy of biomass were measured and used as indicators of the protective capacity of microwave radiation in this experiment. Our results revealed that microwave pretreatment of seeds enhanced UV-B stress resistance in the seedlings by decreasing the concentration of malondialdehyde (MDA) and increasing the concentration of ascorbic acid (AsA) and UV-B-absorbing compounds, increasing the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), and increasing the energy accumulation of photosynthesis. All these results suggest that microwave radiation enhances plant metabolism and results in increased UV-B stress resistance. This is the first investigation reporting the use of microwave pretreatment to protect the cells of Isatis indigotica from UV-B-induced lesions.

  18. Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

    PubMed Central

    Zeng, Qingchun; Song, Rui; Fullerton, David A.; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B.; Cleveland, Joseph C.; Reece, T. Brett; McKinsey, Timothy A.; Xu, Dingli; Dinarello, Charles A.; Meng, Xianzhong

    2017-01-01

    Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease. PMID:28137840

  19. Quantitative investigation of red blood cell three-dimensional geometric and chemical changes in the storage lesion using digital holographic microscopy.

    PubMed

    Jaferzadeh, Keyvan; Moon, Inkyu

    2015-11-01

    Quantitative phase information obtained by digital holographic microscopy (DHM) can provide new insight into the functions and morphology of single red blood cells (RBCs). Since the functionality of a RBC is related to its three-dimensional (3-D) shape, quantitative 3-D geometric changes induced by storage time can help hematologists realize its optimal functionality period. We quantitatively investigate RBC 3-D geometric changes in the storage lesion using DHM. Our experimental results show that the substantial geometric transformation of the biconcave-shaped RBCs to the spherocyte occurs due to RBC storage lesion. This transformation leads to progressive loss of cell surface area, surface-to-volume ratio, and functionality of RBCs. Furthermore, our quantitative analysis shows that there are significant correlations between chemical and morphological properties of RBCs.

  20. Structure-function relationships in radiation-induced cell and tissue lesions: special references to the contributions of scanning electron microscopy and hematopoietic tissue responses

    SciTech Connect

    Seed, T.M.

    1987-03-01

    Contributions of scanning electron microscopy to the field of radiation biology are briefly reviewed and presented in terms of an overall goal to identify and characterize the structural features of radiation-induced lesions in vital cell and tissue targets. In the context of lesion production, the major radiation-elicited response sequences, the types and nature of measured end points, and governing temporal and radiobiological parameters are discussed and illustrated by using results derived from both in vitro cell systems and in vivo studies that measured tissue responses from various organ systems (respiratory, digestive, circulatory, and central nervous systems). Work in our laboratory on the nature of early and late hematopathologic tissue responses (aplastic anemia and myeloid leukemia) induced by protracted radiation exposure and the bridging effect of repair processes relative to the expression of these pathologies is highlighted.

  1. Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas

    PubMed Central

    Parween, Saba; Kostromina, Elena; Nord, Christoffer; Eriksson, Maria; Lindström, Per; Ahlgren, Ulf

    2016-01-01

    The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function. PMID:27713548

  2. Ccr6 is dispensable for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22-producing cells.

    PubMed

    Cochez, Perrine M; Michiels, Camille; Hendrickx, Emilie; Dauguet, Nicolas; Warnier, Guy; Renauld, Jean-Christophe; Dumoutier, Laure

    2017-01-20

    Expression of the chemokine receptor Ccr6 is shared by most IL-22 producing cells and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Whereas epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from non-treated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures. Taking advantage of Ccr6-LacZ-knock-in mice, we showed that Ccr6 is necessary for the homing of Ccr6-positive cells, probably a γδ T cell subset, which represents the main potential IL-22 source in the epidermis. Similar results were observed in Rag1(-/-) epidermis and dermis primary cultures, where a subset of innate lymphoid cells expressing Ccr6 represents the main potential source of IL-22. Taken together, our data show that Ccr6 is not required for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22 producing cells.

  3. Growth of modern branched columnar stromatolites in Lake Joyce, Antarctica.

    PubMed

    Mackey, T J; Sumner, D Y; Hawes, I; Jungblut, A D; Andersen, D T

    2015-07-01

    Modern decimeter-scale columnar stromatolites from Lake Joyce, Antarctica, show a change in branching pattern during a period of lake level rise. Branching patterns correspond to a change in cyanobacterial community composition as preserved in authigenic calcite crystals. The transition in stromatolite morphology is preserved by mineralized layers that contain microfossils and cylindrical molds of cyanobacterial filaments. The molds are composed of two populations with different diameters. Large diameter molds (>2.8 μm) are abundant in calcite forming the oldest stromatolite layers, but are absent from younger layers. In contrast, <2.3 μm diameter molds are common in all stromatolites layers. Loss of large diameter molds corresponds to the transition from smooth-sided stromatolitic columns to branched and irregular columns. Mold diameters are similar to trichome diameters of the four most abundant living cyanobacteria morphotypes in Lake Joyce: Phormidium autumnale morphotypes have trichome diameters >3.5 μm, whereas Leptolyngbya antarctica, L. fragilis, and Pseudanabaena frigida morphotypes have diameters <2.3 μm. P. autumnale morphotypes were only common in mats at <12 m depth. Mats containing abundant P. autumnale morphotypes were smooth, whereas mats with few P. autumnale morphotypes contained small peaks and protruding bundles of filaments, suggesting that the absence of P. autumnale morphotypes allowed small-scale topography to develop on mats. Comparisons of living filaments and mold diameters suggest that P. autumnale morphotypes were present early in stromatolite growth, but disappeared from the community through time. We hypothesize that the mat-smoothing behavior of P. autumnale morphotypes inhibited nucleation of stromatolite branches. When P. autumnale morphotypes were excluded from the community, potentially reflecting a rise in lake level, short-wavelength roughness provided nuclei for stromatolite branches. This growth history provides a

  4. Feral livestock threatens landscapes dominated by columnar cacti

    NASA Astrophysics Data System (ADS)

    Malo, J. E.; Acebes, P.; Giannoni, S. M.; Traba, J.

    2011-05-01

    The introduction and naturalization of alien species represents a serious threat to many natural protected areas. One such case of worldwide concern is the impact of feral livestock on arid ecosystems. Damage suffered by Echinopsis (= Trichocereus) terscheckii dominating the landscape of rocky slopes was surveyed in seven locations within the Ischigualasto-Talampaya World Heritage Site (Argentina) by measuring the frequency, position on the plant and extent of damage. At the same time we employed transects to estimate the abundance of autochtonous and feral large herbivores ( Lama guanicoe, Bos taurus, Equus asinus) from their dung. Our results show relatively high damage levels (40-77% of individuals damaged, more than 5 dm 3 removed by plant in some sites), particularly within 0.50-1.75 m above the ground, showing herbivores to be the main responsible for them. We also found significant differences between sites in variables measuring damage level and in the intensity of use by the two feral livestock species but not by guanacos. The frequency of damaged cacti below 1.75 m (but not above) was significantly positively correlated among locations with the frequencies of cattle and donkey dung, and the damage suffered by individual cacti was also correlated with donkey and cattle dung in their surroundings after correcting for spatial effects. However, all correlations were non-significant in the case of guanacos. We conclude that the continued presence of feral livestock, particularly donkeys, leads to damages to columnar cacti with potential effects on their populations and the physiognomy of this protected landscape.

  5. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    PubMed Central

    Koltz, Brooke R.; Russell, Donna K.; Lu, Naiji; Bonfiglio, Thomas A.; Varghese, Sharlin

    2013-01-01

    Introduction: Automated screening of Thin Prep® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep® Imaging System (TIS). Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H) and high-grade squamous intraepithelial lesion (HGSIL) results on Thin Prep® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07). The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study's initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33%) of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32%) were interpreted as ASC-H and 164 (0.35%) were interpreted as HGSIL. During the same time period automated screening (TIS) was performed on 23,111 Pap tests. Interpretation of 62 (0.27%) cases provided an ASC-H result, while 71 (0.31%) were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III) was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71% of TIS cases

  6. Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions.

    PubMed Central

    Fu, Tao; Borensztajn, Jayme

    2002-01-01

    Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL-CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway. PMID:12033985

  7. Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study

    PubMed Central

    Anjos, Rita; Vieira, Luisa; Costa, Livio; Vicente, André; Santos, Arnaldo; Alves, Nuno; Amado, Duarte; Ferreira, Joana; Cunha, João Paulo

    2016-01-01

    ABSTRACT The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway. PMID:27928376

  8. Functional trade-offs in succulent stems predict responses to climate change in columnar cacti.

    PubMed

    Williams, David G; Hultine, Kevin R; Dettman, David L

    2014-07-01

    Columnar cacti occur naturally in many habitats and environments in the Americas but are conspicuously dominant in very dry desert regions. These majestic plants are widely regarded for their cultural, economic, and ecological value and, in many ecosystems, support highly diverse communities of pollinators, seed dispersers, and frugivores. Massive amounts of water and other resources stored in the succulent photosynthetic stems of these species confer a remarkable ability to grow and reproduce during intensely hot and dry periods. Yet many columnar cacti are potentially under severe threat from environmental global changes, including climate change and loss of habitat. Stems in columnar cacti and other cylindrical-stemmed cacti are morphologically diverse; stem volume-to-surface area ratio (V:S) across these taxa varies by almost two orders of magnitude. Intrinsic functional trade-offs are examined here across a broad range of V:S in species of columnar cacti. It is proposed that variation in photosynthetic gas exchange, growth, and response to stress is highly constrained by stem V:S, establishing a mechanistic framework for understanding the sensitivity of columnar cacti to climate change and drought. Specifically, species that develop stems with low V:S, and thus have little storage capacity, are expected to express high mass specific photosynthesis and growth rates under favourable conditions compared with species with high V:S. But the trade-off of having little storage capacity is that low V:S species are likely to be less tolerant of intense or long-duration drought compared with high V:S species. The application of stable isotope measurements of cactus spines as recorders of growth, water relations, and metabolic responses to the environment across species of columnar cacti that vary in V:S is also reviewed. Taken together, our approach provides a coherent theory and required set of observations needed for predicting the responses of columnar cacti to

  9. Single crystal to single crystal polymerization of a columnar assembled diacetylene macrocycle

    NASA Astrophysics Data System (ADS)

    Xu, Weiwei

    Organic tubular materials have attracted lots of attentions for their potential applications as nanoscale fluidic transport systems, specific ion sensors, molecular sieves and confined molecular reaction containers. While conjugated polymers, due to delocalized Pi electrons, exhibit interesting solar cells and sensors applications. In this thesis, we developed a conjugated polymer which combines the attributes of conjugated polymers with tubular materials, which should have great potential to work as a sensing material. We reproduced and scaled-up the synthesis of a polymerizable macrocycle 1 that contains two rigidly separated diacetylene units. We found that, through hydrogen bonding, 1 can assemble into columnar crystals and can be polymerized under a single crystal to single crystal transformation process to afford porous polydiacetylene (PDA) crystals. We studied the assembly of the macrocycles 1 under different conditions to give three different crystalline forms and micro-phase crystals, and also investigated their subsequent polymerizations. The macrocycle assembly and polymerized materials were characterized by a variety of technique. Since the gas adsorption measurement exhibited PDA crystals still retained its porosity and the polymer should have ability to uptake suitable guest molecules, therefore the absorption of iodine for PDA crystals was investigated as well.

  10. Thermal conduction effects impacting morphology during synthesis of columnar nanostructured TiO2 thin films

    SciTech Connect

    An, Woo-Jin; Jiang, David D.; Matthews, James R.; Borrelli, Nicholas F.; Biswas, Pratim

    2011-01-01

    The aerosol chemical vapor deposition (ACVD) process allows for the synthesis of nanostructured films with well tuned morphologies that can be controlled based on the desired functionality and application. A robust understanding of the process parameters that result in desired features of the film is elucidated. One dimensional TiO₂ nanostructured columns that have superior properties for solar energy harvesting and conversion applications were deposited on tin doped indium oxide (ITO) substrates. The sintering of the deposited particles was a key factor in the growth of the 1D structure with desired crystal planes. By ensuring that the sintering rate is faster than the arrival rate of deposited particles; a 1D columnar structure could be obtained. The sintering rate was controlled by the temperature and depositing particle size. As the columns grew in length, the increased thermal conduction resistance resulted in a drop in temperature and subsequently a slowing of the sintering process in upper regions of the film. This led to growth of branched structures rather than continued growth in a preferred direction. The growth of the branched structure could be overcome by enhancing the sintering rate by increasing the substrate temperature or reducing the depositing particle size (by lowering the feed rate of the precursor). The phenomenon was also confirmed by using different deposition substrates, such as FTO and glass. Dye sensitized solar cell performance efficiencies with different column lengths of 2 and 7 µm were determined to be 1.8 and 2.7% respectively.

  11. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    PubMed

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  12. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    PubMed Central

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

  13. Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

    PubMed

    Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-02-01

    Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis.

  14. Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3.

    PubMed Central

    Printseva OYu; Peclo, M. M.; Gown, A. M.

    1992-01-01

    The specificity of monoclonal antibody 10F3, generated to smooth muscle cells isolated from fetal human aorta, has been further explored in a series of biological, biochemical, and immunocytochemical studies. In the first assay, it was found that 10F3 could inhibit aggregation of phytohemagglutinin (PHA)-induced lymphocytes in a manner comparable to that of antibody RR1/1, an anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody. In immunoprecipitation experiments followed by one-dimensional gel electrophoresis, both 10F3 and RR1/1 immunoprecipitated 90 kd proteins, with results suggesting that the two antibodies recognized different epitopes of the same molecule. A series of immunocytochemical studies on human atherosclerotic lesions was performed; using single-labeling techniques, 10F3-positive cells were found in the vessel wall and in lesions of virtually all specimens of fatty streaks and fibrous plaques. Using double-labeling techniques, 10F3-positive macrophages and 10F3-positive smooth muscle cells were found; however, there were also a significant number of non-smooth muscle, nonmacrophage 10F3-positive cells. These studies demonstrate that 10F3 identifies ICAM-1, and that this protein is expressed on a variety of cell types in human atherosclerotic lesions. ICAM-1 may represent a developmentally regulated protein that is expressed in fetal but not adult mesenchymal cells, but can be re-expressed in pathologic processes such as atherosclerosis. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1348606

  15. Planar and SPECT Tc-99m red blood cell imaging in hepatic cavernous hemangiomas and other hepatic lesions

    SciTech Connect

    Intenzo, C.; Kim, S.; Madsen, M.; Desai, A.; Park, C.

    1988-04-01

    The utility of Tc-99m RBC imaging in the diagnosis of hepatic cavernous hemangiomas has been established. Of the 25 patients with various focal hepatic lesions evaluated, 16 were diagnosed as having hemangiomas: eight proven by surgery, two proven by angiography, and six proven by maintaining a stable clinical course ranging from 6 to 12 months with normal follow-up liver function tests. Although fourteen of these were detected by planar imaging, two were detected by SPECT only. Two patients with large hemangiomas had false-negative scans, whereas the remaining seven patients had other liver lesions.

  16. The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

    SciTech Connect

    Gillies, N.E.; Obioha, F.I.

    1982-03-01

    When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality.

  17. Ozone sensitivity in hybrid poplar correlates with insensitivity to both salicylic acid and jasmonic acid. The role of programmed cell death in lesion formation.

    PubMed

    Koch, J R; Creelman, R A; Eshita, S M; Seskar, M; Mullet, J E; Davis, K R

    2000-06-01

    Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response.

  18. Lesion bypass in yeast cells: Pol η participates in a multi-DNA polymerase process

    PubMed Central

    Bresson, Anne; Fuchs, Robert P.P.

    2002-01-01

    Replication through (6–4)TT and G-AAF lesions was compared in Saccharomyces cerevisiae strains proficient and deficient for the RAD30-encoded DNA polymerase η (Pol η). In the RAD30 strain, the (6–4)TT lesion is replicated both inaccurately and accurately 60 and 40% of the time, respectively. Surprisingly, in a rad30Δ strain, the level of mutagenic bypass is essentially suppressed, while error-free bypass remains unchanged. Therefore, Pol η is responsible for mutagenic replication through the (6–4)TT photoproduct, while another polymerase mediates its error-free bypass. Deletion of the RAD30 gene also reduces the levels of both accurate and inaccurate bypass of AAF lesions within two different sequence contexts up to 8-fold. These data show that, in contrast to the accurate bypass by Pol η of TT cyclobutane dimers, it is responsible for the mutagenic bypass of other lesions. In conclusion, this paper shows that, in yeast, translesion synthesis involves the combined action of several polymerases. PMID:12110599

  19. An eggshell-like mineralized recurrent lesion in the popliteal region after treatment of giant cell tumor of the bone with denosumab.

    PubMed

    Akaike, Keisuke; Suehara, Yoshiyuki; Takagi, Tatsuya; Kaneko, Kazuo; Saito, Tsuyoshi

    2014-12-01

    We report a case of recurrent giant cell tumor of the bone (GCTB) in which treatment with denosumab gradually enhanced the eggshell-like mineralization at the periphery of the tumor. A 28-year-old male presented with a mass on his left distal femur that had enlarged within the past few months. Before curettage, GCTB of the distal femur was diagnosed based on histological analysis of a biopsy specimen; the tumor consisted of a proliferation of ovoid mononuclear stromal cells with evenly scattered multinucleated osteoclast-like giant cells. The tumor recurred three times after the initial diagnosis; at the time of the third relapse, the patient underwent en bloc resection and reconstruction with a knee joint prosthesis. He was also treated with denosumab postoperatively because some studies have recently shown the benefits of the receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab as adjuvant therapy in patients with GCTB. Six months after starting adjuvant treatment with denosumab, radiography revealed a mineralized nodule >2 cm in diameter at the popliteal region; this lesion was considered a soft tissue recurrence of GCTB. Treatment with denosumab was continued for another 1.5 years, and the lesion was resected. Histological examination showed residual mononuclear stromal cells expressing RANKL without multinucleated giant cells surrounded by the peripheral mineralization. The patient was successfully treated by complete resection with the support of adjuvant treatment with denosumab.

  20. Localization of two major GABA(A) receptor subunits in the dentate gyrus of the rat and cell type-specific up-regulation following entorhinal cortex lesion.

    PubMed

    Simbürger, E; Plaschke, M; Fritschy, J M; Nitsch, R

    2001-01-01

    GABA(A) receptor subunits show a specific regional distribution in the CNS during development and in the adult animal. In the hippocampal formation, individual subsets of GABAergic interneurons are highly immunoreactive for the alpha1-subunit, whereas granule and pyramidal cells show a strong expression of the alpha2-subunit. Using confocal microscopy and digital image analysis, we demonstrate that in the dentate gyrus the alpha1-subunit immunolabeling appears in differently sized clusters. The large clusters, which are confined to dendrites of interneurons, show no alpha2 labeling, whereas the smaller ones coincide with alpha2-subunit-positive clusters. In the molecular layer, the clusters of both alpha-subunits co-localize with the anchoring protein gephyrin. In the granule cell layer and hilus, we found alpha1- and alpha2-subunit-positive clusters which were devoid of gephyrin labeling. Lesions of the medial entorhinal cortex led to the deafferentation of dendrites in the middle molecular layer of the dentate gyrus. This resulted in a significantly increased concentration of alpha2-subunit-positive clusters. We also observed an increase of alpha1-subunit immunolabeling in the deafferented area. We found no change in the co-localization between alpha1 and alpha2, and no significant change in the number of large alpha1-positive clusters along individual dendritic segments of interneurons. In a previous study, we demonstrated that calbindin-immunoreactive dendrites of granule cells revealed a significant increase in gephyrin immunoreactivity following lesion, whereas parvalbumin-positive dendrites showed no such alterations. The predominant localization of small gephyrin clusters in dendrites of granule cells, which was also described in this study, leads to the conclusion that the increase of the alpha2-subunit-positive clusters, demonstrated in the present study, indicates that, following entorhinal cortex lesion, new GABAergic synapses may be formed and that

  1. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice

    PubMed Central

    Holland, Eric C.; Hively, Wendy P.; DePinho, Ronald A.; Varmus, Harold E.

    1998-01-01

    The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%–50% of human gliobastoma multiforme (GBM). These mutations are associated usually with deletions of the INK4a–ARF locus, which encodes two gene products (p16INK4a and p19ARF) involved in cell-cycle arrest and apoptosis. We have investigated the role of EGFR mutation in gliomagenesis, using avian retroviral vectors to transfer a mutant EGFR gene to glial precursors and astrocytes in transgenic mice expressing tv-a, a gene encoding the retrovirus receptor. TVA, under control of brain cell type-specific promoters. We demonstrate that expression of a constitutively active, mutant form of EGFR in cells in the glial lineage can induce lesions with many similarities to human gliomas. These lesions occur more frequently with gene transfer to mice expressing tv-a from the progenitor-specific nestin promoter than to mice expressing tv-a from the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, suggesting that tumors arise more efficiently from immature cells in the glial lineage. Furthermore, EGFR-induced gliomagenesis appears to require additional mutations in genes encoding proteins involved in cell-cycle arrest pathways. We have produced these combinations by simultaneously infecting tv-a transgenic mice with vectors carrying cdk4 and EGFR or by infecting tv-a transgenic mice bearing a disrupted INK4a–ARF locus with the EGFR-carrying vector alone. Moreover, EGFR-induced gliomagenesis does not occur in conjunction with p53 deficiency, unless the mice are also infected with a vector carrying cdk4. The gliomagenic combinations of genetic lesions required in mice are similar to those found in human gliomas. PMID:9851974

  2. Stem biomechanics of three columnar cacti from the Sonoran Desert.

    PubMed

    Molina-Freaner, F; Tinoco-Ojanguren, C; Niklas, K

    1998-08-01

    The allometric relationship of stem length L with respect to mean stem diameter D was determined for 80 shoots of each of three columnar cactus species (Stenocereus thurberi, Lophocereus schottii, and S. gummosus) to determine whether this relationship accords with that predicted by each of three contending models purporting to describe the mechanical architecture of vertical shoots (i.e., geometric, stress, and elastic similitude, which predict L proportional to D(alpha), with alpha = 1/1, 1/2, and 2/3, respectively). In addition, anatomical, physical, and biomechanical stem properties were measured to determine how the stems of these three species maintain their elastic stability as they increase in size. Reduced major axis regression of L with respect to D showed that alpha = 2.82 ± 0.14 for S. thurberi, 2.32 ± 0.19 for L. schottii, and 4.21 ± 0.31 for S. gummosus. Thus, the scaling exponents for the allometry of L differed significantly from that predicted by each of the three biomechanical models. In contrast, these exponents were similar to that for the allometry previously reported for saguaro. Analyses of biomechanical data derived from bending tests performed on 30 stems selected from each of the three species indicated that the bulk stem tissue stiffness was roughly proportional to L2, while stem flexural rigidity (i.e., the ability to resist a bending force) scaled roughly as L3. Stem length was significantly and positively correlated with the volume fraction of wood, while regression analysis of the pooled data from the three species (i.e., 90 stems) indicated that bulk tissue stiffness scaled roughly as the 5/3-power of the volume fraction of wood in stems. These data were interpreted to indicate that wood served as the major stiffening agent in stems and that this tissue accumulates at a sufficient rate to afford unusually high scaling exponents tot stem length with respect to stem diameter (i.e., disproportionately large increments of stem length

  3. Mechanical behavior and elastic properties of prestrained columnar ice

    NASA Astrophysics Data System (ADS)

    Snyder, Scott Aaron

    Experiments on columnar-grained ice at --10 °C reveal changes to its mechanical behavior and elastic properties due to compressive prestrain. Laboratory-grown (152-mm cube) specimens of freshwater and saline ice were prestrained under uniaxial across-column compression (to levels from epsilon p = 0.003 to epsilonp = 0.20, at constant strain rates in the ductile regime) and then reloaded, again under uniaxial across-column compression (at rates from 1x10--6 s--1 to 3 x 10--2s--1). Prestrain caused solid-state recrystallization as well as damage in the form of non-propagating microcracks. These microstructural changes were quantified by analysis of thin sections. Elastic properties in across-column directions, both parallel (x1) and perpendicular ( x2) to the initial loading direction, were obtained from P-wave and S-wave ultrasonic velocities. As a result (and depending on the level) of the prestrain imparted in both materials, Young's modulus E was reduced by as much as 30%; the ductile-to-brittle (D--B) transition strain rate epsilon D/B was increased up to a factor of 3 to 10; and the ductile behavior with respect to loading along a direction within the horizontal ( x1-x2) plane of the parent ice sheet changed from isotropic to anisotropic. As the prestrain rate approached the nominal D--B transition rate of initially undamaged material, the magnitudes of prestrain effects on elastic compliance increased. The shift in the D--B transition, on the other hand, was less sensitive to the prestrain rate. The results are interpreted within the framework of a recent model that predicts the transition strain rate based on the micromechanical boundary between creep and fracture processes. Prestrain primarily affected certain parameters in the model, specifically the power-law creep coefficient B (more so than the creep exponent n), Young's modulus E and, by extension, the fracture toughness KIc. The physical implications of these effects are discussed.

  4. Biofilm Formation by the Fish Pathogen Flavobacterium columnare: Development and Parameters Affecting Surface Attachment

    PubMed Central

    Cai, Wenlong; De La Fuente, Leonardo

    2013-01-01

    Flavobacterium columnare is a bacterial fish pathogen that affects many freshwater species worldwide. The natural reservoir of this pathogen is unknown, but its resilience in closed aquaculture systems posits biofilm as the source of contagion for farmed fish. The objectives of this study were (i) to characterize the dynamics of biofilm formation and morphology under static and flow conditions and (ii) to evaluate the effects of temperature, pH, salinity, hardness, and carbohydrates on biofilm formation. Nineteen F. columnare strains, including representatives of all of the defined genetic groups (genomovars), were compared in this study. The structure of biofilm was characterized by light microscopy, confocal laser scanning microscopy, and scanning electron microscopy. F. columnare was able to attach to and colonize inert surfaces by producing biofilm. Surface colonization started within 6 h postinoculation, and microcolonies were observed within 24 h. Extracellular polysaccharide substances and water channels were observed in mature biofilms (24 to 48 h). A similar time course was observed when F. columnare formed biofilm in microfluidic chambers under flow conditions. The virulence potential of biofilm was confirmed by cutaneous inoculation of channel catfish fingerlings with mature biofilm. Several physicochemical parameters modulate attachment to surfaces, with the largest influence being exerted by hardness, salinity, and the presence of mannose. Maintenance of hardness and salinity values within certain ranges could prevent biofilm formation by F. columnare in aquaculture systems. PMID:23851087

  5. Thermal Cycling Behavior of Quasi-Columnar YSZ Coatings Deposited by PS-PVD

    NASA Astrophysics Data System (ADS)

    Yang, Jiasheng; Zhao, Huayu; Zhong, Xinghua; Shao, Fang; Liu, Chenguang; Zhuang, Yin; Ni, Jinxing; Tao, Shunyan

    2017-01-01

    Columnar-structured thermal barrier coatings, owing to their high strain tolerance, are expected for their potential possibilities to substantially extend turbine lives and improve engine efficiencies. In this paper, plasma spray-physical vapor deposition (PS-PVD) process was used to deposit yttria partially stabilized zirconia (YSZ) coatings with quasi-columnar structures. Thermal cyclic tests on burner rigs and thermal shock tests by heating and water-quenching method were involved to evaluate the thermal cycling and thermal shock behaviors of such kind of structured thermal barrier coatings (TBCs). Evolution of the microstructures, phase composition, residual stresses and failure behaviors of quasi-columnar YSZ coatings before and after the thermal tests was investigated. The quasi-columnar coating obtained had an average life of around 623 cycles when the spallation area reached about 10% of the total coating surface during burner rig tests with the coating surface temperature of 1250 °C. Failure of the coating is mainly due to the break and pull-out of center columnar segments.

  6. Biofilm formation by the fish pathogen Flavobacterium columnare: development and parameters affecting surface attachment.

    PubMed

    Cai, Wenlong; De La Fuente, Leonardo; Arias, Covadonga R

    2013-09-01

    Flavobacterium columnare is a bacterial fish pathogen that affects many freshwater species worldwide. The natural reservoir of this pathogen is unknown, but its resilience in closed aquaculture systems posits biofilm as the source of contagion for farmed fish. The objectives of this study were (i) to characterize the dynamics of biofilm formation and morphology under static and flow conditions and (ii) to evaluate the effects of temperature, pH, salinity, hardness, and carbohydrates on biofilm formation. Nineteen F. columnare strains, including representatives of all of the defined genetic groups (genomovars), were compared in this study. The structure of biofilm was characterized by light microscopy, confocal laser scanning microscopy, and scanning electron microscopy. F. columnare was able to attach to and colonize inert surfaces by producing biofilm. Surface colonization started within 6 h postinoculation, and microcolonies were observed within 24 h. Extracellular polysaccharide substances and water channels were observed in mature biofilms (24 to 48 h). A similar time course was observed when F. columnare formed biofilm in microfluidic chambers under flow conditions. The virulence potential of biofilm was confirmed by cutaneous inoculation of channel catfish fingerlings with mature biofilm. Several physicochemical parameters modulate attachment to surfaces, with the largest influence being exerted by hardness, salinity, and the presence of mannose. Maintenance of hardness and salinity values within certain ranges could prevent biofilm formation by F. columnare in aquaculture systems.

  7. CD8(+)/perforin(+)/WC1(-) gammadelta T cells, not CD8(+) alphabeta T cells, infiltrate vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever.

    PubMed

    Nelson, Danielle D; Davis, William C; Brown, Wendy C; Li, Hong; O'Toole, Donal; Oaks, J Lindsay

    2010-08-15

    Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a gamma-herpesvirus in the Macavirus genus, is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to their high susceptibility to this disease. Currently, the pathogenesis of disease in SA-MCF is poorly understood, and the immunophenotype of lymphocytes that infiltrate the vascular lesions of bison and cattle with SA-MCF has been only partially defined. Previous single-color immunohistochemistry studies have demonstrated that CD8(+) cells and CD4(+) cells predominate within vascular infiltrates in cattle and bison. The CD8(+) cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic alphabeta T lymphocytes. However, polychromatic immunophenotyping analyses in this study showed that CD8(+)/perforin(+) gammadelta T cells, CD4(+)/perforin(-) alphabeta T cells, and B cells infiltrate vascular lesions in the urinary bladder, kidney, and liver of six bison with experimentally-induced SA-MCF. CD8(+) alphabeta T cells and WC1(+) gammadelta T cell cells were only infrequently and inconsistently identified. This study confirmed our hypothesis that the predominant CD8(+) lymphocytes infiltrating the vascular lesions of bison with SA-MCF are cytotoxic lymphocytes of the innate immune system, not CD8(+) alphabeta T cells. Results of the present study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.

  8. HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities

    PubMed Central

    Graham, D A; Herrington, C S

    2000-01-01

    Aim—To test the hypothesis that, because the human papillomavirus (HPV) E2 protein represses viral early gene transcription, E2 gene sequence variation or disruption could play a part in the induction of the numerical chromosome abnormalities that have been described in squamous cervical lesions. Methods—The integrity and sequence of the E2 gene from 11 cervical intraepithelial neoplasia (CIN) grade 3 lesions and 14 invasive squamous cell carcinomas, all of which contained HPV-16, were analysed by the polymerase chain reaction (PCR). The E2 gene was amplified in three overlapping fragments and PCR products sequenced directly. Chromosome abnormalities were identified by interphase cytogenetics using chromosome specific probes for chromosomes 1, 3, 11, 17, 18, and X. Results—E2 gene disruption was present in significantly more invasive carcinomas (eight of 14) than CIN 3 lesions (one of 11) (p = 0.03). No association was found between E2 disruption and the presence of a numerical chromosome abnormality. The E2 gene from the non-disrupted isolates was sequenced and wild-type (n = 5) and variant (n = 11) sequences identified. Variant sequences belonged to European and African classes and contained from one to 15 amino acid substitutions. Although numerical chromosome abnormalities were significantly more frequent in invasive squamous cell carcinoma than CIN 3 (p = 0.04), there was no significant relation between the presence of sequence variation and either histological diagnosis or chromosome abnormality. Conclusions—These data do not support the hypothesis that E2 gene disruption or variation is important in the induction of chromosome imbalance in these lesions. However, there is a relation between E2 gene disruption and the presence of invasive disease. PMID:11040943

  9. Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion.

    PubMed

    Vakiani, Efsevia; Nandula, Subhadra V; Subramaniyam, Shivakumar; Keller, Christian E; Alobeid, Bachir; Murty, Vundavalli V; Bhagat, Govind

    2007-02-01

    Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)-like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD.

  10. Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis.

    PubMed

    Fujiyama, T; Ito, T; Ogawa, N; Suda, T; Tokura, Y; Hashizume, H

    2014-07-01

    Dermatomyositis (DM) and polymyositis (PM) are collectively termed autoimmune myopathy. To investigate the difference between muscle- and skin-infiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM. Muscle and skin biopsied specimens were immersed in cRPMI medium supplemented with interleukin (IL)-2 and anti-CD3/CD28 antibody-conjugated microbeads. The expanded cells were subjected to flow cytometry to examine their phenotypes. We analysed the cytokine concentration in the culture supernatants from the expanded T cells and the frequencies of cytokine-bearing cells by intracellular staining. There was non-biased in-vitro expansion of tissue-infiltrating CD4(+) and CD8(+) T cells from the muscle and skin specimens. The majority of expanded T cells were chemokine receptor (CCR) type 7(-) CD45RO(+) effecter memory cells with various T cell receptor (TCR) Vβs. The skin-derived but not muscle-derived T cells expressed cutaneous lymphocyte antigen (CLA) and CCR10 and secreted large amounts of IL-17A, suggesting that T helper type 17 (Th17) cells may have a crucial role in the development of skin lesions. Notably, the frequency of IL-4-producing chemokine (C-X-C motif) receptor (CXCR)4(+) Th2 cells was significantly higher in the muscle-derived cells and correlated inversely with the serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels. stromal-derived factor (SDF)-1/CXCL12, a ligand for CXCR4, was expressed at a high level in the vascular endothelial cells between muscular fasciculi. Our study suggests that T cell populations in the muscle and skin are different, and the Th2 cell infiltrate in the muscle is associated with the low severity of myositis in DM.

  11. Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis

    PubMed Central

    Fujiyama, T; Ito, T; Ogawa, N; Suda, T; Tokura, Y; Hashizume, H

    2014-01-01

    Dermatomyositis (DM) and polymyositis (PM) are collectively termed autoimmune myopathy. To investigate the difference between muscle- and skin-infiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM. Muscle and skin biopsied specimens were immersed in cRPMI medium supplemented with interleukin (IL)-2 and anti-CD3/CD28 antibody-conjugated microbeads. The expanded cells were subjected to flow cytometry to examine their phenotypes. We analysed the cytokine concentration in the culture supernatants from the expanded T cells and the frequencies of cytokine-bearing cells by intracellular staining. There was non-biased in-vitro expansion of tissue-infiltrating CD4+ and CD8+ T cells from the muscle and skin specimens. The majority of expanded T cells were chemokine receptor (CCR) type 7–CD45RO+ effecter memory cells with various T cell receptor (TCR) Vβs. The skin-derived but not muscle-derived T cells expressed cutaneous lymphocyte antigen (CLA) and CCR10 and secreted large amounts of IL-17A, suggesting that T helper type 17 (Th17) cells may have a crucial role in the development of skin lesions. Notably, the frequency of IL-4-producing chemokine (C-X-C motif) receptor (CXCR)4+ Th2 cells was significantly higher in the muscle-derived cells and correlated inversely with the serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels. stromal-derived factor (SDF)-1/CXCL12, a ligand for CXCR4, was expressed at a high level in the vascular endothelial cells between muscular fasciculi. Our study suggests that T cell populations in the muscle and skin are different, and the Th2 cell infiltrate in the muscle is associated with the low severity of myositis in DM. PMID:24580543

  12. Lignin-stimulated reduction of oxidative DNA lesions in testicular cells and lymphocytes of sprague-dawley rats in vitro and ex vivo.

    PubMed

    Lábaj, Juraj; Slameoová, Darina; Lazarová, Monika; Kosiková, Bozena

    2004-01-01

    Lignin biopolymers constitute 30% of plant biomass and belong to the most abundant organic polymers on earth. We showed previously that this important component of dietary fiber exhibited a protective effect against the overall DNA damage induced by H2O2 or N-methyl-N'-nitro-N-nitrosoguanidine in hamster lung cells and human foreskin cells cultured in vitro. The objective of the present work was to examine DNA-protective effects of lignin in rat testicular cells and rat peripheral blood lymphocytes using in vitro and ex vivo experiments. H2O2 and visible light-excited methylene blue (MB) were used as DNA-damaging agents. Testicular cells were chosen because the germinal epithelium of testes is one of the most proliferately active tissues potentially susceptible to DNA-damaging effects. As a second target peripheral blood lymphocytes were chosen because dietary lignin or its metabolites circulate in the animal organism probably through the blood system. For the in vitro experiments, isolated cells were preincubated with lignin for 2 h before treatment with one of the oxidative agents. In ex vivo experiments, the cells were exposed to H2O2 or visible light-excited MB after isolation from rats fed either a common diet or a lignin-supplemented diet. The water-soluble, sulfur-free lignin used in experiments was obtained by fractionation of hardwood hydrolysate. The level of direct single-strand DNA breaks in H2O2-treated cells was measured by the classical comet assay, and the level of oxidative DNA lesions in visible light-treated cells was measured by a modified comet assay. We found that lignin reduced DNA lesions induced by H2O2 or visible light-excited MB both in vitro and ex vivo. The major conclusion of our study is that lignin polymer obtained by fractionation of hardwood hydrolysate manifested a specific type of antimutagenic effect.

  13. UVA and visible light photons produce frank strand breaks in human P3 cell DNA as well as a new class of alkali-labile lesion

    SciTech Connect

    Peak, M.J.; Peak, J.G.

    1994-05-01

    Human P3 epithelioid cells were exposed to UVA (290--400 nm), as well as to blue and green photons in the 400--520 mm region of the spectrum, and the production of strand breaks in their DNA was measured by using elution. After exposure to blue photons the profiles were convex (downturning), shown to be due to the induction of a mixture of frank single-strand DNA breaks (SSB) plus rapidly developing alkali-labile sites (ALS). as well as latent breaks that develop during the first 6 h of the elution, termed slowly developing alkali-labile sites (SDALS). A significant proportion of the lesions produced by P3 cells by blue light photons are SDALS, whereas green light photons at 520 nm and UVA photons at 365 nm produce no SDALS and the elution profiles are exponential. This is also the case for Chinese hamster ovary cells exposed to 405 nm, evidence that a unique chromophore in P3 cells that absorbs strongly in the blue region leads to the formation of SDALS. The similarity in induction of SDALS at 460 and 405 nm is evidence that the chromophore is not a porphyrin, because these compounds have sharp absorption maxima in the lower 400 nm region. The chemical nature of these lesions as well as the cellular responses to them remain enigmatic.

  14. ISS-Experiments of Columnar-to-Equiaxed Transition in Solidification Processing

    NASA Technical Reports Server (NTRS)

    Sturz, Laszlo; Zimmermann, Gerhard; Gandin, Charles, Andre; Billia, Bernard; Magelinck, Nathalie; Nguyen-Thi, Henry; Browne, David John; Mirihanage, Wajira U.; Voss, Daniela; Beckermann, Christoph; Karma, Alain

    2012-01-01

    The main topic of the research project CETSOL in the framework of the Microgravity Application Promotion (MAP) programme of the European Space Agency (ESA) is the investigation of the transition from columnar to equiaxed grain growth during solidification. Microgravity environment allows for suppression of buoyancy-driven melt flow and for growth of equiaxed grains free of sedimentation and buoyancy effects. This contribution will present first experimental results obtained in microgravity using hypo-eutectic AlSi alloys in the Materials Science Laboratory (MSL) on-board the International Space Station (ISS). The analysis of the experiments confirms the existence of a columnar to equiaxed transition, especially in the refined alloy. Temperature evolution and grain structure analysis provide critical values for the position, the temperature gradient and the solidification velocity at the columnar to equiaxed transition. These data will be used to improve modeling of solidification microstructures and grain structure on different lengths scales.

  15. First identification of Flavobacterium columnare infection in farmed freshwater striped catfish Pangasianodon hypophthalmus.

    PubMed

    Tien, Nguyen Thi; Dung, Tu Thanh; Tuan, Nguyen Anh; Crumlish, Mags

    2012-08-13

    The bacterium Flavobacterium columnare was recovered and identified as the aetiological agent causing freshwater columnaris infection in farmed striped catfish Pangasianodon hypophthalmus (Sauvage) fingerlings that had suffered high mortality rates within commercial hatchery ponds in Vietnam. The gross clinical signs were typical of columnaris-infected fish. Histological examination found numerous Gram-negative, filamentous bacteria present on the skin, muscle and gill tissues of affected fish. The yellow-pigmented bacteria were isolated and identified as F. columnare using primary, biochemical and PCR methods. An experimental immersion-challenge study with 2 strains was also performed. It fulfilled Koch's postulates and showed a median lethal concentration (LC50) of 4.27 × 105 and 1.66 × 106 cfu ml-1 for the F. columnare strains FC-HN and FC-CT, respectively. To the best of our knowledge this is the first report of freshwater columnaris infection in P. hypophthalmus.

  16. Moisture proof columnar Cesium Iodide (CsI) layers for gas avalanche microdetectors

    SciTech Connect

    Park, I.J.; Cho, H.S.; Hong, W.S.; Perez-Mendez, V.; Kadyk, J.

    1999-05-05

    Cesium iodide columnar layers having a diameter of 3 {micro}m, and wall spacing of {approx} 1 {micro}m act as secondary electron emitters and can be used for detection of radiation: charged particles, X-rays and gamma rays. With a large enough electric field across the columnar layers, {approx} 400 {micro}m in thickness, gas avalanche gain is evident when placed in a suitable gas, such as P10 or argon-ethane mixtures. The cesium iodide columns are damaged by ambient moisture. This damage can be prevented by evaporating protective layers of insoluble, low boiling point inorganic materials, such as mercuric iodide. Columnar layers with 20 nm coatings of mercuric iodide yield more than 30,000 electrons on average when traversed by electrons from a {sup 90}Sr beta source.

  17. Columnar order in jammed LiFePO4 cathodes: ion transport catastrophe and its mitigation.

    PubMed

    Smith, Kyle C; Mukherjee, Partha P; Fisher, Timothy S

    2012-05-21

    The high-rate, high-capacity potential of LiFePO4-based lithium-ion battery cathodes has motivated numerous experimental and theoretical studies aiming to realize such performance through nano-sizing, tailoring of particle shape through synthesis conditions, and doping. Here, a granular mechanics study of microstructures formed by dense jammed packings of experimentally and theoretically inspired LiFePO4 particle shapes is presented. A strong dependence of the resultant packing structures on particle shapes is observed, in which columnar structures aligned with the [010] direction inhibit diffusion along [010] in anisotropic LiFePO4. Transport limitations are induced by [010] columnar order and lead to catastrophic performance degradation in anisotropic LiFePO4 electrodes. Further, judicious mixing of nanoplatelets with additive nanoparticles can frustrate columnar ordering and thereby enhance the rate capability of LiFePO4 electrodes by nearly an order of magnitude.

  18. Columnar transmitter based wireless power delivery system for implantable device in freely moving animals.

    PubMed

    Eom, Kyungsik; Jeong, Joonsoo; Lee, Tae Hyung; Lee, Sung Eun; Jun, Sang Bum; Kim, Sung June

    2013-01-01

    A wireless power delivery system is developed to deliver electrical power to the neuroprosthetic devices that are implanted into animals freely moving inside the cage. The wireless powering cage is designed for long-term animal experiments without cumbersome wires for power supply or the replacement of batteries. In the present study, we propose a novel wireless power transmission system using resonator-based inductive links to increase power efficiency and to minimize the efficiency variations. A columnar transmitter coil is proposed to provide lateral uniformity of power efficiency. Using this columnar transmitter coil, only 7.2% efficiency fluctuation occurs from the maximum transmission efficiency of 25.9%. A flexible polymer-based planar type receiver coil is fabricated and assembled with a neural stimulator and an electrode. Using the designed columnar transmitter coil, the implantable device successfully operates while it moves freely inside the cage.

  19. Simultaneous occurrence of biphenotypic T cell/myeloid lesions involving t(12;13)(p13;q14) in a pediatric patient.

    PubMed

    Carneiro Borba, Claudio; de Lourdes Chauffaille, Maria; Saeed Sanabani, Sabri; Saeed Sanabnai, Sabri; Folloni Fernandes, Juliana; Aiko Kumeda, Cristina; Rodrigues Pereira Velloso, Elvira Deolinda; Jarandilha dos Santos, Katia; Puato Vieira Pupim, Marcia; Hamerschlak, Nelson; Odone Filho, Vicente; Bendit, Israel

    2012-01-01

    This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected.

  20. Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo.

    PubMed

    Sasaki, Kotaro; Zhao, Xi; Pardee, Angela D; Ueda, Ryo; Fujita, Mitsugu; Sehra, Sarita; Kaplan, Mark H; Kane, Lawrence P; Okada, Hideho; Storkus, Walter J

    2008-07-01

    VLA-4 plays a critical role in T cell trafficking into inflammatory sites. Our recent studies have suggested that VLA-4 expression on CD8+ T cells is negatively controlled by IL-4 and serves as a functionally distinguishing variable for why Type-1, but not Type-2, CD8+ T cells are able to traffic into tumors. In this study, using in vitro culture of murine CD8+ T cells under Type-1 and Type-2 cytokine conditions, we show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-deficient CD8+ T cells. Conversely, CD8+ T cells expressing a constitutively active mutant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimulation. Notably, Type-2 CD8+ T cells developed from Stat6-/- but not wild-type mice were competent to migrate into tumor lesions in vivo. These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8+ T cell infiltration into tumors.

  1. Stat6 Signaling Suppresses VLA-4 Expression by CD8+ T Cells and Limits Their Ability to Infiltrate Tumor Lesions In Vivo1

    PubMed Central

    Sasaki, Kotaro; Zhao, Xi; Pardee, Angela D.; Ueda, Ryo; Fujita, Mitsugu; Sehra, Sarita; Kaplan, Mark H.; Kane, Lawrence P.; Okada, Hideho; Storkus, Walter J.

    2008-01-01

    VLA-4 plays a critical role in T cell trafficking into inflammatory sites. Our recent studies have suggested that VLA-4 expression on CD8+ T cells is negatively controlled by IL-4 and serves as a functionally distinguishing variable for why Type-1, but not Type-2, CD8+ T cells are able to traffic into tumors. In this study, using in vitro culture of murine CD8+ T cells under Type-1 and Type-2 cytokine conditions, we show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-deficient CD8+ T cells. Conversely, CD8+ T cells expressing a constitutively active mutant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimulation. Notably, Type-2 CD8+ T cells developed from Stat6−/− but not wild-type mice were competent to migrate into tumor lesions in vivo. These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8+ T cell infiltration into tumors. PMID:18566374

  2. Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

    PubMed Central

    TANIO, SHUNSUKE; MATSUSHITA, MICHIKO; KUWAMOTO, SATOSHI; HORIE, YASUSHI; KODANI, ISAMU; MURAKAMI, ICHIRO; RYOKE, KAZUO; HAYASHI, KAZUHIKO

    2015-01-01

    It was recently demonstrated that ~80% of Merkel cell carcinomas (MCCs) harbour a novel polyomavirus, Merkel cell polyomavirus (MCPyV). MCPyV has been detected in various human tissue samples. However, previous studies on the prevalence of MCPyV in oral tumours or tumour-like lesions are incomplete. To address this issue, we measured MCPyV DNA quantity using quantitative polymerase chain reaction (qPCR) in 327 oral tumours or tumour-like lesions and 54 jaw tumours or cyst lesions from 381 immunocompetent patients, as well as in 4 oral lesions from 4 immunosuppressed patients. qPCR revealed a low MCPyV prevalence (25/381, 6.6%) with low viral loads (0.00024-0.026 copies/cell) in oral and maxillofacial tumours and tumour-like lesions from immunocompetent patients. The prevalence was 7/176 (4.0%) in invasive squamous cell carcinomas (SCCs) [2/60 (3.33%) SCCs of the tongue, 4/52 (7.7%) SCCs of the gingiva and 1/19 (5.3%) SCCs of the floor of the mouth], 1/10 (10%) in dysplasias, 1/5 (20%) in adenocarcinomas, 2/13 (15.4%) in adenoid cystic carcinomas, 1/10 (10%) in non-Hodgkin's lymphomas, 3/10 (30%) in lipomas, 3/5 (60%) in neurofibromas, 1/3 (33.3%) in Schwannomas, 2/12 (16.7%) in Warthin's tumours, 2/11 (18.2%) in pyogenic granulomas, 1/14 (7.1%) in radicular cysts and 1/12 (8.3%) in ameloblastomas. The prevalence in lesions from immunosuppressed patients (1/4, 25%) was higher compared with that in lesions from immunocompetent patients (25/381, 6.6%), but the difference was not statistically significant. To the best of our knowledge, this study was the first to report prevalence data of MCPyV in tumours and cysts of the jaws (2/54, 3.7%). These data indicated absence of MCPyV-related tumours or tumour-like lesions in the oral cavity and jaws and suggested that the detected MCPyV DNA was derived from non-neoplastic background tissues with widespread low-level MCPyV infection. PMID:26807237

  3. Ionic Switch Induced by a Rectangular-Hexagonal Phase Transition in Benzenammonium Columnar Liquid Crystals.

    PubMed

    Soberats, Bartolome; Yoshio, Masafumi; Ichikawa, Takahiro; Zeng, Xiangbing; Ohno, Hiroyuki; Ungar, Goran; Kato, Takashi

    2015-10-21

    We demonstrate switching of ionic conductivities in wedge-shaped liquid-crystalline (LC) ammonium salts. A thermoreversible phase transition between the rectangular columnar (Colr) and hexagonal columnar (Colh) phases is used for the switch. The ionic conductivities in the Colh phase are about four orders of magnitude higher than those in the Colr phase. The switching behavior of conductivity can be ascribed to the structural change of assembled ionic channels. X-ray experiments reveal a highly ordered packing of the ions in the Colr phase, which prevents the ion transport.

  4. Columnar discharge mode between parallel dielectric barrier electrodes in atmospheric pressure helium

    SciTech Connect

    Hao, Yanpeng; Zheng, Bin; Liu, Yaoge

    2014-01-15

    Using a fast-gated intensified charge-coupled device, end- and side-view photographs were taken of columnar discharge between parallel dielectric barrier electrodes in atmospheric pressure helium. Based on three-dimensional images generated from end-view photographs, the number of discharge columns increased, whereas the diameter of each column decreased as the applied voltage was increased. Side-view photographs indicate that columnar discharges exhibited a mode transition ranging from Townsend to glow discharges generated by the same discharge physics as atmospheric pressure glow discharge.

  5. Columnar/herringbone dual crystal packing of pyrenylsumanene and its photophysical properties

    PubMed Central

    Shrestha, Binod Babu

    2014-01-01

    Summary A single crystal of pyrenylsumanene was found to exhibit both columnar and herringbone crystal packing. The sumanene moieties form unidirectional columnar structures based on π–π stacking while the pyrene moieties generate herringbone structures due to CH–π interactions. The absorption and emission maxima of pyrenylsumanene were both red-shifted relative to those of sumanene and pyrene, owing to the extension of π-conjugation. Monomer emission with high quantum yield (0.82) was observed for pyrenylsumanene in solution, while excimer-type red-shifted emission was evident in the crystalline phase. PMID:24778739

  6. Synthesis and structural investigation of a unique columnar phase in the Bi2O3–TeO2–V2O5 System.

    PubMed

    Thakral, Vaishali; Bhardwaj, Neha; Uma, S

    2012-02-06

    A new columnar phase Bi(11.65)Te(1.35)V(5)O(34-δ) (δ ∼ 1.3) containing VO(4) tetrahedra has been identified for the first time in the Bi(2)O(3)-TeO(2)-V(2)O(5) system. The phase formation and the extent of substitution of Te(4+) for Bi(3+) ions in order to stabilize V(5+) in this composition have been confirmed by the single crystal analysis, combined with the powder X-ray diffraction of the solid state synthesized bulk crystalline samples. The oxide crystallizes in a monoclinic crystal system, space group P2/c, with unit cell parameters a = 11.4616(7) Å, b = 5.7131(3) Å, c = 23.5090(18) Å, β = 101.071° (6) (Z = 2). The structure retains the basic features of the columnar oxides with the presence of [Bi(10.65)Te(1.35)O(14)](n)(9.35n+) columns along the (010) direction, surrounded by (VO(4)) tetrahedra placed in the planes parallel to (100) and (001), with an isolated bismuth atom in between the columns. The composition with a limited Te(4+) substitution, Bi(11.65)Te(1.35)V(5)O(34-δ) (δ ∼ 1.3), exists with a surprisingly high oxygen deficiency as compared to the stoichiometrically known columnar oxides such as Bi(13)Mo(4)VO(34), Bi(12)Te(1)Mo(3)V(2)O(34), and Bi(11)Te(2)Mo(2)V(3)O(34). The structure of this interesting member of the columnar family of oxides based on the single crystal X-ray diffraction and the Raman spectroscopic studies indicates the possibility of the distribution of the oxygen vacancies among the VO(4) tetrahedral units. Further confirmation for the formation of vanadium stabilized columnar structures has been provided by the successful preparation of Bi(11.65)Te(1.35)V(4)CrO(34-δ) (δ ∼ 0.83) and Bi(11.65)Te(1.35)V(4)WO(34-δ) (δ ∼ 0.83) phases. Preliminary investigation of the photocatalytic efficiencies of the oxides Bi(11.65)Te(1.35)V(5)O(34-δ), Bi(11.65)Te(1.35)V(4)CrO(34-δ), and Bi(11.65)Te(1.35)V(4)WO(34-δ) revealed moderate photocatalytic activities for the decomposition of the dyes such as Rhodamine B under UV

  7. Differential diagnosis of ovarian tumors based primarily on their patterns and cell types.

    PubMed

    Young, R H; Scully, R E

    2001-08-01

    The differential diagnosis of ovarian tumors is reviewed based on their patterns and cell types. This approach, which differs from the standard textbook discussion of each neoplasm as an entity, has practical value as differential diagnosis depends largely on the pattern or patterns and cell type or types of tumors. Awareness of the broad range of lesions that may exhibit particular patterns or contain one or more cell types is crucial in formulating a differential diagnosis. The following patterns are considered: moderate-to-large-glandular and hollow-tubular; solid tubular and pseudotubular; cords and ribbons; insular; trabecular; slit-like and reticular spaces; microglandular and microfollicular; macrofollicular and pseudomacrofollicular; papillary; diffuse; fibromatous-thecomatous; and biphasic and pseudobiphasic. The following cell types are considered: small round cells; spindle cells; mucinous cells, comprising columnar, goblet cell and signet ring cell subtypes; clear cells; hobnail cells; oxyphil cells; and transitional cells. The morphologic diversity of ovarian tumors poses many challenges; knowledge of the occurrence and frequency of these patterns and cell types in various tumors and tumor-like lesions is of paramount diagnostic importance. A specific diagnosis can usually be made by evaluating routinely stained slides, but much less often, special staining, immunohistochemical staining or, very rarely, ultrastructural examination is also required. Finally, clinical data, operative findings, and gross features of the lesions may provide important, and at times decisive diagnostic clues.

  8. Development of a reproducible challenge model to investigate the virulence of Flavobacterium columnare genomovars in rainbow trout Oncorhynchus mykiss (Walbaum)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is a Gram-negative bacterium that causes columnaris disease and has significant economic impacts on aquaculture production worldwide. Molecular analyses have demonstrated that there is genetic diversity among F. columnare isolates. A review of the published literature that...

  9. Growth and survival of the fish pathogenic bacterium, Flavobacterium columnare, in tilapia mucus and porcine gastric mucin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is an economically important gram negative bacterium that infects most freshwater farmed fish worldwide. Flavobacterium columnare colonizes the skin and gills of fish in the initial steps of pathogenesis. The fish’s surface is coated with mucus made up of high molecular we...

  10. Impact of oral and waterborne administration of rhamnolipids on the susceptibility of channel catfish (Ictalurus punctatus) to Flavobacterium columnare infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the causative agent of columnaris disease and causes tremendous morbidity and mortality of farmed fish globally. Previously, we identified a potential lectin-mediator (a rhamnose-binding lectin; RBL1a) of F. columnare adhesion and showed higher RBL1a expression in suscept...

  11. Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response*

    PubMed Central

    Tan, Xun; Juan, Fan-guo; Shah, Ali Q.

    2017-01-01

    Plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). Endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133+ and VEGFR-2+ cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. Broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using gene-modified inflammation-resistant EPCs. PMID:28070997

  12. Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response.

    PubMed

    Tan, Xun; Juan, Fan-Guo; Shah, Ali Q

    Plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). Endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133(+) and VEGFR-2(+) cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. Broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using gene-modified inflammation-resistant EPCs.

  13. Block of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS.

    PubMed Central

    Ensoli, B; Markham, P; Kao, V; Barillari, G; Fiorelli, V; Gendelman, R; Raffeld, M; Zon, G; Gallo, R C

    1994-01-01

    Kaposi's sarcoma (KS) is the most frequent tumor of HIV-1-infected individuals (AIDS-KS). Typical features of KS are proliferating spindle-shaped cells, considered to be the tumor cells of KS, and endothelial cells forming blood vessels. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is highly expressed by KS spindle cells in vivo and after injection in nude mice it induces vascular lesions closely resembling early KS in humans. Similar lesions are induced by inoculating nude mice with cultured spindle cells from AIDS-KS lesions (AIDS-KS cells) which produce and release bFGF. Here we show that phosphorothioate antisense (AS) oligonucleotides directed against bFGF mRNA (ASbFGF) inhibit both the growth of AIDS-KS cells derived from different patients and the angiogenic activity associated with these cells, including the induction of KS-like lesions in nude mice. These effects are due to the block of the production of bFGF which is required by AIDS-KS cells to enter the cell cycle and which, after release, mediates angiogenesis. The effects of ASbFGF are specific, dose dependent, achieved at low (0.1-1 microM), nontoxic, oligomer concentrations, and are reversed by the addition of bFGF to the cells, suggesting that ASbFGF oligomers are promising drug candidates for KS therapy. Images PMID:7525646

  14. Bazex Syndrome in Lung Squamous Cell Carcinoma: High Expression of Epidermal Growth Factor Receptor in Lesional Keratinocytes with Th2 Immune Shift

    PubMed Central

    Amano, Maki; Hanafusa, Takaaki; Chikazawa, Sakiko; Ueno, Makiko; Namiki, Takeshi; Igawa, Ken; Miura, Keiko; Yokozeki, Hiroo

    2016-01-01

    An 82-year-old Japanese man was referred for detailed examination of hyperkeratotic erythematous plaques on his palms and soles for 6 months. Two weeks before his first visit, he had undergone lung lobectomy for right lung squamous cell carcinoma (SCC). Laboratory findings showed elevations of eosinophil counts, serum IgE, thymus and activation-regulated chemokine, SCC antigen, and soluble interleukin-2 receptor levels. Histological results of a skin biopsy involving the left palm showed psoriasiform dermatitis. Before lung lobectomy, the hyperkeratotic erythematous plaques on the palms and soles and the erythemas on the trunk and extremities were difficult to treat with topical steroids. After lobectomy, the skin symptoms dramatically and rapidly subsided with topical steroids. Therefore, we diagnosed Bazex syndrome (BS), also known as acrokeratosis paraneoplastica, as a paraneoplastic cutaneous disease in lung SCC. The mild eosinophilia subsided and levels of SCC antigen, IgE, and soluble interleukin-2 receptor were reduced. BS is a paraneoplastic cutaneous disease characterized by acral psoriasiform lesions associated with an underlying neoplasm. In a previous report, a shift to the Th2 immune condition was found in patients with non-small cell lung cancer, as shown in our patient. Epidermal growth factor receptor (EGFR) is also known as tumor growth factor-α receptor; it is increased in psoriatic keratinocytes. In our case, EGFR expression increased in lesional keratinocytes 2 weeks after surgery and decreased 4 weeks after surgery. We speculate that a shift to Th2 immune reactions in lung SCC may be the pathogenesis of BS, whereby lesional keratinocytes highly express EGFR in parallel with disease activity. PMID:28101024

  15. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

    PubMed Central

    Mansfield, A. S.; Aubry, M. C.; Moser, J. C.; Harrington, S. M.; Dronca, R. S.; Park, S. S.; Dong, H.

    2016-01-01

    Background The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. Experimental design Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ2 or Fisher's exact test were used for analysis. Results We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). Conclusions We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment. PMID:27502709

  16. MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas.

    PubMed

    Nie, Kui; Gomez, Mario; Landgraf, Pablo; Garcia, Jose-Francisco; Liu, Yifang; Tan, Leonard H C; Chadburn, Amy; Tuschl, Thomas; Knowles, Daniel M; Tam, Wayne

    2008-07-01

    PRDM1/Blimp-1, a master regulator in terminal B-cell differentiation, has been recently identified as a tumor suppressor target for mutational inactivation in diffuse large B-cell lymphomas of the activated B-cell type. Our studies here demonstrate that PRDM1/blimp-1 is also a target for microRNA (miRNA)-mediated down-regulation by miR-9 and let-7a in Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). MiRNA expression profiling by direct miRNA cloning demonstrated that both of these miRNAs are among the most highly expressed in cultured HRS cells. These miRNAs functionally targeted specific binding sites in the 3' untranslated region of PRDM1/blimp-1 mRNA and repressed luciferase reporter activities through repression of translation. In addition, high levels of miR-9 and let-7a in HL cell lines correlated with low levels of PRDM1/Blimp-1. Similar to their in vitro counterparts, the majority of HRS cells in primary HL cases showed weak or no PRDM1/Blimp-1 expression. Over-expression of miR-9 or let-7a reduced PRDM1/Blimp-1 levels in U266 cells by 30% to 50%, whereas simultaneous inhibition of their activities in L428 cells resulted in an approximately 2.6-fold induction in PRDM1/Blimp-1. MiRNA-mediated down-regulation of PRDM1/Blimp-1 may contribute to the phenotype maintenance and pathogenesis of HRS cells by interfering with normal B-cell terminal differentiation, thus representing a novel molecular lesion, as well as a potential therapeutic target in HL.

  17. Rhamnose binding lectins influence Flavobacterium columnare pathogenesis in channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide and commonly leads to tremendous losses of both wild and cultured freshwater fish, particularly in intensively farmed aquaculture species such as channel catfish. Despite its ecol...

  18. Kaolinitic clay protects against Flavobacterium columnare infection in channel catfish Ictalurus punctatus (Rafinesque)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide in aquaculture settings. Despite the far-reaching negative impacts of columnaris disease, safe and efficacious preventatives and curatives for this disease remain limited. In th...

  19. Induced stabilization of columnar phases in binary mixtures of discotic liquid crystals.

    PubMed

    Cienega-Cacerez, Octavio; García-Alcántara, Consuelo; Moreno-Razo, José Antonio; Díaz-Herrera, Enrique; Sambriski, Edward John

    2016-01-28

    Three discotic liquid-crystalline binary mixtures, characterized by their extent of bidispersity in molecular thickness, were investigated with molecular dynamics simulations. Each equimolar mixture contained A-type (thin) and B-type (thick) discogens. The temperature-dependence of the orientational order parameter reveals that A-type liquid samples produce ordered phases more readily, with the (hexagonal) columnar phase being the most structured variant. Moderately and strongly bidisperse mixtures produce globally-segregated samples for temperatures corresponding to ordered phases; the weakly bidisperse mixture displays microheterogeneities. Ordered phases in the B-type liquid are induced partially by the presence of the A-type fluid. In the moderately bidisperse mixture, order is induced through orientational frustration: a mixed prenematic-like phase precedes global segregation to yield nematic and columnar mesophases upon further cooling. In the strongly bidisperse mixture, order is induced less efficiently through a paranematic-like mechanism: a highly-ordered A-type fluid imparts order to B-type discogens found at the interface of a fully-segregated sample. This ordering effect permeates into the disordered B-type domain until nematic and columnar phases emerge upon further cooling. At sufficiently low temperatures, all samples investigated exhibit the (hexagonal) columnar mesophase.

  20. More than just antibodies: protective mechanisms of a mucosal vaccine against fish pathogen Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recently developed attenuated vaccine (17-23) for Flavobacterium columnare has been demonstrated to provide superior protection for channel catfish, Ictalurus punctatus, against genetically diverse columnaris isolates. First, we were interested in elucidating the host responses generated by a viru...

  1. There must be something in the water (for F. columnare pathogenesis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Why can we routinely produce columnaris infections in our lab, while the lab on the other side of the ditch can't? Anecdotal reports suggest that tannins may inhibit F. columnare. Do tannins in their water prevent this, or are other water chemistry parameters involved? In the first experiment, tw...

  2. A liquid-crystalline hexagonal columnar phase in highly-dilute suspensions of imogolite nanotubes

    NASA Astrophysics Data System (ADS)

    Paineau, Erwan; Krapf, Marie-Eve M.; Amara, Mohamed-Salah; Matskova, Natalia V.; Dozov, Ivan; Rouzière, Stéphan; Thill, Antoine; Launois, Pascale; Davidson, Patrick

    2016-01-01

    Liquid crystals have found wide applications in many fields ranging from detergents to information displays and they are also increasingly being used in the `bottom-up' self-assembly approach of material nano-structuration. Moreover, liquid-crystalline organizations are frequently observed by biologists. Here we show that one of the four major lyotropic liquid-crystal phases, the columnar one, is much more stable on dilution than reported so far in literature. Indeed, aqueous suspensions of imogolite nanotubes, at low ionic strength, display the columnar liquid-crystal phase at volume fractions as low as ~0.2%. Consequently, due to its low visco-elasticity, this columnar phase is easily aligned in an alternating current electric field, in contrast with usual columnar liquid-crystal phases. These findings should have important implications for the statistical physics of the suspensions of charged rods and could also be exploited in materials science to prepare ordered nanocomposites and in biophysics to better understand solutions of rod-like biopolymers.

  3. A bundled-stack discotic columnar liquid crystalline phase with inter-stack electronic coupling

    DOE PAGES

    Wang, Bin; Sun, Runkun; Günbaş, Duygu D.; ...

    2015-06-15

    The first compound proving to be capable of forming a bundled-stack discotic columnar liquid crystalline (BSDCLC) phase was designed and synthesized. Finally, the unique perylene anhydride inter-stack interaction was found to be the key to the formation of the BSDCLC structure and inter-stack electronic coupling (ISEC).

  4. A solutal interaction mechanism for the columnar-to-equiaxed transition in alloy solidification

    NASA Astrophysics Data System (ADS)

    Martorano, M. A.; Beckermann, C.; Gandin, C.-A.

    2003-08-01

    A multiphase/multiscale model is used to predict the columnar-to-equiaxed transition (CET) during solidification of binary alloys. The model consists of averaged energy and species conservation equations, coupled with nucleation and growth laws for dendritic structures. A new mechanism for the CET is proposed based on solutal interactions between the equiaxed grains and the advancing columnar front—as opposed to the commonly used mechanical blocking criterion. The resulting differences in the CET prediction are demonstrated for cases where a steady state can be assumed, and a revised isotherm velocity (V T ) vs temperature gradient (G) map for the CET is presented. The model is validated by predicting the CET in previously performed unsteady, unidirectional solidification experiments involving Al-Si alloys of three different compositions. Good agreement is obtained between measured and predicted cooling curves. A parametric study is performed to investigate the dependence of the CET position on the nucleation undercooling and the density of nuclei in the equiaxed zone. Nucleation undercoolings are determined that provide the best agreement between measured and calculated CET positions. It is found that for all three alloy compositions, the nucleation undercoolings are very close to the maximum columnar dendrite tip undercoolings, indicating that the origin of the equiaxed grains may not be heterogeneous nucleation, but rather a breakdown or fragmentation of the columnar dendrites.

  5. Two-dimensional simulation of spatiotemporal generation of dielectric barrier columnar discharges in atmospheric helium

    SciTech Connect

    Huang, Zhiming; Hao, Yanpeng; Yang, Lin; Han, Yongxia; Li, Licheng

    2015-12-15

    A two-dimensional (2D) fluid model is presented to investigate the spatiotemporal generation and dynamic mechanics of dielectric barrier columnar discharges in atmospheric helium. The model was examined with discharge currents measured in experiments and images taken by an intensified charge couple device camera. Based on the model, a columnar discharge was simulated for several cycles after being ignited. The discharge could be regarded as an initial unstable stage for the first three and a half cycles, then a steady state for the following cycles. In the initial stage, the discharge evolves from a uniform pattern into a columnar one. The calculated equipotential lines, 2D radial electric field, and electron density distributions at the edge of uniform discharges show the radial electric field accounts for the shrinking discharge area and the formation of discharge columns in the end. The columnar glow discharges and the Townsend discharges beyond the columns could coexist in the initial stage, and a Townsend discharge might develop into a new glow column in the next half-cycle. The radial electric field surrounding a glow discharge column has an inhibiting effect on the ionization in the peripheral area.

  6. Compounds from Terminalli brownii extracts with toxicity against the fish pathogenic bacterium Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pond-raised channel catfish (Ictalurus punctatus) industry in the United States of America can incur losses of over a $100 million annually due to bacterial diseases including columnaris disease caused by Flavobacterium columnare. One management approach available to catfish producers is the use...

  7. Host-specific association between Flavobacterium columnare genomovars and fish species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 90 Flavobacterium columnare isolates were recovered from predominant wild fish species in the Mobile River, Alabama, USA. Isolates were identified and confirmed by fatty acid methyl ester analysis and specific PCR amplification. Genomovar ascription was performed using 16S-restriction fra...

  8. Draft genome sequence of the fish pathogen Flavobacterium columnare strain CSF-298-10

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We announce the genome assembly of Flavobacterium columnare strain CSF-298-10, a strain isolated from an outbreak of Columnaris disease at a commercial trout farm in Snake River Valley Idaho, USA. The complete genome consists of 13 contigs totaling 3,284,579 bp, average G+C content of 31.5% and 2933...

  9. Characterization of atypical Flavobacterium columnare and identification of a new genomovar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the etiological agent of columnaris disease and is the second most prevalent disease in farm-raised channel catfish. This is a Gram-negative bacterium characterized by adherent yellow pigmented rhizoid colonies. It can be further described by gliding motility, growth in t...

  10. Columnaris (Flavobacterium columnare) challenge using fathead minnows (Pimephales promelas) in an ultra-low flow system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arkansas baitfish farms routinely struggle with columnaris disease, which is caused by Flavobacterium columnare. Columnaris is ubiquitous in fathead minnows (Pimephales promelas) especially after harvest while they are being held in vats and during the transport prior to being sold. Columnaris disea...

  11. A liquid-crystalline hexagonal columnar phase in highly-dilute suspensions of imogolite nanotubes

    PubMed Central

    Paineau, Erwan; Krapf, Marie-Eve M.; Amara, Mohamed-Salah; Matskova, Natalia V.; Dozov, Ivan; Rouzière, Stéphan; Thill, Antoine; Launois, Pascale; Davidson, Patrick

    2016-01-01

    Liquid crystals have found wide applications in many fields ranging from detergents to information displays and they are also increasingly being used in the ‘bottom-up' self-assembly approach of material nano-structuration. Moreover, liquid-crystalline organizations are frequently observed by biologists. Here we show that one of the four major lyotropic liquid-crystal phases, the columnar one, is much more stable on dilution than reported so far in literature. Indeed, aqueous suspensions of imogolite nanotubes, at low ionic strength, display the columnar liquid-crystal phase at volume fractions as low as ∼0.2%. Consequently, due to its low visco-elasticity, this columnar phase is easily aligned in an alternating current electric field, in contrast with usual columnar liquid-crystal phases. These findings should have important implications for the statistical physics of the suspensions of charged rods and could also be exploited in materials science to prepare ordered nanocomposites and in biophysics to better understand solutions of rod-like biopolymers. PMID:26728415

  12. Flavobacterium columnare type IX secretion system mutations result in defects in gliding motility and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The gliding bacterium Flavobacterium columnare causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. The related bacterium Flavobacterium johnsoniae uses a type IX secretion system (T9SS) to secrete enzy...

  13. Evaluation of the antibody response to the LV-359-01 strain of flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, the causative agent of columnaris disease produces substantial mortality worldwide among numerous freshwater farmed finfish species. As aquaculture production continues to increase the frequency of columnaris disease will only continue to rise. Add to this an increase in re...

  14. Growth and survival of Flavobacterium columnare in fish mucus and porcine gastric mucin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, an economically important gram negative bacterium of freshwater farmed fish, colonizes the skin and gills in the initial steps of pathogenesis. The surface of fish is coated with mucus made up of high molecular weight glycoproteins. Limited studies have described the abili...

  15. Study of the photoinduced supramolecular chirality in columnar liquid crystals by infrared and VCD spectroscopies.

    PubMed

    Avilés Moreno, Juan Ramón; López González, Juan Jesús; Partal Ureña, Francisco; Vera, Francisco; Ros, M Blanca; Sierra, Teresa

    2012-04-26

    IR and VCD spectroscopies are employed to clarify the molecular origins of supramolecular chirality in azobenzene-containing columnar liquid crystals. The different columnar mesomorphic assemblies, Colr and Colh, of an achiral and a chiral propeller-like hydrogen-bonded complex, respectively, are used for this study. The mesomorphic behavior of the achiral complex is studied here for the first time, and the structural parameters of its Colr mesophase are determined by X-ray diffraction. Both complexes bear azobenzene units and this makes it possible to implement photoresponsive columnar architectures, the chirality of which can be induced and modulated by irradiation with 488 nm circularly polarized light (CPL). Thin films of the respective rectangular and hexagonal columnar phases of these complexes have been processed in order to study the IR absorption spectra and the vibrational circular dichroism responses upon irradiation with CPL. These studies allow confirming that the outer part of the columns, consisting on azobenzene groups, is mainly involved in the photoinduced supramolecular chirality, rather than the inner part of the columns where a melamine core is located. This supports a structural model based on the helical disposition of the azobenzene groups along the stacked propeller-like complexes.

  16. New hosts and genetic diversity of Flavobacterium columnare isolated from Brazilian native species and Nile tilapia.

    PubMed

    Barony, G M; Tavares, G C; Assis, G B N; Luz, R K; Figueiredo, H C P; Leal, C A G

    2015-11-17

    Flavobacterium columnare is responsible for disease outbreaks in freshwater fish farms. Several Brazilian native fish have been commercially exploited or studied for aquaculture purposes, including Amazon catfish Leiarius marmoratus × Pseudoplatystoma fasciatum and pacamã Lophiosilurus alexandri. This study aimed to identify the aetiology of disease outbreaks in Amazon catfish and pacamã hatcheries and to address the genetic diversity of F. columnare isolates obtained from diseased fish. Two outbreaks in Amazon catfish and pacamã hatcheries took place in 2010 and 2011. Four F. columnare strains were isolated from these fish and identified by PCR. The disease was successfully reproduced under experimental conditions for both fish species, fulfilling Koch's postulates. The genomovar of these 4 isolates and of an additional 11 isolates from Nile tilapia Oreochromis niloticus was determined by 16S rRNA restriction fragment length polymorphism PCR. The genetic diversity was evaluated by phylogenetic analysis of the 16S rRNA gene and repetitive extragenic palindromic PCR (REP-PCR). Most isolates (n = 13) belonged to genomovar II; the remaining 2 isolates (both from Nile tilapia) were assigned to genomovar I. Phylogenetic analysis and REP-PCR were able to demonstrate intragenomovar diversity. This is the first report of columnaris in Brazilian native Amazon catfish and pacamã. The Brazilian F. columnare isolates showed moderate diversity, and REP-PCR was demonstrated to be a feasible method to evaluate genetic variability in this bacterium.

  17. Optical characterization of lesions and identification of surgical margins in pancreatic metastasis from renal cell carcinoma by using two-photon excited fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Hong, Zhipeng; Chen, Hong; Chen, Youting; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

    2014-11-01

    Two-photon excited fluorescence (TPEF) microscopy has become a powerful instrument for imaging unstained tissue samples in biomedical research. The purpose of this study was to determine whether TPEF imaging of histological sections without hematoxylin-eosin (H-E) stain can be used to characterize lesions and identify surgical margins in pancreatic metastasis from renal cell carcinoma (RCC). The specimens of a pancreatic metastasis from RCC, as well as a primary RCC from a patient, were examined by TPEF microscopy and compared with their corresponding H-E stained histopathological results. The results showed that high-resolution TPEF imaging of unstained histological sections of pancreatic metastasis from RCC can reveal that the typical morphology of the tissue and cells in cancer tissues is different from the normal pancreas. It also clearly presented histopathological features of the collagenous capsule, which is an important boundary symbol to identify normal and cancerous tissue and to instruct surgical operation. It indicated the feasibility of using TPEF microscopy to make an optical diagnosis of lesions and identify the surgical margins in pancreatic metastasis from RCC.

  18. MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia

    PubMed Central

    Zhang, Chao; Arentz, Georgia; Winderbaum, Lyron; Lokman, Noor A.; Klingler-Hoffmann, Manuela; Mittal, Parul; Carter, Christopher; Oehler, Martin K.; Hoffmann, Peter

    2016-01-01

    Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC. PMID:27399691

  19. Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: comparison of intraventricular and intranigral delivery.

    PubMed

    Lapchak, P A; Miller, P J; Collins, F; Jiao, S

    1997-05-01

    The effects of intranigrally- or intraventricularly-administered glial cell line-derived neurotrophic factor were tested on low dose (0.05 mg/kg) apomorphine-induced rotations and tyrosine hydroxylase activity in the substantia nigra and striatum of stable 6-hydroxydopamine-lesioned rats. In addition, we determined if 6-hydroxydopamine lesions in the absence or presence of treatment affected neuropeptide (substance P, met-enkephalin, dynorphin) content in the striatum. Glial cell line-derived neurotrophic factor, when administered intranigrally, prevented apomorphine-induced rotational behaviour for 11 weeks following a single injection. In comparison, intraventricularly-administered glial cell line-derived neurotrophic factor produced a transient reduction in rotational behaviour that lasted for two to three weeks following a single injection. We also show that rotational behaviour is reduced following each subsequent intraventricular injection of glial cell line-derived neurotrophic factor given every six weeks, a time-point when baseline rotation deficits were re-established. Intranigrally- or intraventricularly-administered glial cell line-derived neurotrophic factor significantly reduced weight gain in all 6-hydroxydopamine-lesioned rats in this study. Following behavioural analysis where a confirmed improvement of behaviour was established, tissues were dissected for neurochemical analysis. In lesioned rats with intranigral injections of administered glial cell line-derived neurotrophic factor, significant increases of nigral, but not striatal tyrosine hydroxylase activity were measured. Additionally, 6-hydroxydopamine lesions significantly increased striatal dynorphin (61-139%) and met-enkephalin (81-139%), but not substance P levels. In these rats, intranigrally-administered glial cell line-derived neurotrophic factor injections reversed lesion-induced increases in nigral dynorphin A levels and increased nigral dopamine levels, but did not alter nigral met

  20. EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking-Induced Lesions in the Human Airway Epithelium

    PubMed Central

    Zuo, Wu-Lin; Yang, Jing; Gomi, Kazunori; Chao, IonWa; Crystal, Ronald G.; Shaykhiev, Renat

    2017-01-01

    The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of epidermal growth factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity. Further, AREG promoted its own expression and suppressed expression of EGF, establishing an autonomous self-amplifying signaling loop in airway BC relevant for promotion of EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC stem/progenitor cells is one of the mechanisms that mediates the interconnected pathogenesis of all major smoking-induced lesions in the human airway epithelium. PMID:27709733

  1. No detection of HTLV-I proviral DNA in lesional skin biopsies from Swiss and German patients with cutaneous T-cell lymphoma.

    PubMed

    Böni, R; Davis-Daneshfar, A; Burg, G; Fuchs, D; Wood, G S

    1996-02-01

    The search for an infective agent linked to cutaneous T-cell lymphoma (CTCL) has also included the human T-cell lymphotropic virus type I (HTLV-I). Using sensitive techniques such as Southern blotting under low stringency conditions of hybridization and polymerase chain reaction (PCR) with primer sets designed to match pol, env and pX sequences of HTLV-I, we have screened lesional skin biopsies of 50 Swiss and German patients suffering from CTCL. No evidence of proviral integration of HTLV-I could be demonstrated in any of our patients. Our results, as well as a review of the literature, indicate that at least for European patients, HTLV-I does not seem to play a role in the aetiology of CTCL.

  2. Variance in transneuronal retrograde ganglion cell degeneration in monkeys after removal of striate cortex: effects of size of the cortical lesion.

    PubMed

    Cowey, A; Stoerig, P; Williams, C

    1999-10-01

    The extent of transneuronal retrograde degeneration of ganglion cells in the primate retina depends on the age at which striate cortex was damaged, the survival time, the species, and retinal eccentricity. We here report on the effect of lesion size beyond striate cortex, which we assessed along with retinal ganglion cell degeneration in three groups of macaque monkeys who, in each group, had undergone striate cortical ablation at similar ages and survived for similar periods, which ranged from 302 days to 8 years. Where possible, the number of surviving projection neurones in the degenerated dLGN and its volume were also estimated. Results confirm that both geniculate and retinal degeneration correlate significantly with survival time but that the differences within a group can exceed differences between groups and are best accounted for by the extent of the damage to extra-striate visual cortex and underlying white matter.

  3. Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

    SciTech Connect

    Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong Tang Jian

    2007-11-16

    Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.

  4. Neuronal markers expression of NGF-primed bone marrow cells (BMCs) transplanted in the brain of 6-hydroxydopamine and ibotenic acid lesioned littermate mice.

    PubMed

    Triaca, Viviana; Aloe, Luigi

    In the present study, we aim to show that non-adherent bone marrow cells (BMCs) express TrkA, the nerve growth factor (NGF) receptor, and that addition of NGF promotes the survival and neuronal commitment of BMC transplanted into the experimentally injured brain of littermates mice. Immunohistochemical analysis revealed that transplanted BMCs express tyrosine hydroxylase (TH) in proximity of the damaged dopaminergic tissues and choline acetyltransferase (ChAT) in the lesioned cholinergic regions. These results suggest that NGF supports the survival and differentiation of uncommitted BMCs and concurs with other local environmental signals to promote the expression of neuronal markers in these cells. The possible functional significance of these observations will be discussed.

  5. α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium

    PubMed Central

    Ng, Bing Fu; Selvaraj, Gokul Kannan; Santa-Cruz Mateos, Carmen; Grosheva, Inna; Alvarez-Garcia, Ines; Martín-Bermudo, María Dolores; Palacios, Isabel M.

    2016-01-01

    The spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and β-Spectrin are essential to maintain a monolayered FE, but, contrary to previous work, spectrins are not required to control proliferation. Furthermore, spectrin mutant cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-Spectrin and integrin mutant cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-Myosin II pathway enhances and decreases multilayering of α-Spectrin cells, respectively. Similarly, higher Myosin II activity enhances the integrin multilayering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequate forces, in order to maintain a monolayered epithelium. PMID:26952981

  6. α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium.

    PubMed

    Ng, Bing Fu; Selvaraj, Gokul Kannan; Santa-Cruz Mateos, Carmen; Grosheva, Inna; Alvarez-Garcia, Ines; Martín-Bermudo, María Dolores; Palacios, Isabel M

    2016-04-15

    The spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and β-Spectrin are essential to maintain a monolayered FE, but, contrary to previous work, spectrins are not required to control proliferation. Furthermore, spectrin mutant cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-Spectrin and integrin mutant cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-Myosin II pathway enhances and decreases multilayering of α-Spectrin cells, respectively. Similarly, higher Myosin II activity enhances the integrin multilayering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequate forces, in order to maintain a monolayered epithelium.

  7. Analysis of EDZ Development of Columnar Jointed Rock Mass in the Baihetan Diversion Tunnel

    NASA Astrophysics Data System (ADS)

    Hao, Xian-Jie; Feng, Xia-Ting; Yang, Cheng-Xiang; Jiang, Quan; Li, Shao-Jun

    2016-04-01

    Due to the time dependency of the crack propagation, columnar jointed rock masses exhibit marked time-dependent behaviour. In this study, in situ measurements, scanning electron microscope (SEM), back-analysis method and numerical simulations are presented to study the time-dependent development of the excavation damaged zone (EDZ) around underground diversion tunnels in a columnar jointed rock mass. Through in situ measurements of crack propagation and EDZ development, their extent is seen to have increased over time, despite the fact that the advancing face has passed. Similar to creep behaviour, the time-dependent EDZ development curve also consists of three stages: a deceleration stage, a stabilization stage, and an acceleration stage. A corresponding constitutive model of columnar jointed rock mass considering time-dependent behaviour is proposed. The time-dependent degradation coefficient of the roughness coefficient and residual friction angle in the Barton-Bandis strength criterion are taken into account. An intelligent back-analysis method is adopted to obtain the unknown time-dependent degradation coefficients for the proposed constitutive model. The numerical modelling results are in good agreement with the measured EDZ. Not only that, the failure pattern simulated by this time-dependent constitutive model is consistent with that observed in the scanning electron microscope (SEM) and in situ observation, indicating that this model could accurately simulate the failure pattern and time-dependent EDZ development of columnar joints. Moreover, the effects of the support system provided and the in situ stress on the time-dependent coefficients are studied. Finally, the long-term stability analysis of diversion tunnels excavated in columnar jointed rock masses is performed.

  8. Population dynamics of arterial cells during atherogenesis. XIII. Mitogenic and cytotoxic effects of a hyperlipidemic (HL) diet on cells in advanced lesions in the abdominal aortas of swine fed an HL diet for 270-345 days.

    PubMed

    Thomas, W A; Kim, D N; Lee, K T; Reiner, J M; Schmee, J

    1983-12-01

    The abdominal aortas of five groups of young male Yorkshire swine were studied: (1) 0-day baseline group; (2) hyperlipidemic (HL) group with ballooning; (3) mash group with ballooning; (4) mash group without ballooning; and (5) HL group without ballooning. The last four groups were injected with [3H]thymidine at 270 days and sacrificed subsequently in subsets at intervals up to 75 days in order to study births and deaths (or loss by migration) among cells over the period 270-345 days. However, only in the HL-ballooned group were there enough swine for the isotopic data to be useful for most purposes. In the 0-day baseline group there were 6 +/- 2 X 10(6) cells in intimal cell masses (ICM); in the 270- to 345-day mash group without ballooning the number was 10 +/- 2 X 10(6), which is not a statistically significant increase over 0-day. This supports the hypothesis that in the normal state births and deaths (or loss by migration) among cells in ICM are nearly balanced at least up to 1 year of age. In the 270- to 345-day mash group with ballooning there were 61 +/- 12 X 10(6) cells in the ICM. Thus a single episode of deendothelialization results in tremendous hyperplasia of ICM. However, even the largest ICM (atherosclerotic lesion) in this group showed essentially no necrosis. In the 270- to 345-day HL group with ballooning there were 108 +/- 17 X 10(6) cells in the ICM turned atherosclerotic lesions. In addition an average of one-third of the lesion volume was occupied by lipid-rich, calcific necrotic debris. Thus the HL diet appears to have associated with it both mitogenic and cytotoxic influences on ICM cells. In the 270- to 345-day HL group not ballooned there were 130 +/- 30 X 10(6) lesion cells and lesions were somewhat more extensive and necrotic than in the HL-ballooned group, probably because the former group included by chance more hyperresponders (as regards serum cholesterol values) to the HL diet than the latter. Regardless of this, the data suggest

  9. Photodynamic effects on T-cells and skin lesions of a patient with mycosis fungoides using porphyrin photosensitizers

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Boehncke, Wolf-Henning; Rueck, Angelika C.; Kaufmann, Roland; Steiner, Rudolf W.; Sterry, Wolfram

    1994-02-01

    PUVA is a well established phototreatment modality for various dermatoses, like T cell lymphomas, using long-wavelength UV radiation. In contrast, PDT bases on the combination of photosensitizers, especially porphyrins, and radiation mainly in the red spectral region. We analyzed the photochemical effects of both treatments on cell lines MyLa and HuT78, established from patients with cutaneous T cell lymphomas. Our observations document the capability of PDT to inhibit proliferation of transformed T cells similar to PUVA thus pointing out its potential in the treatment of cutaneous T cell lymphomas.

  10. Human Adipose-Derived Stem Cells Expanded Under Ambient Oxygen Concentration Accumulate Oxidative DNA Lesions and Experience Procarcinogenic DNA Replication Stress.

    PubMed

    Bétous, Rémy; Renoud, Marie-Laure; Hoede, Claire; Gonzalez, Ignacio; Jones, Natalie; Longy, Michel; Sensebé, Luc; Cazaux, Christophe; Hoffmann, Jean-Sébastien

    2017-01-01

    Adipose-derived stem cells (ADSCs) have led to growing interest in cell-based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA-seq) that culture of ADSCs under atmospheric oxygen concentration leads to misexpression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress-associated transformation, as occurs in neoplastic tissues. Stem Cells Translational Medicine 2017;6:68-76.

  11. Evaluation of the hormonal state of columnar apple trees (Malus x domestica) based on high throughput gene expression studies.

    PubMed

    Krost, Clemens; Petersen, Romina; Lokan, Stefanie; Brauksiepe, Bastienne; Braun, Peter; Schmidt, Erwin R

    2013-02-01

    The columnar phenotype of apple trees (Malus x domestica) is characterized by a compact growth habit with fruit spurs instead of lateral branches. These properties provide significant economic advantages by enabling high density plantings. The columnar growth results from the presence of a dominant allele of the gene Columnar (Co) located on chromosome 10 which can appear in a heterozygous (Co/co) or homozygous (Co/Co) state. Although two deep sequencing approaches could shed some light on the transcriptome of columnar shoot apical meristems (SAMs), the molecular mechanisms of columnar growth are not yet elaborated. Since the influence of phytohormones is believed to have a pivotal role in the establishment of the phenotype, we performed RNA-Seq experiments to study genes associated with hormone homeostasis and clearly affected by the presence of Co. Our results provide a molecular explanation for earlier findings on the hormonal state of columnar apple trees. Additionally, they allow hypotheses on how the columnar phenotype might develop. Furthermore, we show a statistically approved enrichment of differentially regulated genes on chromosome 10 in the course of validating RNA-Seq results using additional gene expression studies.

  12. Krüppel-Like Factor 13 Deficiency in Uterine Endometrial Cells Contributes to Defective Steroid Hormone Receptor Signaling but Not Lesion Establishment in a Mouse Model of Endometriosis.

    PubMed

    Heard, Melissa E; Velarde, Michael C; Giudice, Linda C; Simmen, Frank A; Simmen, Rosalia C M

    2015-06-01

    Krüppel-like Factor (KLF) 13 and the closely related KLF9 are members of the Sp/KLF family of transcription factors that have collectively emerged as essential regulators of tissue development, differentiation, proliferation, and programmed cell death. Steroid hormone-responsive tissues express multiple KLFs that are linked to progesterone receptor (PGR) and estrogen receptor (ESR) actions either as integrators or as coregulators. Endometriosis is a chronic disease characterized by progesterone resistance and dysregulated estradiol signaling; nevertheless, distinct KLF members' contributions to endometriosis remain largely undefined. We previously demonstrated promotion of ectopic lesion establishment by Klf9 null endometrium in a mouse model of endometriosis. Here we evaluated whether KLF13 loss of expression in endometrial cells may equally contribute to lesion formation. KLF13 transcript levels were lower in the eutopic endometria of women with versus women without endometriosis at menstrual midsecretory phase. In wild-type (WT) mouse recipients intraperitoneally administered WT or Klf13 null endometrial fragments, lesion incidence did not differ with donor genotype. No differences were noted for lesion volume, number, proliferation status, and apoptotic index as well. Klf13 null lesions displayed reduced total PGR and ESR1 (RNA and immunoreactive protein) and altered expression of several PGR and ESR1 target genes, relative to WT lesions. Unlike for Klf9 null lesions, changes in transcript levels for PGR-A, ESR1, and Notch/Hedgehog-associated pathway components were not observed for Klf13 null lesions. Results demonstrate lack of a causative relationship between endometrial KLF13 deficiency and lesion establishment in mice, and they support the broader participation of multiple signaling pathways, besides those mediated by steroid receptors, in the pathology of endometriosis.

  13. Th17 and regulatory T cells contribute to the in situ immune response in skin lesions of Jorge Lobo's disease.

    PubMed

    Kanashiro-Galo, Luciane; Pagliari, Carla; Barboza, Tania Cristina; de Brito, Arival Cardoso; Xavier, Marilia Brasil; de Oliveira, Clivia Maria Moraes; Unger, Deborah Aben Athar; Sotto, Mirian Nacagami; Quaresma, Juarez Antonio Simões; Duarte, Maria Irma Seixas

    2016-01-01

    Jorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.

  14. Histomorphometric Analysis of Angiogenesis using CD31 Immunomarker and Mast Cell Density in Oral Premalignant and Malignant Lesions: A Pilot Study

    PubMed Central

    Jyothsna, M; Rammanohar, M

    2017-01-01

    Introduction Mast cells have been implicated in promoting angiogenesis in malignant tumors of lung, oesophagus and breast, but there are few studies on Oral Squamous Cell Carcinomas (OSCC). Most oral squamous cell carcinomas arise from pre-existing precancerous lesions exhibiting epithelial dysplasia. Aim The present pilot study attempts to compare Mast Cell Density (MCD), Microvessel Density (MVD), Microvessel Area (MVA) histomorphometrically between normal buccal mucosa, severe epithelial dysplasia and OSCC and to correlate the role of mast cells and angiogenesis in tumor progression. Material and Methods The retrospective study was conducted on eight cases of OSCC, eight cases of severe epithelial dysplasia and five cases of normal buccal mucosa. Immunohistochemical staining with anti CD–31, to demonstrate angiogenesis and toluidine blue staining for mast cells were employed. MVA, MVD and MCD were calculated using the measurement tools of the image analysis software and compared between the groups. One way ANOVA (Analysis of Variance) was used for comparing the parameter for multiple groups followed by Games Howell test. To assess the relationship between micro vessel density and mast cell density, Karl Pearson’s correlation was used. Results MCD and MVD increased with disease progression and were statistically higher in OSCC than in severe epithelial dysplasia and normal buccal mucosa (p<0.001). MVA increased from normal to severe dysplasia and decreased from dysplasia to OSCC, may be due to revascularization of tumor tissue. A positive correlation was observed between MCD and MVD in OSCC and dysplasia, though were not statistically significant. Conclusion These findings suggest that mast cells may up regulate angiogenesis in OSCC. MCD and MVD may be used as indicators for disease progression. PMID:28274041

  15. [Metastatic penile lesions secondary to transitional cell carcinoma of the bladder: a rare cause of "malignant priapism"].

    PubMed

    Casoli, Eugenio; Di Fiore, Francesco; Longobardi, Santina; Intilla, Oliviero; Pone, Domenico

    2002-03-01

    Metastases to the penis from transitional cell carcinoma of the bladder are rare. In the literature about 300 cases of secondary penile malignancies were described; 35% out of these cases were from primary neoplasms of the bladder. The Authors describe a case of priapism secondary to penile metastases from a transitional cell carcinoma of the bladder.

  16. VEGF-A immunohistochemical and mRNA expression in tissues and its serum levels in potentially malignant oral lesions and oral squamous cell carcinomas.

    PubMed

    Nayak, Seema; Goel, Madhu Mati; Chandra, Saumya; Bhatia, Vikram; Mehrotra, Divya; Kumar, Sandeep; Makker, Annu; Rath, S K; Agarwal, S P

    2012-03-01

    The aim of the study was to investigate whether the estimation of circulating Vascular endothelial growth factor-A (VEGF-A) levels by ELISA could be used as surrogate of VEGF-A expression in tissues of pre-malignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC) as compared to that in healthy controls. The study samples comprised of tissue and blood samples from 60 PMOLs, 60 OSCC, and 20 healthy controls. Serum VEGF-A levels were determined by an ELISA based assay (Quantikine human VEGF; R & D System, Minneapolis USA). Tissue VEGF-A expression and microvessel density (MVD) were assessed by immunohistochemistry (IHC) using antibodies against VEGF-A and CD-34 on formalin fixed paraffin embedded (FFPE) tissue sections. VEGF-A mRNA expression was analyzed by real-time PCR in snap frozen tissues. Serum VEGF-A levels and immunohistochemical VEGF-A expression were significantly high in PMOLs and OSCC in comparison with controls. VEGF mRNA gene expression showed more than 50-fold increase in PMOLs and OSCC. VEGF-A levels in serum correlated in a linear fashion with the tissue expression in oral pre-malignant and malignant lesions, suggesting that the serum levels may serve as surrogate material for tissue expression of VEGF-A.

  17. Squamous cell carcinoma of unknown primary site presenting with an abdominal wall lesion as the primary symptom: A case report and review of the literature

    PubMed Central

    ZHANG, YINGLI; CHEN, BO; ZHU, JIANQING; CHEN, LU

    2015-01-01

    Squamous cell carcinoma of unknown primary site (SC CUP) is a rare malignant tumor, and its histogenesis and appropriate treatment are unclear. To the best of our knowledge, this type of carcinoma with abdominal wall lesions as the primary presenting symptom 3 months after laparoscopic surgery, has not been previously described in the literature. In the present study, a postmenopausal 54-year-old female patient was diagnosed with pain from the right abdominal puncture site 3 months after laparoscopic unilateral left salpingo-oophorectomy at a local hospital, at which time the left ovary and Fallopian tube were free of malignant tumor. Computed tomography (CT) imaging showed a subcutaneous nodule with a size of 6.2×3.3 cm. A wide excision of the lesion with safety margins and repair of the abdominal wall was performed, and the histopathological results and various investigations lead to the diagnosis of metastatic well-differentiated SC CUP. The patient underwent three surgeries and eight cycles of Taxol and cisplatin/carboplatin chemotherapy, and received a total of 10.8 Gy palliative radiation. However, the patient succumbed to intestinal bleeding, thrombocytopenia and multiple organ failure with pelvic recurrence and liver metastases at 10 months post-diagnosis. The prognosis of SC CUP, particularly with multiple metastases, is extremely poor. Although chemotherapy, surgery and radiotherapy have a certain role in the treatment, no regimen has been established as a standard therapy and palliative care could be recommended. PMID:26622812

  18. A glial cell line-derived neurotrophic factor-secreting clone of the Schwann cell line SCTM41 enhances survival and fiber outgrowth from embryonic nigral neurons grafted to the striatum and to the lesioned substantia nigra.

    PubMed

    Wilby, M J; Sinclair, S R; Muir, E M; Zietlow, R; Adcock, K H; Horellou, P; Rogers, J H; Dunnett, S B; Fawcett, J W

    1999-03-15

    We have developed a novel Schwann cell line, SCTM41, derived from postnatal sciatic nerve cultures and have stably transfected a clone with a rat glial cell line-derived neurotrophic factor (GDNF) construct. Coculture with this GDNF-secreting clone enhances in vitro survival and fiber growth of embryonic dopaminergic neurons. In the rat unilateral 6-OHDA lesion model of Parkinson's disease, we have therefore made cografts of these cells with embryonic day 14 ventral mesencephalic grafts and assayed for effects on dopaminergic cell survival and process outgrowth. We show that cografts of GDNF-secreting Schwann cell lines improve the survival of intrastriatal embryonic dopaminergic neuronal grafts and improve neurite outgrowth into the host neuropil but have no additional effect on amphetamine-induced rotation. We next looked to see whether bridge grafts of GDNF-secreting SCTM41 cells would promote the growth of axons to their striatal targets from dopaminergic neurons implanted orthotopically into the 6-OHDA-lesioned substantia nigra. We show that such bridge grafts increase the survival of implanted embryonic dopaminergic neurons and promote the growth of axons through the grafts to the striatum.

  19. Genesis of the columnar joints from welded tuff in Mount Mudeung National Geopark, Republic of Korea

    NASA Astrophysics Data System (ADS)

    Lim, Chungwan; Huh, Min; Yi, Keewook; Lee, Changyeol

    2015-09-01

    Mount Mudeung National Geopark (MMNG), Gwangju, Republic of Korea (1187 masl), is known for its huge, broad occurrences of columnar jointed colonnades in the Cretaceous Mudeungsan Tuff. To understand the genesis of columnar joints infilling a volcanic vent, integrated geochemical and geophysical studies were conducted. Most colonnades in the Geopark are located in regions higher than 700 masl and show elevation-dependent variations in the mean face width of the columns. These mean widths are approximately 1.7, 1.3, 2.9, and 1.2 m for the summit (>1100 masl), upper (950-1100 masl), lower (850-950 masl), and lowest (700-850 masl) colonnades, respectively. This variation implies that columnar jointing resulted from discontinuous tuff depositions on relatively planar ground, which is associated with caldera structures and landslides from the emptied caldera rim. Geochemical analyses of major, minor, and trace elements show that the andesitic-dacitic Mudeungsan Tuff resulted from the arc magmatism associated with subduction of the Izanagi Plate and involved crustal components. Few geochemical variations of the Mudeungsan Tuff indicate that tuff originated from a single magma chamber. U-Pb age dating indicates that the Mudeungsan Tuff was deposited at ~85 Ma except for the Chotdae-bong colonnades, which were dated to ~87 Ma. However, a scaling analysis of the elevation-dependent variations of face widths and simplified numerical model calculations indicate that the variation in face widths with elevation indicates the sequential emplacement, cooling, and compaction of separate welded tuffs. Thus, the welded tuffs of MMNG can be thought to be formed by three discontinuous large explosive eruptions with periods of repose after each eruption. These tuffs include 1) the highest-elevation columnar joints of colonnades in the summit area (>1100 m), corresponding to the lower colonnades of the third tuff; 2) the intermediate-elevation columnar joints of colonnades

  20. Cancer stem cells biomarkers in triple negative invasive carcinoma of the breast and associated in situ lesions.

    PubMed

    Comănescu, Maria; Bussolati, Giovanni

    2014-01-01

    Triple negative breast cancer (TNBC) [negative for expression of estrogen and progesterone receptors (ER, PR) and HER2÷neu protein] represent a subtype of breast cancer associated with poor prognosis and highly aggressive behavior. The characterization of stem cell in this type of carcinoma could determine the appearance of new ideas concerning origin and evolution. There is an impressive amount of data in the literature related to TNBC and a growing interest for stem cell research during the past years, but there are no data concerning the genetic characterization of stem cells in the context of cell biology of TNBC as compared with associated DCIS. We performed immunohistochemical studies for the expression and distribution of several stem cell-related antigens, focusing on the association of TNBC with DCIS and comparing the presence of stem cells in the invasive and in the in situ component. Optimization of detection, identification and characterization of tumorigenic breast cancer stem cells might permit further identification of targeted treatment.

  1. Expression of NO-synthase in cells of foreign-body and BCG-induced granulomata in mice: influence of L-NAME on the evolution of the lesion.

    PubMed Central

    Kreuger, M R; Tames, D R; Mariano, M

    1998-01-01

    The microbicidal activity of macrophages in an inflammatory milieu has been related to the production of a large number of cytokins and intermediary metabolites of oxygen and nitrogen among them, nitric oxide (NO). Considering that granulomatous inflammation is predominantly composed of macrophages and epithelioid cells, we decided to investigate the participation of NO in this peculiar type of inflammation. Two models were used: glass cover slip implantation into the subcutaneous tissue of mice and, the inoculation of live bacillus Calmette-Guérin (BCG) into the footpad of the animals. Using a histochemical method for the detection of NO synthase and of the concentration of citrulin metabolized by cells obtained from cover slips implanted on different time intervals or BCG-activated peritoneal cells, it was possible to demonstrate that epithelioid cells do not produce NO. Cells from granuloma induced by BCG inoculation express NO synthase, with different degrees of reactivity with a higher intensity in the cytoplasm of cells located in the edge of the lesions. The expression of NO synthase in the cytoplasm of these cells decreases with the age of the lesions. It could also be demonstrated that in mice treated with l-name, an inhibitor of NO metabolism, the lesions induced by BCG lost the granulomatous architecture, were necrotic, and had a significant increase in the bacillary load of the lesion. These data allow us to conclude that NO production by macrophages is a determining factor in the organization of the granulomatous lesion and that it also controls the bacterial load in BCG-induced lesions in mice. Images Figure 1 Figure 2 Figure 4 Figure 6 PMID:9824487

  2. Systemic application of 3-methyladenine markedly inhibited atherosclerotic lesion in ApoE−/− mice by modulating autophagy, foam cell formation and immune-negative molecules

    PubMed Central

    Dai, Shen; Wang, Bo; Li, Wen; Wang, Liyang; Song, Xingguo; Guo, Chun; Li, Yulan; Liu, Fengming; Zhu, Faliang; Wang, Qun; Wang, Xiaoyan; Shi, Yongyu; Wang, Jianing; Zhao, Wei; Zhang, Lining

    2016-01-01

    A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E−/− mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls. Furthermore, 3-MA had multiple atheroprotective effects, including modulating macrophage autophagy and foam cell formation and altering the immune microenvironment. Long-term treatment with 3-MA promoted oxidized low-density lipoprotein (oxLDL)-induced macrophage autophagy and suppressed foam cell formation and cell viability in vitro. Furthermore, systemic application of 3-MA promoted lipid droplet breakdown and decreased apoptosis, most likely associated with autophagy. 3-MA treatment strikingly enhanced the expression of immune-negative molecules such as interleukin 10 (IL-10), transforming growth factor β and IL-35, as well as forkhead box P3 (Foxp3), the specific transcriptional factor for regulatory T cells, but did not affect the level of proinflammatory cytokines in the arterial wall. We provide strong evidence for the potential therapeutic benefit of 3-MA in inhibiting atherosclerosis development and improving plaque stability. PMID:27906187

  3. Human Adipose-Derived Stem Cells Expanded Under Ambient Oxygen Concentration Accumulate Oxidative DNA Lesions and Experience Procarcinogenic DNA Replication Stress.

    PubMed

    Bétous, Rémy; Renoud, Marie-Laure; Hoede, Claire; Gonzalez, Ignacio; Jones, Natalie; Longy, Michel; Sensebé, Luc; Cazaux, Christophe; Hoffmann, Jean-Sébastien

    2016-08-24

    : Adipose-derived stem cells (ADSCs) have led to growing interest in cell-based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA-seq) that culture of ADSCs under atmospheric oxygen concentration leads to misexpression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress-associated transformation, as occurs in neoplastic tissues.

  4. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions.

    PubMed

    Siess, W; Zangl, K J; Essler, M; Bauer, M; Brandl, R; Corrinth, C; Bittman, R; Tigyi, G; Aepfelbacher, M

    1999-06-08

    Oxidized low density lipoprotein (LDL) is a key factor in the pathogenesis of atherosclerosis and its thrombotic complications, such as stroke and myocardial infarction. It activates endothelial cells and platelets through mechanisms that are largely unknown. Here, we show that lysophosphatidic acid (LPA) was formed during mild oxidation of LDL and was the active compound in mildly oxidized LDL and minimally modified LDL, initiating platelet activation and stimulating endothelial cell stress-fiber and gap formation. Antagonists of the LPA receptor prevented platelet and endothelial cell activation by mildly oxidized LDL. We also found that LPA accumulated in and was the primary platelet-activating lipid of atherosclerotic plaques. Notably, the amount of LPA within the human carotid atherosclerotic lesion was highest in the lipid-rich core, the region most thrombogenic and most prone to rupture. Given the potent biological activity of LPA on platelets and on cells of the vessel wall, our study identifies LPA as an atherothrombogenic molecule and suggests a possible strategy to prevent and treat atherosclerosis and cardiocerebrovascular diseases.

  5. Manganese-Induced Oxidative DNA Damage in Neuronal SH-SY5Y Cells: Attenuation of thymine base lesions by glutathione and N-acetylcysteine

    PubMed Central

    Stephenson, Adrienne P.; Schneider, Jeffrey A.; Nelson, Bryant C.; Atha, Donald H.; Jain, Ashok; Soliman, Karam F. A.; Aschner, Michael; Mazzio, Elizabeth; Reams, R. Renee

    2013-01-01

    Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson’s disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn2+ in human neuroblastoma SH-SY5Y cells. Mn2+ caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 μM Mn2+ (p <0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn2+ (2 μM, 62 μM or 125 μM). In addition, Mn2+ induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1 mM N-acetylcysteine or 1 mM glutathione reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that 1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA nucleotide base damage, 2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and 3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn2+-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants as a

  6. Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells

    PubMed Central

    Clarkson, Edward D.; Rosa, Francisco G. La; Edwards-Prasad, Judith; Weiland, David A.; Witta, Samir E.; Freed, Curt R.; Prasad, Kedar N.

    1998-01-01

    The replacement of dopamine (DA) by DA neuron transplants in the treatment of advanced Parkinson disease (PD) is a rational approach. Because of limitations associated with fetal tissue transplants, a clone (1RB3AN27) of simian virus 40 large tumor antigen (LTa) gene-induced immortalized DA neurons were used in this study. These allogeneic immortalized dopamine neurons, when grafted into striata of normal rats, did not divide, did not form tumors, did not produce LTa, did not extend neurites to host neurons, and were not rejected, for as long as 13 months after transplantation. Grafted cells when recultured in vitro resumed cell proliferation and LTa production, suggesting the presence of a LTa gene-inhibiting factor in the brain. The grafting of undifferentiated and differentiated 1RB3AN27 cells or differentiated murine neuroblastoma (NBP2) cells into striata of 6-hydroxydopamine-lesioned rats (an animal model of PD) caused a time-dependent improvement in neurological deficits (reduction in the methamphetamine-induced turning rate). At 3 months after transplantation, 100% of the animals receiving differentiated 1RB3AN27 cells, 63% of the animals receiving undifferentiated 1RB3AN27 cells, 56% of the animals receiving differentiated NBP2 cells, and 0% of the sham-transplanted animals showed improvements in neurological deficits. At 6 months after transplantation, there was a progressive increase in spontaneous recovery in sham-transplanted animals. These results suggest that immortalized DA neurons should be further studied for their potential use in transplant therapy in advanced PD patients. PMID:9448320

  7. Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

    PubMed Central

    Yang-chun, Feng; Yuan, Zhang; Cheng-ming, Liu; Yan-chun, Huang; Xiu-min, Ma

    2017-01-01

    Abstract Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells’ lesions in different ethnics women. The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women. The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398–13.910) and 3.279 (CI: 1.069–10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3

  8. A Comparative Study of Inflammatory Myofibroblastic Tumors and Tumefactive IgG4-related Inflammatory Lesions: the Relevance of IgG4 Plasma Cells.

    PubMed

    Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Agarwal, Ritesh; Singh, Navneet; Rao, Katragadda L N

    IgG4-related disease is a recently recognized systemic condition characterized by tumefactive lesions at various sites. Inflammatory pseudotumor (IPT), a tumefactive mass lesion with an unknown etiology, belongs to the spectrum of IgG4-related disease. Inflammatory myofibroblastic tumor (IMT), previously considered under the umbrella of IPT, is now classified as a clonal neoplasm. Previously, both the terms were used interchangeably, because of overlapping morphologic features. This study was carried out to compare the morphologic and the immunohistochemical features of these entities and to study the role of IgG4 in their pathogenesis. Thirty-nine cases comprising of IMT (n=18) and IPT (n=21) were retrieved, and their clinical, morphologic, and immunohistochemical features were studied. IMT was more common in children as compared with IPT. IMT cases showed the proliferation of myofibroblastic cells accompanied by a variable inflammatory infiltrate, whereas IPT cases showed predominantly stromal fibrosis and a lymphoplasmacytic infiltrate with a subset of cases showing a storiform fibrosis and obliterative phlebitis. Anaplastic lymphoma kinase-1 (ALK-1) was positive in 12 of the 18 (66.7%) IMT cases, whereas none of the IPT cases showed ALK-1 immunoreactivity. IPT cases showed significantly increased IgG4+ plasma cells (mean, 127.8/high-power fields vs. 17.8/high-power fields) and a higher IgG4/IgG ratio (mean, 48.2% vs. 10.7%) as compared with IMT. Fluorescence in situ hybridization analysis was positive for ALK rearrangement in 6 of the 9 IMT cases tested. In conclusion, most of the IPT cases can be considered as IgG4 related on the basis of their histopathologic features and immunohistochemistry criteria. However, IMT represents a myofibroblastic neoplasm with ALK-1 overexpression and is clearly not IgG4 related.

  9. Ibotenic acid lesions of the lateral hypothalamus: comparison with the electrolytic lesion syndrome.

    PubMed

    Winn, P; Tarbuck, A; Dunnett, S B

    1984-05-01

    Rats received either ibotenic acid, electrolytic or sham lesions of the lateral hypothalamic area. Compared to sham operated rats, both lesion groups showed aphagia and adipsia following the lesion; this was less severe in the ibotenic acid lesioned rats. Once recovered, the ibotenic acid lesioned rats showed residual regulatory impairments in their compensatory responses to glucoprivation and to extracellular and intracellular dehydration. However, unlike the electrolytic lesioned rats, those with ibotenic acid lesions did not show akinesia and exhibited normal responses to both d-amphetamine and apomorphine. Ibotenic acid lesions resulted in extensive loss of cell bodies within the lateral hypothalamic area while sparing ascending dopamine neurones. The results are interpreted as suggesting that the lateral hypothalamic area and ascending dopamine neurones are components of a single system involved in the regulation of food and water intake.

  10. Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats.

    PubMed

    Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A

    2015-07-01

    Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.

  11. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    PubMed Central

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

  12. Pathogen inactivation of whole blood and red cell components: an overview of concept, design, developments, criteria of acceptability and storage lesion.

    PubMed

    Seghatchian, Jerard; Putter, Jeffrey S

    2013-10-01

    Multilayer preventative strategies have been instituted to enhance transfusion safety for patients in need of critical blood components. Presently blood safety is at its highest levels, with the implementation of precautionary/preventative measures against vCJD, bacterial and viral contamination of the blood supply. The implementation of these strategies together with advances in automation and computerization led to significant improvements in standardisation for transfusion practices. These include validation, verification, adherence to GLP and GMP and other regulatory requirements. In most European countries, universal prestorage leukodepletion is routine practice. In France proactive pathogen inactivation treatments [PITs] have been implemented emphasizing patient safety. This at least conceptually reduces the risk of transfusing viable WBCs, emerging bacteria and viruses, all with potential transfusion complications. In the UK, prion removal filters for red cell products are used selectively for special groups of patients. Some research establishments are exploring the potential impact of pathogen inactivation of whole blood or red cell components, using the new generation of S-303 PIT and the prion removal filters in combination. It needs to be determined whether such a combined strategy, applied synergistically, enhances red cell transfusion safety without compromising the overall criteria of acceptability. It is necessary to critically examine the impact of a new generation of PIT technologies, which may exacerbate the red cell storage lesion and cause the development of undesirable antibodies in the recipient. The development of innovative laboratory tools is vital to study impacts of these measures on the quality of stored blood and their clinical outcome. The ultimate aim of red cell transfusion is to provide oxygen enriched red blood cells to the microcirculations and tissues. Definitive studies are needed to establish the potential unforeseen negative

  13. Modelling the viscoplastic behavior and the heterogeneous intracrystalline deformation of columnar ice polycrystals

    SciTech Connect

    Lebensohn, Ricardo A; Montagnat, Maurine; Mansuy, Philippe; Duval, Paul; Philip, A

    2008-01-01

    A full-field formulation based on Fast Fourier Transforms (FFT) has been adapted and used to predict the micromechanical fields that develop in columnar Ih ice polycrystals deforming in compression by dislocation creep. The predicted intragranular mechanical fields are in qualitative good agreement with experimental observations, in particular those involving the formation of shear and kink bands. These localization bands are associated with the large internal stresses that develop during creep in such anisotropic material, and their location, intensity, morphology and extension are found to depend strongly on the crystallographic orientation of the grains and on their interaction with neighbor crystals. The predictions of the model are also discussed in relation with the deformation of columnar sea and lake ice, and with the mechanical behavior of granular ice of glaciers and polar ice sheets, as well.

  14. Evidence for columnar order in the fully frustrated transverse field Ising model on the square lattice.

    PubMed

    Wenzel, Sandro; Coletta, Tommaso; Korshunov, Sergey E; Mila, Frédéric

    2012-11-02

    Using extensive classical and quantum Monte Carlo simulations, we investigate the ground-state phase diagram of the fully frustrated transverse field Ising model on the square lattice. We show that pure columnar order develops in the low-field phase above a surprisingly large length scale, below which an effective U(1) symmetry is present. The same conclusion applies to the quantum dimer model with purely kinetic energy, to which the model reduces in the zero-field limit, as well as to the stacked classical version of the model. By contrast, the 2D classical version of the model is shown to develop plaquette order. Semiclassical arguments show that the transition from plaquette to columnar order is a consequence of quantum fluctuations.

  15. Discotic columnar liquid crystal studied in the bulk and nanoconfined states by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Busselez, Rémi; Cerclier, Carole V.; Ndao, Makha; Ghoufi, Aziz; Lefort, Ronan; Morineau, Denis

    2014-10-01

    A prototypical Gay Berne discotic liquid crystal was studied by means of molecular dynamics simulations both in the bulk state and under confinement in a nanoporous channel. The phase behavior of the confined system strongly differs from its bulk counterpart: the bulk isotropic-to-columnar transition is replaced by a continuous ordering from a paranematic to a columnar phase. Moreover, a new transition is observed at a lower temperature in the confined state, which corresponds to a reorganization of the intercolumnar order. It reflects the competing effects of pore surface interaction and genuine hexagonal packing of the columns. The translational molecular dynamics in the different phases has been thoroughly studied and discussed in terms of collective relaxation modes, non-Gaussian behavior, and hopping processes.

  16. Thermally activated Hall creep of flux lines from a columnar defect

    NASA Astrophysics Data System (ADS)

    Gorokhov, D. A.; Blatter, G.

    1998-02-01

    We analyze the thermally activated depinning of an elastic string (line tension ɛ) governed by Hall dynamics from a columnar defect modeled as a cylindrical potential well of depth V0 for the case of a small external force F. An effective one-dimensional-field Hamiltonian is derived in order to describe the two-dimensional string motion. At high temperatures the decay rate is proportional to F5/2T-1/2exp[F0/F-U(F)/T], with F0 a constant of order of the critical force and U(F)~(ɛV0)1/2V0/F the activation energy. The results are applied to vortices pinned by columnar defects in superclean superconductors.

  17. Topological Control of Columnar Stacking Made of Liquid‐Crystalline Thiophene‐Fused Metallonaphthalocyanines

    PubMed Central

    Suzuki, Hiroyuki; Kawano, Koki; Ohta, Kazuchika; Shimizu, Yo; Kobayashi, Nagao

    2015-01-01

    Abstract The spontaneous organization of two‐dimensional polyaromatic molecules into well‐defined nanostructures through noncovalent interactions is important in the development of organic‐based electronic and optoelectronic devices. Two regioisomers of thiophene‐fused zinc naphthalocyanines ZnTNcendo and ZnTNcexo have been designed and synthesized to obtain photo‐ and electroactive liquid crystalline materials. Both compounds exhibited liquid crystalline behavior over a wide temperature range through intermolecular π–π interactions and local phase segregation between the aromatic cores and peripheral side chains. The structural differences between ZnTNcendo and ZnTNcexo affected the stacking mode in self‐assembled columns, as well as symmetry of the two‐dimensional rectangular columnar lattice. The columnar structure in liquid crystalline phase exhibited an ambipolar charge‐transport behavior. PMID:27308226

  18. Isolation and identification of flavobacterium columnare and Steptococcus iniae antibacterial compounds from the terrestrial plant Atraphaxis laetevirens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, enteric septicemia of catfish, and streptococcosis are common bacterial diseases of certain freshwater fish and are caused by Flavobacterium columnare, Edwardsiella ictaluri, and Streptococcus iniae, respectively. Various plants were selected to evaluate, isolate, and identify co...

  19. In vitro comparisons of the inhibitory activity of florfenicol copper sulfate and potassium permanganate towards Aeromonas hydrophila and Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aeromonas hydrophila and Flavobacterium columnare, the etiological agents of motile aeromonas septicemia (MAS) and columnaris disease, respectively, have been recently causing crippling moralities to the sunshine bass, Morone chrysops female X Morone saxatilis male (Percichthyidae), industry in the ...

  20. Quality control ranges for testing broth microdilution susceptibility of Flavobacterium columnare and F. psychrophilium to nine antimicrobials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A multi-laboratory broth microdilution method trial was performed to standardize the specialized test conditions required for fish pathogens Flavobacterium columnare and F. pyschrophilum. Nine laboratories tested the quality control (QC) strains Escherichia coli ATCC 25922 and Aeromonas salmonicid...

  1. Organization of columnar inputs in the third optic ganglion of a highly visual crab.

    PubMed

    Bengochea, Mercedes; Berón de Astrada, Martín

    2014-01-01

    Motion information provides essential cues for a wide variety of animal behaviors such as mate, prey, or predator detection. In decapod crustaceans and pterygote insects, visual codification of object motion is associated with visual processing in the third optic neuropile, the lobula. In this neuropile, tangential neurons collect motion information from small field columnar neurons and relay it to the midbrain where behavioral responses would be finally shaped. In highly ordered structures, detailed knowledge of the neuroanatomy can give insight into their function. In spite of the relevance of the lobula in processing motion information, studies on the neuroarchitecture of this neuropile are scant. Here, by applying dextran-conjugated dyes in the second optic neuropile (the medulla) of the crab Neohelice, we mass stained the columnar neurons that convey visual information into the lobula. We found that the arborizations of these afferent columnar neurons lie at four main lobula depths. A detailed examination of serial optical sections of the lobula revealed that these input strata are composed of different number of substrata and that the strata are thicker in the centre of the neuropile. Finally, by staining the different lobula layers composed of tangential processes we combined the present characterization of lobula input strata with the previous characterization of the neuroarchitecture of the crab's lobula based on reduced-silver preparations. We found that the third lobula input stratum overlaps with the dendrites of lobula giant tangential neurons. This suggests that columnar neurons projecting from the medulla can directly provide visual input to the crab's lobula giant neurons.

  2. Columnar architecture sculpted by GABA circuits in developing cat visual cortex.

    PubMed

    Hensch, Takao K; Stryker, Michael P

    2004-03-12

    The mammalian visual cortex is organized into columns. Here, we examine cortical influences upon developing visual afferents in the cat by altering intrinsic gamma-aminobutyric acid (GABA)-mediated inhibition with benzodiazepines. Local enhancement by agonist (diazepam) infusion did not perturb visual responsiveness, but did widen column spacing. An inverse agonist (DMCM) produced the opposite effect. Thus, intracortical inhibitory circuits shape the geometry of incoming thalamic arbors, suggesting that cortical columnar architecture depends on neuronal activity.

  3. Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions

    PubMed Central

    Yang, Ju-Hye; Yoo, Jae-Myung; Cho, Won-Kyung; Ma, Jin Yeul

    2016-01-01

    Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms. PMID:27065570

  4. Hypersensitivity to mutation and sister-chromatid-exchange induction in CHO cell mutants defective in incising DNA containing UV lesions

    SciTech Connect

    Thompson, L.H.; Brookman, K.W.; Dillehay, L.E.; Mooney, C.L.; Carrano, A.V.

    1982-01-01

    Five UV-sensitive mutant strains of CHO cells representing different genetic complementation groups were analyzed for their ability to perform the incision step of nucleotide excision repair after UV exposure. The assay utilized inhibitors of DNA synthesis to accumulate the short-lived strand breaks resulting from repair incisions. After 6 J/m/sup 2/, each of the mutants showed < 10% of the incision rate of the parental AA8 cells. After 50 J/m/sup 2/, the rate in AA8 was similar to that at 6 J/m/sup 2/, but the rates in the mutants were significantly higher (approx. 20% of the rate of AA8). Thus by this incision assay the mutants were phenotypically indistinguishable. Each of the mutants were hypersensitive to mutation induction at both the hprt and aprt loci by a factor of 10, and in the one strain tested ouabain resistance was induced sevenfold more efficiently than in AA8 cells. Sister chromatid exchange was also induced with sevenfold increased efficiency in the two mutant strains examined. Thus, here CHO mutants resemble xeroderma pigmentosum cells in terms of their incision defects and their hypersensitivity to DNA damage by UV.

  5. Use of nanoporous columnar thin film in the wafer-level packaging of MEMS devices

    NASA Astrophysics Data System (ADS)

    Lee, Byung-Kee; Choi, Dong-Hoon; Yoon, Jun-Bo

    2010-04-01

    This paper presents a new packaging technology that uses a nanoporous columnar thin film to seal microelectromechanical system (MEMS) devices at the wafer level. In the proposed packaging process, the processing temperature is 350 °C. The process is relatively inexpensive compared to wafer level packaging processes, because the wafer-bonding step is eliminated and the die size is shrunk. In the suggested approach, a sputtered columnar thin film at room temperature forms vertical nanopores as etch holes, and an air cavity is formed by the removal of a sacrificial layer through the nanopores in the columnar membrane. Subsequent hermetic vacuum packaging of the cavity is achieved by depositing thin films over the membrane under low pressure. The hermeticity of the packaging was verified by using an optical surface morphology microscope to measure the deflection change of the sealing membrane before and after breaking of the vacuum through an interconnected membrane. The long-term hermeticity was monitored by measuring the maximum central deflection of the PECVD sealing layer over a period of 170 days. The precise pressure (0.7 Torr) and short-term (30 days) pressure change inside the cavity were measured by encapsulated Ni Pirani gauges, representing packaged freestanding MEMS devices.

  6. Rock Cracking Indices for Improved Tunnel Support Design: A Case Study for Columnar Jointed Rock Masses

    NASA Astrophysics Data System (ADS)

    Feng, Xia-Ting; Hao, Xian-Jie; Jiang, Quan; Li, Shao-jun; Hudson, John A.

    2016-06-01

    Measurements indicate that the development of cracking is a key feature relating to the strength and collapse of a columnar jointed rock mass. In this context, a new support design method utilising rock cracking indices for columnar jointed rock mass under high stress is proposed to restrain the development of cracking in the surrounding rock mass. The method involves limiting the cracking evolution of the surrounding rock mass by designing the appropriate parameters and time of installation of the support system. Two indices are suggested: the allowable depth of the excavation damaged zone (EDZ); and the allowable damage extent of the rock mass in the EDZ. The method involves limiting the evolution of cracking in the surrounding rock mass by designing the parameters and time of installation of the support system. The support system should have a suitable stiffness and installation time so as to restrain the evolution of the depth and damage extent of the EDZ within the surrounding rock. Therefore, the depth and damage extent of the EDZ, as well as the axial stress in the anchor bolts, are calculated at different distances between the support location and the tunnel working face to find the appropriate stiffness and installation time of the support system. The method has been successfully adopted to determine the thickness of shotcrete, the arrangement and installation time of rockbolts, and other parameters, for five large diversion tunnels at the Baihetan hydropower station, China, which were excavated in columnar jointed rock masses.

  7. MH-DAB gene polymorphism and disease resistance to Flavobacterium columnare in grass carp (Ctenopharyngodon idellus).

    PubMed

    Yu, Hui; Tan, Shuwen; Zhao, Hongjuan; Li, Hua

    2013-09-10

    In this study, the association between MH-DAB gene polymorphism and disease resistance was evaluated by challenging grass carp (Ctenopharyngodon idellus) with Flavobacterium columnare. Eight genotypes and six alleles were found, and named by common nomenclature. The genotypes AA, BB, EE, and DE, and the alleles Ctid-DAB1*0101, Ctid-DAB1*0201 and Ctid-DAB1*0401 were more preponderant in fish. The genotype BB was associated with higher resistance to F. columnare, as well as two alleles Ctid-DAB*0101 and Ctid-DAB*0201. Allele Ctid-DAB*0102 has decreased resistance to F. columnare. The expression of MH-DAB gene was decreased in the liver, kidney, and intestine but not in the spleen, gill, and skin at 2 days post infection (dpi), versus to that in the control group. MH-DAB gene expression was up-regulated in most tissues but remained at normal levels in the intestine at 15 days post infection. Our data suggested that MH-DAB polymorphism can be used as a potential genetic marker for disease resistance breeding of grass carp in the future.

  8. Estimation of columnar concentrations of absorbing and scattering fine mode aerosol components using AERONET data

    NASA Astrophysics Data System (ADS)

    Choi, Yongjoo; Ghim, Young Sung

    2016-11-01

    Columnar concentrations of absorbing and scattering components of fine mode aerosols were estimated using Aerosol Robotic Network (AERONET) data for a site downwind of Seoul. The study period was between March 2012 and April 2013 including the period of the Distributed Regional Aerosol Gridded Observation Networks (DRAGON)-Asia campaign in March to May 2012. The Maxwell Garnett mixing rule was assumed for insoluble components embedded in a host solution, while the volume average mixing rule was assumed for the aqueous solution of soluble components. During the DRAGON-Asia campaign the surface concentrations of major components of fine particles were measured. The columnar mass fractions of black carbon (BC), organic carbon (OC), mineral dust (MD), and ammonium sulfate (AS) were 1.5, 5.9, 6.6, and 52%, respectively, which were comparable to the mass fractions measured at the surface for BC, OC, and secondary inorganic aerosols at 2.3, 18, and 55%. The vertical distributions of BC and AS were investigated by employing the concept of a column height. While the column height for BC was similar to the planetary boundary layer (PBL) height, that for AS was 4.4 times higher than the PBL height and increased with air temperature from March to May. The monthly variations of the columnar mass concentrations during the study period were generally well explained in term of meteorology and emission characteristics. However, certain variations of MD were different from those typically observed primarily because only fine mode aerosols were considered.

  9. Growth and survival of the fish pathogenic bacterium, Flavobacterium columnare, in tilapia mucus and porcine gastric mucin.

    PubMed

    Shoemaker, Craig A; LaFrentz, Benjamin R

    2015-02-01

    Flavobacterium columnare, an economically important Gram-negative bacterium of freshwater farmed fish, colonizes the skin and gills in the initial steps of pathogenesis. The surface of fish is coated with mucus made up of high molecular weight glycoproteins. Limited studies have described the ability of bacterial pathogens to grow in fish mucus. Our objective was to determine if F. columnare isolates could grow and survive in formulated water (FW) containing autoclaved tilapia mucus or porcine gastric mucin. We demonstrated the ability of F. columnare genomovars I, II, II-B and III to replicate (2-3 logs) and survive (21 to >100 days) in FW containing tilapia mucus. In a second experiment, genomovar I and II isolates were found to replicate in FW containing tilapia mucus or porcine mucin but not in FW only. From a practical standpoint, fish handling and/or hauling results in stress that leads to mucus sloughing often with subsequent F. columnare infection. Flavobacterium columnare utilizes fish mucus as a nutrient source, and studies are underway to determine if growth in mucus or mucin results in differential protein expression and/or increased virulence of F. columnare towards fish.

  10. Lack of association between Flavobacterium columnare genomovar and virulence in hybrid tilapia Oreochromis niloticus (L.)×Oreochromis aureus (Steindachner).

    PubMed

    Shoemaker, C A; LaFrentz, B R

    2015-05-01

    Columnaris disease can be problematic in tilapia (Oreochromis spp.) production. An understanding of the pathogenesis and virulence of Flavobacterium columnare is needed to develop prevention strategies. The objective of this study was to determine the virulence of genetically defined isolates of F. columnare in sex-reversed hybrid tilapia, Oreochromis niloticus (L.)×O. aureus (Steindachner). A series of immersion challenge trials were performed using isolates of the five established genomovars of F. columnare: I, II, II-B, III and I/II. The mean per cent mortality of fish challenged with genomovar I, II and III isolates ranged from 0 to 100, 3.3-78 and 3.3-75%, respectively. The mean per cent mortality of fish challenged with genomovar II-B ranged from 35 to 96.7%, and the only genomovar I/II isolate tested caused no mortality. Contrary to previous work in other fish species, there did not appear to be an association between F. columnare genomovar and virulence in tilapia. The challenge model used resulted in acute mortality. An alternative challenge model was tested by cohabitating healthy fish with dead fish infected with F. columnare. This method resulted in rapid appearance of clinical signs and mortality, suggesting the potential for F. columnare to increase in virulence upon growth on/in a fish host.

  11. Weeding atypical glandular cell look-alikes from the true atypical lesions in liquid-based Pap tests: a review.

    PubMed

    Wood, Moira D; Horst, Julie A; Bibbo, Marluce

    2007-01-01

    The purpose of this review is to identify features that separate atypical glandular cells (AGC) associated with glandular neoplasia from its mimickers, both benign and neoplastic. We reviewed cases of AGC diagnosed on liquid-based Pap tests (LBP) for which corresponding histological follow-up was available. A review of the literature for similar studies in LBP tests was also conducted. We find that certain benign mimics can be reliably separated from AGC, but recommend caution in attempting to increase specificity at the risk of losing sensitivity. Although accounting for only a small percentage of diagnoses AGC require a thorough clinical evaluation, including colposcopy. Most cases are ultimately found to be benign. When evaluating smears suspicious for AGC, it is important to examine the subtle features which make truly atypical cells discernible from their numerous benign mimickers.

  12. Identification of the novel lesion 8,5'-cyclo-2'-deoxyguanosine in DNA isolated from. gamma. -irradiated human cells

    SciTech Connect

    Dizdaroglu, M.; Dirksen, M.L.; Simic, M.G.; Robbins, J.H.

    1986-05-01

    The authors used capillary gas chromatography (GC)-mass spectrometry (MS) to detect damage in DNA from ..gamma..-irradiated viable cells. Epstein-Barr virus-transformed peripheral blood B-lymphocytes (lines GM 130 and RB 4580) were ..gamma..-irradiated at 0/sup 0/C at 1 to 10 krad (8.2 krad/min). The cells were immediately lysed with sodium dodecyl sulfate and incubated with proteinase K. The DNA was isolated by phenol-chloroform extractions, ethanol precipitations, and RNase A digestion. The DNA was hydrolyzed to 2'-deoxyribonucleosides with a mixture of DNase I, venom and spleen exonucleases, and alkaline phosphatase. The hydrolysate was dried, trimethylsilylated, and analyzed by GC-MS with selected-ion monitoring. Chromatographic retention time and mass spectrum were determined for a trimethylsilylated sample of authentic 8,5'-cyclo-2'-deoxyguanosine (8,5'-cyclo-dGuo). DNA from ..gamma..-irradiated cells gave the characteristic ions of this compound with proper relative intensities. Formation of 8,5'-cyclo-dGuo was dose-dependent. It was detectable in ca. 0.05 mg of DNA from cells irradiated at doses as low as 1 krad. The (5'R)- and the (5'S)-epimer of 8,5'-cyclo-dGuo were observed in a ratio of 1 to 3. The formation of 8,5'-cyclo-dGuo is believed to involve hydrogen atom abstraction from the carbon-5' of 2'-deoxyribose by radiation-generated OH radicals followed by intramolecular cyclization between carbon-5' and carbon-8 and subsequent oxidation of the resulting nitrogen-7 radical.

  13. Example based lesion segmentation

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2014-03-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  14. Putative roles for a rhamnose binding lectin in Flavobacterium columnare pathogenesis in channel catfish Ictalurus punctatus.

    PubMed

    Beck, Benjamin H; Farmer, Bradley D; Straus, David L; Li, Chao; Peatman, Eric

    2012-10-01

    Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide and commonly leads to tremendous losses of both wild and cultured freshwater fish, particularly in intensively farmed aquaculture species such as channel catfish. Despite its ecologic and economic impacts, the fundamental molecular mechanisms of the host immune response to this pathogen remain unclear. While F. columnare can induce marked pathologic changes in numerous ectopic tissues, the adhesion of F. columnare to the gill in particular is strongly associated with pathogen virulence and host susceptibility. Recently, in this regard, using RNA-seq expression profiling we found that a rhamnose-binding lectin (RBL) was dramatically upregulated in the gill of fish infected with F. columnare (as compared to naïve fish). Thus, in the present study we sought to further characterize and understand the RBL response in channel catfish (Ictalurus punctatus). We first identified two distinct catfish families with differential susceptibilities to columnaris disease; one family was found to be completely resistant while the other was susceptible (0% mortality versus 18.3% respectively, P < 0.001). Exclusively, in the susceptible family, we observed an acute and robust upregulation in catfish RBL that persisted for at least 24 h (P < 0.05). To elucidate whether RBL play a more direct role in columnaris pathogenesis, we exposed channel catfish to different doses of the putative RBL ligands l-rhamnose and d-galactose, and found that these sugars, protected channel catfish against columnaris disease, likely through competition with F. columnare binding of host RBL. Finally, we examined the role of nutritional status on RBL regulation and found that RBL expression was upregulated (>120-fold; P < 0.05) in fish fasted for 7 d (as compared to fish fed to satiation daily), yet expression levels returned to those of satiated fish within 4 h after re

  15. Fast magnetic response in gigahertz-band for columnar-structured Fe nanoparticle assembly

    SciTech Connect

    Ogawa, T. Tate, R.; Kura, H.; Oikawa, T.; Hata, K.

    2014-05-07

    High density Fe-based ferromagnetic nanoparticle (NP) assembly is expected to have unique magnetic properties, such as superferromagnetism and super-spin-glass, different from magnetically isolated NP systems due to strong dipole interactions among the NPs. A high dipole interaction field, H{sub dip}, of ∼3.5 kOe can result in a high effective internal field to the magnetic moment of the NP, expecting for ultra-fast magnetic response, that is, a high magnetic resonance frequency, f{sub r}, of ∼10 GHz. However, for a simply molded Fe NP assembly, a low f{sub r} was observed due to inhomogeneous distribution of the internal field, implying the necessity of a unidirectional state of H{sub dip} for higher f{sub r}. In this study, we fabricated a columnar Fe NP assembly for realizing the unidirectional state of H{sub dip} by applying our uniquely developed external field-induced agglomeration method for monodispersed Fe NPs (13 nm in average size) as a function of the field (0–30 kOe) and volume fraction of the Fe NPs (0.5%–51%) in a polymer matrix with dimensions of 4 mm × 4 mm × 0.7 mm{sup t}. A columnar-structured Fe NP assembly was successfully achieved along an in-plane direction (defined as the x-axis) under optimized conditions. From static magnetization curves, induced uniaxial magnetic anisotropy was observed according to the shape of the columnar structure of the Fe NP assembly, where easy and hard axes of magnetization were realized along the parallel (x-axis) and normal directions (in-plane y-axis and z-axis in the thickness direction) to the external field during the process, respectively. Interestingly, this fabricated columnar-structured Fe NP assembly exhibited very high f{sub r} in the range from 3 to 11 GHz judging from the complex susceptibility spectra obtained. The f{sub r} values were well-scaled by a modified Snoek's-limit-law using demagnetization factors quantitatively estimated from the static magnetization curves. Thus, shape

  16. Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic.

    PubMed

    Ho, M W; Field, E A; Field, J K; Risk, J M; Rajlawat, B P; Rogers, S N; Steele, J C; Triantafyllou, A; Woolgar, J A; Lowe, D; Shaw, R J

    2013-10-01

    Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.

  17. Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium.

    PubMed

    Pankova, Olga V; Denisov, Evgeny V; Ponomaryova, Anastasia A; Gerashchenko, Tatiana S; Tuzikov, Sergey A; Perelmuter, Vladimir M

    2016-03-01

    Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77-258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23-3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69-1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5 %; effect size -6.26, 95 % CI -7.31 to -5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.

  18. Brainstem tegmental lesions in neonates with hypoxic-ischemic encephalopathy: Magnetic resonance diagnosis and clinical outcome

    PubMed Central

    Quattrocchi, Carlo Cosimo; Fariello, Giuseppe; Longo, Daniela

    2016-01-01

    Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy (HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supra-tentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults. PMID:26981220

  19. The secreted autotransporter toxin, Sat, functions as a virulence factor in Afa/Dr diffusely adhering Escherichia coli by promoting lesions in tight junction of polarized epithelial cells.

    PubMed

    Guignot, Julie; Chaplais, Cécile; Coconnier-Polter, Marie-Hélène; Servin, Alain L

    2007-01-01

    Afa/Dr diffusely adhering Escherichia coli (DAEC) strains are responsible for urinary tract and intestinal infections. Both in intestine and kidney, the epithelial cells forming epithelium are sealed by junctional domains. We provide evidence that the Secreted autotransporter toxin, Sat, belonging to the subfamily of serine protease autotransporters of Enterobacteriaceae (SPATEs), acts as a virulence factor in Afa/Dr DAEC by promoting lesions in the tight junctions (TJs) of polarized epithelial Caco-2/TC7 cells. Southern blot analysis reveals that the prototype strains of the subclass-1 and subclass-2 typical Afa/Dr DAEC strains, hybridize with a sat probe. Using the wild-type IH11128 strain, the recombinant E. coli AAEC185 strain that expresses Sat, the recombinant E. coli that expresses both Dr adhesin and Sat, we report that Sat in monolayers of cultured enterocyte-like Caco-2/TC7 cells, induces rearrangements of the TJs-associated proteins ZO-1, ZO-3 and occludin, and increases the formation of domes as the result of an increase in the paracellular permeability without affecting the transepithelial electrical resistance of the cell monolayers. Moreover, we observe that Sat-induced disassembly of TJs-associated proteins is dependent on the serine protease motif. Finally, an analysis of the prevalence of the sat gene in three collections of Afa/Dr DAEC strains collected from the stools of children with and without diarrhoea, and from the urine of patients with urinary tract infection (UTI) shows that: (i) the sat gene is highly prevalent in UTI-associated Afa/Dr DAEC strains (88% positive), (ii) the sat gene is generally absent from Afa/Dr DAEC strains collected from the stools of children without diarrhoea (16% positive); whereas (iii) it is present in about half of the strains collected from the stools of children with diarrhoea (46% positive).

  20. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  1. Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

    PubMed

    Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

    2013-10-01

    Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC.

  2. [Direct assay of radiation-induced DNA base lesions to mammalian cells]. Final progress report, September 1, 1991--November 1, 1993

    SciTech Connect

    Not Available

    1993-12-31

    We have successfully developed the GC/MS technique so that an assessment of base damage in mammalian cells can be accomplished. The technique now has a sensitivity that will allow one to perform research in the low dose region suitable for hazards evaluation. The research on the hydrated DNA molecule has been seminal in generating a better understanding of the mechanisms by which low LET radiation induces DNA damage in mammalian cells. Also reported here are (1) the methodology for hydrating and irradiating DNA has been developed, (2) the procedures for identifying and quantitating radiation-induced DNA damage by HPLC and GC/MS have been mastered, (3) an hypotheses that radiation-induced damage in closely associated water molecules can result in DNA damage which is indistinguishable from that caused by direct ionization of the DNA has been generated and supported by experimental data, and (4) mathematical expressions that relate DNA lesion formation to the important parameters in the above hypotheses have been constructed so that the predictions of the hypotheses can now be tested.

  3. Spontaneous proliferative lesions of the adrenal medulla in aging Long-Evans rats. Comparison to PC12 cells, small granule-containing cells, and human adrenal medullary hyperplasia.

    PubMed

    Tischler, A S; DeLellis, R A; Perlman, R L; Allen, J M; Costopoulos, D; Lee, Y C; Nunnemacher, G; Wolfe, H J; Bloom, S R

    1985-10-01

    Aging rats of the Long-Evans strain spontaneously develop diffuse and nodular hyperplasia of the adrenal medulla in association with other abnormalities commonly encountered in human multiple endocrine neoplasia syndromes. The cells which comprise the adrenal nodules resemble those in the parent tumor of the rat PC12 pheochromocytoma cell line in that they show varying degrees of spontaneous or nerve growth factor-induced neurite outgrowth in culture and they contain little or no epinephrine. In addition, cells from at least some of the nodules contain immunoreactive neurotensin and neuropeptide-Y, which are also found in PC12 cells. There are a number of striking resemblances between the cells in adrenal nodules and the small granule-containing cells in the normal rodent adrenal. The findings suggest that spontaneous rat adrenal medullary nodules and PC12 cells might be derived from small granule-containing cells, or that cells within the nodules might regain properties of immature chromaffin cells and acquire characteristics of small granule-containing cells and of PC12 cells in the course of neoplastic progression. They further suggest a possible relationship between proliferative capacity and neurotransmitter phenotype in the adult rat adrenal medulla. By virtue of their sparse epinephrine content and their small granules, the cells in adrenal medullary nodules of Long-Evans rats differ from those in adrenal medullary nodules of humans with multiple endocrine neoplasia syndromes.

  4. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma.

    PubMed

    Yamaguchi, Takahiro; Ohshima, Koichi; Tsuchiya, Takeshi; Suehuji, Hiroaki; Karube, Kennosuke; Nakayama, Juichiro; Suzumiya, Junji; Yoshino, Tadashi; Kikuchi, Masahiro

    2003-01-01

    Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1). In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial. In the present study, to discriminate MF and cutaneous lesion of ATLL using immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not in any MF cases. OX40 was expressed in the large transformed cell population in both disorders. These findings suggest that CLA and ST2 could be potentially useful immunohistochemical markers for discrimination of mycosis fungoides and cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker for the histopathological progression of both disorders.

  5. Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: a metabolomics overview

    PubMed Central

    Pallotta, Valeria; Gevi, Federica; D’Alessandro, Angelo; Zolla, Lello

    2014-01-01

    Background Recent advances in red blood cell metabolomics have paved the way for further improvements of storage solutions. Materials and methods In the present study, we exploited a validated high performance liquid chromatography-mass spectrometry analytical workflow to determine the effects of vitamin C and N-acetylcysteine supplementation (anti-oxidants) on the metabolome of erythrocytes stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol medium under blood bank conditions. Results We observed decreased energy metabolism fluxes (glycolysis and pentose phosphate pathway). A tentative explanation of this phenomenon could be related to the observed depression of the uptake of glucose, since glucose and ascorbate are known to compete for the same transporter. Anti-oxidant supplementation was effective in modulating the redox poise, through the promotion of glutathione homeostasis, which resulted in decreased haemolysis and less accumulation of malondialdehyde and oxidation by-products (including oxidized glutathione and prostaglandins). Discussion Anti-oxidants improved storage quality by coping with oxidative stress at the expense of glycolytic metabolism, although reservoirs of high energy phosphate compounds were preserved by reduced cyclic AMP-mediated release of ATP. PMID:25074788

  6. BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells

    PubMed Central

    Ying, Songmin; Myers, Katie; Bottomley, Sarah; Helleday, Thomas; Bryant, Helen E.

    2009-01-01

    Arsenic exposure constitutes one of the most widespread environmental carcinogens, and is associated with increased risk of many different types of cancers. Here we report that arsenite (As[III]) can induce both replication-dependent DNA double-strand breaks (DSB) and homologous recombination (HR) at doses as low as 5 µM (0.65 mg/l), which are within the typical doses often found in drinking water in contaminated areas. We show that the production of DSBs is dependent on active replication and is likely to be the result of conversion of a DNA single-strand break (SSB) into a toxic DSB when encountered by a replication fork. We demonstrate that HR is required for the repair of these breaks and show that a functional HR pathway protects against As[III]-induced cytotoxicity. In addition, BRCA2-deficient cells are sensitive to As[III] and we suggest that As[III] could be exploited as a therapy for HR-deficient tumours such as BRCA1 and BRCA2 mutated breast and ovarian cancers. PMID:19553191

  7. Increased number of IL-2, IL-2 receptor and IL-10 positive cells in premalignant lesions of the cervix.

    PubMed

    Mindiola, Raimy; Caulejas, Diana; Núñez-Troconis, José; Araujo, Mary; Delgado, Mariela; Mosquera, Jesús

    2008-12-01

    Previous studies have shown the involvement of the immune response in the progression of human uterine cervix cancer. The aim of this study was to determine the expression of Interleukin-2 (IL-2), IL-2 receptor (IL-2R) and Interleukin 10 (IL-10) in different grades of cervical intraepithelial neoplasias of the exocervix (CIN 1, 2 and 3), and its relationship with the serum cytokine profiles and human papilomavirus (HPV) infection status. Indirect immunofluorescence was used to study the expression of IL-2, IL-2R and IL-10 in human cervical samples from 50 patients and 9 normal controls. Serum IL-2, IL-2R and IL-10 were measured by ELISA and HPV DNA and HPV types were identified by PCR. Increased number of IL-2, IL-2R and IL-10 positive cells were observed in the cervix from patients with CIN, associated with the grades of dysplasia. A significant correlation was observed between IL-2 and IL-2R (p>0.0001), IL-2 and IL-10 (p>0.0001), as well as IL-10 and IL-2R (p>0.0001). Twenty percent of patients were HPV positive and 84% of those patients were tissue cytokine positive. These results suggest that IL-2, IL-2R and IL-10 tissue expression may play a role in the development of cervical intraepithelial dysplasias.